Structure, Expression, and Regulation of UDP-GlcNAc: Dolichol Phosphate GlcNAc-1-Phosphate Transferase (DPAGT1)

Abstract

Glycosylation of proteins on asparagine amino acids (N-linked) in proteins of eukaryotic cells is initiated by the biosynthesis of dolichol-pyrophosphate-N-acetylglucosamine from dolichol-phosphate and UDP-N-acetylglucosamine. The enzyme catalyzing this reaction, UDP-GlcNAc:Dolichol Phosphate GlcNAc-1-Phosphate Transferase (DPAGT1), has been further characterized in several cell types with respect to its gene, gene products, membrane topology, functional sites, lipid dependence, and metabolic regulation. This review summarizes these properties as an update from an earlier detailed and critical review by Lehrman (Lehrman, M. A. (1991) Glycobiology, 1, 553-562).

Protein N-glycosylation in oral cancer: Dysregulated cellular networks among DPAGT1, E-cadherin adhesion and canonical Wnt signaling

“…N-Glycosylation is initiated in the endoplasmic reticulum (ER) by the dolichol phosphate-dependent N -acetylglucosamine 1-phospho-transferase (GPT), encoded by the DPAGT1 gene (Rine et al 1983; Bretthauer 2009; Aebi 2013). GPT catalyzes the transfer of N -acetylglucosamine (GlcNAc) from UDP-GlcNAc to dolichol phosphate to produce dolichol-PP-GlcNAc, which is the first step in the synthesis of a lipid-linked oligosaccharide (LLO) precursor (Figure 1).…”

“…DPAGT1 functions at a rate-limiting step in the N-glycosylation pathway, so modest changes in its expression result in robust changes in the N-glycosylation status of proteins (Clark et al 1983; Hayes and Lucas 1983; Welply et al 1985; Meissner et al 1999; Mendelsohn et al 2005; Bretthauer 2009). Human fibroblasts from a patient bearing mutations in both alleles of DPAGT1 display dramatically reduced GPT activity that is associated with diminished levels of LLO and hypo-glycosylation of proteins (Wu et al 2003).…”

A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin

“…DPAGT1/GPT, which mediates the first committed step in the N-glycosylation pathway, is a multipass ER membrane protein that catalyzes the transfer of GlcNAc-1-phosphate from UDP-GlcNAc to the lipid carrier dolichol monophosphate (Dol-P) to form N-acetylglucosamine-pyrophosphatidyldolichol (GlcNAc-PP-Dol) (19). DPAGT1/GPT is the first enzyme in a series of 14 ER-associated glycosyltransferases assembling a 14-mer oligosaccharide core that is transferred en bloc onto asparagine residues within potential N-glycosylation sites by the oligosaccharyltransferase (OST) complex (19,20).…”

Congenital myasthenic syndromes and the neuromuscular junction

“…DPAGT1 encodes the enzyme dolichyl-phosphate-N-acetylglucosamine-phosphotransferase-1, a transmembrane ER protein essential for N-linked glycosylation [47]. A study on five unrelated patients with similar clinical features to GFPT1-CMS identified DAPGT1 as a novel CMS gene [2].…”