Dolichyl-phosphate (UDP-N-Acetylglucosamine) N-Acetylglucosaminephospho transferase 1 (GlcNAc-1-P transferase) (DPAGT1)

Abstract

In eukaryotes, N-linked protein glycosylation starts with the synthesis of a highly conserved lipid-linked oligosaccharide (LLO) on the endoplasmic reticulum (ER) membrane. As the committed process of N-glycosylation, 14 monosaccharide residues are sequentially transferred onto dolichyl pyrophosphate (dol-P) carrier molecule by a series of glycosyltransferases (GTase) to form the core oligosaccharide precursor Glc3Man9GlcNAc2-P-P-dol. The first half of GTase reactions in LLO synthesis takes place on the cytoplasmic face of ER (Fig. 124.1), which produces Man5GlcNAc2-P-P-dol intermediate from the soluble nucleotide sugar substrates uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) and guanosine diphosphate d-mannose (GDP-man). Once this intermediate is flipped into the lumen of the ER, the next seven sugars are added from dolichol-sugar substrates Man-P-dol and Glc-P-dol to complete the assembly. Another half of GTase catalyzes these reactions (reviewed in Helenius et al. 2004; Kelleher and Gilmore 2006; Weerapana and Imperiali 2006). DPAGT1 encodes dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 that catalyzes the first reaction of LLO synthesis, by adding GlcNAc-1-P from cytoplasmic UDP-GlcNAc to dol-P. DPAGT1 is essential for N-linked protein glycosylation and considered to be a key regulator among the metabolic pathway of protein N-glycosylation (Lehrman 1991).