Summary

This gene is homolog to the yeast gene ALG7, and it is the initial enzyme in the synthesis of the N-glycan precursor.

Functions (from Uniprot)

Catalyzes the initial step in the synthesis of dolichol-P-P-oligosaccharides.

Disease relevance of DPAGT1

• In the present study we describe the effects of all-trans-retinoic acid (RA) on the levels of GPT protein and enzymic activity, and on the transcription rate of the GPT gene, in mouse P19 teratocarcinoma cells [1].
• Serum markers of liver function [GOT, GPT, gamma-GTP, total bile acids (TBA)], and serum markers of liver fibrosis [hyaluronic acid (HA), type IV collagen (C-IV)], were measured in both groups at the beginning of the study, and at 1, and 3 years after the beginning of the study and the results compared statistically [2].
• Postoperative liver functions showed no marked derangement; the mean peak GPT was 221 U and the mean peak total bilirubin 2.3 mg d/l. Local cooling minimizes the risk of ischemia/reperfusion injury in this very vulnerable population, yet gives the surgeon adequate time to perform a challenging resection in a bloodless field [3].
• There was no statistical difference in the toxicity grading of hemoglobin, glutamic oxaloacetic transaminase/glutamic pyruvic transaminase (GOT/GPT) and stomatitis/ gastritis between the three groups of patients [4].

High impact information on DPAGT1

• The 63-kilobase circular amplicon of tunicamycin-resistant Leishmania amazonensis contains a functional N-acetylglucosamine-1-phosphate transferase gene that can be used as a dominant selectable marker in transfection [5].
• With microsomes from cells treated with translation blockers, there was no interference with LLO initiation by GlcNAc-1-P transferase (GPT), mannose-P-dolichol synthase, glucose-P-dolichol synthase, or LLO synthesis in vitro, as reported previously [6].
• In order to examine the function of the carboxyl terminus of UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase (GPT), an endoplasmic reticulum enzyme that synthesizes GlcNAc-P-P-dolichol and, thus, catalyzes the committed step for N-linked glycosylation, a series of carboxyl-terminal truncation mutations was examined [7].
• Hamster UDP-GlcNAc:dolichol phosphate N-acetylglucosamine-1-phosphate transferase (GPT) differs from the other enzymes by having two PDRSs [8].
• A cDNA clone isolated from Chinese hamster ovary cells conferred elevated GlcNAc-1-P-transferase (GPT) activity and resistance to tunicamycin in transfected cells (Zhu, X., and Lehrman, M. A. (1990) J. Biol. Chem. 265, 14250-14255) [9].

Biological context of DPAGT1

• Deficiency of UDP-GlcNAc:Dolichol Phosphate N-Acetylglucosamine-1 Phosphate Transferase (DPAGT1) causes a novel congenital disorder of Glycosylation Type Ij [10].
• The patient's paternal DPAGT1 allele contains a point mutation (660A>G) that replaces a highly conserved tyrosine with a cysteine (Y170C) [10].
• Enzymic activities paralleled GPT gene expression [1].
• The maternal allele makes only about 12% normal mature mRNA, while the remainder shows a complex exon skipping pattern that shifts the reading frame encoding a truncated non-functional GPT protein [10].
• Analysis of a panel of radiation hybrids led to the assignment of the GlcNAc-1-P transferase gene to chromosome 11, at 4.19 cR from NIB361, according to the location of the homologous sequences in the database at 11q23 [11].

Anatomical context of DPAGT1

• In addition, GPT activity in membranes from RA-treated P19 cells exhibited approx. 4-fold increased resistance to tunicamycin compared with activity in membranes from untreated control cells, demonstrating that resistance to tunicamycin is correlated with induced GPT activity [1].
• This difference suggests that dolichyl phosphate may be limiting for GlcNAc-1-P transferase activity in endoplasmic reticulum of the older animals [12].
• In vitro enzymatic analysis of microsomal fractions from the cultured cells indicated that oligosaccharyltransferase activity is normal, but the GPT activity is reduced to approximately 10% of normal levels while parents have heterozygous levels [10].
• The amount of dolichyl phosphate and GlcNAc-1-P transferase activity in CDG syndrome fibroblasts were similar to those in normal fibroblasts, suggesting that CDG syndrome may not be due to a deficiency of a biosynthetic enzyme for dolichol-oligosaccharide intermediates, but to a metabolic error in assembly of asparagine-linked oligosaccharide [13].
• To initiate the molecular characterization of ALG7 involvement in mammalian growth and differentiation, we have used the postnatally developing hamster submandibular gland (SMG) as an experimental paradigm [14].

Associations of DPAGT1 with chemical compounds

• RA-treated P19 cells were about 4-fold more resistant to tunicamycin, a fungal antibiotic which inhibits GPT, than were control cells [1].
• Regulation of UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosamine-1-phosphate transferase by retinoic acid in P19 cells [1].
• The enzyme UDP-N-acetylglucosamine:dolichyl phosphate, N-acetylglucosamine-1-phosphate transferase (GlcNAc-1-P transferase), the first committed step in the dolichol-linked oligosaccharide pathway for glycoprotein biosynthesis, has been studied in developing rat brain [12].
• We have identified a novel CDG type, CDG-Ij, resulting from deficiency in UDP-GlcNAc: dolichol phosphate N-acetyl-glucosamine-1 phosphate transferase (GPT) activity encoded by DPAGT1 [10].
• Properties of a soluble polyprenyl phosphate. UDP-D-N-acetylglucosamine N-acetylglucosamine-1-phosphate transferase [15].

Other interactions of DPAGT1

• Heterozygous polymorphisms in the VPS11 and DPAGT1 genes were found [16].

Analytical, diagnostic and therapeutic context of DPAGT1

• Using sequence database tools, we deduced the genomic structure of the human GlcNAc-1-P transferase gene, which was experimentally confirmed by sequence analysis [11].

References