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

The protein contains 408 amino acids for an estimated molecular weight of 46090 Da.

 

Catalyzes the initial step of dolichol-linked oligosaccharide biosynthesis in N-linked protein glycosylation pathway: transfers GlcNAc-1-P from UDP-GlcNAc onto the carrier lipid dolichyl phosphate (P-dolichol), yielding GlcNAc-P-P-dolichol. (updated: Oct. 10, 2018)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  2. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is predicted to be membranous by TOPCONS.

Topcons

Interpro domains
Total structural coverage: 0%
Model score: 100
No model available.

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VariantDescription
a breast cancer sample; somatic mutation
CMS13
CMS13
CMS13
CMS13
CDG1J
CMS13
CMS13
dbSNP:rs643788

The reference OMIM entry for this protein is 191350

Dolichyl-phosphate n-acetylglucosamine phosphotransferase; dpagt1
Udp-glcnac:dolichyl-phosphate n-acetylglucosaminephosphotransferase
Dpagt2
Glcnac-1-p transferase

DESCRIPTION

N-linked glycosylation is initiated in all eukaryotic cells with the synthesis of lipid-linked oligosaccharides in a cyclic pathway, the dolichol cycle. DPAGT1 (EC 2.7.8.15) catalyzes the first step in the dolichol cycle, the synthesis of N-acetylglucosaminyl-pyrophosphoryldolichol (GlcNAc-PP-dolichol) from dolichol phosphate and UDP-GlcNAc, and can be inhibited by the antibiotic tunicamycin (Eckert et al., 1998).

CLONING

Rajput et al. (1992) isolated mRNA for the Dpagt1 protein from mouse mammary glands. The mouse cDNA recognized a single mRNA species of about 2 kb in mouse mammary glands when used as a probe in Northern blot analysis. Eckert et al. (1998) cloned a human DPAGT1 cDNA from a human lung fibroblast cDNA library. The cDNA encodes a deduced 400-amino acid protein with a calculated molecular mass of 44.7 kD. DPAGT1 contains an N-terminal signal peptide, 2 potential dolichol-binding sequences, and 4 sites for N-glycosylation. It shares 93% amino acid homology with hamster Dpagt, including 100% identity in the dolichol-binding region, and 42% homology with S. cerevisiae GlcNAc-1-P transferase.

GENE FUNCTION

Protein asparagine-linked glycosylation is a multistep process that is divided into 2 stages. The first stage consists of the synthesis of the lipid-linked oligosaccharide precursor (LLO) and its en bloc transfer to nascent polypeptides in the lumen of the endoplasmic reticulum. This process requires at least 34 genes, of which DPAGT1 is the first. The second stage involves the processing of protein-bound oligosaccharides and requires at least an additional 20 genes to form a bi-antennary sugar chain typical of plasma glycoproteins. Genetic defects in some of these genes, including DPAGT1, cause severe multisystem disorders called congenital disorders of glycosylation (CDGs) (Freeze, 2001) Eckert et al. (1998) demonstrated that S. cerevisiae expressing recombinant DPAGT1 synthesized GlcNAc- and GlcNAc(2)-PP-dolichol. Expression of human DPAGT1 also complemented a conditional lethal S. cerevisiae strain defective for GlcNAc-1-P transferase. Expression of recombinant DPAGT1 from a multicopy expression vector also conferred a higher tolerance toward tunicamycin due to elevated enzyme synthesis, thus showing a gene dosage effect.

MAPPING

Using FISH and somatic cell hybrid analysis, Smith et al. (1993) mapped the DPAGT1 gene (D11S366) to chromosome 11q23.3. Using a panel of mouse/hamster somatic cell hybrids and a specific probe derived from the 3-prime noncoding region of the mouse cDNA, Rajput et al. (1992) mapped the mouse Dpagt1 gene to chromosome 17.

ANIMAL MODEL

Marek et al. (1999) found that Dpagt1-null mice died 4 to 5 days postfertilization, just after implantation, suggesting that DPAGT1 function and protein N-glycosylation are essential in early embryogenesis.

MOLECULAR GENETICS

- Congenital Disorder of Glycosylation Type Ij In a patient with CDG Ij (CDGIJ; 608093), Wu et al. (2003) identified a tyr170-to-cys mutation (Y170C; 191350.0001) in the DPAGT1 gene. Timal et al. (2012) identified compound heterozygosity for 2 mutations in the DPAGT1 gene (191350.0007 and 191350.0008) in a Caucasian boy with CDG Ij. The mutations were found by exome sequencing and confirmed by Sanger sequencing. In 2 sibs, born of consanguineous Turkish parents, with severe CDG Ij, Wurde et al. (2012) identified a homozygous mutation in the DPAGT1 gene (A114G; 191350. ... More on the omim web site

Subscribe to this protein entry history

July 1, 2020: Protein entry updated
Automatic update: OMIM entry 191350 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).