Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 48 kDa subunit (DDOST)
The protein contains 456 amino acids for an estimated molecular weight of 50801 Da.
Essential subunit of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. Required for the assembly of both SST3A- and SS3B-containing OST complexes. Required for efficient N-glycosylation.', 'Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity (By similarity). Required for the assembly of both SST3A- and SS3B-containing OST complexes (PubMed:22467853). (updated: Dec. 5, 2018)
Protein identification was indicated in the following studies:
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs537816 | |
| CDG1R |
Biological Process
Neutrophil degranulation
Protein glycosylation
Protein N-linked glycosylation
Protein N-linked glycosylation via asparagine
Regulation of protein stability
Response to cytokine
T cell activation
Viral protein processing
The reference OMIM entry for this protein is 602202
Dolichyl-diphosphooligosaccharide-protein glycosyltransferase; ddost
Oligosaccharyltransferase; ost
Oligosaccharyltransferase, 48-kd; ost48
DESCRIPTION
The DDOST gene encodes the enzyme oligosaccharyltransferase (dolichyl-diphosphooligosaccharide-protein glycosyltransferase (EC 2.4.1.119)), which catalyzes the transfer of a high-mannose oligosaccharide from a dolichyl-linked oligosaccharide donor onto the asparagine acceptor site in nascent polypeptide chains across the membrane of the rough endoplasmic reticulum (Yamagata et al., 1997).CLONING
Kelleher et al. (1992) reported that mammalian oligosaccharyltransferase activity is associated with a protein complex composed of ribophorin I (180470), ribophorin II (180490), and a 48-kD protein, OST48. Yamagata et al. (1997) isolated mouse and human DDOST cDNAs from retinoic acid-treated mouse and human cells. DDOST mRNA was expressed intensely in heart and pancreas, but at lower levels in brain.GENE STRUCTURE
Yamagata et al. (1997) showed that the gene encoding the human DDOST 48-kD gene is organized into 11 exons spanning about 9 kb.MAPPING
By fluorescence in situ hybridization, Yamagata et al. (1997) assigned the DDOST gene to chromosome 1p36.1.GENE FUNCTION
Advanced glycosylation end products (AGE) contribute to kidney disease due to diabetes or aging by means of mesangial cell receptors, such as receptor for AGE (RAGE; 600214), which promote oxidant stress-dependent activation of NF-kappa-B (see 164011) and inflammatory gene expression. Lu et al. (2004) found that DDOST, which they referred to as AGE receptor-1 (AGE-R1), enhances AGE removal, but is also a distinct receptor in that it suppresses AGE-mediated mesangial cell inflammatory injury through negative regulation of RAGE, a previously uncharacterized pathway that may protect from renal and other tissue injury due to diabetes and aging.MOLECULAR GENETICS
By whole-exome sequencing of a European boy with congenital disorder of glycosylation type 1r (CDG1R; 614507), Jones et al. (2012) identified compound heterozygosity for 2 mutations in the DDOST gene (602202.0001 and 602202.0002). The patient presented in infancy with failure to thrive, gastroesophageal reflux, developmental delay, and oromotor dysfunction. He later showed hypotonia, external strabismus, and mild to moderate liver dysfunction. He had delayed psychomotor development with walking acquired at age 3 years, and never developed speech. ... More on the omim web site
Dec. 9, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 602202 was added.