Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1)
The protein contains 113 amino acids for an estimated molecular weight of 12497 Da.
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 (PubMed:22467853). 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. Loss of the DAD1 protein triggers apoptosis (PubMed:22467853). (updated: Dec. 5, 2018)
Protein identification was indicated in the following studies:
- 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.
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 predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs5742796 |
No binding partner found
Biological Process
Apoptotic process
Blastocyst development
Negative regulation of apoptotic process
Protein glycosylation
Protein N-linked glycosylation
Protein N-linked glycosylation via asparagine
Regulation of protein stability
Response to drug
Response to nutrient
Viral protein processing
The reference OMIM entry for this protein is 600243
Defender against cell death 1; dad1
DESCRIPTION
DAD1 is a core component of the multisubunit oligosaccharyltransferase (OST; EC 2.4.1.119). OST catalyzes the transfer of preassembled high mannose oligosaccharides onto target asparagines of nascent polypeptide chains within the lumen of the endoplasmic reticulum (ER) (Sanjay et al., 1998).CLONING
Nakashima et al. (1993) studied a temperature-sensitive mutant cell line, tsBN7, that died by apoptosis following a shift to the nonpermissive temperature. The tsBN7 cell line had been derived from the hamster BHK21 cell line. The induced apoptosis was inhibited by a protein synthesis inhibitor, cycloheximide, but not by the BCL2 (151430) protein, which acts as a brake against programmed cell death. By DNA-mediated gene transfer, Nakashima et al. (1993) cloned a human DAD1 cDNA that complemented the tsBN7 mutation. The deduced 113-amino acid human DAD1 protein is hydrophobic and shares 100% amino acid identity with its hamster homolog. Northern blot analysis detected high expression of a 0.8-kb transcript in all tissues examined.GENE STRUCTURE
Nakashima et al. (1993) determined that the DAD1 gene contains 3 exons.MAPPING
By fluorescence in situ hybridization using YACs containing the DAD1 gene, Yulug et al. (1995) mapped the gene to chromosome 14q11-q12. They inferred that the mouse homolog is probably located in the middle of mouse chromosome 14.GENE FUNCTION
Nakashima et al. (1993) demonstrated that the hamster Dad1 gene is mutated in the tsBN7 cell line (gly38 to arg). The Dad1 protein disappeared in temperature-sensitive cells following a shift to the nonpermissive temperature, suggesting that loss of Dad1 triggered apoptosis. Makishima et al. (1997) confirmed that loss of Dad1 function in tsBN7 cells caused a defect in N-glycosylation and resulted in apoptosis. However, tunicamycin, an inhibitor of N-glycosylation, did not induce apoptosis in either tsBN7 cells or the parental BHK21 cell line. Kelleher and Gilmore (1997) identified DAD1 as a core component of the functional OST complex purified from the rough ER fraction of WI38 human fibroblasts and from canine and porcine pancreatic microsomes. In canine OST preparations, Dad1 was obtained in roughly equimolar amounts relative to the 3 other OST components, ribophorin I (RPN1; 180470), ribophorin II (RPN2; 180490), and Ost48 (DDOST; 602202). Protein crosslinking confirmed tight association of Dad1 with Ost48, ribophorin I, and ribophorin II. Protein digestion experiments showed that Dad1 was exposed on the cytoplasmic face of the rough ER. Using Western blot analysis, Sanjay et al. (1998) showed that shifting tsBN7 cells to the nonpermissive temperature resulted in loss of Dad1 and Ost48 proteins and reduced ribophorin protein levels to about 50% of those found in cells at the permissive temperature. N-glycosylation of the ribophorins and a test secretory glycoprotein was seriously affected following loss of OST components. Sanjay et al. (1998) concluded that degradation of Dad1 at the nonpermissive temperature affects both the stability of Ost48 and ribophorins and results in functional inactivation of the OST complex. Using a yeast 2-hybrid screen with a human B-cell cDNA library, Makishima et al. (2000) showed that DAD1 interacted with the C-terminal region of the antiapoptotic protein MCL1 (159552) and with the proapoptotic protein NIP3 (BNIP3; 603293). DAD1 did not interact with full-length MCL1 in yeast 2-hybr ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 600243 was added.
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).