Protein disulfide-isomerase A3 (PDIA3)
The protein contains 505 amino acids for an estimated molecular weight of 56782 Da.
No function (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
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.
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| Variant | Description |
|---|---|
| dbSNP:rs6413485 |
Biological Process
Antigen processing and presentation of exogenous peptide antigen via MHC class I
Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
Antigen processing and presentation of peptide antigen via MHC class I
Cell redox homeostasis
Cellular protein metabolic process
Cellular response to interleukin-7
Oxidation-reduction process
Positive regulation of extrinsic apoptotic signaling pathway
Post-translational protein modification
Protein folding
Protein folding in endoplasmic reticulum
Protein import into nucleus
Protein N-linked glycosylation via asparagine
Protein retention in ER lumen
Proteolysis
Response to endoplasmic reticulum stress
Signal transduction
The reference OMIM entry for this protein is 602046
Protein disulfide isomerase, family a, member 3; pdia3
Glucose-regulated protein, 58-kd; grp58
Erp57
Er60
CLONING
The cDNA encoding human GRP58 was cloned independently by Bourdi et al. (1995), Koivunen et al. (1996), and Hirano et al. (1995). All reported that the gene encodes a 505-amino acid polypeptide with significant homology to human protein disulfide isomerase (PDI; 176790). Bourdi et al. (1995) noted that the sequence includes a putative nuclear localization motif and an endoplasmic reticulum (ER)-retention/retrieval motif. Koivunen et al. (1997) noted that the GRP58 sequence has 2 thioredoxin-like domains. Koivunen et al. (1997) showed by Northern blotting that GRP58 is expressed as a 2-kb message most abundantly in liver, placenta, and lung, and at lower levels in all other tissues tested.GENE FUNCTION
Several laboratories have examined the functional properties of GRP58. Bourdi et al. (1995) found that the GRP58 protein had protein disulfide isomerase activity. Koivunen et al. (1996) showed that GRP58 could not substitute for the beta subunit of PDI. When coexpressed with alpha prolyl 4-hydroxylase, GRP58 did not form prolyl 4-hydroxylase tetramers, nor did it have prolyl 4-hydroxylase activity. Hirano et al. (1995) expressed human GRP58 and found that the protein had a thiol-dependent reductase activity. They showed that the expression level of GRP58 is increased after oncogenic transformation of normal rat kidney cells and NIH 3T3 cells. Oliver et al. (1997) used a crosslinking approach to screen antisera to several ER luminal proteins in order to find proteins that interact specifically with glycoproteins in the ER. They identified GRP58 as one such protein. The authors suggested that GRP58 functions in combination with calnexin (114217) and calreticulin (109091) as a molecular chaperone of glycoprotein biosynthesis. Using specific antibodies and inhibitors of PDI activity, Ellerman et al. (2006) determined that Erp57 on the surface of the mouse sperm head was involved in sperm-egg fusion. They hypothesized that thiol-disulfide exchange in gamete fusion may produce conformational changes in fusion-active proteins.GENE STRUCTURE
Koivunen et al. (1997) examined the genomic organization of the GRP58 gene and reported that it is encoded on 13 exons spanning 18 kb; no similarity was found between the genomic structures of the GRP58, PDI, and thioredoxin (187700) genes.MAPPING
Koivunen et al. (1997) used fluorescence in situ hybridization to map the GRP58 gene to human chromosome 15q15. They also observed that humans have a processed pseudogene, GRP58P, which is nearly identical to GRP58 and maps to chromosome 1q21. By Southern blot analysis of an interspecific backcross, Briquet-Laugier et al. (1998) mapped the Grp58 gene to mouse chromosome 2.ANIMAL MODEL
PDIA3 is part of the major histocompatibility complex (MHC) class I peptide-loading complex (see TAP1; 170260), which is essential for final antigen conformation and export from the ER to the cell surface. To avoid embryonic lethality, Garbi et al. (2006) generated mice with a conditional deletion of Pdia3 in the B-cell compartment. These mice retained functional B cells with decreased MHC class I expression, as shown by flow cytometry and immunoblot analysis. Immunoprecipitation analysis showed that Pdia3 mediated recruitment of MHC class I molecules and Calr (109091) into the peptide-loading complex. Lack of Pdia3 resulted in suboptimal peptide loading and decreased T-cell activation. Garbi et al. (2006) concluded that ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602046 was added.