Thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3)
The protein contains 256 amino acids for an estimated molecular weight of 27693 Da.
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides (PubMed:7733872, PubMed:17707404). Acts synergistically with MAP3K13 to regulate the activation of NF-kappa-B in the cytosol (PubMed:12492477). (updated: Jan. 31, 2018)
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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
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| Variant | Description |
|---|---|
| dbSNP:rs34698541 | |
| dbSNP:rs11554902 | |
| dbSNP:rs36064375 | |
| dbSNP:rs35697338 |
Biological Process
Cell redox homeostasis
Cellular response to oxidative stress
Cellular response to reactive oxygen species
Hydrogen peroxide catabolic process
Maternal placenta development
Mitochondrion organization
Myeloid cell differentiation
Negative regulation of apoptotic process
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Negative regulation of kinase activity
Peptidyl-cysteine oxidation
Positive regulation of cell population proliferation
Positive regulation of NF-kappaB transcription factor activity
Regulation of mitochondrial membrane potential
Response to hydrogen peroxide
Response to lipopolysaccharide
Response to oxidative stress
Response to reactive oxygen species
The reference OMIM entry for this protein is 604769
Peroxiredoxin 3; prdx3
Prx3
Antioxidant protein 1; aop1
DESCRIPTION
Peroxiredoxins inactivate H2O2 by oxidizing a key cysteine residue in their catalytic center, which is subsequently reduced by thioredoxins (see 187700). The thioredoxins are subsequently reduced by electrons from NADPH via thioredoxin reductases (see TXNRD1; 601112). PRDX3 is localized exclusively in mitochondria (summary by Chiribau et al., 2008).CLONING
The mouse Aop1 protein, also called Mer5, may promote early events in the differentiation of murine erythroleukemia (MEL) cells (Nemoto et al., 1990). Tsuji et al. (1995) found that mouse Aop1 shares 38% amino acid sequence identity with the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase. By screening a human leukemia cell line cDNA library with a mouse Aop1 cDNA, Tsuji et al. (1995) isolated a cDNA encoding human AOP1. The deduced 256-amino acid human AOP1 protein shares 86% amino acid sequence similarity with mouse Aop1, and significant similarity with both the human proliferation-associated gene A product (PAGA; 176763) and the mouse stress-induced peritoneal macrophage protein Msp23. AOP1 also shows sequence similarity to the S. cerevisiae thiol-specific antioxidant protein TSA; a surface antigen of Entamoeba histolytica, which is a pathogenic protozoan that causes diarrhea and organ abscess formation; and a protein of H. pylori, which is a causative agent in gastritis, ulcers, and gastric adenocarcinoma.GENE FUNCTION
Tsuji et al. (1995) demonstrated that recombinant mouse Aop1 could complement an alkylhydroperoxide reductase mutation in E. coli, suggesting that Aop1 functions as an antioxidant protein. Shih et al. (2001) determined that AOP1 interacts with Abrin A-chain (ABRA), which inhibits protein synthesis and can induce apoptosis. By immunolocalization studies, they determined that both AOP1 and ABRA colocalize within the mitochondria. By assays of thiol-dependent antioxidant activity, they determined that ABRA can attenuate AOP1 activity in a dose-dependent manner. Ectopic expression of AOP1 also blocked the release of cytochrome c from mitochondria and inhibited apoptosis in ABRA-treated cells. Deregulated expression of the MYC transcription factor (190080) is found in a wide variety of human tumors. The primary transforming activity of MYC is thought to arise through transcriptional regulation of numerous target genes. Wonsey et al. (2002) showed that PRDX3, which encodes a mitochondrial protein of the peroxiredoxin gene family, is such a target. Expression of PRDX3 is induced by MYC and is reduced in c-myc -/- cells. Chromatin immunoprecipitation analysis spanning the entire PRDX3 genomic sequence revealed that MYC binds preferentially to a 930-bp region surrounding exon 1. Wonsey et al. (2002) showed that PRDX3 is required for MYC-mediated proliferation, transformation, and apoptosis after glucose withdrawal. Results using mitochondria-specific fluorescent probes demonstrated that PRDX3 is essential for maintaining mitochondrial mass and membrane potential in transformed rat and human cells. These data provided evidence that PRDX3 is a MYC target gene that is required to maintain normal mitochondrial function. Chiribau et al. (2008) found that the forkhead box transcription factor FOXO3A (602681) was required for basal expression of PRX3 in human cardiac fibroblasts. They identified 2 FOXO regulatory sequences in the promoter region of PRX3 and showed that binding of FOXO3A to both regulatory sequences w ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604769 was added.