Peroxiredoxin-1 (PRDX1)
The protein contains 199 amino acids for an estimated molecular weight of 22110 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 and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2) (PubMed:9497357). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation (By similarity). (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.
- 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.
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| Variant | Description |
|---|---|
| dbSNP:rs34034070 |
Biological Process
Cell population proliferation
Cell redox homeostasis
Cellular response to oxidative stress
Erythrocyte homeostasis
Hydrogen peroxide catabolic process
Leukocyte activation
Natural killer cell activation
Natural killer cell mediated cytotoxicity
Regulation of NF-kappaB import into nucleus
Regulation of NIK/NF-kappaB signaling
Regulation of stress-activated MAPK cascade
Removal of superoxide radicals
Response to oxidative stress
Response to reactive oxygen species
Retina homeostasis
Skeletal system development
The reference OMIM entry for this protein is 176763
Peroxiredoxin 1; prdx1
Prxi
Proliferation-associated gene a; paga
Natural killer-enhancing factor a; nkefa
DESCRIPTION
PRDX1 is a thiol reductase that plays critical roles in oxidative and thermal stress defense mechanisms through its abilities to metabolize H2O2 and act as a molecular chaperone, respectively. PRDX1 also reduces intramolecular cystine bridges (summary by Yan et al., 2009).CLONING
A cDNA of the PAGA gene was isolated by differential cloning between the untransformed and the RAS transformed human mammary epithelial cell line HBL100 (Prosperi et al., 1993). The PAGA gene is constitutively expressed in most human tissues, but its expression is higher in organs having a higher level of proliferation. The PAGA cDNA hybridizes to a single mRNA species of 1.2 kb, encoding a 22-kD protein devoid of known consensus motifs. Shau et al. (1994) identified a red blood cell factor, NKEF, that enhances natural killer (NK) cell activity. By immunoscreening an erythroleukemia cDNA library, they isolated cDNAs encoding NKEFA and NKEFB (PRDX2; 600538). The NKEFA and NKEFB proteins contain 199 and 198 amino acids, respectively, and are 75% identical. The authors noted that proteins related to NKEFA and NKEFB appear to be induced by oxidative stress. Shau et al. (1994) concluded that in addition to immunoregulation of NK activity, the NKEFs may be important for cells in coping with oxidative insults.GENE FUNCTION
Yan et al. (2009) found that Prdx1 was expressed in differentiating motor neuron cells in developing embryonic chicken and mouse spinal cords. Ablation of Prdx1 caused deficits in motor neuron differentiation similar to those in Gde2 (GDPD5; 609632)-knockout motor neuron progenitor cells. Immunoprecipitation analysis showed that GDE2 interacted directly with PRDX1 in embryonic chicken spinal cord extracts and in transfected HEK293T cells. In differentiating spinal cord, Prdx1 was required to activate Gde2 by reducing an intramolecular cystine bridge between the Gde2 N- and C-terminal domains. Reduction of Gde2 involved formation of a mixed-disulfide Prdx1-Gde2 intermediate and did not involve the chaperone function of Prdx1. Gde2 mutants that failed to form the intramolecular cystine showed potent Prdx1-independent induction of motor neuron differentiation. Yan et al. (2009) concluded that an intramolecular disulfide bond between the GDE2 N- and C-terminal domains inhibits GDE2 function, and that reduction of this cystine by PRDX1 activates GDE2 for the induction of motor neuron differentiation.GENE STRUCTURE
By physical mapping of the gene from a human genomic cosmid library, Prosperi et al. (1994) determined that the PAGA gene spans 13 kb and contains 6 exons. The promoter region is GC-rich and contains a TFIID motif located 25 nucleotides upstream of the potential site for initiation of transcription, as well as potential recognition sites for a variety of trans-acting factors.BIOCHEMICAL FEATURES
- Crystal Structure Jonsson et al. (2008) presented the 2.6-angstrom crystal structure of the human sulfiredoxin (SRX)-PRXI complex. This complex reveals the complete unfolding of the carboxy terminus of PRX, and its unexpected packing onto the backside of SRX away from the SRX active site. Binding studies and activity analyses of site-directed mutants at this interface showed that the interaction is required for repair to occur. Moreover, rearrangements in the PRX active site lead to a juxtaposition of the PRX gly-gly-leu-gly and SRX ATP-binding motifs, providing a structural basis ... 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
Nov. 23, 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 176763 was added.