Peroxiredoxin-2 (PRDX2)

The protein contains 198 amino acids for an estimated molecular weight of 21892 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). (updated: Dec. 20, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. 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.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 100
MODL_ROSETTA-3.4
MODL_MODELLER-9.18

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VariantDescription
dbSNP:rs34012472

The reference OMIM entry for this protein is 600538

Peroxiredoxin 2; prdx2
Prx2
Peroxide reductase, thioredoxin-dependent; tdpx1; tpx1
Natural killer-enhancing factor b; nkefb

CLONING

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 (PRDX1; 176763) and NKEFB. 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. Reactive oxygen species (ROS) and free radicals that are produced during normal metabolism have the potential of damaging cellular macromolecules. Defenses against such damage include a number of antioxidant enzymes that specifically target the removal or dismutation of the reactive agent. Pahl et al. (1995) isolated a human gene, symbolized TDPX1 (for thioredoxin-dependent peroxide reductase-1), that encodes an enzyme homologous to the yeast thioredoxin peroxidase (TPX). The human coding sequence was determined from the product of a PCR amplification of human cDNA using primers based on the rat sequence (Chae et al., 1994). The 198-amino acid rat protein was, in turn, isolated as a cDNA from a brain expression library with antibodies to bovine thiol-specific antioxidant (TSA) enzyme. The rat and yeast TSA proteins show significant similarity to Salmonella typhimurium alkyl hydroperoxide reductase.

MAPPING

Based on PCR analysis of DNAs from a human/rodent somatic cell hybrid panel, Pahl et al. (1995) assigned the TDPX1 locus to chromosome 13. Further localization to 13q12 was achieved by fluorescence in situ hybridization, using as a probe DNA from a YAC that contained the TDPX1 gene. However, Gross (2012) mapped the PRDX2 gene to chromosome 19p13.2 based on an alignment of the PRDX2 sequence (GenBank GENBANK BC003022) with the genomic sequence (GRCh37).

GENE FUNCTION

To clarify the physiologic relevance of peroxiredoxins, Lee et al. (2003) generated a mouse model deficient in PRDX2, which is abundantly expressed in all types of cells. The Prdx2 -/- mice were healthy in appearance and fertile. However, they had splenomegaly caused by the congestion of red pulp with hemosiderin accumulation. Heinz bodies were detected in their peripheral blood, and morphologically abnormal cells were increased in the dense red blood cell (RBC) fractions, which contained markedly higher levels of ROS. The null mice had significantly decreased hematocrit levels, but increased reticulocyte counts and erythropoietin levels, indicative of a compensatory action to maintain hematologic homeostasis. A labeling experiment in null mice showed that a variety of RBC proteins were highly oxidized. The results suggested that Prdx -/- mice have hemolytic anemia and that peroxiredoxin II plays a major role in protecting RBCs from oxidative stress in mice. Choi et al. (2005) demonstrated that PRDX2 is a negative regulator of PDGF (see 190040) signaling. Prx II deficiency results in increased production of peroxide, enhanced activation of PDGF receptor (PDGFR; see 173490) and phospholipase C-gamma-1 (172420), and subsequently increased cell proliferation and migration in response to PDGF. These responses are suppressed by expression of wildtype Prx II, but not an inactive mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and suppresses protein tyr ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

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 600538 was added.

Feb. 25, 2016: Protein entry updated
Automatic update: model status changed

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed