Peroxiredoxin-4 (PRDX4)

The protein contains 271 amino acids for an estimated molecular weight of 30540 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. Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation. (updated: Oct. 25, 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. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. 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: 94%
Model score: 100
MODL_MODELLER-9.18

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The reference OMIM entry for this protein is 300927

Peroxiredoxin 4; prdx4
Antioxidant enzyme 372; aoe372

DESCRIPTION

Antioxidants govern intracellular reduction-oxidation (redox) status, which plays a critical role in NFKB (see 164011) transcription factor activation. PRDX4 is a thioredoxin peroxidase that regulates NFKB activation (Jin et al., 1997).

CLONING

Using a yeast 2-hybrid screen of a HeLa cell cDNA library with PAG (PRDX1; 176763) as bait, followed by 5-prime RACE, Jin et al. (1997) isolated cDNAs encoding PRDX4, which they termed 'antioxidant enzyme AOE372.' Sequence analysis predicted that the 271-amino acid protein, 70% identical to a yeast thiol-specific antioxidant, contains a signal peptide and 2 peroxide catalysis cysteine motifs conserved in all human peroxiredoxins. Northern blot analysis revealed ubiquitous expression of a 1.0-kb transcript in numerous cell lines and variable expression in tissues, with highest expression in pancreas and none detected in peripheral blood leukocytes. Western blot analysis showed expression of a 23-kD protein with highest levels in pancreas, followed by liver, heart, spleen, and thymus. Confocal microscopy as well as immunoblotting demonstrated predominant cytoplasmic expression.

GENE FUNCTION

Functional analysis by Jin et al. (1997) showed that PRDX4 protected glutamine synthetase (GLUL; 138290) from inactivation. Yeast 2-hybrid, immunoprecipitation, and immunoblot analyses indicated that PRDX4 and PRDX1 were capable of homodimerization and heterodimerization with each other, but not with the mitochondrial PRDX3 (604769). Gel mobility shift and immunoblot analyses found that PRDX4 depleted NFKB binding activity together with a reduction in the amounts of p50, p65 (RELA; 164014), and phosphorylated IKBA (164008), as well as a reduction in the expression of HIV-1 viral proteins. Expression of PRDX4, alone or with PRDX1, increased the resistance of yeast cells to oxidant-induced toxicity. Jin et al. (1997) suggested PRDX4 modulates IKBA phosphorylation in the cytoplasm and thus affects a peroxiredoxin-dependent redox step.

MAPPING

Gross (2014) mapped the PRDX4 gene to chromosome Xp22.11 based on an alignment of the PRDX4 sequence (GenBank GENBANK BC003609) with the genomic sequence (GRCh38). ... More on the omim web site

Subscribe to this protein entry history

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 300927 was added.

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

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