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PRDX2

gene
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Also known as PRPNKEFBTSAPRXIIPRX2MGC4104

Summary

PRDX2 (peroxiredoxin 2, HGNC:9353) is a protein-coding gene on chromosome 19p13.13, encoding Peroxiredoxin-2 (P32119). Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.

This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides. The encoded protein plays an antioxidant protective role in cells, and it may contribute to the antiviral activity of CD8(+) T-cells. The crystal structure of this protein has been resolved to 2.7 angstroms. This protein prevents hemolytic anemia from oxidative stress by stabilizing hemoglobin, thus making this gene a therapeutic target for patients with hemolytic anemia. This protein may have a proliferative effect and play a role in cancer development or progression. Related pseudogenes have been identified on chromosomes 5, 6, 10 and 13.

Source: NCBI Gene 7001 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 20 total
  • GTEx eGene: eQTL in 26 tissues, sQTL in 2 (q < 0.05)
  • Constraint (gnomAD): pLI 0.04 (LoF-tolerant), LOEUF 0.85 (unconstrained)
  • MANE Select transcript: NM_005809

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:9353
Approved symbolPRDX2
Nameperoxiredoxin 2
Location19p13.13
Locus typegene with protein product
StatusApproved
AliasesPRP, NKEFB, TSA, PRXII, PRX2, MGC4104
Ensembl geneENSG00000167815
Ensembl biotypeprotein_coding
OMIM600538
Entrez7001

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 16 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

MANE Select: ENST00000301522

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 1

ENST00000301522, ENST00000334482, ENST00000466174, ENST00000477555, ENST00000478908, ENST00000498785, ENST00000866178, ENST00000866180, ENST00000866181, ENST00000955165, ENST00000992591, ENST00001013549, ENST00001013550, ENST00001058160, ENST00001058164, ENST00001100813, ENST00001100814, ENST00001100815, ENST00001100816, ENST00001100817, ENST00001100818, ENST00001140878

RefSeq mRNA: 1 — MANE Select: NM_005809 NM_005809

CCDS: CCDS12281

Canonical transcript exons

ENST00000301522 — 6 exons

ExonStartEnd
ENSE000011174001280017712800299
ENSE000017185271279985912799989
ENSE000018994891280174012801800
ENSE000035334361280115912801270
ENSE000035749691280091612801069
ENSE000036449401279682312797166

Expression profiles

Bgee: expression breadth ubiquitous, 304 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 192.8225 / max 5871.7591, expressed in 1800 samples.

Highest expression (Bgee): lateral nuclear group of thalamus, substantia nigra pars compacta, trabecular bone tissue, substantia nigra pars reticulata, lateral globus pallidus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRDX2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Artery Tibialeqtl1.2e-28+0.2019:12766150:G:C
Artery Aortaeqtl4.1e-24+0.2919:12766150:G:C
Cells Cultured fibroblastseqtl6.1e-21-0.2419:12828978:T:C
Nerve Tibialeqtl1.1e-17-0.1819:12811689:A:G
Whole Bloodeqtl2.5e-15+0.1419:12766150:G:C
Cells EBV-transformed lymphocyteseqtl4.6e-15+0.5919:12766150:G:C
Skin Sun Exposed Lower legeqtl2.9e-14+0.1319:12766150:G:C
Lungeqtl7.4e-14+0.1919:12766150:G:C
Spleeneqtl2.9e-12+0.3419:12766150:G:C
Esophagus Mucosaeqtl1.8e-10-0.1519:12828978:T:C
Thyroideqtl1.0e-09+0.1019:12766150:G:C
Muscle Skeletaleqtl1.2e-08-0.0919:12811689:A:G
Adipose Subcutaneouseqtl2.6e-08-0.1319:12811689:A:G
Esophagus Musculariseqtl6.0e-08-0.1119:12828978:T:C
Colon Transverseeqtl8.9e-08+0.1319:12766150:G:C
Colon Sigmoideqtl3.4e-07+0.1519:12766150:G:C
Stomacheqtl2.0e-05+0.1519:12766150:G:C
Skin Not Sun Exposed Suprapubiceqtl6.2e-05+0.1119:12766150:G:C
Artery Coronaryeqtl3.5e-04+0.1819:12766150:G:C
Small Intestine Terminal Ileumeqtl4.4e-04+0.1419:12685621:T:C

FANTOM5 promoters

6 alternative TSS:

Promoter IDTPM avgSamples expressed
179391123.52531789
17939329.95081738
17939229.12241726
1793949.15031630
1793900.8358402
1793890.2380100

Top tissues by expression

showing 100 of 304 tissues by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
lateral nuclear group of thalamusUBERON:000273699.86gold quality
substantia nigra pars compactaUBERON:000196599.84gold quality
trabecular bone tissueUBERON:000248399.84gold quality
substantia nigra pars reticulataUBERON:000196699.81gold quality
lateral globus pallidusUBERON:000247699.71gold quality
ponsUBERON:000098899.70gold quality
heart right ventricleUBERON:000208099.65gold quality
apex of heartUBERON:000209899.64gold quality
right adrenal gland cortexUBERON:003582799.64gold quality
right adrenal glandUBERON:000123399.63gold quality
left adrenal glandUBERON:000123499.59gold quality
adrenal cortexUBERON:000123599.58gold quality
left adrenal gland cortexUBERON:003582599.57gold quality
superior vestibular nucleusUBERON:000722799.54gold quality
embryoUBERON:000092299.49gold quality
adrenal glandUBERON:000236999.48gold quality
prefrontal cortexUBERON:000045199.47gold quality
cardiac ventricleUBERON:000208299.47gold quality
heart left ventricleUBERON:000208499.47gold quality
ganglionic eminenceUBERON:000402399.45gold quality
right frontal lobeUBERON:000281099.44gold quality
right atrium auricular regionUBERON:000663199.44gold quality
Brodmann (1909) area 10UBERON:001354199.43gold quality
penisUBERON:000098999.42gold quality
mammalian vulvaUBERON:000099799.42gold quality
cerebellar vermisUBERON:000472099.41gold quality
cardiac atriumUBERON:000208199.40gold quality
right hemisphere of cerebellumUBERON:001489099.40gold quality
pituitary glandUBERON:000000799.39gold quality
cerebellar cortexUBERON:000212999.37gold quality
adenohypophysisUBERON:000219699.37gold quality
cerebellar hemisphereUBERON:000224599.37gold quality
adult organismUBERON:000702399.36gold quality
cerebellumUBERON:000203799.35gold quality
ventral tegmental areaUBERON:000269199.35gold quality
middle temporal gyrusUBERON:000277199.34gold quality
cingulate cortexUBERON:000302799.34gold quality
dorsolateral prefrontal cortexUBERON:000983499.33gold quality
anterior cingulate cortexUBERON:000983599.33gold quality
dorsal root ganglionUBERON:000004499.31gold quality
renal medullaUBERON:000036299.31gold quality
nucleus accumbensUBERON:000188299.31gold quality
endometrium epitheliumUBERON:000481199.31gold quality
pigmented layer of retinaUBERON:000178299.30gold quality
Brodmann (1909) area 9UBERON:001354099.30gold quality
retinaUBERON:000096699.28gold quality
seminal vesicleUBERON:000099899.28gold quality
body of tongueUBERON:001187699.27gold quality
heartUBERON:000094899.26gold quality
caudate nucleusUBERON:000187399.26gold quality
amygdalaUBERON:000187699.24gold quality
putamenUBERON:000187499.21gold quality
parotid glandUBERON:000183199.20gold quality
medulla oblongataUBERON:000189699.20gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450299.20gold quality
mucosa of transverse colonUBERON:000499199.20gold quality
neocortexUBERON:000195099.19gold quality
ventricular zoneUBERON:000305399.19gold quality
cerebral cortexUBERON:000095699.17gold quality
frontal cortexUBERON:000187099.17gold quality
frontal lobeUBERON:001652599.17gold quality
oral cavityUBERON:000016799.13gold quality
forebrainUBERON:000189099.13gold quality
telencephalonUBERON:000189399.12gold quality
frontal poleUBERON:000279599.12gold quality
upper leg skinUBERON:000426299.12gold quality
brainUBERON:000095599.11gold quality
gastrocnemiusUBERON:000138899.10gold quality
hindlimb stylopod muscleUBERON:000425299.10gold quality
central nervous systemUBERON:000101799.09gold quality
vastus lateralisUBERON:000137999.09gold quality
inferior olivary complexUBERON:000212799.09gold quality
temporal lobeUBERON:000187199.08gold quality
cortical plateUBERON:000534399.08gold quality
pharyngeal mucosaUBERON:000035599.07gold quality
jejunal mucosaUBERON:000039999.07gold quality
hypothalamusUBERON:000189899.07gold quality
jejunumUBERON:000211599.06gold quality
upper arm skinUBERON:000426399.06gold quality
triceps brachiiUBERON:000150999.05gold quality
dorsal plus ventral thalamusUBERON:000189799.04gold quality
bone marrowUBERON:000237199.04gold quality
adrenal tissueUBERON:001830399.04gold quality
Ammon’s hornUBERON:000195499.02gold quality
metanephros cortexUBERON:001053399.02gold quality
midbrainUBERON:000189199.00gold quality
nippleUBERON:000203099.00gold quality
duodenumUBERON:000211499.00gold quality
trigeminal ganglionUBERON:000167598.99gold quality
gluteal muscleUBERON:000200098.99gold quality
biceps brachiiUBERON:000150798.97gold quality
substantia nigraUBERON:000203898.96gold quality
quadriceps femorisUBERON:000137798.95gold quality
tongueUBERON:000172398.95gold quality
myocardiumUBERON:000234998.95gold quality
body of stomachUBERON:000116198.94gold quality
skin of abdomenUBERON:000141698.94gold quality
zone of skinUBERON:000001498.92gold quality
paraflocculusUBERON:000535198.92gold quality
adult mammalian kidneyUBERON:000008298.91gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 17.

ExperimentMarker?Max mean expression
E-MTAB-10042yes7131.29
E-MTAB-7407yes6350.25
E-GEOD-130473yes5140.73
E-CURD-112yes4116.43
E-HCAD-24yes3629.86
E-HCAD-4yes3590.30
E-CURD-122yes3522.79
E-MTAB-8205yes2106.04
E-CURD-6yes2088.35
E-GEOD-81383yes501.34
E-HCAD-6yes55.81
E-HCAD-10yes49.70
E-MTAB-9221yes16.15
E-HCAD-9yes9.72
E-MTAB-9067yes8.05

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Tonguetissue791.4
Skeletal muscletissue677.5high
Heart muscletissue659.2medium
Bone marrowtissue647.0high
Superior colliculitissue467.6
Thalamustissue461.0
Ponstissue444.2
Postcentral gyrustissue443.6
Spinal cordtissue436.6
Parathyroid glandtissue426.5high
Locus coeruleustissue401.1
Midbraintissue389.5
Cerebral cortextissue371.4high
Somatosensory cortextissue371.4
Medulla oblongatatissue370.0
Putamentissue365.7
Adrenal glandtissue365.2high
Basal gangliatissue350.4high
Occipital cortextissue341.0
Frontal cortextissue339.4
Motor cortextissue335.1
Caudate putamentissue326.3
Substantia nigratissue323.4
Hippocampal formationtissue321.5
Choroid plexustissue321.4
Pituitary glandtissue318.6
Ventral forebraintissue318.2
Prefrontal cortextissue302.5
Septumtissue302.2
Retrosplenial and cingulate cortextissue299.8
Temporal cortextissue293.2
Hippocampustissue284.5high
Entorhinal cortextissue284.4
Cerebellumtissue283.5high
Nucleus accumbenstissue277.4
Hypothalamustissue275.0
Olfactory bulbtissue272.0
Retrosplenial cortextissue270.7
Periaqueductal graytissue263.9
Insular cortextissue253.7
Amygdalatissue240.4
Duodenumtissue236.5medium
Ovarytissue230.1medium
Esophagustissue219.5medium
Livertissue210.5medium
Corpus callosumtissue207.4
Skin 1tissue200.3medium
Retinatissue192.4
Small intestinetissue189.3medium
Salivary glandtissue188.4medium
Adipose tissuetissue186.7medium
Kidneytissue185.1high
Pancreastissue183.7high
Vaginatissue170.9not detected
Thymustissue168.8
Thyroid glandtissue140.7high
Urinary bladdertissue138.8high
Colontissue137.3medium
Epididymistissue136.6high
Fallopian tubetissue133.5high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (436.6), Spinal trigeminal nucleus, interpolar (410.8), Cerebellar nuclei (409.8), Nuclei of the trapezoid body (405.1), Nucleus raphe magnus (401.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARNT, EPAS1, HIF1A

miRNA regulators (miRDB)

Targeting PRDX2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

11 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-6783-3P99.8967.922059
HSA-MIR-6756-5P99.8267.972466
HSA-MIR-6766-5P99.6867.702325
HSA-MIR-361299.4566.021333
HSA-MIR-65099.4565.771309
HSA-MIR-431899.3866.941505
HSA-MIR-3922-3P99.2564.961136
HSA-MIR-317699.2564.35954
HSA-MIR-444398.0266.251928
HSA-MIR-6515-5P97.0865.481219
HSA-MIR-7847-3P96.6364.58952

Functional genomics

gnomAD constraint: pLI 0.0444, LOEUF 0.854, missense Z 1.02 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000301522 — one region, missense o/e 0.87.

Literature-anchored findings (GeneRIF, showing 40)

  • Protein levels of Prx-I and Prx-II were significantly increased in Alzheimer Disease and Down Syndrome. (PMID:11771746)
  • Proteomics analysis of cellular response to oxidative stress. Evidence for in vivo overoxidation of peroxiredoxins at their active site (PMID:11904290)
  • 2-Cys Prxs act in a mutually nonredundant and sometimes stress-specific fashion to protect human cells from oxidant injury. The substantial resistance of human cells to hydroperoxides may result in part from the additive action of multiple Prxs (PMID:12080185)
  • Peroxiredoxin 2 levels are significantly increased in the frontal cortex of patients with Down syndrome, Alzheimer and Pick’s disease and provides evidence for existence of compensatory response in increased cell loss. (PMID:12650976)
  • decreased expression of PRDX2 may contribute to the altered redox state in Down syndrome at levels comparable to that of the increased expression of SOD1 (PMID:12943237)
  • Prx II can be used as a novel marker of vascular tumors and preferential expression of Prx II is found in benign vascular tumors. (PMID:12963914)
  • results show that sestrins, a family of proteins whose expression is modulated by p53, are required for regeneration of peroxiredoxins containing Cys-SO(2)H (PMID:15105503)
  • Prx I and Prx II are induced at the early and late stage of differentiation of normal human epidermal keratinocytes. (PMID:15864612)
  • loss of IDPc and Prx-II during tumor development may involve in tumor progression and metastasis (PMID:15936593)
  • PDX2 was involved in malignant transformation of human bronchial epithelial cell induced by crystalline nickel sulfide. (PMID:16188094)
  • in the erythrocyte Prx2 is extremely efficient at scavenging H(2)O(2) noncatalytically (PMID:17105810)
  • We propose a model in which Prxs function as peroxide dosimeters in subcellular processes that involve redox cycling, with hyperoxidation controlling structural transitions that alert cells of perturbations in peroxide homeostasis. (PMID:17145963)
  • peroxiredoxin 2 has a tertiary structure that facilitates reaction of the active site thiol with hydrogen peroxide while restricting its reactivity with other thiol reagents (PMID:17329258)
  • Human Prdx1 and Prdx2 possess unique functions and regulatory mechanisms and that Cys(83) bestows a distinctive identity to Prdx1. (PMID:17519234)
  • PrxII might play an important role in hepatocarcinogenesis and might be used as a molecular target for HCC prevention and treatment. (PMID:17524271)
  • observation of increased SNO-Prx2 in human Parkinson’s disease (PD) brains, and S-nitrosylation of Prx2 inhibited both its enzymatic activity and protective function from oxidative stress (PMID:18003920)
  • Peroxiredoxin II (PRXII) exclusively expressed in bronchiolitis obliterans syndrome. (PMID:18022079)
  • Significantly decreased expression of Prx-2, -3, and -5 in FED may suggest an alteration in the ability of endothelial cells to withstand oxidant-induced damage and may be closely related to the pathogenesis of this disease. (PMID:18378575)
  • study reports identification of Prx2 in the erythrocyte membrane from hereditary spherocytosis patients; presence of Prx2 in erythrocyte membranes was linked to higher levels of oxidative stress, as reflected by increased membrane bound hemoglobin (PMID:18387321)
  • 2-cysteine peroxiredoxins from Homo sapiens, Arabidopsis thaliana, and Pisum sativum as well as a carboxy-terminally truncated variant were subjected to isothermal titration calorimetry analysis. (PMID:18553980)
  • Silencing of PRDX2 caused decreased rates of Hep3B cell growth and clone formation, increased rates of cell apoptosis, and increased the levels of endogenous ROS and MDA. (PMID:18578994)
  • analysis of a protein thiosulfinate intermediate in the reduction of cysteine sulfinic acid in peroxiredoxin by human sulfiredoxin (PMID:18593714)
  • The results suggest that Prx II oxidation does not relate to the pathogenesis of IPF/UIP (PMID:18606608)
  • peroxiredoxin (Prx) I and Prx II are specific targets of HDAC6 (PMID:18606987)
  • inhibiting peroxiredoxin II sensitizes glioma cells to oxidative stress (PMID:18718523)
  • Prx2 is a key antioxidant enzyme for the erythrocyte and reveal red blood cells as active oxidant scrubbers in the bloodstream. (PMID:19061854)
  • These results indicate that both nipradilol and timolol possess a novel mechanism of action and function as potent protective agents against oxidative stress. (PMID:19151395)
  • Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
  • Prx II is more susceptible than Prx I to hyperoxidation and that the majority of the hyperoxidized Prx II formation is reversible. However, the hyperoxidized Prx I showed much less reversibility (PMID:19286652)
  • Conclude that Prx II and III are upregulated in response to the development of cervical cancer. (PMID:19424615)
  • Deglutathionylation of 2-Cys Prx is specifically catalyzed by Srx. (PMID:19561357)
  • Resutls show that three of five autoantibodies, FKBP52, PPIA, and PRDX2, showed significantly increased reactivity in primary breast cancer and CIS compared with healthy controls. (PMID:19584157)
  • P. falciparum imports the human redox-active protein peroxiredoxin 2 (hPrx-2, hTPx1) into its cytosol. (PMID:19666612)
  • Exposure to Chloramines and hypochlorous acid inflammatory oxidants will result in Prx2 oxidation and could compromise the erythrocyte’s ability to resist damaging oxidative insult. (PMID:19716412)
  • could act as an autoantigen of a streptococcal-induced autoimmune response and represents a target of the exaggerated T cell response in psoriasis. (PMID:20363977)
  • Data suggest that anti-Prx2 autoantibodies would be a useful marker for systemic vasculitis and would be involved in the inflammatory processes of systemic vasculitis. (PMID:20646000)
  • PRDX2 was up-regulated in women older than 38 years, and its expression in cumulus cells was associated with embryo quality (PMID:20721618)
  • Addition of an uncharged derivative of leucine hydroperoxide to intact erythrocytes caused Prx2 oxidation with no concomitant loss in glutathione. (PMID:20840079)
  • proteomic profiling used to identify the target proteins of miR-122a in hepatocellular carcinoma; PRDXII was identified to be the new target of miR-122a (PMID:20859956)
  • High PRDX2 expression in the cytoplasm is associated with uterine cervix carcinogenesis. (PMID:21119665)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
mus_musculusPrdx2ENSMUSG00000005161
rattus_norvegicusPrdx2ENSRNOG00000003520
drosophila_melanogasterPrx6cFBGN0033518
drosophila_melanogasterPrx6bFBGN0033520
drosophila_melanogasterCG12896FBGN0033521

Paralogs (4): PRDX1 (ENSG00000117450), PRDX6 (ENSG00000117592), PRDX4 (ENSG00000123131), PRDX3 (ENSG00000165672)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:109486) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)Records
decreased hematocrit1
abnormal erythropoiesis1
echinocytosis1
schistocytosis1
enlarged spleen1
hemolytic anemia1
abnormal bone marrow cell morphology/development1
abnormal proerythroblast morphology1
abnormal erythrocyte morphology1
reticulocytosis1
spherocytosis1
decreased hemoglobin content1
increased spleen weight1
hemosiderosis1
increased cellular sensitivity to hydrogen peroxide induced cell death1
increased cellular sensitivity to oxidative stress1
increased spleen red pulp amount1
increased number of Heinz bodies1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Staphylococcus aureus subsp. aureus Mu50P0A0B5100.0%Diamond
Staphylococcus aureus subsp. aureus MW2P0A0B6100.0%Diamond
Staphylococcus aureus subsp. aureus NCTC 8325P0A0B7100.0%Diamond
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2P0A251100.0%Diamond
Salmonella enterica subsp. enterica serovar TyphiP0A252100.0%Diamond
Escherichia coli K-12P0AE08100.0%Diamond
Escherichia coli CFT073P0AE09100.0%Diamond
Escherichia coli O157:H7P0AE10100.0%Diamond
Shigella flexneriP0AE11100.0%Diamond
Candida albicans SC5314P0CU34100.0%Diamond
Mycobacterium tuberculosis variant bovis AF2122/97P65689100.0%Diamond
Staphylococcus aureus subsp. aureus N315P99074100.0%Diamond
Mycobacterium tuberculosis CDC1551P9WIE0100.0%Diamond
Mycobacterium tuberculosis H37RvP9WIE1100.0%Diamond
Staphylococcus aureus subsp. aureus USA300Q2FJN4100.0%Diamond
Macaca fascicularisQ2PFZ3100.0%Diamond
Staphylococcus aureus RF122Q2YVK2100.0%Diamond
Staphylococcus aureus subsp. aureus COLQ5HIR5100.0%Diamond
Staphylococcus aureus subsp. aureus MSSA476Q6GC91100.0%Diamond
Staphylococcus aureus subsp. aureus MRSA252Q6GJR7100.0%Diamond
Triticum aestivumP8060299.5%Diamond
Staphylococcus epidermidis RP62AQ5HRY199.5%Diamond
Staphylococcus epidermidis ATCC 12228Q8CMQ299.5%Diamond
Hordeum vulgareQ9646899.5%Diamond
Pongo abeliiQ5RC6399.4%Diamond
Myotis lucifugusQ6B4U999.0%Diamond
Spinacia oleraceaO2436498.5%Diamond
Helicobacter pylori 26695P2176298.5%Diamond
Helicobacter pylori J99P5687698.5%Diamond
Arabidopsis thalianaQ9629198.5%Diamond
Bromus secalinusP5257197.5%Diamond
Bos taurusO7783497.3%Diamond
Sus scrofaQ9TSX997.3%Diamond
Methanococcus maripaludis C5A4FWZ997.2%Diamond
Thermotoga petrophila RKU-1A5IIX797.2%Diamond
Methanococcus maripaludis S2Q6LY1997.2%Diamond
Thermotoga maritima MSB8Q9WZR497.2%Diamond
Cricetulus griseusQ8K3U796.5%Diamond
Methanothermobacter thermautotrophicus str. Delta HO2626295.7%Diamond
Methanothermobacter marburgensis str. MarburgQ5710995.7%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
HOOK2protein-coding29911
JUNBprotein-coding3726
GET3protein-coding439
BEST2protein-coding54831
MIR6794ncRNA102466196
RTBDN-AS1ncRNA105372281
THSD8protein-coding111644133
MAST1protein-coding22983
RTBDNprotein-coding83546
RNASEH2Aprotein-coding10535
MIR5684ncRNA100847071

Protein

Protein identifiers

Peroxiredoxin-2 — P32119 (reviewed: P32119)

Alternative names: Natural killer cell-enhancing factor B, PRP, Thiol-specific antioxidant protein, Thioredoxin peroxidase 1, Thioredoxin-dependent peroxide reductase 1, Thioredoxin-dependent peroxiredoxin 2

All UniProt accessions (3): P32119, A6NIW5, V9HW12

UniProt curated annotations — full annotation on UniProt →

Function. 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).

Subunit / interactions. Homodimer; disulfide-linked, upon oxidation. 5 homodimers assemble to form a ring-like decamer. Interacts with TIPIN.

Subcellular location. Cytoplasm.

Post-translational modifications. The enzyme can be inactivated by further oxidation of the cysteine sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) instead of its condensation to a disulfide bond. It can be reactivated by forming a transient disulfide bond with sulfiredoxin SRXN1, which reduces the cysteine sulfinic acid in an ATP- and Mg-dependent manner. Acetylation increases resistance to transition to high molecular-mass complexes. Deacetylated by HDAC6 which decreases reducing activity.

Miscellaneous. The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this typical 2-Cys peroxiredoxin, C(R) is provided by the other dimeric subunit to form an intersubunit disulfide. The disulfide is subsequently reduced by thioredoxin. Due to intron retention. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.

Isoforms (2)

UniProt IDNamesCanonical?
P32119-11yes
P32119-22

RefSeq proteins (1): NP_005800* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000866AhpC/TSADomain
IPR013766Thioredoxin_domainDomain
IPR019479Peroxiredoxin_CDomain
IPR024706Peroxiredoxin_AhpC-typFamily
IPR036249Thioredoxin-like_sfHomologous_superfamily
IPR050217PeroxiredoxinFamily

Pfam: PF00578, PF10417

Enzyme classification (BRENDA)

  • EC 1.11.1.24 — thioredoxin-dependent peroxiredoxin (BRENDA: 72 organisms, 110 substrates, 31 inhibitors, 72 Km, 50 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
H2O20.0004–11.723
CUMENE HYDROPEROXIDE0.0066–0.1918
THIOREDOXIN0.001–0.07947
TERT-BUTYL HYDROPEROXIDE—5
THIOREDOXIN A0.0009–0.01225
THIOREDOXIN B0.0022–0.02085
T-BUTYL HYDROPEROXIDE0.072–0.1934
THIOREDOXIN Q0.0007–0.00284
REDUCED THIOREDOXIN0.0024–0.0042
REDUCED THIOREDOXIN A0.0079–0.00872
ETHYL HYDROPEROXIDE0.00451
LINOLEIC ACID HYDROPEROXIDE0.1171
TRYPAREDOXIN 20.03191

Catalyzed reactions (Rhea)

  • a hydroperoxide + [thioredoxin]-dithiol = an alcohol + [thioredoxin]-disulfide + H2O (RHEA:62620)

UniProt features (38 total): helix 9, sequence conflict 7, strand 7, modified residue 4, turn 2, disulfide bond 2, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, mutagenesis site 1, domain 1, active site 1

Structure

Experimental structures (PDB)

7 structures by resolution:

PDBTitleMethodResolution (Å)
1QMVthioredoxin peroxidase B from red blood cellsX-RAY DIFFRACTION1.7
7KIZreduced human peroxiredoxin 2X-RAY DIFFRACTION1.7
5IJTHuman Peroxiredoxin 2 Oxidized (SS)X-RAY DIFFRACTION2.15
7KJ1human peroxiredoxin 2 - C172S mutantX-RAY DIFFRACTION2.15
7KJ0hyperoxidized human peroxiredoxin 2X-RAY DIFFRACTION2.29
5B8ACrystal structure of oxidized chimeric EcAhpC1-186-YFSKHNX-RAY DIFFRACTION2.7
5B8BCrystal structure of reduced chimeric E.coli AhpC1-186-YFSKHNX-RAY DIFFRACTION3.1

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P32119-F197.870.99

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH supported · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

PositionRole
51cysteine sulfenic acid (-soh) intermediate

Post-translational modifications (4)

TypePositions
N-acetylalanine2
Phosphoserine112
Phosphothreonine182
N6-acetyllysine196

Disulfide bonds (2)

TypePositions
Interchain (with c-172)51
Interchain (with c-51)172

Mutagenesis-validated functional residues (1)

PositionPhenotype
196abolishes acetylation.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 14; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

14 pathways:

IDPathwayEvidence
R-HSA-3299685Detoxification of Reactive Oxygen Speciescurated
R-HSA-5628897TP53 Regulates Metabolic Genescurated
R-HSA-9734009Defective Intrinsic Pathway for Apoptosis ⚕—
R-HSA-8862803Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models ⚕electronic
R-HSA-1643685Disease ⚕—
R-HSA-9645723Diseases of programmed cell death ⚕—
R-HSA-8863678Neurodegenerative Diseases ⚕—
R-HSA-9711123Cellular response to chemical stress—
R-HSA-8953897Cellular responses to stimuli—
R-HSA-2262752Cellular responses to stress—
R-HSA-74160Gene expression (Transcription)—
R-HSA-212436Generic Transcription Pathway—
R-HSA-73857RNA Polymerase II Transcription—
R-HSA-3700989Transcriptional Regulation by TP53—

MSigDB gene sets: 361 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GNF2_PRDX2, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_COAGULATION, JAEGER_METASTASIS_DN, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_POSITIVE_REGULATION_OF_COAGULATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE

GO Biological Process (11): defense response to tumor cell (GO:0002357), response to oxidative stress (GO:0006979), removal of superoxide radicals (GO:0019430), positive regulation of blood coagulation (GO:0030194), cellular response to oxidative stress (GO:0034599), hydrogen peroxide catabolic process (GO:0042744), regulation of apoptotic process (GO:0042981), negative regulation of apoptotic process (GO:0043066), leukocyte activation (GO:0045321), cell redox homeostasis (GO:0045454), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (7): thioredoxin peroxidase activity (GO:0008379), antioxidant activity (GO:0016209), peroxidase activity (GO:0004601), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), peroxiredoxin activity (GO:0051920), thioredoxin-dependent peroxiredoxin activity (GO:0140824)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

11 top-level categories:

CategoryPathways
Cellular response to chemical stress1
Transcriptional Regulation by TP531
Neurodegenerative Diseases1
RNA Polymerase II Transcription1
Cellular responses to stimuli1
Generic Transcription Pathway1
Gene expression (Transcription)1
Defective Intrinsic Pathway for Apoptosis1
Disease1
Cellular responses to stress1
Diseases of programmed cell death1

GO top-level categories

35 GO namespaces:

CategoryTerms
cellular oxidant detoxification2
apoptotic process2
cellular anatomical structure2
response to tumor cell1
defense response1
response to stress1
superoxide metabolic process1
cellular response to superoxide1
blood coagulation1
regulation of blood coagulation1
positive regulation of coagulation1
positive regulation of wound healing1
positive regulation of hemostasis1
response to oxidative stress1
cellular response to chemical stress1
catabolic process1
hydrogen peroxide metabolic process1
regulation of programmed cell death1
regulation of apoptotic process1
negative regulation of programmed cell death1
cell activation1
immune system process1
cellular homeostasis1
cellular detoxification1
thioredoxin-dependent peroxiredoxin activity1
molecular_function1
antioxidant activity1
oxidoreductase activity, acting on peroxide as acceptor1
binding1
catalytic activity1
peroxidase activity1
peroxiredoxin activity1
intracellular anatomical structure1
cytoplasm1
extracellular vesicle1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO termNSEvidence
cellular response to oxidative stressBPdirect assay
defense response to tumor cellBPmutant phenotype
regulation of apoptotic processBPmutant phenotype
removal of superoxide radicalsBPdirect assay
response to oxidative stressBPmutant phenotype
cytosolCCdirect assay
extracellular exosomeCChigh-throughput assay
antioxidant activityMFdirect assay
thioredoxin peroxidase activityMFdirect assay

Protein interactions and networks

IntAct

Human interaction partners of PRDX2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

26 partners by confidence:

PartnerInteraction typeMIscoreRecords
TXNassociation0.5602
PRDX3association0.5102
STAT3physical association0.5003
BADphysical association0.4402
DNMT3Aphysical association0.4001
A2Mphysical association0.3701
CA4physical association0.3701
CD320physical association0.3701
CDC37physical association0.3701
COPS5physical association0.3701
ECSITphysical association0.3701
EXOC6physical association0.3701
IFIT5physical association0.3701
MAST1physical association0.3701
NLGN3physical association0.3701
PRDX4physical association0.3701
RNF32physical association0.3701
SAT1physical association0.3701
UTYphysical association0.3701
YWHAZphysical association0.3701
FAM171A2association0.3501
TXNDC9association0.3501
COL14A1physical association0.0001
KCTD5physical association0.0001
MAKphysical association0.0001
RTL9physical association0.0001

BioGRID (408 interactions; top human partners by supporting records): PRDX1 (Co-fractionation; 21 records), RPL4 (Affinity Capture-MS; 4 records), TXNDC5 (Affinity Capture-MS; 4 records), DPYSL2 (Affinity Capture-MS; 3 records), MYC (Affinity Capture-MS; 3 records), PARK2 (Affinity Capture-MS; 3 records), PRDX5 (Co-fractionation; 3 records), PRDX6 (Co-fractionation; 3 records), SOD1 (Co-fractionation; 3 records), AGR2 (Proximity Label-MS; 2 records), APP (Affinity Capture-MS; 2 records), CCT2 (Affinity Capture-MS; 2 records), CDK1 (Co-fractionation; 2 records), CDK2 (Affinity Capture-Western; 2 records), CFTR (Affinity Capture-MS; 2 records)

SIGNOR signaling

2 signaling interactions:

AEffectBMechanism
LCK“down-regulates activity”PRDX2phosphorylation
ABL1“down-regulates activity”PRDX2phosphorylation

Disease & clinical

Genetic variants

Variant evidence for PRDX2: 20 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

20 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance12
Likely benign0
Benign0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 460):

Position(s)EffectΔscoreSites
19:12799857–12799858donor_loss1.00005
19:12800175–12800176donor_loss1.00004
19:12800195donor_gain1.0000
19:12800300–12800301acceptor_loss1.00005
19:12800914donor_loss1.0000
19:12801070–12801071acceptor_loss1.00006
19:12801157–12801158donor_loss1.00003
19:12799861donor_gain0.9900
19:12800176donor_loss0.9900
19:12800300acceptor_loss0.9900

AlphaMissense

684 missense substitutions predicted likely pathogenic (of 1,292 scored), across 156 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
D7880.9920.997
H8380.9840.997
D10680.9790.993
D4680.9770.996
F4980.9720.999
F4780.9670.999
D14580.9580.983
F19480.9520.991
F6580.9440.995
D13380.9430.990
F5880.9190.988
F4280.9110.992
F1580.8820.981
F2580.8770.973
E5470.9930.998
W8670.9920.998
R12770.9921.000
W17670.9910.998
C5170.9870.998
F8170.9850.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

CancerPrognosticp-value
Kidney Renal Clear Cell Carcinoma (TCGA)favorable7.87e-07
Kidney Renal Papillary Cell Carcinoma (TCGA)favorable1.13e-06
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)favorable0.000423
Lung Squamous Cell Carcinoma (TCGA)favorable0.000605
Kidney Renal Clear Cell Carcinoma (validation)favorable0.000645

Disease associations

OMIM: gene MIM:600538 | disease phenotypes:

GWAS associations

1 associations:

StudyTraitp-value
GCST90002401_233Platelet distribution width3e-21

EFO canonical traits (from GWAS)

1 canonical traits:

EFO IDTrait name
EFO:0007984platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295744 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

2 measured of 2 human assays (4 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
CHEMBL5565154IC50350 nM
CHEMBL5653589KD1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
5.16Kd6924nMCHEMBL5653589
5.16ED506924nMCHEMBL5653589
5.10Kd7995nMCHEMBL3752910
5.10ED507995nMCHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 27 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149062: Binding affinity to human PRDX2 incubated for 45 mins by Kinobead based pull down assaykd6.9239uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149062: Binding affinity to human PRDX2 incubated for 45 mins by Kinobead based pull down assaykd7.9953uM

CTD chemical–gene interactions

101 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Aaffects expression, decreases expression, decreases methylation, increases expression4
sodium arseniteincreases expression4
Hydrogen Peroxideincreases expression, increases oxidation, decreases response to substance4
Valproic Acidaffects expression, decreases expression, increases methylation4
Cisplatinincreases expression, affects response to substance, decreases response to substance3
bisphenol Fincreases expression, affects cotreatment, decreases expression2
ochratoxin Aincreases acetylation, increases expression2
S-(1,2-dichlorovinyl)cysteinedecreases reaction, increases expression, decreases expression2
Aerosolsdecreases expression2
Benzo(a)pyrenedecreases expression, increases expression, decreases reaction2
Cocaineaffects expression, decreases expression2
Doxorubicinaffects expression, decreases response to substance2
Estradioldecreases expression2
Formaldehydeincreases expression, decreases expression, decreases reaction, increases activity2
Leadaffects expression, decreases expression2
Paraquatincreases expression, affects cotreatment2
Quercetinaffects cotreatment, increases expression, decreases expression, decreases reaction2
Tobacco Smoke Pollutionaffects expression2
Cyclosporinedecreases expression2
tert-Butylhydroperoxidedecreases expression, increases expression2
Nanotubes, Carbonaffects expression, increases expression2
Particulate Matterincreases expression, increases response to substance, decreases expression2
dicrotophosincreases expression1
uranyl acetateaffects expression1
cumene hydroperoxideincreases expression1
deoxynivalenoldecreases expression1
lead acetateaffects cotreatment, increases expression1
pyrogallol 1,3-dimethyl etheraffects cotreatment, affects localization, increases expression1
4-vinyl-1-cyclohexene dioxideincreases expression1
arseniteaffects binding, increases reaction1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4144685BindingBinding affinity to wild type recombinant human N-terminal 6His-tagged peroxiredoxin-2 expressed in Escherichia coli BL21 after 1 hr by LC-MS/MS analysisent-Jungermannenone C Triggers Reactive Oxygen Species-Dependent Cell Differentiation in Leukemia Cells. — *J Nat Prod*

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B3ESAbcam HEK293T PRDX2 KOTransformed cell lineFemale
CVCL_KT96HeLa SilenciX PRDX2Cancer cell lineFemale
CVCL_TG44HAP1 PRDX2 (-) 1Cancer cell lineMale
CVCL_TG45HAP1 PRDX2 (-) 2Cancer cell lineMale
CVCL_TG46HAP1 PRDX2 (-) 3Cancer cell lineMale
CVCL_TG47HAP1 PRDX2 (-) 4Cancer cell lineMale

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRDX2 across ~30M SureChEMBL compounds — explore on Sugi Predict.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.