PRDX3 peroxiredoxin 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PRDX3provided by HGNC
Official Full Name: peroxiredoxin 3provided by HGNC
Primary source: HGNC:HGNC:9354
See related: Ensembl:ENSG00000165672 MIM:604769
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AOP1; MER5; AOP-1; SP-22; HBC189; PRO1748; prx-III
Summary: This gene encodes a mitochondrial protein with antioxidant function. The protein is similar to the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase, and it can rescue bacterial resistance to alkylhydroperoxide in E. coli that lack the C22 subunit. The human and mouse genes are highly conserved, and they map to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian homologs suggest that these genes consist of a family that is responsible for the regulation of cellular proliferation, differentiation and antioxidant functions. This family member can protect cells from oxidative stress, and it can promote cell survival in prostate cancer. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1, 3, 13 and 22. [provided by RefSeq, Oct 2014]
Expression: Ubiquitous expression in adrenal (RPKM 195.5), kidney (RPKM 144.1) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 10q26.11

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	10	NC_000010.11 (119167699..119178865, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (120927215..120938377, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

the role of Spalt like protein 4 (SALL4) in pancreatic ductal adenocarcinoma cell proliferation, mobility and its regulation in mitochondrial ROS via FoxM1/Prx III axis.
Title: SALL4 suppresses reactive oxygen species in pancreatic ductal adenocarcinoma phenotype via FoxM1/Prx III axis.
tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD.
Title: Tubular Peroxiredoxin 3 as a Predictor of Renal Recovery from Acute Tubular Necrosis in Patients with Chronic Kidney Disease.
results suggest that decreased PRDX3 by excessive bile acids in trophoblasts plays a critical role in the pathogenesis and progression of Intrahepatic cholestasis of pregnancy.
Title: Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts.
Mutants created to investigate link between oligomerisation and peroxidase activity. Obligate dimer is less active than wildtype but still displays peroxidase activity. 2.4A structure (PDB: 5UCX) shows cysteine-stabilised protein interface.
Title: Quaternary structure influences the peroxidase activity of peroxiredoxin 3.
the present study identified the protein profiles of the PRDX family in LSCC and showed that down-regulation of PRDX3 in Hep-2 cells induced cell apoptosis and inhibited cell proliferation and cell migration.
Title: Differential expression of peroxiredoxin 3 in laryngeal squamous cell carcinoma.
The UNG1-PRDX3 interaction protected UNG1 from reactive oxygen species-mediated degradation and prevented mitochondrial DNA oxidation.
Title: Hydrogen peroxide mediated mitochondrial UNG1-PRDX3 interaction and UNG1 degradation.
PRDX3 knockdown led to the down-regulation of ATP synthases and the decreased cellular ATP level, contributing to the slow-down of cell growth. Furthermore, silencing PRDX3 enhanced invasive properties of HepG2 cells via TIMP-1 down-regulation and the increased ECM degradation
Title: Silencing PRDX3 Inhibits Growth and Promotes Invasion and Extracellular Matrix Degradation in Hepatocellular Carcinoma Cells.
Prx3 and Trx2 comprise an adaptive system to sense changes in atmospheric oxygen tension and influence cellular injury responses through both detoxification of mitochondrial oxidants and regulation of mitochondrial redox-dependent signaling
Title: Detoxification of Mitochondrial Oxidants and Apoptotic Signaling Are Facilitated by Thioredoxin-2 and Peroxiredoxin-3 during Hyperoxic Injury.
PRX3 plays a crucial role in mitochondrial homeostasis.
Title: Featured Article: Accelerated decline of physical strength in peroxiredoxin-3 knockout mice.
High PRX3 expression is associated with invasion of lung adenocarcinoma.
Title: DACH1 inhibits the proliferation and invasion of lung adenocarcinoma through the downregulation of peroxiredoxin 3.

Submit: New GeneRIF Correction See all GeneRIFs (66)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of peroxiredoxin 3 (PRDX3; PRO1748) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of peroxiredoxin 1, 3, and 4 proteins in umbilical cord blood mononuclear cells and T-cell lines	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Cellular responses to stress, organism-specific biosystem (from REACTOME)
Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
Detoxification of Reactive Oxygen Species, organism-specific biosystem (from REACTOME)
Detoxification of Reactive Oxygen Species, organism-specific biosystemReactive oxygen species such as superoxide (O2.-), peroxides (ROOR), singlet oxygen, peroxynitrite (ONOO-), and hydroxyl radical (OH.) are generated by cellular processes such as respiration (reviewe...
Selenium Micronutrient Network, organism-specific biosystem (from WikiPathways)
Selenium Micronutrient Network, organism-specific biosystem
Selenium Micronutrient Network
Validated targets of C-MYC transcriptional activation, organism-specific biosystem (from Pathway Interaction Database)
Validated targets of C-MYC transcriptional activation, organism-specific biosystem
Validated targets of C-MYC transcriptional activation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH68895 (e-PCR)
- UniSTS:90662

RH71324 (e-PCR)
- UniSTS:28207

RH11191 (e-PCR)
- UniSTS:22089

PRDX3-1 (e-PCR)
- UniSTS:512648

G43270 (e-PCR)
- UniSTS:94914

Homology

Homologs of the PRDX3 gene: The PRDX3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, and frog.
Orthologs from Annotation Pipeline: 257 organisms have orthologs with human gene PRDX3
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
alkyl hydroperoxide reductase activity	NAS Non-traceable Author Statement more info	PubMed
cysteine-type endopeptidase inhibitor activity involved in apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
kinase binding	IPI Inferred from Physical Interaction more info	PubMed
protein C-terminus binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
thioredoxin peroxidase activity	EXP Inferred from Experiment more info	PubMed
thioredoxin peroxidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
thioredoxin peroxidase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
apoptotic process	IEA Inferred from Electronic Annotation more info
cell redox homeostasis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular oxidant detoxification	IEA Inferred from Electronic Annotation more info
cellular response to oxidative stress	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
cellular response to oxidative stress	TAS Traceable Author Statement more info
cellular response to reactive oxygen species	IMP Inferred from Mutant Phenotype more info	PubMed
hydrogen peroxide catabolic process	IDA Inferred from Direct Assay more info	PubMed
hydrogen peroxide catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
maternal placenta development	IEA Inferred from Electronic Annotation more info
mitochondrion organization	IMP Inferred from Mutant Phenotype more info	PubMed
myeloid cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	IEA Inferred from Electronic Annotation more info
negative regulation of kinase activity	IDA Inferred from Direct Assay more info	PubMed
peptidyl-cysteine oxidation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
regulation of mitochondrial membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
response to hydrogen peroxide	IDA Inferred from Direct Assay more info	PubMed
response to lipopolysaccharide	ISS Inferred from Sequence or Structural Similarity more info
response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
early endosome	IDA Inferred from Direct Assay more info	PubMed
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrion	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitochondrion	IDA Inferred from Direct Assay more info	PubMed
protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: thioredoxin-dependent peroxide reductase, mitochondrial

Names: antioxidant protein 1; epididymis secretory sperm binding protein; peroxiredoxin III; protein MER5 homolog

NP_001289201.1

EC 1.11.1.15

NP_006784.1

EC 1.11.1.15

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001302272.1 → NP_001289201.1 thioredoxin-dependent peroxide reductase, mitochondrial isoform c precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate exon that results in a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (c) has a distinct C-terminus and is shorter than isoform a.

Source sequence(s)

BC008435, BG282768, BM144742, BX382389, HY173455

UniProtKB/Swiss-Prot

P30048

Conserved Domains (2) summary

COG0450
Location:65 → 186

AhpC; Alkyl hydroperoxide reductase subunit AhpC (peroxiredoxin) [Defense mechanisms]

cd03015
Location:65 → 186

PRX_Typ2cys; Peroxiredoxin (PRX) family, Typical 2-Cys PRX subfamily; PRXs are thiol-specific antioxidant (TSA) proteins, which confer a protective role in cells through its peroxidase activity by reducing hydrogen peroxide, peroxynitrite, and organic hydroperoxides. ...
NM_006793.5 → NP_006784.1 thioredoxin-dependent peroxide reductase, mitochondrial isoform a precursor

See identical proteins and their annotated locations for NP_006784.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a).

Source sequence(s)

BC007062, BC008435, CD687044

Consensus CDS

CCDS7611.1

UniProtKB/Swiss-Prot

P30048

Related

ENSP00000298510.2, ENST00000298510.3

Conserved Domains (1) summary

cd03015
Location:65 → 236

PRX_Typ2cys; Peroxiredoxin (PRX) family, Typical 2-Cys PRX subfamily; PRXs are thiol-specific antioxidant (TSA) proteins, which confer a protective role in cells through its peroxidase activity by reducing hydrogen peroxide, peroxynitrite, and organic hydroperoxides. ...

RNA

NR_126102.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate exon in the 5' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AV761690, BC008435, BM144742, CD687044, HY173455
NR_126103.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks two alternate exons in the 5' region, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC008435, BG115645, BM144742, CD687044, HY173455
NR_126105.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) uses two alternate splice sites and lacks an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC008435, BF209381, BM144742, CD687044, HY173455
NR_126106.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) uses two alternate splice sites and lacks three internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC008435, BM144742, HY082255, HY173455

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p12 Primary Assembly

Range

119167699..119178865 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_014098.3: Suppressed sequence

Description

NM_014098.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein, and the transcript contains unsupported non-consensus splice sites.