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FLASH GENE
Symbol PRDX4 contributors: mct - updated : 23-01-2017
HGNC name peroxiredoxin 4
HGNC id 17169
DNA
TYPE functioning gene
STRUCTURE 18.87 kb     7 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
7 - 921 - 271 - 2010 20610706
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
Endocrinepancreas   highly
Nervousnervecranial nerveoptic nerve   Rattus norvegicus
Reproductivefemale systemovary    Homo sapiens
 male systemtestis    Homo sapiens
Visualeyeretina    Rattus norvegicus
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Nervouscentral    Homo sapiensAdult
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousglia Homo sapiensAdult
Reproductivegranulosa cell Homo sapiens
Reproductivespermatogonia Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text pancreas
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a signal peptide
  • two peroxide catalysis cysteine motifs conserved in all peroxiredoxins
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    Homologene
    FAMILY peroxiredoxin family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • localized mainly in the nucleus of neural cells
  • only endoplasmic reticulum localized peroxiredoxin
  • basic FUNCTION
  • playing a regulatory role in the activation of the transcription factor NF-kappaB
  • involved in protection against oxidative stress through the detoxification of cellular peroxides
  • endoplasmic reticulum-localized enzyme forming oligomeric complexes in human cells
  • important for spermatogenesis, but not an absolute requisite
  • essential for preventing respiratory syncytial virus-induced oxidative damage in a subset of nuclear intermediate filament and actin binding proteins in epithelial cells
  • ER-localized and implicated in a previously unanticipated, parallel, ERO1-independent pathway that couples hydroperoxide production to oxidative protein folding in mammalian cells
  • PRDX3 and PRDX4, may act as new placental immune targets, and are involved in recurrent pregnancy loss
  • different binding properties of ERO1A and PRDX4 increase the robustness of ER redox homeostasis
  • may have a close relationship with follicular development
  • PRDX4-recycling in the endoplasmic reticulum is much less efficient than in the cytosol or mitochondria, leading to the protection of PRDX4 from hyperoxidation
  • ER-specific antioxidative peroxidase that can utilize luminal H2O2 as driving force for reoxidizing protein disulfide isomerase family members, thus efficiently contributing to disulfide bond formation
  • important role of PRDX4 in maintaining insulin levels and improving the ER folding capacity also under conditions of a high insulin requirement
  • functions not only to eliminate peroxide but also to promote oxidative protein folding via oxidizing protein disulfide isomerase (PDI)
  • novel function of secreted PRDX4 in mediating osteoclast activation by cancer cells
  • PRDX4 oxidative activity acts as a sensor to directly couple neuronal differentiation with redox environments in the ER
  • PRDX2 and PRDX4 are negative regulators of hypoxia-inducible factors under conditions of prolonged hypoxia
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component heterodimer with PRDX1; disulfide-linked, upon oxidation
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NFKB (activation of NFKB)
  • ER-resident antioxidant PRDX4 interacts with the cytoplasmic domain of the granulocyte colony-stimulating factor receptor (CSF3)
  • PTPN1 might keep PRDX4 active by reducing its phosphorylation
  • TXNDC5 is involved in insulin production as well as in adiponectin signaling and interacts specifically with the redox-regulatory endoplasmic reticulum proteins ERO1A and PRDX4
  • PDIA2 binds preferentially ERO1A, whereas ERP44 equally retains ERO1A and PRDX4
  • GDPD5 is targeted by PRDX4 oxidative activity (PRDX4 dimers oxidize two cysteine residues within the GDPD5 enzymatic domain, which blocks GDPD5 trafficking to the plasma membrane and prevents GDPD5 neurogeneic function)
  • cell & other
    REGULATION
    inhibited by TNFSF10 at the transcriptional level, and downregulation of PRDX4 might facilitate cell death induced by TNFSF10
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    highly expressed in human lung cancer
    constitutional     --over  
    associated with a significantly higher risk of incident cardiovascular disease (CVD) events or CVD mortality and all-cause mortality after adjustment for clinical risk factors
    tumoral     --over  
    in prostate cancer tissue
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting the SRXN1-PRDX4 axis may provide unique effective strategies for cancer prevention and treatment
    ANIMAL & CELL MODELS