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FLASH GENE
Symbol GPX3 contributors: mct - updated : 25-09-2019
HGNC name glutathione peroxidase 3 (plasma)
HGNC id 4555
Location 5q33.1      Physical location : 150.399.998 - 150.408.553
Synonym symbol(s) GSHP, GPx-P, GSHPx-3, GSHPx-P
EC.number 1.11.1.9
DNA
TYPE functioning gene
STRUCTURE 8.40 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   transcription factor
text structure Sp-1- and hypoxia-inducible factor-1-binding sites
MAPPING cloned Y linked   status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 1779 - 226 - 2004 15096516
6 - 1630 - 235 - 2004 15096516
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivefemale systembreast  lowly
 male systemmale genital tractepididymis highly Homo sapiens
Respiratoryrespiratory tractlarynx  lowly
Urinarykidney   highly Homo sapiens
Visualeye   lowly
cell lineage
cell lines
fluid/secretion plasma
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer homomer , tetramer
HOMOLOGY
interspecies homolog to murine Gpx3
Homologene
FAMILY glutathione peroxidase family
CATEGORY enzyme
SUBCELLULAR LOCALIZATION extracellular
text plasma
basic FUNCTION
  • involved in free radical detoxification and reduction of hydrogen peroxide
  • catalyzing the reduction of hydrogen peroxide, organic hydroperoxide, and lipid peroxides by reduced glutathione
  • functioning in the protection of cells against oxidative damage
  • having potent extracellular antioxidant activity
  • major antioxidative enzyme that was induced upon nontoxic proteasome inhibition in endothelial cells
  • borderline defense mechanism of endothelial cell-derived GPx-3 to protect the vasculature from oxidative stress
  • GPX5 protein, and the epithelial proteins GPX1, GPX3, and cellular GPX4, all functioning in the mammalian epididymis at different stages of the sperm epididymal journey, and in different epididymis compartments
  • from the blood binds to basement membranes of specific epithelial cells and the cells modify their basement membranes to cause the binding
  • importance of this plasma antioxidant enzyme in regulating platelet activity, endothelial function, platelet-dependent thrombosis, and vascular thrombotic propensity
  • plasma antioxidant enzyme, maintaining genomic integrity by inactivating reactive oxygen species (ROS), known DNA-damaging agents and mediators of cancer chemotherapy response
  • new retinoid target gene, crucial for human skeletal muscle precursor cell survival
  • plays a main role in removing hydro- and lipoperoxides from the body
  • has an important function of scavenging hydrogen peroxide and preventing cancer
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS detoxification
    PATHWAY
    metabolism
    signaling
  • catabolic pathway of activated oxygen species
  • a novel signaling pathway of GPX3-TP53I3 in the regulation of cell death in prostate cancer
  • a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor,
    selenocysteine
    protein
  • MAF may be transcriptional regulator of GPX3 expression and modulate the antioxidative pathway in the kidney
  • overexpression of GPX3 could reduce the levels of HIF1A and HIF2A, which could regulate metabolic levels
  • suppresses the growth of melanoma cells through reactive oxygen species (ROS)-dependent stabilization of HIF1A, HIF2A
  • cell & other
    REGULATION
    Other regulated by regulated by hypoxia
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    by hypermethylation in Barrett's tumorigenesis
    tumoral     --over  
    by hypomethylation in leukemia stem cells
    tumoral     --low  
    by promoter hypermethylation is frequently observed in a wide spectrum of malignancies
    constitutional       loss of function
    results in a prothrombotic state and vascular dysfunction that promotes platelet-dependent arterial thrombosis
    tumoral     --low  
    through promoter hypermethylation in esophageal squamous cell carcinoma
    constitutional     --low  
    significant reductions in expression of GPX1, GPX3, GPX4 in placentae from women with preeclampsia
    tumoral     --low  
    by methylation, is associated with cancer and has a value in predicting tumor lymph node metastasis
    constitutional     --other  
    methylation and expression of GPX3 are altered in Kashin-Beck Disease (KBD), and these changes are reversible by selenium supplementation
    tumoral     --low  
    GPX3 methylation in bone marrow is associated with adverse prognosis and leukemia transformation in myelodysplastic syndrome (MDS)
    Susceptibility to cerebral venous thrombosis (CVT)
    Variant & Polymorphism other
  • a novel GPX3 promoter haplotype is a strong, independent risk factor for CVT
  • Candidate gene
    Marker potential biomarker of esophageal squamous cell carcinoma
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    may be a therapeutic target for insulin resistance and diabetes mellitus
    ANIMAL & CELL MODELS
  • GPx-3(-/-) mice displayed increased plasma levels of soluble P-selectin and decreased plasma cyclic cGMP compared with wild-type mice