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    GPX4 glutathione peroxidase 4 [ Homo sapiens (human) ]

    Gene ID: 2879, updated on 5-Feb-2017
    Official Symbol
    GPX4provided by HGNC
    Official Full Name
    glutathione peroxidase 4provided by HGNC
    Primary source
    HGNC:HGNC:4556
    See related
    Ensembl:ENSG00000167468 MIM:138322; Vega:OTTHUMG00000181874
    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
    MCSP; SMDS; GPx-4; PHGPx; snGPx; GSHPx-4; snPHGPx
    Summary
    The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of hydrogen peroxide, organic hydroperoxides and lipid hydroperoxides, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme has a high preference for lipid hydroperoxides and protects cells against membrane lipid peroxidation and cell death. It is also required for normal sperm development; thus, it has been identified as a 'moonlighting' protein because of its ability to serve dual functions as a peroxidase, as well as a structural protein in mature spermatozoa. Mutations in this gene are associated with Sedaghatian type of spondylometaphyseal dysplasia (SMDS). This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2016]
    Orthologs
    Location:
    19p13.3
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 19 NC_000019.10 (1103926..1106789)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (1103936..1106787)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATP binding cassette subfamily A member 7 Neighboring gene Rho GTPase activating protein 45 Neighboring gene RNA polymerase II subunit E Neighboring gene strawberry notch homolog 2 Neighboring gene uncharacterized LOC102723798 Neighboring gene collagen alpha-1(VII) chain-like

    • 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 Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Spondylometaphyseal dysplasia Sedaghatian type
    MedGen: C1855229 OMIM: 250220 GeneReviews: Not available
    Compare labs

    NHGRI GWAS Catalog

    Description
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    NHGRI GWA Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    NHGRI GWA Catalog

    Replication interactions

    Interaction Pubs
    Knockdown of glutathione peroxidase 4 (GPX4) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat causes a greater than 50% decrease in intracellular reduced glutathione (GSH), leading to the extracellular appearance of acidic FGF-1, an effect that is partially mediated through modulation of GSH biosynthetic enzymes PubMed
    tat Expression of HIV-1 Tat in HeLa cells downregulates cytoplasmic glutathione peroxidase while upregulating phospholipid hydroperoxide glutathione peroxidase, thereby deregulating intracellular oxidant/antioxidant balance and amplifying UV sensitivity PubMed

    Go to the HIV-1, Human Interaction Database

    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    glutathione peroxidase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    phospholipid-hydroperoxide glutathione peroxidase activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    cellular oxidant detoxification IEA
    Inferred from Electronic Annotation
    more info
     
    lipoxygenase pathway TAS
    Traceable Author Statement
    more info
     
    multicellular organism development IEA
    Inferred from Electronic Annotation
    more info
     
    oxidation-reduction process TAS
    Traceable Author Statement
    more info
    PubMed 
    phospholipid metabolic process TAS
    Traceable Author Statement
    more info
    PubMed 
    response to oxidative stress IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    cytosol TAS
    Traceable Author Statement
    more info
     
    extracellular exosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    mitochondrion IDA
    Inferred from Direct Assay
    more info
     
    mitochondrion TAS
    Traceable Author Statement
    more info
    PubMed 
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    phospholipid hydroperoxide glutathione peroxidase, mitochondrial; phospholipid hydroperoxide glutathione peroxidase
    Names
    phospholipid hydroperoxidase
    sperm nucleus glutathione peroxidase
    NP_001034936.1
    NP_001034937.1
    NP_002076.2

    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.

    Genomic

    1. NG_050621.1 RefSeqGene

      Range
      5001..7864
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001039847.2NP_001034936.1  phospholipid hydroperoxide glutathione peroxidase, mitochondrial isoform B precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate acceptor splice site in the 3' coding region, which causes a frame-shift, compared to variant 1. The resulting isoform (B) has a longer and a distinct C-terminus compared to isoform A.
      Source sequence(s)
      AI274351, AL558552, BC039849, HY049693
      UniProtKB/Swiss-Prot
      P36969
      Conserved Domains (1) summary
      cd00340
      Location:40168
      GSH_Peroxidase; Glutathione (GSH) peroxidase family; tetrameric selenoenzymes that catalyze the reduction of a variety of hydroperoxides including lipid peroxidases, using GSH as a specific electron donor substrate. GSH peroxidase contains one selenocysteine residue per ...
    2. NM_001039848.3NP_001034937.1  phospholipid hydroperoxide glutathione peroxidase isoform C

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate 5' terminal exon compared to variant 1. The resulting isoform (C) has a longer and a distinct N-terminus compared to isoform A.
      Source sequence(s)
      AI274351, BC046163, BF740029, BG037088, BM764133
      UniProtKB/TrEMBL
      Q6PI42
      Related
      ENSP00000477503, ENST00000622390
      Conserved Domains (1) summary
      cd00340
      Location:77230
      GSH_Peroxidase; Glutathione (GSH) peroxidase family; tetrameric selenoenzymes that catalyze the reduction of a variety of hydroperoxides including lipid peroxidases, using GSH as a specific electron donor substrate. GSH peroxidase contains one selenocysteine residue per ...
    3. NM_002085.4NP_002076.2  phospholipid hydroperoxide glutathione peroxidase, mitochondrial isoform A precursor

      See identical proteins and their annotated locations for NP_002076.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript and encodes the canonical isoform A. A similar isoform in rat has been shown to be localized to the mitochondria (PMID:9988735).
      Source sequence(s)
      AI274351, BC039849, HY049693
      Consensus CDS
      CCDS42457.1
      UniProtKB/Swiss-Prot
      P36969
      Related
      ENSP00000346103, OTTHUMP00000267719, ENST00000354171, OTTHUMT00000458052
      Conserved Domains (1) summary
      cd00340
      Location:40193
      GSH_Peroxidase; Glutathione (GSH) peroxidase family; tetrameric selenoenzymes that catalyze the reduction of a variety of hydroperoxides including lipid peroxidases, using GSH as a specific electron donor substrate. GSH peroxidase contains one selenocysteine residue per ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p7 Primary Assembly

      Range
      1103926..1106789
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018930.2 Alternate CHM1_1.1

      Range
      1103518..1106381
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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