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    Gpx4 glutathione peroxidase 4 [ Mus musculus (house mouse) ]

    Gene ID: 625249, updated on 27-Nov-2024

    Summary

    Official Symbol
    Gpx4provided by MGI
    Official Full Name
    glutathione peroxidase 4provided by MGI
    Primary source
    MGI:MGI:104767
    See related
    Ensembl:ENSMUSG00000075706 AllianceGenome:MGI:104767
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    GPx-4; PHGPx; snGPx; GSHPx-4; mtPHGPx
    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. Disruption of this gene in mouse spermatocytes is associated with male infertility. 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. Transcript variants resulting from alternative splicing or use of alternate promoters have been described to encode isoforms with different subcellular localization. Pseudogenes of this locus have been identified on chromosomes 10 and 17. [provided by RefSeq, Jan 2019]
    Expression
    Ubiquitous expression in testis adult (RPKM 772.1), kidney adult (RPKM 308.6) and 28 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See Gpx4 in Genome Data Viewer
    Location:
    10 C1; 10 39.72 cM
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 10 NC_000076.7 (79883000..79892273)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 10 NC_000076.6 (80047166..80056439)

    Chromosome 10 - NC_000076.7Genomic Context describing neighboring genes Neighboring gene Rho GTPase activating protein 45 Neighboring gene STARR-positive B cell enhancer ABC_E2948 Neighboring gene STARR-positive B cell enhancer ABC_E6880 Neighboring gene polymerase (RNA) II (DNA directed) polypeptide E Neighboring gene STARR-seq mESC enhancer starr_27262 Neighboring gene STARR-positive B cell enhancer ABC_E900 Neighboring gene strawberry notch 2 Neighboring gene STARR-seq mESC enhancer starr_27263 Neighboring gene STARR-seq mESC enhancer starr_27266 Neighboring gene serine/threonine kinase 11 Neighboring gene calcium channel, voltage-dependent, beta subunit associated regulatory protein

    Genomic regions, transcripts, and products

    Expression

    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Variation

    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Endonuclease-mediated (6) 
    • Targeted (13)  1 citation

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC103187, MGC118087, 1700027O09Rik

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables glutathione peroxidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables glutathione peroxidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables glutathione peroxidase activity ISO
    Inferred from Sequence Orthology
    more info
    PubMed 
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables identical protein binding ISO
    Inferred from Sequence Orthology
    more info
     
    enables phospholipid-hydroperoxide glutathione peroxidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables phospholipid-hydroperoxide glutathione peroxidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables phospholipid-hydroperoxide glutathione peroxidase activity ISO
    Inferred from Sequence Orthology
    more info
     
    enables selenium binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables selenium binding ISO
    Inferred from Sequence Orthology
    more info
     
    Process Evidence Code Pubs
    acts_upstream_of_or_within apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in arachidonate metabolic process ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in arachidonate metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular oxidant detoxification IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within cerebellum development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of_or_within chromatin organization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within dendrite development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in lipoxygenase pathway ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in lipoxygenase pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    acts_upstream_of_or_within multicellular organism growth IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of ferroptosis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein polymerization IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein polymerization ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in response to estradiol IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within response to lipopolysaccharide IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to oxidative stress IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of_or_within spermatogenesis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in spermatogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol ISO
    Inferred from Sequence Orthology
    more info
     
    located_in mitochondrial inner membrane HDA PubMed 
    located_in mitochondrion HDA PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nuclear envelope IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of protein-containing complex IEA
    Inferred from Electronic Annotation
    more info
     
    part_of protein-containing complex ISO
    Inferred from Sequence Orthology
    more info
     

    General protein information

    Preferred Names
    phospholipid hydroperoxide glutathione peroxidase GPX4
    Names
    phospholipid hydroperoxide glutathione peroxidase, mitochondrial
    phospholipid hydroperoxide glutathione peroxidase, nuclear
    sperm nuclei glutathione peroxidase
    NP_001032830.2
    NP_001354924.1
    NP_032188.3

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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)

    1. NM_001037741.4NP_001032830.2  phospholipid hydroperoxide glutathione peroxidase GPX4 isoform B

      See identical proteins and their annotated locations for NP_001032830.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternate 5' terminal exon compared to variant 1. The resulting isoform (B) has a longer and a distinct N-terminus compared to isoform A. A similar isoform in rat (snGPx) has been reported to be localized in the sperm nucleus (PMID:11344099).
      Source sequence(s)
      AC159999, AK006441, CX733872
      Consensus CDS
      CCDS24007.1
      UniProtKB/TrEMBL
      Q76LV0
      Related
      ENSMUSP00000094863.5, ENSMUST00000097227.11
      Conserved Domains (1) summary
      cd00340
      Location:96249
      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_001367995.1NP_001354924.1  phospholipid hydroperoxide glutathione peroxidase GPX4 isoform C

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate promoter, which results in translation initiation from an in-frame downstream AUG start codon compared to variant 1. The encoded isoform (C) has a shorter N-terminus compared to isoform A. A similar isoform in rat (S-form) has been reported to be localized to the cytoplasm (PMID:9988735).
      Source sequence(s)
      AK006441, CX733872
      UniProtKB/TrEMBL
      Q3TI34, Q5XJZ8
      Related
      ENSMUSP00000138186.3, ENSMUST00000183037.3
    3. NM_008162.4NP_032188.3  phospholipid hydroperoxide glutathione peroxidase GPX4 isoform A precursor

      See identical proteins and their annotated locations for NP_032188.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript and encodes the canonical isoform A (also known as phGPx). A similar isoform in rat(L-form) has been shown to be localized to the mitochondria (PMID:9988735).
      Source sequence(s)
      AK006441, BY238083, CX733872
      Consensus CDS
      CCDS35973.1
      UniProtKB/Swiss-Prot
      O35560, O70325, Q8K4U8, Q91XR9, Q9JK35
      UniProtKB/TrEMBL
      Q3TIF2
      Related
      ENSMUSP00000101011.3, ENSMUST00000105372.9
      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 ...

    RNA

    1. NR_110342.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains alternate 5' terminal exons and lacks an internal exon compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
      Source sequence(s)
      AA510431, AK145770
      Related
      ENSMUST00000144698.8

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000076.7 Reference GRCm39 C57BL/6J

      Range
      79883000..79892273
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)