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O70325

- GPX41_MOUSE

UniProt

O70325 - GPX41_MOUSE

Protein

Phospholipid hydroperoxide glutathione peroxidase, mitochondrial

Gene

Gpx4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 4 (26 Feb 2008)
      Previous versions | rss
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    Functioni

    Protects cells against membrane lipid peroxidation and cell death. Isoform mitochondrial is required for normal sperm development and male fertility. Could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. Essential for embryonic development. Protects from radiation and oxidative damage.3 Publications

    Catalytic activityi

    2 glutathione + a lipid hydroperoxide = glutathione disulfide + lipid + 2 H2O.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei73 – 731

    GO - Molecular functioni

    1. glutathione peroxidase activity Source: MGI
    2. phospholipid-hydroperoxide glutathione peroxidase activity Source: UniProtKB-EC

    GO - Biological processi

    1. chromatin organization Source: MGI
    2. multicellular organismal development Source: UniProtKB-KW
    3. response to oxidative stress Source: InterPro
    4. spermatogenesis Source: MGI

    Keywords - Molecular functioni

    Developmental protein, Oxidoreductase, Peroxidase

    Enzyme and pathway databases

    ReactomeiREACT_196559. Synthesis of 15-eicosatetraenoic acid derivatives.
    REACT_196569. Synthesis of 12-eicosatetraenoic acid derivatives.
    REACT_206751. Synthesis of 5-eicosatetraenoic acids.

    Protein family/group databases

    PeroxiBasei3714. MmGPx04-A.
    3867. MmGPx04-C.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phospholipid hydroperoxide glutathione peroxidase, mitochondrial (EC:1.11.1.12)
    Short name:
    PHGPx
    Alternative name(s):
    Glutathione peroxidase 4
    Short name:
    GPx-4
    Short name:
    GSHPx-4
    Gene namesi
    Name:Gpx4
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 10

    Organism-specific databases

    MGIiMGI:104767. Gpx4.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: MGI
    2. mitochondrial inner membrane Source: MGI
    3. mitochondrion Source: MGI
    4. nuclear envelope Source: MGI
    5. nucleus Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion

    Pathology & Biotechi

    Disruption phenotypei

    Embryonic lethality. The embryos die after about 7.5 days of development. Causes neurodegeneration. Selective disruption of isoform mitochondrial causes sperm abnormalities and male infertility.2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini? – 197Phospholipid hydroperoxide glutathione peroxidase, mitochondrialPRO_0000013069
    Transit peptidei1 – ?MitochondrionSequence Analysis

    Proteomic databases

    PaxDbiO70325.
    PRIDEiO70325.

    Expressioni

    Tissue specificityi

    Detected in testis and sperm midpiece (at protein level). Present primarily in testis.1 Publication

    Gene expression databases

    BgeeiO70325.
    CleanExiMM_GPX4.
    GenevestigatoriO70325.

    Interactioni

    Subunit structurei

    Monomer.By similarity

    Protein-protein interaction databases

    BioGridi551619. 1 interaction.
    IntActiO70325. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliO70325.
    SMRiO70325. Positions 33-197.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the glutathione peroxidase family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0386.
    GeneTreeiENSGT00740000115371.
    HOGENOMiHOG000277054.
    HOVERGENiHBG004333.
    KOiK05361.
    OMAiLVDKNGC.
    OrthoDBiEOG7B5WZH.

    Family and domain databases

    Gene3Di3.40.30.10. 1 hit.
    InterProiIPR000889. Glutathione_peroxidase.
    IPR012336. Thioredoxin-like_fold.
    [Graphical view]
    PANTHERiPTHR11592. PTHR11592. 1 hit.
    PfamiPF00255. GSHPx. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000303. Glutathion_perox. 1 hit.
    PRINTSiPR01011. GLUTPROXDASE.
    SUPFAMiSSF52833. SSF52833. 1 hit.
    PROSITEiPS00460. GLUTATHIONE_PEROXID_1. 1 hit.
    PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
    PS51355. GLUTATHIONE_PEROXID_3. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. Align

    Isoform Mitochondrial (identifier: O70325-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSWGRLSRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID    50
    GHMVCLDKYR GFVCIVTNVA SQUGKTDVNY TQLVDLHARY AECGLRILAF 100
    PCNQFGRQEP GSNQEIKEFA AGYNVKFDMY SKICVNGDDA HPLWKWMKVQ 150
    PKGRGMLGNA IKWNFTKFLI DKNGCVVKRY GPMEEPQVIE KDLPCYL 197
    Length:197
    Mass (Da):22,229
    Last modified:February 26, 2008 - v4
    Checksum:i5CED4991A484F31C
    GO
    Isoform Nuclear (identifier: Q91XR9-1) [UniParc]FASTAAdd to Basket

    The sequence of this isoform can be found in the external entry Q91XR9.
    Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
    Length:253
    Mass (Da):29,252
    GO
    Isoform Cytoplasmic (identifier: O70325-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-27: Missing.

    Note: Produced by alternative initiation at Met-28 of isoform Mitochondrial.

    Show »
    Length:170
    Mass (Da):19,522
    Checksum:i89AD1F6B28946C95
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti39 – 391R → A in BAA22780. (PubMed:9370288)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2727Missing in isoform Cytoplasmic. CuratedVSP_018743Add
    BLAST

    Non-standard residue

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Non-standard residuei73 – 731Selenocysteine

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D87896 mRNA. Translation: BAA22780.1.
    AJ012104 Genomic DNA. Translation: CAB42657.2.
    AF045768 mRNA. Translation: AAC15832.1.
    AF045769 mRNA. Translation: AAC15833.1.
    AF044056 Genomic DNA. Translation: AAC14560.1.
    AB030643 Genomic DNA. Translation: BAC06507.1.
    AB030643 Genomic DNA. Translation: BAC06508.1.
    AB030728 Genomic DNA. Translation: BAC06511.1.
    AK006441 mRNA. Translation: BAC55251.1.
    CCDSiCCDS35973.1. [O70325-1]
    RefSeqiNP_001032830.2. NM_001037741.3.
    NP_032188.3. NM_008162.3. [O70325-1]
    UniGeneiMm.332810.
    Mm.359573.

    Genome annotation databases

    EnsembliENSMUST00000105372; ENSMUSP00000101011; ENSMUSG00000075706. [O70325-1]
    GeneIDi625249.
    KEGGimmu:625249.
    UCSCiuc007gbk.1. mouse. [O70325-1]

    Keywords - Coding sequence diversityi

    Alternative initiation, Alternative splicing, Selenocysteine

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D87896 mRNA. Translation: BAA22780.1 .
    AJ012104 Genomic DNA. Translation: CAB42657.2 .
    AF045768 mRNA. Translation: AAC15832.1 .
    AF045769 mRNA. Translation: AAC15833.1 .
    AF044056 Genomic DNA. Translation: AAC14560.1 .
    AB030643 Genomic DNA. Translation: BAC06507.1 .
    AB030643 Genomic DNA. Translation: BAC06508.1 .
    AB030728 Genomic DNA. Translation: BAC06511.1 .
    AK006441 mRNA. Translation: BAC55251.1 .
    CCDSi CCDS35973.1. [O70325-1 ]
    RefSeqi NP_001032830.2. NM_001037741.3.
    NP_032188.3. NM_008162.3. [O70325-1 ]
    UniGenei Mm.332810.
    Mm.359573.

    3D structure databases

    ProteinModelPortali O70325.
    SMRi O70325. Positions 33-197.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 551619. 1 interaction.
    IntActi O70325. 1 interaction.

    Protein family/group databases

    PeroxiBasei 3714. MmGPx04-A.
    3867. MmGPx04-C.

    Proteomic databases

    PaxDbi O70325.
    PRIDEi O70325.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000105372 ; ENSMUSP00000101011 ; ENSMUSG00000075706 . [O70325-1 ]
    GeneIDi 625249.
    KEGGi mmu:625249.
    UCSCi uc007gbk.1. mouse. [O70325-1 ]

    Organism-specific databases

    CTDi 2879.
    MGIi MGI:104767. Gpx4.

    Phylogenomic databases

    eggNOGi COG0386.
    GeneTreei ENSGT00740000115371.
    HOGENOMi HOG000277054.
    HOVERGENi HBG004333.
    KOi K05361.
    OMAi LVDKNGC.
    OrthoDBi EOG7B5WZH.

    Enzyme and pathway databases

    Reactomei REACT_196559. Synthesis of 15-eicosatetraenoic acid derivatives.
    REACT_196569. Synthesis of 12-eicosatetraenoic acid derivatives.
    REACT_206751. Synthesis of 5-eicosatetraenoic acids.

    Miscellaneous databases

    ChiTaRSi GPX4. mouse.
    NextBioi 418158.
    PROi O70325.
    SOURCEi Search...

    Gene expression databases

    Bgeei O70325.
    CleanExi MM_GPX4.
    Genevestigatori O70325.

    Family and domain databases

    Gene3Di 3.40.30.10. 1 hit.
    InterProi IPR000889. Glutathione_peroxidase.
    IPR012336. Thioredoxin-like_fold.
    [Graphical view ]
    PANTHERi PTHR11592. PTHR11592. 1 hit.
    Pfami PF00255. GSHPx. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000303. Glutathion_perox. 1 hit.
    PRINTSi PR01011. GLUTPROXDASE.
    SUPFAMi SSF52833. SSF52833. 1 hit.
    PROSITEi PS00460. GLUTATHIONE_PEROXID_1. 1 hit.
    PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
    PS51355. GLUTATHIONE_PEROXID_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and sequencing of the cDNA encoding a phospholipid hydroperoxide glutathione peroxidase."
      Nam S.-Y., Nakamuta N., Kurohmaru M., Hayashi Y.
      Gene 198:245-249(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: CD-1.
      Tissue: Testis.
    2. "Cloning of the mouse phospholipid hydroperoxide glutathione peroxidase gene."
      Borchert A., Schnurr K., Thiele B.J., Kuehn H.
      FEBS Lett. 446:223-227(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: C57BL/6N.
    3. "Murine phospholipid hydroperoxide glutathione peroxidase: cDNA sequence, tissue expression, and mapping."
      Knopp E.A., Arndt T.L., Eng K.L., Caldwell M., LeBoeuf R.C., Deeb S.S., O'Brien K.D.
      Mamm. Genome 10:601-605(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
      Strain: BALB/c and C57BL/6J.
      Tissue: Myocardium and Testis.
    4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 129/SvJ.
      Tissue: Liver.
    5. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Testis.
    6. "The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults."
      Yant L.J., Ran Q., Rao L., Van Remmen H., Shibatani T., Belter J.G., Motta L., Richardson A., Prolla T.A.
      Free Radic. Biol. Med. 34:496-502(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death."
      Seiler A., Schneider M., Foerster H., Roth S., Wirth E.K., Culmsee C., Plesnila N., Kremmer E., Raadmark O., Wurst W., Bornkamm G.W., Schweizer U., Conrad M.
      Cell Metab. 8:237-248(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    8. Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiGPX41_MOUSE
    AccessioniPrimary (citable) accession number: O70325
    Secondary accession number(s): O35560, Q9JK35
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 11, 2001
    Last sequence update: February 26, 2008
    Last modified: October 1, 2014
    This is version 137 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3