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P36969

- GPX4_HUMAN

UniProt

P36969 - GPX4_HUMAN

Protein

Phospholipid hydroperoxide glutathione peroxidase, mitochondrial

Gene

GPX4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 155 (01 Oct 2014)
      Sequence version 3 (26 Feb 2008)
      Previous versions | rss
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    Functioni

    Protects cells against membrane lipid peroxidation and cell death. 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 By similarity.By similarity

    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 binding Source: Ensembl
    2. glutathione peroxidase activity Source: UniProtKB
    3. phospholipid-hydroperoxide glutathione peroxidase activity Source: UniProtKB-EC
    4. selenium binding Source: Ensembl

    GO - Biological processi

    1. aging Source: Ensembl
    2. arachidonic acid metabolic process Source: Reactome
    3. chromatin organization Source: Ensembl
    4. glutathione metabolic process Source: Ensembl
    5. hydrogen peroxide catabolic process Source: Ensembl
    6. lipoxygenase pathway Source: Reactome
    7. multicellular organismal development Source: UniProtKB-KW
    8. oxidation-reduction process Source: UniProtKB
    9. phospholipid metabolic process Source: UniProtKB
    10. regulation of inflammatory response Source: Ensembl
    11. response to estradiol Source: Ensembl
    12. small molecule metabolic process Source: Reactome
    13. spermatogenesis Source: Ensembl

    Keywords - Molecular functioni

    Developmental protein, Oxidoreductase, Peroxidase

    Enzyme and pathway databases

    BioCyciMetaCyc:HS09562-MONOMER.
    ReactomeiREACT_150201. Synthesis of 12-eicosatetraenoic acid derivatives.
    REACT_150209. Synthesis of 5-eicosatetraenoic acids.
    REACT_150422. Synthesis of 15-eicosatetraenoic acid derivatives.
    SABIO-RKP36969.

    Protein family/group databases

    PeroxiBasei3603. HsGPx04-A.
    3632. HsGPx04-B.
    3633. HsGPx04-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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:4556. GPX4.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. extracellular vesicular exosome Source: UniProt
    3. mitochondrial inner membrane Source: Ensembl
    4. mitochondrion Source: UniProtKB
    5. nuclear envelope Source: Ensembl
    6. nucleus Source: UniProt

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi73 – 731U → A: Loss of enzyme activity. 1 Publication
    Mutagenesisi73 – 731U → C: Almost complete loss of enzyme activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA28952.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini? – 197Phospholipid hydroperoxide glutathione peroxidase, mitochondrialPRO_0000013067
    Transit peptidei1 – ?MitochondrionSequence Analysis

    Proteomic databases

    MaxQBiP36969.
    PaxDbiP36969.
    PRIDEiP36969.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00304814.
    UCD-2DPAGEP36969.

    PTM databases

    PhosphoSiteiP36969.

    Expressioni

    Tissue specificityi

    Present primarily in testis.

    Gene expression databases

    ArrayExpressiP36969.
    BgeeiP36969.
    CleanExiHS_GPX4.
    GenevestigatoriP36969.

    Organism-specific databases

    HPAiCAB008630.

    Interactioni

    Subunit structurei

    Monomer. Has a tendency to form higher mass oligomers.1 Publication

    Protein-protein interaction databases

    BioGridi109137. 4 interactions.
    IntActiP36969. 3 interactions.
    STRINGi9606.ENSP00000346103.

    Structurei

    Secondary structure

    1
    197
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi35 – 373
    Helixi41 – 433
    Beta strandi45 – 484
    Beta strandi53 – 553
    Helixi56 – 594
    Beta strandi62 – 698
    Beta strandi71 – 733
    Helixi76 – 9015
    Helixi91 – 933
    Beta strandi95 – 1017
    Turni104 – 1074
    Helixi113 – 1219
    Turni122 – 1243
    Beta strandi127 – 1304
    Beta strandi134 – 1374
    Helixi142 – 1487
    Turni151 – 1533
    Beta strandi156 – 1605
    Beta strandi167 – 1704
    Beta strandi176 – 1805
    Helixi187 – 1904
    Helixi194 – 1963

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2GS3X-ray1.90A36-197[»]
    2OBIX-ray1.55A29-197[»]
    ProteinModelPortaliP36969.
    SMRiP36969. Positions 33-197.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP36969.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the glutathione peroxidase family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG0386.
    HOGENOMiHOG000277054.
    HOVERGENiHBG004333.
    InParanoidiP36969.
    KOiK05361.
    OrthoDBiEOG7B5WZH.
    PhylomeDBiP36969.
    TreeFamiTF338735.

    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.
    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 (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative initiation. Align

    Isoform Mitochondrial (identifier: P36969-1) [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

    MSLGRLCRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID    50
    GHMVNLDKYR GFVCIVTNVA SQUGKTEVNY TQLVDLHARY AECGLRILAF 100
    PCNQFGKQEP GSNEEIKEFA AGYNVKFDMF SKICVNGDDA HPLWKWMKIQ 150
    PKGKGILGNA IKWNFTKFLI DKNGCVVKRY GPMEEPLVIE KDLPHYF 197
    Length:197
    Mass (Da):22,175
    Last modified:February 26, 2008 - v3
    Checksum:i1AE3BC7AE42FDDB1
    GO
    Isoform Cytoplasmic (identifier: P36969-2) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:170
    Mass (Da):19,525
    Checksum:iB7FA0B3831DEF7DB
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti2 – 21S → N.2 Publications
    Corresponds to variant rs8178967 [ dbSNP | Ensembl ].
    VAR_017063
    Natural varianti120 – 1201A → T in a patient affected by cryptorchidism. 1 Publication
    Corresponds to variant rs76201145 [ dbSNP | Ensembl ].
    VAR_017064

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2727Missing in isoform Cytoplasmic. CuratedVSP_018740Add
    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
    X71973 mRNA. Translation: CAA50793.1.
    AF060972 Genomic DNA. Translation: AAC32261.1.
    AY324108 Genomic DNA. Translation: AAP72965.1.
    AC004151 Genomic DNA. Translation: AAC03239.1.
    AC005390 Genomic DNA. Translation: AAC28920.1.
    BC011836 mRNA. Translation: AAH11836.1.
    BC021567 mRNA. Translation: AAH21567.1.
    BC022071 mRNA. Translation: AAH22071.1.
    BC032695 mRNA. Translation: AAH32695.3.
    BC039849 mRNA. Translation: AAH39849.1.
    CCDSiCCDS42457.1. [P36969-1]
    PIRiT02747.
    RefSeqiNP_001034936.1. NM_001039847.2.
    NP_002076.2. NM_002085.4. [P36969-1]
    UniGeneiHs.433951.

    Genome annotation databases

    EnsembliENST00000354171; ENSP00000346103; ENSG00000167468. [P36969-1]
    GeneIDi2879.
    KEGGihsa:2879.
    UCSCiuc021umf.1. human. [P36969-1]

    Polymorphism databases

    DMDMi172045844.

    Keywords - Coding sequence diversityi

    Alternative initiation, Polymorphism, Selenocysteine

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X71973 mRNA. Translation: CAA50793.1 .
    AF060972 Genomic DNA. Translation: AAC32261.1 .
    AY324108 Genomic DNA. Translation: AAP72965.1 .
    AC004151 Genomic DNA. Translation: AAC03239.1 .
    AC005390 Genomic DNA. Translation: AAC28920.1 .
    BC011836 mRNA. Translation: AAH11836.1 .
    BC021567 mRNA. Translation: AAH21567.1 .
    BC022071 mRNA. Translation: AAH22071.1 .
    BC032695 mRNA. Translation: AAH32695.3 .
    BC039849 mRNA. Translation: AAH39849.1 .
    CCDSi CCDS42457.1. [P36969-1 ]
    PIRi T02747.
    RefSeqi NP_001034936.1. NM_001039847.2.
    NP_002076.2. NM_002085.4. [P36969-1 ]
    UniGenei Hs.433951.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2GS3 X-ray 1.90 A 36-197 [» ]
    2OBI X-ray 1.55 A 29-197 [» ]
    ProteinModelPortali P36969.
    SMRi P36969. Positions 33-197.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109137. 4 interactions.
    IntActi P36969. 3 interactions.
    STRINGi 9606.ENSP00000346103.

    Chemistry

    DrugBanki DB00143. Glutathione.

    Protein family/group databases

    PeroxiBasei 3603. HsGPx04-A.
    3632. HsGPx04-B.
    3633. HsGPx04-C.

    PTM databases

    PhosphoSitei P36969.

    Polymorphism databases

    DMDMi 172045844.

    2D gel databases

    REPRODUCTION-2DPAGE IPI00304814.
    UCD-2DPAGE P36969.

    Proteomic databases

    MaxQBi P36969.
    PaxDbi P36969.
    PRIDEi P36969.

    Protocols and materials databases

    DNASUi 2879.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000354171 ; ENSP00000346103 ; ENSG00000167468 . [P36969-1 ]
    GeneIDi 2879.
    KEGGi hsa:2879.
    UCSCi uc021umf.1. human. [P36969-1 ]

    Organism-specific databases

    CTDi 2879.
    GeneCardsi GC19P001103.
    HGNCi HGNC:4556. GPX4.
    HPAi CAB008630.
    MIMi 138322. gene.
    neXtProti NX_P36969.
    PharmGKBi PA28952.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0386.
    HOGENOMi HOG000277054.
    HOVERGENi HBG004333.
    InParanoidi P36969.
    KOi K05361.
    OrthoDBi EOG7B5WZH.
    PhylomeDBi P36969.
    TreeFami TF338735.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS09562-MONOMER.
    Reactomei REACT_150201. Synthesis of 12-eicosatetraenoic acid derivatives.
    REACT_150209. Synthesis of 5-eicosatetraenoic acids.
    REACT_150422. Synthesis of 15-eicosatetraenoic acid derivatives.
    SABIO-RK P36969.

    Miscellaneous databases

    ChiTaRSi GPX4. human.
    EvolutionaryTracei P36969.
    GeneWikii GPX4.
    GenomeRNAii 2879.
    NextBioi 11367.
    PROi P36969.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P36969.
    Bgeei P36969.
    CleanExi HS_GPX4.
    Genevestigatori P36969.

    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.
    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 human testis phospholipid hydroperoxide glutathione peroxidase."
      Esworthy R.S., Doan K., Doroshow J.H., Chu F.-F.
      Gene 144:317-318(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Testis.
    2. "Structural organization of the human selenium-dependent phospholipid hydroperoxide glutathione peroxidase gene (GPX4): chromosomal localization to 19p13.3."
      Kelner M.J., Montoya M.A.
      Biochem. Biophys. Res. Commun. 249:53-55(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. NIEHS SNPs program
      Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-2.
    4. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain, Eye, Lung, Pancreas and Testis.
    6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    7. "Structural basis for catalytic activity and enzyme polymerization of phospholipid hydroperoxide glutathione peroxidase-4 (GPx4)."
      Scheerer P., Borchert A., Krauss N., Wessner H., Gerth C., Hoehne W., Kuhn H.
      Biochemistry 46:9041-9049(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 29-197 (ISOFORM CYTOPLASMIC), SUBUNIT, MUTAGENESIS OF SEC-73.
    8. "Crystal structure of the selenocysteine to glycine mutant of human glutathione peroxidase 4 (GPX4)."
      Structural genomics consortium (SGC)
      Submitted (FEB-2009) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 36-197.
    9. Cited for: VARIANTS ASN-2 AND THR-120.

    Entry informationi

    Entry nameiGPX4_HUMAN
    AccessioniPrimary (citable) accession number: P36969
    Secondary accession number(s): O43381, Q6PJ59, Q9UPK2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: February 26, 2008
    Last modified: October 1, 2014
    This is version 155 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3