GPX4_HUMAN
ID GPX4_HUMAN Reviewed; 197 AA.
AC P36969; O43381; Q6PJ59; Q9UPK2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Phospholipid hydroperoxide glutathione peroxidase;
DE Short=PHGPx;
DE EC=1.11.1.12;
DE AltName: Full=Glutathione peroxidase 4 {ECO:0000303|PubMed:9705830};
DE Short=GPx-4 {ECO:0000303|PubMed:9705830};
DE Short=GSHPx-4 {ECO:0000303|PubMed:9705830};
DE Flags: Precursor;
GN Name=GPX4 {ECO:0000303|PubMed:9705830, ECO:0000312|HGNC:HGNC:4556};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=8039723; DOI=10.1016/0378-1119(94)90400-6;
RA Esworthy R.S., Doan K., Doroshow J.H., Chu F.-F.;
RT "Cloning and sequencing of the cDNA encoding a human testis phospholipid
RT hydroperoxide glutathione peroxidase.";
RL Gene 144:317-318(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=9705830; DOI=10.1006/bbrc.1998.9086;
RA Kelner M.J., Montoya M.A.;
RT "Structural organization of the human selenium-dependent phospholipid
RT hydroperoxide glutathione peroxidase gene (GPX4): chromosomal localization
RT to 19p13.3.";
RL Biochem. Biophys. Res. Commun. 249:53-55(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-2.
RG NIEHS SNPs program;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Eye, Lung, Pancreas, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=11115402;
RA Sutherland M., Shankaranarayanan P., Schewe T., Nigam S.;
RT "Evidence for the presence of phospholipid hydroperoxide glutathione
RT peroxidase in human platelets: implications for its involvement in the
RT regulatory network of the 12-lipoxygenase pathway of arachidonic acid
RT metabolism.";
RL Biochem. J. 353:91-100(2001).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP FUNCTION.
RX PubMed=24439385; DOI=10.1016/j.cell.2013.12.010;
RA Yang W.S., SriRamaratnam R., Welsch M.E., Shimada K., Skouta R.,
RA Viswanathan V.S., Cheah J.H., Clemons P.A., Shamji A.F., Clish C.B.,
RA Brown L.M., Girotti A.W., Cornish V.W., Schreiber S.L., Stockwell B.R.;
RT "Regulation of ferroptotic cancer cell death by GPX4.";
RL Cell 156:317-331(2014).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 29-197 (ISOFORM CYTOPLASMIC),
RP SUBUNIT, AND MUTAGENESIS OF SEC-73.
RX PubMed=17630701; DOI=10.1021/bi700840d;
RA Scheerer P., Borchert A., Krauss N., Wessner H., Gerth C., Hoehne W.,
RA Kuhn H.;
RT "Structural basis for catalytic activity and enzyme polymerization of
RT phospholipid hydroperoxide glutathione peroxidase-4 (GPx4).";
RL Biochemistry 46:9041-9049(2007).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 36-197.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the selenocysteine to glycine mutant of human
RT glutathione peroxidase 4 (GPX4).";
RL Submitted (FEB-2009) to the PDB data bank.
RN [13] {ECO:0007744|PDB:5H5Q, ECO:0007744|PDB:5H5R, ECO:0007744|PDB:5H5S}
RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) OF 29-197 OF MUTANT CYS-73.
RX PubMed=27836545; DOI=10.1016/j.bbrc.2016.11.035;
RA Sakamoto K., Sogabe S., Kamada Y., Matsumoto S.I., Kadotani A.,
RA Sakamoto J.I., Tani A.;
RT "Discovery of GPX4 inhibitory peptides from random peptide T7 phage display
RT and subsequent structural analysis.";
RL Biochem. Biophys. Res. Commun. 482:195-201(2017).
RN [14]
RP VARIANTS ASN-2 AND THR-120.
RX PubMed=12606444; DOI=10.1095/biolreprod.102.007500;
RA Maiorino M., Bosello V., Ursini F., Foresta C., Garolla A., Scapin M.,
RA Sztajer H., Flohe L.;
RT "Genetic variations of gpx-4 and male infertility in humans.";
RL Biol. Reprod. 68:1134-1141(2003).
RN [15]
RP VARIANT SMDS 90-TYR--PHE-197 DEL, AND INVOLVEMENT IN SMDS.
RX PubMed=24706940; DOI=10.1136/jmedgenet-2013-102218;
RG FORGE Canada Consortium;
RA Smith A.C., Mears A.J., Bunker R., Ahmed A., MacKenzie M.,
RA Schwartzentruber J.A., Beaulieu C.L., Ferretti E., Majewski J.,
RA Bulman D.E., Celik F.C., Boycott K.M., Graham G.E.;
RT "Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type
RT spondylometaphyseal dysplasia.";
RL J. Med. Genet. 51:470-474(2014).
CC -!- FUNCTION: Essential antioxidant peroxidase that directly reduces
CC phospholipid hydroperoxide even if they are incorporated in membranes
CC and lipoproteins (By similarity). Can also reduce fatty acid
CC hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (By
CC similarity). Plays a key role in protecting cells from oxidative damage
CC by preventing membrane lipid peroxidation (By similarity). Required to
CC prevent cells from ferroptosis, a non-apoptotic cell death resulting
CC from an iron-dependent accumulation of lipid reactive oxygen species
CC (PubMed:24439385). The presence of selenocysteine (Sec) versus Cys at
CC the active site is essential for life: it provides resistance to
CC overoxidation and prevents cells against ferroptosis (By similarity).
CC The presence of Sec at the active site is also essential for the
CC survival of a specific type of parvalbumin-positive interneurons,
CC thereby preventing against fatal epileptic seizures (By similarity).
CC May be required to protect cells from the toxicity of ingested lipid
CC hydroperoxides (By similarity). Required for normal sperm development
CC and male fertility (By similarity). Essential for maturation and
CC survival of photoreceptor cells (By similarity). Plays a role in a
CC primary T-cell response to viral and parasitic infection by protecting
CC T-cells from ferroptosis and by supporting T-cell expansion (By
CC similarity). Plays a role of glutathione peroxidase in platelets in the
CC arachidonic acid metabolism (PubMed:11115402). Reduces hydroperoxy
CC ester lipids formed by a 15-lipoxygenase that may play a role as down-
CC regulator of the cellular 15-lipoxygenase pathway (By similarity).
CC {ECO:0000250|UniProtKB:O70325, ECO:0000250|UniProtKB:P36968,
CC ECO:0000269|PubMed:11115402, ECO:0000269|PubMed:24439385}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a hydroperoxy polyunsaturated fatty acid + 2 glutathione = a
CC hydroxy polyunsaturated fatty acid + glutathione disulfide + H2O;
CC Xref=Rhea:RHEA:19057, ChEBI:CHEBI:15377, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:58297, ChEBI:CHEBI:131871, ChEBI:CHEBI:134019;
CC EC=1.11.1.12; Evidence={ECO:0000250|UniProtKB:P36968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19058;
CC Evidence={ECO:0000250|UniProtKB:P36968};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + 2
CC glutathione = (12S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate +
CC glutathione disulfide + H2O; Xref=Rhea:RHEA:50708, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57444, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297,
CC ChEBI:CHEBI:90680; Evidence={ECO:0000269|PubMed:11115402};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50709;
CC Evidence={ECO:0000305|PubMed:11115402};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione =
CC (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide +
CC H2O; Xref=Rhea:RHEA:48888, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90850;
CC Evidence={ECO:0000250|UniProtKB:P36968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48889;
CC Evidence={ECO:0000250|UniProtKB:P36968};
CC -!- SUBUNIT: Monomer. Has a tendency to form higher mass oligomers.
CC {ECO:0000269|PubMed:17630701}.
CC -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion
CC {ECO:0000250|UniProtKB:O70325}.
CC -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm
CC {ECO:0000269|PubMed:11115402}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Mitochondrial;
CC IsoId=P36969-1; Sequence=Displayed;
CC Name=Cytoplasmic;
CC IsoId=P36969-2; Sequence=VSP_018740;
CC -!- TISSUE SPECIFICITY: Present primarily in testis. Expressed in platelets
CC (at protein level) (PubMed:11115402). {ECO:0000269|PubMed:11115402,
CC ECO:0000269|PubMed:9705830}.
CC -!- DISEASE: Spondylometaphyseal dysplasia, Sedaghatian type (SMDS)
CC [MIM:250220]: A form of spondylometaphyseal dysplasia, a group of short
CC stature disorders distinguished by abnormalities in the vertebrae and
CC the metaphyses of the tubular bones. SMDS is a neonatal lethal form
CC characterized by severe metaphyseal chondrodysplasia with mild limb
CC shortening, platyspondyly, cardiac conduction defects, and central
CC nervous system abnormalities. {ECO:0000269|PubMed:24706940}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glutathione peroxidase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gpx4/";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Life, a subtle balance
CC - Issue 205 of July 2018;
CC URL="https://web.expasy.org/spotlight/back_issues/205/";
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DR EMBL; X71973; CAA50793.1; -; mRNA.
DR EMBL; AF060972; AAC32261.1; -; Genomic_DNA.
DR EMBL; AY324108; AAP72965.1; -; Genomic_DNA.
DR EMBL; AC004151; AAC03239.1; -; Genomic_DNA.
DR EMBL; AC005390; AAC28920.1; -; Genomic_DNA.
DR EMBL; BC011836; AAH11836.1; -; mRNA.
DR EMBL; BC021567; AAH21567.1; -; mRNA.
DR EMBL; BC022071; AAH22071.1; -; mRNA.
DR EMBL; BC032695; AAH32695.3; -; mRNA.
DR EMBL; BC039849; AAH39849.1; -; mRNA.
DR CCDS; CCDS42457.1; -. [P36969-1]
DR PIR; T02747; T02747.
DR RefSeq; NP_001034936.1; NM_001039847.2.
DR RefSeq; NP_002076.2; NM_002085.4. [P36969-1]
DR PDB; 2GS3; X-ray; 1.90 A; A=36-197.
DR PDB; 2OBI; X-ray; 1.55 A; A=29-197.
DR PDB; 5H5Q; X-ray; 1.10 A; A=29-197.
DR PDB; 5H5R; X-ray; 1.20 A; A=29-197.
DR PDB; 5H5S; X-ray; 1.85 A; A=29-197.
DR PDB; 6ELW; X-ray; 1.30 A; A=29-197.
DR PDB; 6HKQ; X-ray; 1.54 A; A=28-197.
DR PDB; 6HN3; X-ray; 1.01 A; A=28-197.
DR PDB; 7L8K; X-ray; 1.38 A; A=30-197.
DR PDB; 7L8L; X-ray; 1.61 A; A=30-197.
DR PDB; 7L8M; X-ray; 2.07 A; A=30-197.
DR PDB; 7L8Q; X-ray; 1.48 A; A=30-197.
DR PDB; 7L8R; X-ray; 1.52 A; A/B=30-197.
DR PDBsum; 2GS3; -.
DR PDBsum; 2OBI; -.
DR PDBsum; 5H5Q; -.
DR PDBsum; 5H5R; -.
DR PDBsum; 5H5S; -.
DR PDBsum; 6ELW; -.
DR PDBsum; 6HKQ; -.
DR PDBsum; 6HN3; -.
DR PDBsum; 7L8K; -.
DR PDBsum; 7L8L; -.
DR PDBsum; 7L8M; -.
DR PDBsum; 7L8Q; -.
DR PDBsum; 7L8R; -.
DR SMR; P36969; -.
DR BioGRID; 109137; 80.
DR DIP; DIP-53543N; -.
DR IntAct; P36969; 16.
DR MINT; P36969; -.
DR STRING; 9606.ENSP00000346103; -.
DR BindingDB; P36969; -.
DR ChEMBL; CHEMBL4295754; -.
DR DrugBank; DB09096; Benzoyl peroxide.
DR DrugBank; DB00143; Glutathione.
DR DrugBank; DB03310; Glutathione disulfide.
DR SwissLipids; SLP:000001633; -.
DR MoonProt; P36969; -.
DR PeroxiBase; 3603; HsGPx04-A.
DR PeroxiBase; 3632; HsGPx04-B.
DR PeroxiBase; 3633; HsGPx04-C.
DR iPTMnet; P36969; -.
DR MetOSite; P36969; -.
DR PhosphoSitePlus; P36969; -.
DR SwissPalm; P36969; -.
DR BioMuta; GPX4; -.
DR DMDM; 172045844; -.
DR REPRODUCTION-2DPAGE; IPI00304814; -.
DR UCD-2DPAGE; P36969; -.
DR EPD; P36969; -.
DR jPOST; P36969; -.
DR MassIVE; P36969; -.
DR MaxQB; P36969; -.
DR PaxDb; P36969; -.
DR PeptideAtlas; P36969; -.
DR PRIDE; P36969; -.
DR ProteomicsDB; 55250; -. [P36969-1]
DR ProteomicsDB; 55251; -. [P36969-2]
DR ABCD; P36969; 1 sequenced antibody.
DR Antibodypedia; 3263; 366 antibodies from 41 providers.
DR DNASU; 2879; -.
DR Ensembl; ENST00000354171.13; ENSP00000346103.7; ENSG00000167468.19. [P36969-1]
DR Ensembl; ENST00000611653.4; ENSP00000483655.1; ENSG00000167468.19. [P36969-2]
DR GeneID; 2879; -.
DR KEGG; hsa:2879; -.
DR MANE-Select; ENST00000354171.13; ENSP00000346103.7; NM_002085.5; NP_002076.2.
DR UCSC; uc021umg.3; human. [P36969-1]
DR CTD; 2879; -.
DR DisGeNET; 2879; -.
DR GeneCards; GPX4; -.
DR HGNC; HGNC:4556; GPX4.
DR HPA; ENSG00000167468; Low tissue specificity.
DR MalaCards; GPX4; -.
DR MIM; 138322; gene.
DR MIM; 250220; phenotype.
DR neXtProt; NX_P36969; -.
DR OpenTargets; ENSG00000167468; -.
DR Orphanet; 93317; Spondylometaphyseal dysplasia, Sedaghatian type.
DR PharmGKB; PA28952; -.
DR VEuPathDB; HostDB:ENSG00000167468; -.
DR eggNOG; KOG1651; Eukaryota.
DR GeneTree; ENSGT00940000161913; -.
DR InParanoid; P36969; -.
DR OMA; FPMMSKI; -.
DR OrthoDB; 225688at2759; -.
DR PhylomeDB; P36969; -.
DR TreeFam; TF338735; -.
DR BioCyc; MetaCyc:HS09562-MON; -.
DR BRENDA; 1.11.1.12; 2681.
DR PathwayCommons; P36969; -.
DR Reactome; R-HSA-2142688; Synthesis of 5-eicosatetraenoic acids.
DR Reactome; R-HSA-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR Reactome; R-HSA-2142770; Synthesis of 15-eicosatetraenoic acid derivatives.
DR Reactome; R-HSA-9018676; Biosynthesis of D-series resolvins. [P36969-2]
DR Reactome; R-HSA-9018896; Biosynthesis of E-series 18(S)-resolvins. [P36969-2]
DR Reactome; R-HSA-9020265; Biosynthesis of aspirin-triggered D-series resolvins. [P36969-2]
DR Reactome; R-HSA-9023661; Biosynthesis of E-series 18(R)-resolvins. [P36969-2]
DR SABIO-RK; P36969; -.
DR SignaLink; P36969; -.
DR BioGRID-ORCS; 2879; 412 hits in 1076 CRISPR screens.
DR ChiTaRS; GPX4; human.
DR EvolutionaryTrace; P36969; -.
DR GeneWiki; GPX4; -.
DR GenomeRNAi; 2879; -.
DR Pharos; P36969; Tbio.
DR PRO; PR:P36969; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P36969; protein.
DR Bgee; ENSG00000167468; Expressed in left testis and 201 other tissues.
DR ExpressionAtlas; P36969; baseline and differential.
DR Genevisible; P36969; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA.
DR GO; GO:0004602; F:glutathione peroxidase activity; IMP:CAFA.
DR GO; GO:0042802; F:identical protein binding; IMP:CAFA.
DR GO; GO:0004601; F:peroxidase activity; IBA:GO_Central.
DR GO; GO:0047066; F:phospholipid-hydroperoxide glutathione peroxidase activity; IDA:UniProtKB.
DR GO; GO:0008430; F:selenium binding; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:Ensembl.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:Ensembl.
DR GO; GO:0019372; P:lipoxygenase pathway; IDA:UniProtKB.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; TAS:Reactome.
DR GO; GO:0110076; P:negative regulation of ferroptosis; ISS:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; TAS:UniProtKB.
DR GO; GO:0051258; P:protein polymerization; IMP:CAFA.
DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR CDD; cd00340; GSH_Peroxidase; 1.
DR InterPro; IPR000889; Glutathione_peroxidase.
DR InterPro; IPR029759; GPX_AS.
DR InterPro; IPR029760; GPX_CS.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR11592; PTHR11592; 1.
DR Pfam; PF00255; GSHPx; 1.
DR PIRSF; PIRSF000303; Glutathion_perox; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS00460; GLUTATHIONE_PEROXID_1; 1.
DR PROSITE; PS00763; GLUTATHIONE_PEROXID_2; 1.
DR PROSITE; PS51355; GLUTATHIONE_PEROXID_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Cytoplasm; Developmental protein;
KW Dwarfism; Lipid metabolism; Mitochondrion; Oxidoreductase; Peroxidase;
KW Phosphoprotein; Reference proteome; Selenocysteine; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..197
FT /note="Phospholipid hydroperoxide glutathione peroxidase"
FT /id="PRO_0000013067"
FT ACT_SITE 73
FT /evidence="ECO:0000250|UniProtKB:O70325"
FT NON_STD 73
FT /note="Selenocysteine"
FT /evidence="ECO:0000305|PubMed:8039723,
FT ECO:0000305|PubMed:9705830"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36970"
FT VAR_SEQ 1..27
FT /note="Missing (in isoform Cytoplasmic)"
FT /evidence="ECO:0000305"
FT /id="VSP_018740"
FT VARIANT 2
FT /note="S -> N (in dbSNP:rs8178967)"
FT /evidence="ECO:0000269|PubMed:12606444, ECO:0000269|Ref.3"
FT /id="VAR_017063"
FT VARIANT 90..197
FT /note="Missing (in SMDS)"
FT /evidence="ECO:0000269|PubMed:24706940"
FT /id="VAR_080140"
FT VARIANT 120
FT /note="A -> T (in a patient affected by cryptorchidism;
FT dbSNP:rs76201145)"
FT /evidence="ECO:0000269|PubMed:12606444"
FT /id="VAR_017064"
FT MUTAGEN 73
FT /note="U->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:17630701"
FT MUTAGEN 73
FT /note="U->C: Almost complete loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:17630701"
FT TURN 35..37
FT /evidence="ECO:0007829|PDB:6HN3"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:6HN3"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:6HN3"
FT STRAND 53..55
FT /evidence="ECO:0007829|PDB:6HN3"
FT HELIX 56..59
FT /evidence="ECO:0007829|PDB:6HN3"
FT STRAND 62..69
FT /evidence="ECO:0007829|PDB:6HN3"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:6HN3"
FT HELIX 76..90
FT /evidence="ECO:0007829|PDB:6HN3"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:6HN3"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:6HN3"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:6HN3"
FT HELIX 113..121
FT /evidence="ECO:0007829|PDB:6HN3"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:6HN3"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:6HN3"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:2GS3"
FT HELIX 142..149
FT /evidence="ECO:0007829|PDB:6HN3"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:6HN3"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:6HN3"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:6HN3"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:6HN3"
FT HELIX 186..192
FT /evidence="ECO:0007829|PDB:6HN3"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:6HN3"
SQ SEQUENCE 197 AA; 22175 MW; 1AE3BC7AE42FDDB1 CRC64;
MSLGRLCRLL KPALLCGALA APGLAGTMCA SRDDWRCARS MHEFSAKDID GHMVNLDKYR
GFVCIVTNVA SQUGKTEVNY TQLVDLHARY AECGLRILAF PCNQFGKQEP GSNEEIKEFA
AGYNVKFDMF SKICVNGDDA HPLWKWMKIQ PKGKGILGNA IKWNFTKFLI DKNGCVVKRY
GPMEEPLVIE KDLPHYF
