GPX4_BOVIN
ID GPX4_BOVIN Reviewed; 197 AA.
AC Q9N2J2;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Phospholipid hydroperoxide glutathione peroxidase {ECO:0000250|UniProtKB:O70325};
DE Short=PHGPx {ECO:0000250|UniProtKB:O70325};
DE EC=1.11.1.12 {ECO:0000250|UniProtKB:O70325};
DE AltName: Full=Glutathione peroxidase 4 {ECO:0000250|UniProtKB:O70325};
DE Short=GPx-4 {ECO:0000250|UniProtKB:O70325};
DE Short=GSHPx-4 {ECO:0000250|UniProtKB:O70325};
DE Flags: Precursor;
GN Name=GPX4 {ECO:0000250|UniProtKB:O70325};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hara S., Imura N.;
RT "Bovine phospholipid hydroperoxide glutathione peroxidase.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). The presence of selenocysteine (Sec) versus Cys at the
CC 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 (By similarity). Reduces hydroperoxy ester
CC 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:0000250|UniProtKB:P36969}.
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:0000250|UniProtKB:P36969};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50709;
CC Evidence={ECO:0000250|UniProtKB:P36969};
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:0000250|UniProtKB:P36969}.
CC -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion
CC {ECO:0000250|UniProtKB:O70325}.
CC -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm
CC {ECO:0000250|UniProtKB:O70325}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Mitochondrial;
CC IsoId=Q9N2J2-1; Sequence=Displayed;
CC Name=Cytoplasmic;
CC IsoId=Q9N2J2-2; Sequence=VSP_018738;
CC -!- SIMILARITY: Belongs to the glutathione peroxidase family.
CC {ECO:0000305}.
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DR EMBL; AB017534; BAA86034.1; -; mRNA.
DR RefSeq; NP_777195.1; NM_174770.4. [Q9N2J2-1]
DR BioGRID; 159929; 1.
DR PeroxiBase; 3637; BtGPx04-A.
DR PRIDE; Q9N2J2; -.
DR Ensembl; ENSBTAT00000070793; ENSBTAP00000067758; ENSBTAG00000053003. [Q9N2J2-1]
DR GeneID; 286809; -.
DR KEGG; bta:286809; -.
DR CTD; 2879; -.
DR VEuPathDB; HostDB:ENSBTAG00000053003; -.
DR GeneTree; ENSGT00940000161913; -.
DR InParanoid; Q9N2J2; -.
DR OMA; FPMMSKI; -.
DR OrthoDB; 1483113at2759; -.
DR BRENDA; 1.11.1.12; 908.
DR Reactome; R-BTA-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR Reactome; R-BTA-9018676; Biosynthesis of D-series resolvins.
DR Reactome; R-BTA-9018896; Biosynthesis of E-series 18(S)-resolvins.
DR Reactome; R-BTA-9020265; Biosynthesis of aspirin-triggered D-series resolvins.
DR Reactome; R-BTA-9023661; Biosynthesis of E-series 18(R)-resolvins.
DR Proteomes; UP000009136; Chromosome 7.
DR Bgee; ENSBTAG00000053003; Expressed in spermatid and 102 other tissues.
DR GO; GO:0005829; C:cytosol; ISS: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; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0004602; F:glutathione peroxidase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004601; F:peroxidase activity; IBA:GO_Central.
DR GO; GO:0047066; F:phospholipid-hydroperoxide glutathione peroxidase activity; ISS:UniProtKB.
DR GO; GO:0019369; P:arachidonic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:Ensembl.
DR GO; GO:0019372; P:lipoxygenase pathway; ISS:UniProtKB.
DR GO; GO:0110076; P:negative regulation of ferroptosis; ISS:UniProtKB.
DR GO; GO:0051258; P:protein polymerization; 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 PRINTS; PR01011; GLUTPROXDASE.
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 2: Evidence at transcript level;
KW Alternative initiation; Cytoplasm; Developmental protein; Lipid metabolism;
KW Mitochondrion; Oxidoreductase; Peroxidase; Phosphoprotein;
KW 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_0000013065"
FT ACT_SITE 73
FT /evidence="ECO:0000250|UniProtKB:O70325"
FT NON_STD 73
FT /note="Selenocysteine"
FT /evidence="ECO:0000250|UniProtKB:O70325"
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_018738"
SQ SEQUENCE 197 AA; 22240 MW; 3C05FF92C4AA8824 CRC64;
MSFSRLYRLL KPALLCGALA APGLASTMCA SRDDWRCARS MHEFSAKDID GRMVNLDKYR
GHVCIVTNVA SQUGKTDVNY TQLVDLHARY AECGLRILAF PCNQFGRQEP GSNAEIKEFA
AGYNVKFDLF SKICVNGDDA HPLWKWMKVQ PKGRGMLGNA IKWNFTKFLI DKNGCVVKRY
GPMEEPLVIE KDLPCYL
