UniProtKB - P36968 (GPX4_PIG)
Protein
Phospholipid hydroperoxide glutathione peroxidase
Gene
GPX4
Organism
Sus scrofa (Pig)
Status
Functioni
Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (PubMed:3978121, PubMed:2386798, PubMed:8135530). Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (PubMed:8135530, PubMed:2386798, PubMed:3978121). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (By similarity). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (By similarity). The presence of selenocysteine (Sec) versus Cys at the active site is essential for life: it provides resistance to overoxidation and prevents cells against ferroptosis (By similarity). The presence of Sec at the active site is also essential for the survival of a specific type of parvalbumin-positive interneurons, thereby preventing against fatal epileptic seizures (By similarity). May be required to protect cells from the toxicity of ingested lipid hydroperoxides (By similarity). Required for normal sperm development and male fertility (By similarity). Essential for maturation and survival of photoreceptor cells (By similarity). Plays a role in a primary T-cell response to viral and parasitic infection by protecting T-cells from ferroptosis and by supporting T-cell expansion (By similarity). Plays a role of glutathione peroxidase in platelets in the arachidonic acid metabolism (By similarity). Reduces hydroperoxy ester lipids formed by a 15-lipoxygenase that may play a role as down-regulator of the cellular 15-lipoxygenase pathway (PubMed:8617728).By similarity4 Publications
Catalytic activityi
- a hydroperoxy polyunsaturated fatty acid + 2 glutathione = a hydroxy polyunsaturated fatty acid + glutathione disulfide + H2O4 PublicationsEC:1.11.1.124 PublicationsThis reaction proceeds in the forward1 Publication direction.
- (13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione = (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide + H2O1 PublicationThis reaction proceeds in the forward1 Publication direction.
- (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + 2 glutathione = (12S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + glutathione disulfide + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 73 | 1 Publication | 1 |
GO - Molecular functioni
- glutathione peroxidase activity Source: GO_Central
- peroxidase activity Source: GO_Central
- phospholipid-hydroperoxide glutathione peroxidase activity Source: UniProtKB
GO - Biological processi
- arachidonic acid metabolic process Source: UniProtKB
- chromatin organization Source: Ensembl
- lipoxygenase pathway Source: UniProtKB
- multicellular organism development Source: UniProtKB-KW
- negative regulation of ferroptosis Source: UniProtKB
- response to oxidative stress Source: UniProtKB
- spermatogenesis Source: UniProtKB
Keywordsi
Molecular function | Developmental protein, Oxidoreductase, Peroxidase |
Protein family/group databases
PeroxiBasei | 3723, SscGPx04 |
Chemistry databases
SwissLipidsi | SLP:000001475 |
Names & Taxonomyi
Protein namesi | Recommended name: Phospholipid hydroperoxide glutathione peroxidase2 Publications (EC:1.11.1.124 Publications)Short name: PHGPx2 Publications Alternative name(s): Glutathione peroxidase 4By similarity Short name: GPx-4By similarity Short name: GSHPx-4By similarity |
Gene namesi | Name:GPX4By similarity |
Organismi | Sus scrofa (Pig) |
Taxonomic identifieri | 9823 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Suina › Suidae › Sus |
Proteomesi |
|
Organism-specific databases
VGNCi | VGNC:99753, GPX4 |
Subcellular locationi
Mitochondrion
- Mitochondrion By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Cytosol
- cytosol Source: UniProtKB
Mitochondrion
- mitochondrion Source: GO_Central
Nucleus
- nuclear envelope Source: Ensembl
- nucleus Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, MitochondrionPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – ? | MitochondrionSequence analysis | ||
ChainiPRO_0000013071 | ? – 197 | Phospholipid hydroperoxide glutathione peroxidase |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 40 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | P36968 |
PeptideAtlasi | P36968 |
PRIDEi | P36968 |
Interactioni
Subunit structurei
Monomer (PubMed:3978121). Has a tendency to form higher mass oligomers (By similarity).
By similarity1 PublicationProtein-protein interaction databases
STRINGi | 9823.ENSSSCP00000021702 |
Family & Domainsi
Sequence similaritiesi
Belongs to the glutathione peroxidase family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG1651, Eukaryota |
GeneTreei | ENSGT00940000161913 |
HOGENOMi | CLU_2782607_0_0_1 |
InParanoidi | P36968 |
OMAi | IGFPANN |
OrthoDBi | 1483113at2759 |
Family and domain databases
CDDi | cd00340, GSH_Peroxidase, 1 hit |
Gene3Di | 3.40.30.10, 1 hit |
InterProi | View protein in InterPro IPR000889, Glutathione_peroxidase IPR029759, GPX_AS IPR029760, GPX_CS IPR036249, Thioredoxin-like_sf |
PANTHERi | PTHR11592, PTHR11592, 1 hit |
Pfami | View protein in Pfam PF00255, GSHPx, 1 hit |
PIRSFi | PIRSF000303, Glutathion_perox, 1 hit |
PRINTSi | PR01011, GLUTPROXDASE |
SUPFAMi | SSF52833, SSF52833, 1 hit |
PROSITEi | View protein in PROSITE PS00460, GLUTATHIONE_PEROXID_1, 1 hit PS00763, GLUTATHIONE_PEROXID_2, 1 hit PS51355, GLUTATHIONE_PEROXID_3, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative initiation. AlignAdd to basketIsoform Mitochondrial (identifier: P36968-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSFSRLFRLL KPTLLCGTLA VPGLAGTMCA SRDDWRCARS MHEFSAKDID
60 70 80 90 100
GHMVNLDKYR GYVCIVTNVA SQUGKTEVNY TQLVDLHARY AECGLRILAF
110 120 130 140 150
PCNQFGRQEP GSDAEIKEFA AGYNVKFDMF SKICVNGDDA HPLWKWMKVQ
160 170 180 190
PKGRGMLGNA IKWNFTKFLI DKNGCVVKRY GPMEEPQVIE KDLPCYL
Isoform Cytoplasmic (identifier: P36968-2) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
1-27: Missing.
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_018744 | 1 – 27 | Missing in isoform Cytoplasmic. 2 PublicationsAdd BLAST | 27 |
Non-standard residue
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Non-standard residuei | 73 | Selenocysteine1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L12743 mRNA Translation: AAA31098.2 L12743 mRNA Translation: AAA31099.2 X76008 Genomic DNA Translation: CAA53595.2 X76009 mRNA Translation: CAA53596.2 S80257 mRNA Translation: AAB21327.2 |
PIRi | JN0608 |
RefSeqi | NP_999572.1, NM_214407.1 [P36968-1] |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative initiation, SelenocysteineSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L12743 mRNA Translation: AAA31098.2 L12743 mRNA Translation: AAA31099.2 X76008 Genomic DNA Translation: CAA53595.2 X76009 mRNA Translation: CAA53596.2 S80257 mRNA Translation: AAB21327.2 |
PIRi | JN0608 |
RefSeqi | NP_999572.1, NM_214407.1 [P36968-1] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
STRINGi | 9823.ENSSSCP00000021702 |
Chemistry databases
SwissLipidsi | SLP:000001475 |
Protein family/group databases
PeroxiBasei | 3723, SscGPx04 |
Proteomic databases
PaxDbi | P36968 |
PeptideAtlasi | P36968 |
PRIDEi | P36968 |
Genome annotation databases
Organism-specific databases
CTDi | 2879 |
VGNCi | VGNC:99753, GPX4 |
Phylogenomic databases
eggNOGi | KOG1651, Eukaryota |
GeneTreei | ENSGT00940000161913 |
HOGENOMi | CLU_2782607_0_0_1 |
InParanoidi | P36968 |
OMAi | IGFPANN |
OrthoDBi | 1483113at2759 |
Gene expression databases
Genevisiblei | P36968, SS |
Family and domain databases
CDDi | cd00340, GSH_Peroxidase, 1 hit |
Gene3Di | 3.40.30.10, 1 hit |
InterProi | View protein in InterPro IPR000889, Glutathione_peroxidase IPR029759, GPX_AS IPR029760, GPX_CS IPR036249, Thioredoxin-like_sf |
PANTHERi | PTHR11592, PTHR11592, 1 hit |
Pfami | View protein in Pfam PF00255, GSHPx, 1 hit |
PIRSFi | PIRSF000303, Glutathion_perox, 1 hit |
PRINTSi | PR01011, GLUTPROXDASE |
SUPFAMi | SSF52833, SSF52833, 1 hit |
PROSITEi | View protein in PROSITE PS00460, GLUTATHIONE_PEROXID_1, 1 hit PS00763, GLUTATHIONE_PEROXID_2, 1 hit PS51355, GLUTATHIONE_PEROXID_3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GPX4_PIG | |
Accessioni | P36968Primary (citable) accession number: P36968 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 1, 1994 |
Last sequence update: | February 26, 2008 | |
Last modified: | April 7, 2021 | |
This is version 142 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families