Gpx4
entrez
625249
canonical
uniprot
O70325
canonical
ensembl
ENSMUSG00000075706
resolver
ensp
ENSMUSP00000094863
resolver
ensp
ENSMUSP00000101011
resolver
ensp
ENSMUSP00000138186
resolver
genesymbol
Gpx4
resolver
genesymbol_syn
GPx4
resolver
uniprot
O35560
resolver
uniprot
Q3TI34
resolver
uniprot
Q76LV0
resolver
uniprot
Q8K4U8
resolver
uniprot
Q91XR9
resolver
uniprot
Q9JK35
resolver
uniprot_entry
GPX4_MOUSE
resolver
uniprot_entry
Q3TI34_MOUSE
resolver
uniprot_entry
Q76LV0_MOUSE
resolver
uniprot_sec
O35560
resolver
uniprot_sec
Q8K4U8
resolver
uniprot_sec
Q91XR9
resolver
uniprot_sec
Q9JK35
resolver
amino_acid_sequence
MSWGRLSRLLKPALLCGALAAPGLAGTMCASRDDWRCARSMHEFSAKDIDGHMVCLDKYRGFVCIVTNVASQUGKTDVNYTQLVDLHARYAECGLRILAFPCNQFGRQEPGSNQEIKEFAAGYNVKFDMYSKICVNGDDAHPLWKWMKVQPKGRGMLGNAIKWNFTKFLIDKNGCVVKRYGPMEEPQVIEKDLPCYL
uniprot
proteins
ec_number
1.11.1.12
uniprot
proteins
ec_number
1.11.1.9
uniprot
proteins
function
FUNCTION: Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (PubMed:29290465). Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (PubMed:12566075). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (PubMed:12566075, PubMed:24439385, PubMed:25402683, PubMed:25922076, PubMed:29290465). 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 (PubMed:29290465). 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 (PubMed:29290465). May be required to protect cells from the toxicity of ingested lipid hydroperoxides (PubMed:12566075). Required for normal sperm development and male fertility (PubMed:19783653, PubMed:25922076). Essential for maturation and survival of photoreceptor cells (PubMed:22207760). 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 (PubMed:25824823). 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 (By similarity). Can also reduce small soluble hydroperoxides such as H2O2 and tert-butyl hydroperoxide (PubMed:12566075). {ECO:0000250|UniProtKB:P36968, ECO:0000250|UniProtKB:P36969, ECO:0000269|PubMed:12566075, ECO:0000269|PubMed:18762024, ECO:0000269|PubMed:19783653, ECO:0000269|PubMed:22207760, ECO:0000269|PubMed:24439385, ECO:0000269|PubMed:25402683, ECO:0000269|PubMed:25824823, ECO:0000269|PubMed:25922076, ECO:0000269|PubMed:29290465}.; FUNCTION: [Isoform Cytoplasmic]: Specifically able to suppress the production of leukotriene and prostaglandin in response to several stimuli by reducing fatty acid hydroperoxide. {ECO:0000250|UniProtKB:P36970}.; FUNCTION: [Isoform Mitochondrial]: Specifically required to prevent mitochondrial cell death by mediating reduction of cardiolipin hydroperoxide (By similarity). Also required for normal sperm development and male fertility (PubMed:19417079). {ECO:0000250|UniProtKB:P36970, ECO:0000269|PubMed:19417079}.; FUNCTION: [Isoform Nuclear]: Required for male fertility by stabilizing the condensed chromatin in sperm nuclei (PubMed:12566075). {ECO:0000269|PubMed:12566075}.
uniprot
proteins
mass_dalton
22229
uniprot
proteins
mutagenesis
MUTAGEN 73; /note="U->C: Mice develop normally and were born at the expected Mendelian ratio. Homozygous mice however lose body weight by P14-P16 and are susceptible to fatal epileptic seizures. Cells are extremely sensitive to peroxide-induced cell death because the enzyme is inactivated: The enzyme undergoes overoxidation and irreversible inactivation in the presence of exceeding concentrations of its substrates. Unlike the wild-type enzyme, which can form a selenylamide in the absence of reducing equivalents, thereby preventing its irreversible overoxidation, the mutant fails to form such an intermediate during its catalytic cycle."; /evidence="ECO:0000269|PubMed:29290465"; MUTAGEN 73; /note="U->S: Early embryonic lethality in homozygous mice. Male subfertility in heterozygous mice due to impaired spermatogenesis."; /evidence="ECO:0000269|PubMed:25922076"; MUTAGEN 124..125; /note="NV->AA: Decreased interaction with HSPA8 and degradation via chaperone-mediated autophagy."; /evidence="ECO:0000269|PubMed:30718432"; MUTAGEN 187..188; /note="QV->AA: Decreased interaction with HSPA8 and degradation via chaperone-mediated autophagy."; /evidence="ECO:0000269|PubMed:30718432
uniprot
proteins
post_translational_modification
PTM: Degraded via chaperone-mediated autophagy, promoting ferroptosis. {ECO:0000269|PubMed:30718432}.; PTM: Hydroxylation by EGLN3/PHD3 promotes its stabilization by preventing degradation via chaperone-mediated autophagy. {ECO:0000250|UniProtKB:P36969}.
uniprot
proteins
protein_family
Glutathione peroxidase family
uniprot
proteins
pubmed
10100845
uniprot
proteins
pubmed
10341094
uniprot
proteins
pubmed
11344099
uniprot
proteins
pubmed
12566075
uniprot
proteins
pubmed
12745070
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
1668477
uniprot
proteins
pubmed
17503194
uniprot
proteins
pubmed
18762024
uniprot
proteins
pubmed
19417079
uniprot
proteins
pubmed
19783653
uniprot
proteins
pubmed
19890015
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22207760
uniprot
proteins
pubmed
24439385
uniprot
proteins
pubmed
24599700
uniprot
proteins
pubmed
25402683
uniprot
proteins
pubmed
25824823
uniprot
proteins
pubmed
25922076
uniprot
proteins
pubmed
27710939
uniprot
proteins
pubmed
28204974
uniprot
proteins
pubmed
29290465
uniprot
proteins
pubmed
30718432
uniprot
proteins
pubmed
9370288
uniprot
proteins
sequence_length
197
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion {ECO:0000269|PubMed:12566075, ECO:0000269|PubMed:22207760}.; SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm {ECO:0000269|PubMed:12566075}.; SUBCELLULAR LOCATION: [Isoform Nuclear]: Nucleus {ECO:0000269|PubMed:11344099}.
uniprot
proteins