GPX4
entrez
2879
canonical
uniprot
P36969
canonical
ensembl
ENSG00000167468
resolver
ensp
ENSP00000346103
resolver
ensp
ENSP00000473614
resolver
ensp
ENSP00000483655
resolver
enst
ENST00000354171
resolver
enst
ENST00000611653
resolver
genesymbol
GPX4
resolver
hgnc
HGNC:4556
resolver
uniprot
O43381
resolver
uniprot
Q6PI42
resolver
uniprot
Q6PJ59
resolver
uniprot
Q9UPK2
resolver
uniprot_entry
GPX4_HUMAN
resolver
uniprot_entry
Q6PI42_HUMAN
resolver
uniprot_sec
O43381
resolver
uniprot_sec
Q6PJ59
resolver
uniprot_sec
Q9UPK2
resolver
amino_acid_sequence
MSLGRLCRLLKPALLCGALAAPGLAGTMCASRDDWRCARSMHEFSAKDIDGHMVNLDKYRGFVCIVTNVASQUGKTEVNYTQLVDLHARYAECGLRILAFPCNQFGKQEPGSNEEIKEFAAGYNVKFDMFSKICVNGDDAHPLWKWMKIQPKGKGILGNAIKWNFTKFLIDKNGCVVKRYGPMEEPLVIEKDLPHYF
uniprot
proteins
disease_involvement
DISEASE: Spondylometaphyseal dysplasia, Sedaghatian type (SMDS) [MIM:250220]: A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDS is a neonatal lethal form characterized by severe metaphyseal chondrodysplasia with mild limb shortening, platyspondyly, cardiac conduction defects, and central nervous system abnormalities. {ECO:0000269|PubMed:24706940}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:40281343). Can also reduce cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (PubMed:40281343). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (PubMed:24439385, PubMed:40281343). 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 (PubMed:11115402). 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 reduce fatty acid-derived hydroperoxides (PubMed:11115402, PubMed:36608588). Can also reduce small soluble hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl hydroperoxide (PubMed:17630701, PubMed:36608588). {ECO:0000250|UniProtKB:O70325, ECO:0000250|UniProtKB:P36968, ECO:0000269|PubMed:11115402, ECO:0000269|PubMed:17630701, ECO:0000269|PubMed:24439385, ECO:0000269|PubMed:36608588, ECO:0000269|PubMed:40281343}.
uniprot
proteins
mass_dalton
22175
uniprot
proteins
mutagenesis
MUTAGEN 73; /note="U->A: Loss of enzyme activity."; /evidence="ECO:0000269|PubMed:17630701"; MUTAGEN 73; /note="U->C: Almost complete loss of enzyme activity."; /evidence="ECO:0000269|PubMed:17630701"; MUTAGEN 186; /note="P->A: Abolished hydroxylation by EGLN3, leading to degradation by chaperone-mediated autophagy."; /evidence="ECO:0000269|PubMed:40281343
uniprot
proteins
post_translational_modification
PTM: Degraded via chaperone-mediated autophagy, promoting ferroptosis. {ECO:0000269|PubMed:40281343}.; PTM: Hydroxylation by EGLN3/PHD3 promotes its stabilization by preventing degradation via chaperone-mediated autophagy. {ECO:0000269|PubMed:40281343}.
uniprot
proteins
protein_family
Glutathione peroxidase family
uniprot
proteins
pubmed
11115402
uniprot
proteins
pubmed
12606444
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17630701
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24439385
uniprot
proteins
pubmed
24706940
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27836545
uniprot
proteins
pubmed
36608588
uniprot
proteins
pubmed
36828120
uniprot
proteins
pubmed
40281343
uniprot
proteins
pubmed
8039723
uniprot
proteins
pubmed
9705830
uniprot
proteins
sequence_length
197
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion {ECO:0000250|UniProtKB:O70325}.; SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm {ECO:0000269|PubMed:11115402}.
uniprot
proteins