GPX4

The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of hydrogen peroxide, organic hydroperoxides and lipid hydroperoxides, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme has a high preference for lipid hydroperoxides and protects cells against membrane lipid peroxidation and cell death. It is also required for normal sperm development; thus, it has been identified as a 'moonlighting' protein because of its ability to serve dual functions as a peroxidase, as well as a structural protein in mature spermatozoa. Mutations in this gene are associated with Sedaghatian type of spondylometaphyseal dysplasia (SMDS). This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene.

Glutathione Peroxidase 4

Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (By similarity).

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 (By similarity).

Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (PubMed:24439385).

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).

Aging Source: Ensembl
Arachidonic acid metabolic process Source: UniProtKB
Chromatin organization Source: Ensembl
Glutathione metabolic process Source: Ensembl
Lipoxygenase pathway Source: UniProtKB
Long-chain fatty acid biosynthetic process Source: Reactome
Negative regulation of ferroptosis Source: UniProtKB
Phospholipid metabolic process Source: UniProtKB
Protein polymerization Source: CAFA
Regulation of inflammatory response Source: Ensembl
Response to estradiol Source: Ensembl
Response to oxidative stress Source: UniProtKB
Spermatogenesis Source: UniProtKB

Isoform Mitochondrial: Mitochondrion
Isoform Cytoplasmic: Cytoplasm

Spondylometaphyseal dysplasia, Sedaghatian type (SMDS):
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.