Protein Name:
Phospholipid hydroperoxide glutathione peroxidase GPX4
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UniprotKB/SwissProt ID: O70325 (O70325)
Gene Name:
Gpx4
Organism: Mus musculus (Mouse)
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) Specifically able to suppress the production of leukotriene and prostaglandin in response to several stimuli by reducing fatty acid hydroperoxide 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) Required for male fertility by stabilizing the condensed chromatin in sperm nuclei (PubMed:12566075)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Mitochondrion. Cytoplasm. Nucleus
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Graphical Visualization of S-nitrosylation Sites:
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The S-nitrosylation sites of O70325
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| No. |
Position |
S-nitrosylated Peptide |
Secondary Structure of S-nitrosylated Peptide |
Solvent Accessibility of nitrosylated Site |
PubMed ID |
| 1 |
102 |
ECGLRILAFP C NQFGRQEPGS |
CCHHHHHHHH H HHHHHHHHCC |
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24895380
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| 2 |
134 |
NVKFDMYSKI C VNGDDAHPLW |
CCHHHHHHHH H HHHHHHHHCC |
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21278135
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| 3 |
175 |
FTKFLIDKNG C VVKRYGPMEE |
CCHHHHHHHH H HHHHHHHHCC |
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21278135
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| 4 |
195 |
EPQVIEKDLP C YL-------- |
CCHHHHHHHH H HHHHHHHHCC |
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21278135
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| 5 |
55 |
SAKDIDGHMV C LDKYRGFVCI |
CCHHHHHHHH H HHHHHHHHCC |
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21278135
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