Search Results
Overview
| Uniprot ID | P36969 |
|---|---|
| Protein Name | Phospholipid hydroperoxide glutathione peroxidase GPX4 |
| Gene Name | GPX4 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 107 | FPCNQFGKQEPGSNE |
| 154 | MKIQPKGKGILGNAI |
| 162 | GILGNAIKWNFTKFL |
| 172 | FTKFLIDKNGCVVKR |
| 47 | SMHEFSAKDIDGHMV |
| 58 | GHMVNLDKYRGFVCI |
| 75 | NVASQUGKTEVNYTQ |
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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0005739 | mitochondrion |
| Cellular Component | GO:0005635 | nuclear envelope |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0032991 | protein-containing complex |
| Molecular Function | GO:0004602 | glutathione peroxidase activity |
| Molecular Function | GO:0042802 | identical protein binding |
| Molecular Function | GO:0047066 | phospholipid-hydroperoxide glutathione peroxidase activity |
| Molecular Function | GO:0008430 | selenium binding |
| Biological Process | GO:0019369 | arachidonate metabolic process |
| Biological Process | GO:0034599 | cellular response to oxidative stress |
| Biological Process | GO:0019372 | lipoxygenase pathway |
| Biological Process | GO:0042759 | long-chain fatty acid biosynthetic process |
| Biological Process | GO:0110076 | negative regulation of ferroptosis |
| Biological Process | GO:0006644 | phospholipid metabolic process |
| Biological Process | GO:0051258 | protein polymerization |
| Biological Process | GO:0032355 | response to estradiol |
| Biological Process | GO:0006979 | response to oxidative stress |
| Biological Process | GO:0007283 | spermatogenesis |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] Yan M, Tu H, Tang S, Gai Z, Shi Q et al.. Lactylated Proteomic Analysis Reveals Functional Implications of Lysine Lactylation In Asthenozoospermia.. Mol Cell Proteomics 24(12):101439. 2025 Dec. PMID: 41192556.
[3] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.