UniProt ID: Q1ECZ2 |
FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting nfe2l2/nrf2 for ubiquitination (PubMed:18057000). Keap1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of nfe2l2/nrf2, a transcription factor regulating expression of many cytoprotective genes (PubMed:18057000). In response to oxidative stress, different electrophile metabolites trigger non- enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting nfe2l2/nrf2 nuclear accumulation and expression of phase II detoxifying enzymes (By similarity). {ECO:0000250|UniProtKB:Q9Z2X8, ECO:0000269|PubMed:18057000}. ACTIVITY REGULATION: Ubiquitin ligase activity of the BCR(KEAP1) complex is inhibited by oxidative stress and electrophile metabolites such as sulforaphane. Electrophile metabolites react with reactive cysteine residues in keap1 and trigger non-enzymatic covalent modifications of these cysteine residues, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex. {ECO:0000250|UniProtKB:Q9Z2X8}. PATHWAY: Protein modification; protein ubiquitination. {ECO:0000250|UniProtKB:Q9Z2X8}. SUBUNIT: Homodimer and heterodimer; heterodimerizes with keap1b (PubMed:18057000). Component of the BCR(KEAP1) E3 ubiquitin ligase complex, at least composed of 2 molecules of cul3, 2 molecules of keap1 (keap1a and/or keap1b), and rbx1 (By similarity). Interacts with nfe2l2/nrf2; the interaction is direct (By similarity). {ECO:0000250|UniProtKB:Q9Z2X8, ECO:0000269|PubMed:18057000}. SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Z2X8}. Nucleus {ECO:0000250|UniProtKB:Q9Z2X8}. Note=Mainly cytoplasmic. {ECO:0000250|UniProtKB:Q9Z2X8}. TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:18057000}. DOMAIN: Keap1 contains reactive cysteine residues that act as sensors for endogenously produced and exogenously encountered small molecules, which react with sulfhydryl groups and modify the cysteine sensors, leading to impair ability of the BCR(KEAP1) complex to ubiquitinate target proteins. {ECO:0000269|PubMed:18057000}. PTM: Non-enzymatic covalent modifications of reactive cysteines by electrophile metabolites inactivate the BCR(KEAP1) complex. {ECO:0000250|UniProtKB:Q9Z2X8}. SIMILARITY: Belongs to the KEAP1 family. {ECO:0000305}. |
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