Keap1 est un gène codé par le symbole KEAP1. Communément appelé aussi: Kelch-like ECH-associated protein 1; Cytosolic inhibitor of Nrf2; INrf2; Kelch-like protein 19; INRF2; KIAA0132; KLHL19. Keap1 a une masse de 69.67kDa et une longueur d'acide aminé de 624.
Nous proposons 7 Keap1 kits ELISA pour la détection qualitative ou quantitative de Keap1 à partir d'échantillons Humain, Souris et Rat.
Informations sur les Gènes et les Protéines
Résumé UniProt
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:14585973, PubMed:15379550, PubMed:15572695, PubMed:15983046, PubMed:15601839). 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:15601839, PubMed:16006525). 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 (PubMed:19489739, PubMed:16006525, PubMed:17127771, PubMed:18251510, PubMed:29590092). In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2 (PubMed:20452972). The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation (PubMed:28380357). The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome (PubMed:15379550, PubMed:17046835).
Résumé Entrez
This gene encodes a protein containing KELCH-1 like domains, as well as a BTB/POZ domain. Kelch-like ECH-associated protein 1 interacts with NF-E2-related factor 2 in a redox-sensitive manner and the dissociation of the proteins in the cytoplasm is followed by transportation of NF-E2-related factor 2 to the nucleus. This interaction results in the expression of the catalytic subunit of gamma-glutamylcysteine synthetase. Two alternatively spliced transcript variants encoding the same isoform have been found for this gene.
Spécificité tissulaire
Broadly expressed, with highest levels in skeletal muscle.
Similitudes de séquence
Belongs to the KEAP1 family.
Modification post-traductionnelle
Non-enzymatic covalent modifications of reactive cysteines by electrophile metabolites inactivate the BCR(KEAP1) complex (PubMed:17127771, PubMed:18251510, PubMed:29590092, PubMed:30323285). Accumulation of fumarate promotes the formation of cysteine S-succination (S-(2-succinyl)cysteine), leading to inactivate the BCR(KEAP1) complex and promote NFE2L2/NRF2 nuclear accumulation and activation (By similarity). Nitric oxide-dependent 8-Nitro-cGMP formation promotes cysteine guanylation (S-cGMP-cysteine), leading to NFE2L2/NRF2 nuclear accumulation and activation (By similarity). Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates cysteines, activating NFE2L2/NRF2 (PubMed:29590092). Methylglyoxal, a reactive metabolite that accumulates when the glycolytic enzyme PGK1 is inhibited, promotes formation of a methylimidazole cross-link between proximal Cys-151 and Arg-135 on another KEAP1 molecule, resulting in an inactive dimer that inactivates the BCR(KEAP1) complex (PubMed:30323285).
Localisation cellulaire
Cytoplasm. Nucleus.
Mainly cytoplasmic (PubMed:15601839). In response to selective autophagy, relocalizes to inclusion bodies following interaction with SQSTM1/p62 (PubMed:20452972).
