Mouse anti-Human/Mouse/Rat sapiens (Human) KEAP1 Monoclonal Antibody

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:14585973, PubMed:15379550, PubMed:15572695, PubMed:15601839, PubMed:15983046, PubMed:37339955). 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:16006525, PubMed:17127771, PubMed:18251510, PubMed:19489739, 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)

Subcellular Location

Cytoplasm; Nucleus

Tissue Specificity

Broadly expressed, with highest levels in skeletal muscle

Subunit

(Microbial infection) Interacts with ebolavirus protein VP24; this interaction activates transcription factor NFE2L2/NRF2 by blocking its interaction with KEAP1

Pathway

Protein modification; protein ubiquitination

• Dhakshinamoorthy S. et al. Human INrf2 gene structure and nucleotide sequence. (MAR-)
• Nagase T. et al. Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1. — DNA Res. (1995)
• Ohara O. et al. PubMed: CI-5HVI1USDMT80D (DEC-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Grimwood J. et al. The DNA sequence and biology of human chromosome 19. — Nature (2004)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Zhang D.D. et al. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. — Mol. Cell. Biol. (2003)
• Strachan G.D. et al. Fetal Alz-50 clone 1 interacts with the human orthologue of the Kelch-like Ech-associated protein. — Biochemistry (2004)