FEATURES

FAMILY

DESCRIPTION

Also known as KEAP1_MOUSE, Keap1, Inrf2, Kiaa0132. 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:9887101, PubMed:12682069, PubMed:15282312, PubMed:15367669, PubMed:15581590). 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:9887101, PubMed:12193649, PubMed:14764894). 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:12193649, PubMed:20498371, PubMed:22014577, 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:20421418, PubMed:20173742, PubMed:24011591). 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 (By similarity). Component of the BCR(KEAP1) E3 ubiquitin ligase complex, at least composed of 2 molecules of CUL3, 2 molecules of KEAP1, and RBX1 (PubMed:15282312, PubMed:16790436, PubMed:27697860). Interacts with NFE2L2/NRF2; the interaction is direct (PubMed:15282312, PubMed:15367669, PubMed:15581590, PubMed:16790436, PubMed:16581765, PubMed:27697860, PubMed:16507366). Forms a ternary complex with NFE2L2/NRF2 and PGAM5 (By similarity). Interacts with (phosphorylated) SQSTM1/p62; the interaction is direct and inactivates the BCR(KEAP1) complex by sequestering it in inclusion bodies, promoting its degradation (PubMed:20495340, PubMed:20421418, PubMed:20173742, PubMed:24011591). Interacts with NFE2L1 (By similarity). Interacts with BPTF and PTMA (By similarity). Interacts with MAP1LC3B (By similarity). Interacts indirectly with ENC1 (By similarity). Interacts with SESN1 and SESN2 (By similarity). Interacts with HSP90AA1 and HSP90AB1 (By similarity).

EXTERNAL LINKS

Keap1

Kelch-like ECH-associated protein 1

Keap1

Molecular Synopsis