KEAP1 — Kelch like ECH associated protein 1
KEAP1 belongs to a gene co-expression module in 2 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
KEAP1's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| Gamma-delta T cells | T cell Survival T cell maturation | ARFRP1, BCL2L1, C6orf47, CHD9, DAXX, DEF6, DENND2D, DHPS +26 more | |
| Mucosal-associated invariant T cell | Oxidative Stress Response Stress | ATIC, CD244, CYTH4, EIF2S2, GPR68, GSDMD, ING4, MCM3 +11 more |
About the gene
| Synonyms | INrf2, KIAA0132, KLHL19, MGC10630, MGC1114, MGC20887, MGC4407, MGC9454 |
|---|---|
| Chromosome | 19: 10486125-10503558 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Cancer-related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins |
| Biological process | Host-virus interaction, Ubl conjugation pathway |
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. 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. 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. 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. The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation. The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.