Molecule Details
| General Information of the Molecule | ||||
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| Name |
Kelch-like ECH-associated protein 1 (KEAP1)
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| Synonyms |
Cytosolic inhibitor of Nrf2; INrf2; Kelch-like protein 19
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| Gene Name |
KEAP1
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| Gene ID | ||||
| Sequence |
MQPDPRPSGAGACCRFLPLQSQCPEGAGDAVMYASTECKAEVTPSQHGNRTFSYTLEDHT
KQAFGIMNELRLSQQLCDVTLQVKYQDAPAAQFMAHKVVLASSSPVFKAMFTNGLREQGM EVVSIEGIHPKVMERLIEFAYTASISMGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLD PSNAIGIANFAEQIGCVELHQRAREYIYMHFGEVAKQEEFFNLSHCQLVTLISRDDLNVR CESEVFHACINWVKYDCEQRRFYVQALLRAVRCHSLTPNFLQMQLQKCEILQSDSRCKDY LVKIFEELTLHKPTQVMPCRAPKVGRLIYTAGGYFRQSLSYLEAYNPSDGTWLRLADLQV PRSGLAGCVVGGLLYAVGGRNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGV IDGHIYAVGGSHGCIHHNSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAVGGFDG TNRLNSAECYYPERNEWRMITAMNTIRSGAGVCVLHNCIYAAGGYDGQDQLNSVERYDVE TETWTFVAPMKHRRSALGITVHQGRIYVLGGYDGHTFLDSVECYDPDTDTWSEVTRMTSG RSGVGVAVTMEPCRKQIDQQNCTC Click to Show/Hide
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| 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.
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| Uniprot ID | ||||
| Pfam | ||||
| KEGG ID | ||||
| A List of Drug Combination(s) Able to Regulate This Molecule | ||||
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| Expression Regulation | Click to Show/Hide the Drug Combination Regulating This Molecule | |||
| Down-regulation | Click to Show/Hide | |||
| Drug Combination 1 Down-regulating the Expression of This Molecule | [1] | |||
| Detail(s) |
Combination Info
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| Name | Apocynin NP Info | + | Cyclophosphamide Drug Info | |
| Structure |
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| Natural Product(s) of This Target | ||||
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| 1 | Brusatol | NP Info | Investigative | Brucea javanica |
| 2 | Lycopene | NP Info | Phase 2 | Daucus carota |
| 3 | N-containing chalcone derivative | NP Info | . | Not Available |
| 4 | Polydatin | NP Info | Investigative | Polygonum cuspidatum |
| Drug(s) of This Target | ||||
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| 1 | Cisplatin | Drug Info | Approved | Bladder cancer |