Details of the BTS
General Information of Binding Target of SBP (BTS) (ID: ST00152) | ||||||
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BTS Name |
Kelch-like ECH-associated protein 1
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Synonyms |
Cytosolic inhibitor of Nrf2; INrf2; Kelch-like protein 19
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BTS Type |
Protein
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Family |
KEAP1 family
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Gene Name |
KEAP1
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Organism |
Homo sapiens (Human)
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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 | ||||||
UniProt Entry | ||||||
PFam | ||||||
Gene ID | ||||||
Sequence |
MQPDPRPSGAGACCRFLPLQSQCPEGAGDAVMYASTECKAEVTPSQHGNRTFSYTLEDHT
KQAFGIMNELRLSQQLCDVTLQVKYQDAPAAQFMAHKVVLASSSPVFKAMFTNGLREQGM EVVSIEGIHPKVMERLIEFAYTASISMGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLD PSNAIGIANFAEQIGCVELHQRAREYIYMHFGEVAKQEEFFNLSHCQLVTLISRDDLNVR CESEVFHACINWVKYDCEQRRFYVQALLRAVRCHSLTPNFLQMQLQKCEILQSDSRCKDY LVKIFEELTLHKPTQVMPCRAPKVGRLIYTAGGYFRQSLSYLEAYNPSDGTWLRLADLQV PRSGLAGCVVGGLLYAVGGRNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGV IDGHIYAVGGSHGCIHHNSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAVGGFDG TNRLNSAECYYPERNEWRMITAMNTIRSGAGVCVLHNCIYAAGGYDGQDQLNSVERYDVE TETWTFVAPMKHRRSALGITVHQGRIYVLGGYDGHTFLDSVECYDPDTDTWSEVTRMTSG RSGVGVAVTMEPCRKQIDQQNCTC |
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Sequence Length |
624
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Synthetic Binding Protein (SBP) Targeting This BTS |
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SBP Name | Highest Status | Mechanism | Affinity | Application | Details | Ref |
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Designed TPR protein anti-Keap1 Charge Nrf2 CTPR2 | Research | Binder | Kd: 817 nM | Research tool | [1] | |
Designed TPR protein anti-Keap1 CIDER Nrf2 CTPR2 | Research | Binder | Kd: 103 nM | Research tool | [1] | |
Designed TPR protein anti-Keap1 Flexible Nrf2 CTPR2 | Research | Binder | Kd: 109 nM | Research tool | [1] | |
Monobody anti-Keap1 D1 | Research | Inhibitor | Kd: 201 nM | Research tool | [2] | |
Monobody anti-Keap1 D4 | Research | Inhibitor | Kd: 690 nM | Research tool | [2] | |
Monobody anti-Keap1 R1 | Research | Inhibitor | Kd: 0.3 nM | Tools as inhibitor of the KEAP1-NRF2 interaction | [2] | |
References |
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