Recombinant Human Keap1 protein (Tagged) is a Human Full Length protein, in the 1 to 624 aa range, expressed in Wheat germ and suitable for SDS-PAGE, ELISA, WB.
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Application | Reactivity | Dilution info | Notes |
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Application SDS-PAGE | Reactivity Reacts | Dilution info - | Notes - |
Application ELISA | Reactivity Reacts | Dilution info - | Notes - |
Application WB | Reactivity Reacts | Dilution info - | Notes - |
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).
INRF2, KIAA0132, KLHL19, KEAP1, Kelch-like ECH-associated protein 1, Cytosolic inhibitor of Nrf2, Kelch-like protein 19, INrf2
Recombinant Human Keap1 protein (Tagged) is a Human Full Length protein, in the 1 to 624 aa range, expressed in Wheat germ and suitable for SDS-PAGE, ELISA, WB.
pH: 8
Constituents: 0.79% Tris HCl, 0.31% Glutathione
Glutathione Sepharose 4 Fast Flow
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).
Belongs to the KEAP1 family.
Non-enzymatic covalent modifications of reactive cysteines by electrophile metabolites inactivate the BCR(KEAP1) complex (PubMed:17127771, PubMed:18251510, PubMed:29590092, PubMed:30323285). Accumulation of fumarate promotes the formation of cysteine S-succination (S-(2-succinyl)cysteine), leading to inactivate the BCR(KEAP1) complex and promote NFE2L2/NRF2 nuclear accumulation and activation (By similarity). Nitric oxide-dependent 8-Nitro-cGMP formation promotes cysteine guanylation (S-cGMP-cysteine), leading to NFE2L2/NRF2 nuclear accumulation and activation (By similarity). Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates cysteines, activating NFE2L2/NRF2 (PubMed:29590092). Methylglyoxal, a reactive metabolite that accumulates when the glycolytic enzyme PGK1 is inhibited, promotes formation of a methylimidazole cross-link between proximal Cys-151 and Arg-135 on another KEAP1 molecule, resulting in an inactive dimer that inactivates the BCR(KEAP1) complex (PubMed:30323285).
Keap1 also known as Kelch-like ECH-associated protein 1 plays an important role in regulating the NRF2 protein. Keap1 has a molecular weight of around 70 kDa. It expresses widely throughout mammalian tissues reflecting its significance in cellular functions. As a substrate adaptor protein for the cullin-3-based E3 ubiquitin ligase complex its main function involves the promotion of NRF2 degradation. Keap1 recognizes and binds to specific motifs on NRF2 tagging it for ubiquitination and subsequent proteasomal degradation under homeostatic conditions.
Keap1 serves as a sensor for oxidative stress within the cell. It constitutes part of a larger biological complex that includes the NRF2 protein and the cullin-3-based E3 ligase complex. In the presence of oxidative or electrophilic stress modifications in Keap1 cysteine thiol groups lead to conformational changes inhibiting Keap1’s ability to target NRF2 for degradation. This results in the accumulation and activation of NRF2 which migrates to the nucleus where it promotes the expression of antioxidant response element (ARE)-driven genes important for cellular defense mechanisms.
Keap1 plays a central role in the NRF2-ARE signaling pathway a major player in the antioxidant response of cells. This pathway connects to various processes including detoxification and the regulation of oxidative stress. Keap1 interacts with other proteins such as cullin-3 which is vital for ubiquitin tagging of NRF2. Additionally Keap1 influences the WNT signaling pathway through its interactions with other proteins impacting processes related to cellular proliferation and differentiation.
Keap1 relates prominently to certain cancers and neurodegenerative diseases. Mutations or dysregulations in Keap1 or its pathway can lead to abnormal accumulation of NRF2 potentially resulting in enhanced cell survival and proliferation which is characteristic of some cancer types. Moreover Keap1 has been linked to neurodegenerative disorders like Alzheimer's disease where oxidative stress and disrupted NRF2 signaling play contributory roles. Connections within these conditions often involve proteins like NRF2 which interacts closely with Keap1 in the context of pathophysiological cellular responses.
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12.5% SDS-PAGE analysis of ab132384 stained with Coomassie Blue.
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