Host: | Rabbit |
Applications: | WB/IF/ICC/ELISA |
Reactivity: | Human/Mouse/Rat |
Note: | STRICTLY FOR FURTHER SCIENTIFIC RESEARCH USE ONLY (RUO). MUST NOT TO BE USED IN DIAGNOSTIC OR THERAPEUTIC APPLICATIONS. |
Clonality : | Polyclonal |
Conjugation: | Unconjugated |
Isotype: | IgG |
Formulation: | PBS with 0.09% Sodium Azide, 50% Glycerol, pH 7.3. |
Purification: | Affinity purification |
Concentration: | Lot specific |
Dilution Range: | WB:1:500-1:1000 IF/ICC:1:50-1:200 ELISA:Recommended starting concentration is 1 Mu g/mL. Please optimize the concentration based on your specific assay requirements. |
Storage Instruction: | Store at-20°C for up to 1 year from the date of receipt, and avoid repeat freeze-thaw cycles. |
Gene Symbol: | KEAP1 |
Gene ID: | 9817 |
Uniprot ID: | KEAP1_HUMAN |
Immunogen Region: | 320-510 |
Specificity: | A synthetic peptide corresponding to a sequence within amino acids 320-510 of human KEAP1 (NP_036421.2). |
Immunogen Sequence: | RAPKVGRLIYTAGGYFRQSL SYLEAYNPSDGTWLRLADLQ VPRSGLAGCVVGGLLYAVGG RNNSPDGNTDSSALDCYNPM TNQWSPCAPMSVPRNRIGVG VIDGHIYAVGGSHGCIHHNS VERYEPERDEWHLVAPMLTR RIGVGVAVLNRLLYAVGGFD GTNRLNSAECYYPERNEWRM ITAMNTIRSGA |
Tissue Specificity | Broadly expressed, with highest levels in skeletal muscle. |
Post Translational Modifications | Non-enzymatic covalent modifications of reactive cysteines by electrophile metabolites inactivate the BCR(KEAP1) complex. 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. Nitric oxide-dependent 8-Nitro-cGMP formation promotes cysteine guanylation (S-cGMP-cysteine), leading to NFE2L2/NRF2 nuclear accumulation and activation. Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates cysteines, activating NFE2L2/NRF2. 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. Degraded via a proteasomal-independent process during selective autophagy: interaction with phosphorylated SQSTM1/p62 sequesters KEAP1 in inclusion bodies, leading to its degradation. Auto-ubiquitinated by the BCR(KEAP1) complex. Quinone-induced oxidative stress, but not sulforaphane, increases its ubiquitination. Ubiquitination and subsequent degradation is most pronounced following prolonged exposure of cells to oxidative stress, particularly in glutathione-deficient cells that are highly susceptible to oxidative stress. Deubiquitinated by USP25.leading to stabilization. |
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. |
Protein Name | Kelch-Like Ech-Associated Protein 1 Cytosolic Inhibitor Of Nrf2 Inrf2 Kelch-Like Protein 19 |
Database Links | Reactome: R-HSA-5689880 Reactome: R-HSA-8951664 Reactome: R-HSA-9679191 Reactome: R-HSA-9755511 Reactome: R-HSA-9759194 Reactome: R-HSA-983168 |
Cellular Localisation | Cytoplasm Nucleus Mainly Cytoplasmic In Response To Selective Autophagy Relocalizes To Inclusion Bodies Following Interaction With Sqstm1/P62 |
Alternative Antibody Names | Anti-Kelch-Like Ech-Associated Protein 1 antibody Anti-Cytosolic Inhibitor Of Nrf2 antibody Anti-Inrf2 antibody Anti-Kelch-Like Protein 19 antibody Anti-KEAP1 antibody Anti-INRF2 antibody Anti-KIAA0132 antibody Anti-KLHL19 antibody |
Information sourced from Uniprot.org