| Applications: |
Immunodepletion/Immunocompetition |
| Note: |
STRICTLY FOR FURTHER SCIENTIFIC RESEARCH USE ONLY (RUO). MUST NOT TO BE USED IN DIAGNOSTIC OR THERAPEUTIC APPLICATIONS. |
| Short Description: |
Keap1 Blocking Peptide for STJ506354 is synthetically produced from the 500-550 sequence and is suitable for use in western blot applications. |
| Formulation: |
Liquid form at 2.5mg/ml concentration in PBS. Up to 5% DMSO can be added. Orders with >1mg can be supplied in lyophilized powder form, or in buffer of choice. |
| Storage Instruction: |
Store at-20°C for long term storage. Avoid freeze-thaw cycles. |
| Gene Symbol: |
KEAP1 |
| Gene ID: |
9817 |
| Uniprot ID: |
KEAP1_HUMAN |
| Immunogen Region: |
500-550 |
| Specificity: |
This blocking peptide is recommended for use in combination with Keap1 antibody, STJ506354 |
| 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. |
| 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. |
| Peptide Name | Kelch-Like Ech-Associated Protein 1Cytosolic Inhibitor Of Nrf2Inrf2Kelch-Like Protein 19 |
| Database Links | Reactome: R-HSA-5689880Reactome: R-HSA-8951664Reactome: R-HSA-9679191Reactome: R-HSA-9755511Reactome: R-HSA-983168 |
| Cellular Localisation | CytoplasmNucleusMainly CytoplasmicIn Response To Selective AutophagyRelocalizes To Inclusion Bodies Following Interaction With Sqstm1/P62 |
| Alternative Peptide Names | Kelch-Like Ech-Associated Protein 1 proteinCytosolic Inhibitor Of Nrf2 proteinInrf2 proteinKelch-Like Protein 19 proteinKEAP1 proteinINRF2 proteinKIAA0132 proteinKLHL19 protein |
Information sourced from Uniprot.org
12 months for antibodies. 6 months for ELISA Kits. Please see website T&Cs for further guidance
