Recombinant Mouse Kelch-Like Ech-Associated Protein 1 (KEAP1) Protein (His-SUMO)

Name: Recombinant Mouse Kelch-Like Ech-Associated Protein 1 (KEAP1) Protein (His-SUMO)
Brand: Beta LifeScience
SKU: BLC-09506P
Availability: InStock

Greater than 90% as determined by SDS-PAGE.

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Product Overview

Description	Recombinant Mouse Kelch-Like Ech-Associated Protein 1 (KEAP1) Protein (His-SUMO) is produced by our E.coli expression system. This is a full length protein.
Purity	Greater than 90% as determined by SDS-PAGE.
Uniprotkb	Q9Z2X8
Target Symbol	KEAP1
Synonyms	Keap1; Inrf2; Kiaa0132Kelch-like ECH-associated protein 1; Cytosolic inhibitor of Nrf2; INrf2
Species	Mus musculus (Mouse)
Expression System	E.coli
Tag	N-6His-SUMO
Target Protein Sequence	MQPEPKLSGAPRSSQFLPLWSKCPEGAGDAVMYASTECKAEVTPSQDGNRTFSYTLEDHTKQAFGVMNELRLSQQLCDVTLQVKYEDIPAAQFMAHKVVLASSSPVFKAMFTNGLREQGMEVVSIEGIHPKVMERLIEFAYTASISVGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLDPSNAIGIANFAEQIGCTELHQRAREYIYMHFGEVAKQEEFFNLSHCQLATLISRDDLNVRCESEVFHACIDWVKYDCPQRRFYVQALLRAVRCHALTPRFLQTQLQKCEILQADARCKDYLVQIFQELTLHKPTQAVPCRAPKVGRLIYTAGGYFRQSLSYLEAYNPSNGSWLRLADLQVPRSGLAGCVVGGLLYAVGGRNNSPDGNTDSSALDCYNPMTNQWSPCASMSVPRNRIGVGVIDGHIYAVGGSHGCIHHSSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAVGGFDGTNRLNSAECYYPERNEWRMITPMNTIRSGAGVCVLHNCIYAAGGYDGQDQLNSVERYDVETETWTFVAPMRHHRSALGITVHQGKIYVLGGYDGHTFLDSVECYDPDSDTWSEVTRMTSGRSGVGVAVTMEPCRKQIDQQNCTC
Expression Range	1-624aa
Protein Length	Full Length
Mol. Weight	85.6kDa
Research Area	Epigenetics And Nuclear Signaling
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target 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.
Subcellular Location	Cytoplasm. Nucleus.
Database References	KEGG: mmu:50868 STRING: 10090.ENSMUSP00000062467 UniGene: Mm.248266

Gene Functions References

Nrf2/Keap1 system regulates VSMC apoptosis during neointimal formation, thereby inhibiting neointimal hyperplasia after a vascular injury. PMID: 27198574
Renal tubular deletion of Keap1 promotes nephrogenic diabetes insipidus features, confirming that Nrf2 activation in developing tubular cells causes a water reabsorption defect. PMID: 28233855
By inhibiting binding of Keap1 to Nrf2. PMID: 30021365
these studies are the first to demonstrate that Brain ischemic preconditioning protects the blood-brain barrier against ischemic injury by generation of endogenous electrophiles and activation of the Nrf2 pathway through inhibition of Keap1- and GSK3beta-dependent Nrf2 degradation. PMID: 29775963
these results suggested that trehalose can function as a novel activator of the p62-Keap1/Nrf2 pathway, in addition to inducing autophagy. Therefore, trehalose may be useful to treat many chronic diseases involving oxidative stress and dysfunction of autophagy. PMID: 29241092
While injury tended to suppress these genes in wild-type mice, the suppression was attenuated or reversed in Keap1 hypomorphs, suggesting that protection in these mice was mediated by increased Nrf2 transcriptional activity. PMID: 27804998
These findings suggest that Keap1-Nrf2 system plays a key role in depression and that dietary intake of sulforaphane-rich food during juvenile stages and adolescence can confer stress resilience in adulthood. PMID: 27470577
these results indicated that inactivation of KEAP1 protein by epigallocatechin gallate may mediate epigallocatechin gallate function in activating NRF2 PMID: 28457936
the incidence, multiplicity and burden of Cutaneous squamous cell carcinomas that form in Keap1(flox/flox)/Nrf2(-/-) mice are much greater than in their Keap1(flox/flox)/Nrf2(+/+) counterparts, establishing Nrf2 activation as the protection mediator. PMID: 27216826
The p62-keap1-Nrf2 antioxidant pathway was primarily activated in the early stage of APAP hepatotoxicity. PMID: 29331651
Keap1 deletion in renal tubular cells results in an abnormal kidney development consistent with hydronephrosis. PMID: 27484495
serine 351 phosphorylation of p62 did not enhance its binding to Keap1 or stabilise the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor in this neuronal context. Nrf2 protein levels were markedly decreased despite transcriptional activation of the Nrf2 gene PMID: 28055010
These results suggest that the Keap1/Nrf2 axis plays a critical role in NFATc1 expression and osteoclastogenic progression. PMID: 28515152
Results show that Keap1 deficiency in long-term hematopoietic stem cells increases the number of multipotent progenitor cells in steady-state hematopoiesis, and impairs their hematopoietic regeneration capacity . PMID: 28674188
During cellular stress or electrolytic imbalance, cysteine residue modification in Keap1 induces Nrf2 release from the Nrf2-Keap1 complex, which stabilizes Nrf2 and causes its nuclear translocation. PMID: 28045693
This study found that under oxidative stress induced by experimental periodontitis, the Nrf2/antioxidant defense pathway was activated and could be visualized from the luciferase activity in the in Keap1-dependent oxidative stress detector-luciferase mice model. PMID: 27854327
Caffeic acid induces Nrf2 activation by decreasing the expression of its inhibitor protein Keap1 and blocking the binding of Nrf2 with Keap1. PMID: 26721592
Hepatocyte-specific deletion of Keap1 triggering constitutive Nrf2 activation shifts hepatic metabolism towards increased lipid catabolism, reduced liponeogenesis and activation of the pentose phosphate pathway. PMID: 26698665
findings reveal that Keap1 regulates cell migration by affecting the subcellular localization and activity of cortactin independently of its role in oxidant stress responses. PMID: 26602019
chronic hyperglycemic conditions, Keap1 inhibition increased Nrf2 nuclear translocation, increased antioxidant gene expression, and reduced ROS production to normoglycemic levels. PMID: 26647385
conclusion, increased Keap1/Nrf2 signaling in the liver is accompanied by repressed gluconeogenesis and lipogenesis that can, at least partially, explain the ameliorated diabetic phenotype in the Keap1-hypo mice. PMID: 26701603
Keap1 utilizes multiple cysteine residues specifically and/or collaboratively as sensors for the detection of a wide range of environmental stresses. PMID: 26527616
iron deficiency induced the nuclear translocation of Nrf2 via Keap1 degradation by autophagy and subsequently upregulated expression of HO-1. PMID: 25754743
These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. PMID: 26282199
high-fat diet altered short-term glucose homeostasis to a greater degree in Keap-KD mice compared to C57BL/6 mice PMID: 23507082
Keap1 knockdown caused severe disruption in both the redox cycle and the cell cycle of replicating hepatocytes. PMID: 25483186
data confirm a role for GNOM in endoplasmic reticulum (ER)-Golgi trafficking and reveal that a GNL1/GNOM-mediated early secretory pathway selectively regulates PIN1 basal polarity establishment in a manner essential for normal plant development PMID: 24997191
Results implicate p62-dependent autophagic degradation of Keap1 by palmitate as a mechanism contributing to hepatocyte lipoapoptosis. PMID: 24769730
the high degree of selectivity of CDDO-me for the Nrf2:Keap1 signalling pathway. PMID: 24859727
Data indicate feedback activation of the kelch-like ECH-associated protein 1 (Keap1)-NF-E2-Related Factor 2 (Nrf2) pathway when the proteasome is impaired. PMID: 25049227
forced expression of WT mKeap1 restored the ability of oxaliplatin to activate the transcription factor. Cys(151) in Keap1 was required for the response stimulated by oxaliplatin. PMID: 24556415
Nrf2 activation by Keap1 knockdown attenuates glomerulosclerosis. These results indicate that the Nrf2-Keap1 system is a promising drug target for the treatment of chronic kidney diseases. PMID: 24523358
Keap1-Nrf2 complex prevents oxidative injury in ischemia/reperfusion-stressed orthotopic liver transplantation through Keap1 signaling, which negatively regulates Nrf2 pathway. PMID: 23867319
The bone marrow cells of Keap1-deficient mice showed enhanced granulocyte-monocyte differentiation and lower erythroid and lymphoid, suggesting granulocyte-monocyte lineage priming in Keap1-null HSCs. PMID: 24580727
Caloric restriction induced induction of fatty acid oxidation gene expression was augmented with Keap1 knockdown, which was associated with differential expression of several miRNAs implicated in fatty acid oxidation and lipid accumulation. PMID: 23884569
Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. PMID: 24011591
Silencing of Keap1 in macrophages boosts induced transcription of Il-6 via NF-kappaB activation. PMID: 23906629
the Keap1/Nrf2 axis regulates RANKL-dependent osteoclastogenesis through modulation of intracellular ROS signaling via expression of cytoprotective enzymes. PMID: 23801334
Genetic activation of Nrf2 signaling by Keap1 gene hypomorphic knockdown (Keap1flox/-) markedly suppresses the onset of diabetes. PMID: 23716596
This study assigns a novel positive role of Keap1 in upregulating p62-mediated autophagic clearance of ubiquitin aggregates. PMID: 20495340
R-alpha-lipoic acid exerts a neuroprotective effect against oxidative stress in retinal neurons in vitro and in vivo by inducing HO-1 through Keap1/Nrf2 signaling. PMID: 23295186
the Keap1-C151-dependent mechanism of Nrf2 activation is protective, while p62-mediated activation or somatic mutations leading to persistent or prolonged Nrf2 activation comprise the side of Nrf2 that is expected to promote tumor growth and survival. PMID: 23589329
The Keap1-Nrf2 system regulates an important defense mechanism against upper aerodigestive tract carcinogenesis. PMID: 23250896
study discovered that the Nrf2/Keap1 pathway detects loss of loricrin and directly upregulates the expression of genes involved in the compensatory response, thus ensuring postnatal survival PMID: 23237955
HFD-induced obesity and lipid accumulation in white adipose tissue was decreased in Keap1-KD mice PMID: 22936178
The autophagy pathway maintains the integrity of the Keap1-Nrf2 system for the normal liver function by governing the Keap1 turnover PMID: 22872865
Morphological changes of the esophageal epithelium are associated with dynamic changes in gene expression. Nrf2/Keap1 pathway activity is required for maturation of mouse esophageal epithelium. PMID: 22567161
Activation of endogenous intracellular levels of Nrf2 by siRNA knockdown of Keap1 is sufficient to protect in models of oxidative stress and Parkinson's disease. PMID: 22342405
The p62-Nrf2-Nqo1 cascade functions to assure mammalian longevity by stabilizing mitochondrial integrity. PMID: 22222206
Induction of antioxidative stress protein keap1 after cerebral ischemia may play an important endogenous neuroprotective response. PMID: 21075092

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