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

Name: Recombinant Human Kelch-Like Ech-Associated Protein 1 (KEAP1) Protein (His)
Brand: Beta LifeScience
SKU: BLC-10459P
Availability: InStock

Greater than 90% as determined by SDS-PAGE.

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Product Overview

Description	Recombinant Human Kelch-Like Ech-Associated Protein 1 (KEAP1) Protein (His) is produced by our Yeast expression system. This is a full length protein.
Purity	Greater than 90% as determined by SDS-PAGE.
Uniprotkb	Q14145
Target Symbol	KEAP1
Synonyms	Cytosolic inhibitor of Nrf2; INrf 2; INrf2; Keap 1; KEAP1; KEAP1_HUMAN; Kelch like ECH associated protein 1; Kelch like family member 19; Kelch like protein 19 ; Kelch-like ECH-associated protein 1; Kelch-like protein 19; KIAA0132; KLHL 19; KLHL19; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454
Species	Homo sapiens (Human)
Expression System	Yeast
Tag	N-6His
Target Protein Sequence	MQPDPRPSGAGACCRFLPLQSQCPEGAGDAVMYASTECKAEVTPSQHGNRTFSYTLEDHTKQAFGIMNELRLSQQLCDVTLQVKYQDAPAAQFMAHKVVLASSSPVFKAMFTNGLREQGMEVVSIEGIHPKVMERLIEFAYTASISMGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLDPSNAIGIANFAEQIGCVELHQRAREYIYMHFGEVAKQEEFFNLSHCQLVTLISRDDLNVRCESEVFHACINWVKYDCEQRRFYVQALLRAVRCHSLTPNFLQMQLQKCEILQSDSRCKDYLVKIFEELTLHKPTQVMPCRAPKVGRLIYTAGGYFRQSLSYLEAYNPSDGTWLRLADLQVPRSGLAGCVVGGLLYAVGGRNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGVIDGHIYAVGGSHGCIHHNSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAVGGFDGTNRLNSAECYYPERNEWRMITAMNTIRSGAGVCVLHNCIYAAGGYDGQDQLNSVERYDVETETWTFVAPMKHRRSALGITVHQGRIYVLGGYDGHTFLDSVECYDPDTDTWSEVTRMTSGRSGVGVAVTMEPCRKQIDQQNCTC
Expression Range	1-624aa
Protein Length	Full Length
Mol. Weight	71.7kDa
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	HGNC: 23177 OMIM: 606016 KEGG: hsa:9817 STRING: 9606.ENSP00000171111 UniGene: PMID: 29717933 the ability of porphyra-334 and shinorine to dissociate Nrf2 from Keap1 was confirmed also by measurement of increased mRNA expression of Nrf2 targeted genes encoding oxidative stress defense proteins in primary skin fibroblasts prior and post UVR exposure. PMID: 30071261 Aberrant Nrf2/Keap1 system integrity may affect self-defence mechanisms against oxidative stress in primary biliary cholangitis. PMID: 28333129 this study shows changes of KEAP1 expression levels induced by cell-free DNA in different cell types PMID: 29743966 Here we present a proof-of-concept application for the rational design of an epitope-specific antibody binding with the target protein Keap1, by grafting pre-defined structural interaction patterns from the native binding partner protein, Nrf2, onto geometrically matched positions of a set of antibody scaffolds. The designed antibodies bind to Keap1 and block the Keap1-Nrf2 interaction in an epitope-specific way PMID: 28128368 In the present review we briefly introduce the Nrf2-Keap1 system and describe Nrf2 functions, illustrate the Nrf2-NF-kappaB cross-talk, and highlight the effects of the Nrf2-Keap1 system in the physiology and pathophysiology of striated muscle tissue taking into account its role(s) in oxidative stress and reductive stress PMID: 29499228 Results show that KEAP1 expression in esophageal squamous cell carcinoma is regulated by miR-432-3p that binds directly its 3'UTR. PMID: 28760781 An intact complex of PGAM5-KEAP1-Nrf2 preserves mitochondrial motility by suppressing dominant-negative KEAP1 activity. PMID: 28839075 Hydrogen sulfide attenuates vascular smooth muscle cell calcification in vitro via the KEAP1-NRF2 redox sensing/stress response system by enhancing NQO1 expression. PMID: 28865326 Keap1 silencing in melanocytes induced melanogenesis and the expression of melanogenesis-associated molecules through HO-1-associated beta-catenin activation. Keap1 downregulation in melanocytes is important for cell proliferation and survival. PMID: 28583303 itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities PMID: 29590092 results demonstrate a multifaceted protective potential of KEAP1-NRF2 signaling in key cell types relevant to Huntington disease pathology PMID: 28533375 Curcumin Protects Skin against UVB-Induced Cytotoxicity via the Keap1-Nrf2 Pathway: The Use of a Microemulsion Delivery System. PMID: 28757910 The research demonstrated that Keap1 should be a promising E3 ligase adaptor to be used in the design of novel PROTACs. PMID: 29407955 High cytoplasmic Keap1 expression, which might prevent nuclear translocation of Nrf2 in ovarian cancer cells, was associated with lower disease recurrence and death rate. PMID: 28129239 The ratio of thioredoxin/Keap1 protein level may be useful for suggesting distant metastasis in colorectal cancer. PMID: 29053012 our study pinpoints that PAQR3 functions as an adaptor protein to promote Nrf2-Keap1 complex formation, thereby modulating the Nrf2-Keap2 pathway and playing an important role in controlling antioxidant response of the cell PMID: 27212020 provide a rationale for stratification of human patients with lung cancer harboring KRAS/KEAP1- or KRAS/NRF2-mutant lung tumors as likely to respond to glutaminase inhibition PMID: 28967920 Our results identified ECG as a novel Keap1-Nrf2 interaction disruptor and LPS-induced TLR4 activation inhibitor, thereby providing an innovative strategy to prevent or treat immune, oxidative stress and inflammatory-related diseases PMID: 26878775 The Keap-1/Nrf2 redox system is a biological target of SSNO. PMID: 27663261 Molecular docking studies revealed that Wogonin can disrupt KEAP-1/Nrf-2 interaction by directly blocking the binding site of Nrf-2 in the KEAP-1 protein. The study provides novel insights into the development of Nrf2 as a promising candidate and Wogonin as a therapeutic agent for the management of Osteoarthritis . PMID: 28237856 Data show that genistein induced re-expression of the methylated Keap1 genes through demethylation in A549 cells, however, no Keap1 mRNA expression changes were detected in MRC-5 fibroblast cells. PMID: 27029077 Punicalagin protects HepG2 cells from lipotoxicity induced by free fatty acids through activating Nrf2/Keap1 pathway. PMID: 26989875 Data suggest that Keap1, rather than Nrf2, is critical for the recruitment of iASPP into the Keap1-Nrf2 complex PMID: 29033244 The modification of NRF2 or KEAP1 expression in non-small cell lung cancer cell lines disrupted downstream gene expression and cell sensitivity to platinum-based drugs. PMID: 27601007 These data demonstrate that the beneficial properties of SFN extend beyond activation of the KEAP1-Nrf2-ARE system and warrant further interrogation given the current use of this agent in multiple clinical trials PMID: 27889639 Result showed that there was a significant association between Keap1 and phosphorylated (p) Nrf2 expression in hepatocellular carcinoma. Higher pNrf2 expression was more likely observed in those specimens with reduced Keap1 expression. PMID: 27650414 Results provide evidence for a critical role of mutations in TP53 and KEAP1 during lung squamous cell carcinoma (LSCC oncogenesis, because deletion of either gene leads to increased self-renewal of airway basal stem cells. Also, KEAP1/NRF2 mutations increase radioresistance and predict local tumor recurrence in radiotherapy treated LSCC patients. PMID: 27663899 Study showed that Sequestosome 1-mediated sequestration of Keap1 is associated with chronic activation of the Nrf2 stress response pathway in the autophagic vacuolar myopathie muscle; demonstrated that Nrf2 signaling is upregulated in autophagic muscle disorders and raise the possibility that autophagy disruption in skeletal muscle leads to dysregulation of cellular redox homeostasis. PMID: 27799074 Keap1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of Cullin 3-based E3 ubiquitin ligase. Keap1 regulates the activity of Nrf2 and acts as a sensor for oxidative and electrophilic stresses. PMID: 28842501 NRF2 is regulated at protein level by proteasomal degradation via KEAP1. Data suggest that antioxidant-induced up-regulation of NRF2 expression (a) overcomes KEAP1 regulation, (b) activates NRF2 translocation to nucleus, and (c) activates antioxidant response element. (NRF2 = nuclear factor [erythroid-derived 2]-like 2 protein; KEAP1 = Kelch-like ECH-associated protein 1) PMID: 28684421 Results indicate that microRNA miR-141 targets kelch like ECH associated protein 1 (Keap1) to activate NF-E2-related factor 2 (Nrf2) signaling, which protects retinal pigment epithelium cells (RPEs) and retinal ganglion cells (RGCs) from UV radiation. PMID: 28061435 Data indicate the role of kelch like ECH associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2) axis deregulation with potential new function as independent epigenetic prognostic marker in renal cell carcinoma. PMID: 28061437 clinical cholangiocarcinoma samples displayed FoxO3-Keap1 down-regulation and Nrf2 hyperactivation PMID: 26857210 the dual role of nuclear factor-erythroid 2 signaling in induction of colorectal cancer cell survival and death as well as the possibility of targeting nuclear factor-erythroid 2-kelch-like ECH-associated protein 1 axis as an advanced strategy in prevention and effective treatment of colorectal cancer patients have been discussed. PMID: 28621229 Using a combination of biochemical and mass spectrometry studies, the authors show that VP24 is a dimer in solution that directly binds to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) to regulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). PMID: 27497688 These data establish new functions for KEAP1 within the nucleus and identify MCM3 as a novel substrate of the KEAP1-CUL3-RBX1 E3 ligase. PMID: 27621311 ur results identify WDR23 as an alternative regulator of NRF2 proteostasis and uncover a cellular pathway that regulates NRF2 activity and capacity for cytoprotection independently of KEAP1. PMID: 28453520 Keap1 orchestrates the antioxidant response; the system can be targeted for therapy [review] PMID: 27769838 Keap1 is the main negative regulator of Nrf2 [review] PMID: 27497696 Results show that GSTP potentiates S-glutathionylation of Keap1, which leads to Nrf2 activation and subsequently increases expression of GSTP. This positive feedback regulatory loop represents a novel mechanism by which GSTP elicits antioxidant protection in the brain. PMID: 27086966 EMT signalling and the KEAP1/NFE2L2-axis are likely to be involved in metastatic spread of malignant melanoma and also appear to have potential interactions. PMID: 27170270 the expression of NRF2, KEAP1, NQO-1 and HO-1 are increased significantly in advanced laryngeal squamous cell carcinoma, compared with the adjacent normal mucosa. Remarkable relevance exists between high expression of KEAP1, NQO-1, HO-1 and nuclear NRF2. their expression levels were independent of age, tumor stage (clinical stage III and IV), tumor size and lymph node metastasis. PMID: 27840932 miR-200a was found to interact with the 3'-untranslated region of Keap1, the native regulator of Nrf2. PMID: 27573160 We present the case that chemoprevention through the Keap1/Nrf2 system may be context dependent and that the Nrf2 "dose-response curve" for electrophilic and redox balance may not be monotonic. PMID: 27806574 Immunohistochemical assays were used to measure the expression of Keap1 protein in breast cancer tissue and adjacent normal tissue, and its clinical significance was explored. We observed that 24.6% breast cancer tissue samples were positive for Keap1, a significantly lower proportion than that seen with adjacent normal tissue specimens PMID: 27323010 c-myc plays a key role in MBD1 mediated epigenetic silencing of KEAP1. PMID: 26980696 Results show up-regulation of TrkB and down-regulation of Runx3 and Keap1 in breast cancer cells and suggest that TrkB plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of Runx3 or Keap1. PMID: 26657794 Inhibition of NRF2 by KEAP1 overexpression compromises metabolic reprogramming of fibroblasts and results in reduced efficiency of induced pluripotent stem cells colony formation. PMID: 26904936 Induction of GSH-related genes xCT and GCLM were oxygen and Bach1-insensitive during long-term culture under 5% O2, providing the first evidence that genes related to GSH synthesis mediate protection afforded by Nrf2-Keap1 defense pathway PMID: 26698668

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Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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

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

Product Overview

Target Details

FAQs