Product: KEAP1 Antibody
Catalog: BF0010
Description: Mouse monoclonal antibody to KEAP1
Application: WB IHC ELISA FACS
Reactivity: Human
Mol.Wt.: 69.7kDa; 70kD(Calculated).
Uniprot: Q14145
RRID: AB_2834071

View similar products>>

   Size Price Inventory
 50ul $250 In stock
 100ul $350 In stock
 200ul $450 In stock

Lead Time: Same day delivery

For pricing and ordering contact:
Local distributors

Product Info

Source:
Mouse
Application:
ELISA 1:10000, WB 1:500-1:2000, IHC 1:200-1:1000, FCM 1:200-1:400
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human
Clonality:
Monoclonal [AFB2049]
Specificity:
KEAP1 antibody detects endogenous levels of total KEAP1.
RRID:
AB_2834071
Cite Format: Affinity Biosciences Cat# BF0010, RRID:AB_2834071.
Conjugate:
Unconjugated.
Purification:
Affinity-chromatography.
Storage:
Mouse IgG1 in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

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;

Immunogens

Immunogen:

Purified recombinant fragment of human KEAP1 expressed in E. Coli.

Uniprot:
Gene(ID):
Expression:
Q14145 KEAP1_HUMAN:

Broadly expressed, with highest levels in skeletal muscle.

Description:
This gene encodes a protein containing KELCH-1 like domains, as well as a BTB/POZ domain. Kelch-like ECH-associated protein 1 interacts with NF-E2-related factor 2 in a redox-sensitive manner and the dissociation of the proteins in the cytoplasm is followed by transportation of NF-E2-related factor 2 to the nucleus. This interaction results in the expression of the catalytic subunit of gamma-glutamylcysteine synthetase. Two alternatively spliced transcript variants encoding the same isoform have been found for this gene.
Sequence:
MQPDPRPSGAGACCRFLPLQSQCPEGAGDAVMYASTECKAEVTPSQHGNRTFSYTLEDHTKQAFGIMNELRLSQQLCDVTLQVKYQDAPAAQFMAHKVVLASSSPVFKAMFTNGLREQGMEVVSIEGIHPKVMERLIEFAYTASISMGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLDPSNAIGIANFAEQIGCVELHQRAREYIYMHFGEVAKQEEFFNLSHCQLVTLISRDDLNVRCESEVFHACINWVKYDCEQRRFYVQALLRAVRCHSLTPNFLQMQLQKCEILQSDSRCKDYLVKIFEELTLHKPTQVMPCRAPKVGRLIYTAGGYFRQSLSYLEAYNPSDGTWLRLADLQVPRSGLAGCVVGGLLYAVGGRNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGVIDGHIYAVGGSHGCIHHNSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAVGGFDGTNRLNSAECYYPERNEWRMITAMNTIRSGAGVCVLHNCIYAAGGYDGQDQLNSVERYDVETETWTFVAPMKHRRSALGITVHQGRIYVLGGYDGHTFLDSVECYDPDTDTWSEVTRMTSGRSGVGVAVTMEPCRKQIDQQNCTC

PTMs - Q14145 As Substrate

Site PTM Type Enzyme
Ubiquitination
Y33 Phosphorylation
K39 Ubiquitination
T43 Phosphorylation
Y54 Phosphorylation
T55 Phosphorylation
T60 Phosphorylation
K61 Ubiquitination
K84 Ubiquitination
Y85 Phosphorylation
K97 Ubiquitination
K108 Ubiquitination
T112 Phosphorylation
K131 Acetylation
Y141 Phosphorylation
C273 S-Nitrosylation
T277 Phosphorylation
K287 Ubiquitination
C288 S-Nitrosylation
S293 Phosphorylation
S295 Phosphorylation
K298 Ubiquitination
K312 Ubiquitination
S599 Phosphorylation Q02156 (PRKCE)
S602 Phosphorylation Q02156 (PRKCE)
K615 Ubiquitination

Research Backgrounds

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.

PTMs:

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 (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. 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.

Subcellular Location:

Cytoplasm. Nucleus.
Note: Mainly cytoplasmic (PubMed:15601839). In response to selective autophagy, relocalizes to inclusion bodies following interaction with SQSTM1/p62 (PubMed:20452972).

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Broadly expressed, with highest levels in skeletal muscle.

Subunit Structure:

Component of the BCR(KEAP1) E3 ubiquitin ligase complex, at least composed of 2 molecules of CUL3, 2 molecules of KEAP1, and RBX1. Interacts with NFE2L2/NRF2; the interaction is direct. Forms a ternary complex with NFE2L2/NRF2 and PGAM5. Interacts with (phosphorylated) SQSTM1/p62; the interaction is direct and inactivates the BCR(KEAP1) complex by sequestering it in inclusion bodies, promoting its degradation. Interacts with NFE2L1. Interacts with BPTF and PTMA. Interacts with MAP1LC3B. Interacts indirectly with ENC1. Interacts with SESN1 and SESN2. Interacts with HSP90AA1 and HSP90AB1.

(Microbial infection) Interacts with ebolavirus protein VP24; this interaction activates transcription factor NFE2L2/NRF2 by blocking its interaction with KEAP1.

Family&Domains:

KEAP1 contains reactive cysteine residues that act as sensors for endogenously produced and exogenously encountered small molecules, which react with sulfhydryl groups and modify the cysteine sensors, leading to impair ability of the BCR(KEAP1) complex to ubiquitinate target proteins.

The Kelch repeats mediate interaction with NFE2L2/NRF2, BPTF and PGAM5.

Belongs to the KEAP1 family.

Research Fields

· Genetic Information Processing > Folding, sorting and degradation > Ubiquitin mediated proteolysis.   (View pathway)

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

References

1). Sodium Danshensu Cream Promotes the Healing of Pressure Ulcers in Mice through the Nrf2/HO-1 and NF-κB Pathways. Pharmaceuticals (PubMed: 36558999) [IF=4.6]

Application: WB    Species: Mouse    Sample:

Figure 6. Effect of SDSS on the protein levels of the Nrf2/HO-1 pathway (n = 5). (A) Western blot; the protein expression levels of Keap1 (B), Nrf2 (C), HO-1 (D), NQO1 (E), and GCLM (F) levels. * p < 0.05, ** p < 0.01 when compared to the control group. # p < 0.05, ## p < 0.01 when compared to the positive group.

Restrictive clause

 

Affinity Biosciences tests all products strictly. Citations are provided as a resource for additional applications that have not been validated by Affinity Biosciences. Please choose the appropriate format for each application and consult Materials and Methods sections for additional details about the use of any product in these publications.

For Research Use Only.
Not for use in diagnostic or therapeutic procedures. Not for resale. Not for distribution without written consent. Affinity Biosciences will not be held responsible for patent infringement or other violations that may occur with the use of our products. Affinity Biosciences, Affinity Biosciences Logo and all other trademarks are the property of Affinity Biosciences LTD.