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Protein Page:
KEAP1 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
KEAP1 a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Has tumor suppressor activity. Retains NRF2, BPTF and PGAM5 in the cytosol. Targets NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and of antioxidant response element-mediated detoxifying enzyme gene expression. Somatic mutations of KEAP1 or NRF2 commonly occur in solid cancers, irrespective of histological type, resulting in the constitutive transcription of cytoprotective genes. Genetic disruption of the KEAP1/CUL3 E3 ubiquitin ligase complex leads to the activation of the NF-kappaB pathway in lung cancer. Alternative activation of the cytoprotective NRF2 pathway exist in the absence of mutations in KEAP1 and HRF2: WTX, PALB2, SQSTM1, and DPP3 can competitively bind KEAP1. These proteins and others that bind KEAP1 contain an ¿ETGE¿ amino acid motif, which matches the KEAP1 interaction motif found in NRF2. Binding of these ¿ETGE¿-containing proteins can displace NRF2, freeing it to translocate to the nucleus and implement its cytoprotective transcriptional pathway. The DPP3 gene is frequently overexpressed in squamous cell lung carcinomas with high wt NRF2 activity. Its expression level significantly correlates with the response rate and progression-free survival of platinum-based first-line chemotherapy. May be a useful biomarker for predicting the chemosensitivity of patients with advanced-stage NSCLC. Broadly expressed, with highest levels in skeletal muscle. Ubiquitination and subsequent degradation of PGAM5 is inhibited by oxidative stress and sulforaphane. Note: This description may include information from UniProtKB.
Protein type: Endoplasmic reticulum; Transcription regulation; Ubiquitin conjugating system; Motility/polarity/chemotaxis
Cellular Component: endoplasmic reticulum; cytoplasm; nucleolus; microtubule organizing center; midbody; nucleus
Molecular Function: protein binding
Biological Process: regulation of transcription, DNA-dependent; transcription, DNA-dependent; in utero embryonic development; proteasomal ubiquitin-independent protein catabolic process; protein ubiquitination; regulation of epidermal cell differentiation
Reference #:  Q14145 (UniProtKB)
Alt. Names/Synonyms: Cytosolic inhibitor of Nrf2; INRF2; KEAP1; Kelch-like ECH-associated protein 1; Kelch-like protein 19; KIAA0132; KLHL19; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454
Gene Symbols: KEAP1
Molecular weight: 69,666 Da
Basal Isoelectric point: Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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KEAP1

Protein Structure Not Found.


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Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 15 Y33-p GAGDAVMyASTECKA
0 1 T43-p TECKAEVtPSQHGNR
0 1 T55-p GNRTFSYtLEDHtkQ
0 1 T60-p SYtLEDHtkQAFGIM
0 2 K61-ub YtLEDHtkQAFGIMN
0 1 K84-ub CDVTLQVkYQDAPAA
1 0 Y85 DVTLQVkYQDAPAAQ
0 6 K108-ub ASSSPVFkAMFTNGL
0 5 K131-ac SIEGIHPkVMERLIE
1 0 Y141 ERLIEFAYTASISMG
0 2 T277-p AVRCHSLtPNFLQMQ
0 6 K287-ub FLQMQLQkCEILQsD
0 1 S293-p QkCEILQsDsRCKDY
0 1 S295-p CEILQsDsRCKDYLV
0 9 K312-ub FEELTLHkPTQVMPC
1 0 S599-p SEVTRMTsGRsGVGV
1 0 S602-p TRMTsGRsGVGVAVT
0 3 K615-ub VTMEPCRkQIDQQNC
  mouse

 
Y33 GAGDAVMYASTECKA
T43 TECKAEVTPSQDGNR
T55 GNRTFSYTLEDHTKQ
T60 SYTLEDHTKQAFGVM
K61 YTLEDHTKQAFGVMN
K84 CDVTLQVKyEDIPAA
Y85-p DVTLQVKyEDIPAAQ
K108 ASSSPVFKAMFTNGL
K131 SIEGIHPKVMERLIE
Y141-p ERLIEFAyTASISVG
T277 AVRCHALTPRFLQTQ
K287 FLQTQLQKCEILQAD
A293 QKCEILQADARCKDY
A295 CEILQADARCKDYLV
K312 FQELTLHKPTQAVPC
S599 SEVTRMTSGRSGVGV
S602 TRMTSGRSGVGVAVT
K615 VTMEPCRKQIDQQNC
  rat

 
Y33 GAGDAVMYASTECKA
T43 TECKAEVTPSQDGNR
T55 GNRTFSYTLEDHTKQ
T60 SYTLEDHTKQAFGIM
K61 YTLEDHTKQAFGIMN
K84 CDVTLQVKYEDIPAA
Y85 DVTLQVKYEDIPAAQ
K108 ASSSPVFKAMFTNGL
K131 SIEGIHPKVMERLIE
Y141 ERLIEFAYTASISVG
T277 AVRCHALTPRFLQTQ
K287 FLQTQLQKCEILQAD
A293 QKCEILQADARCKDY
A295 CEILQADARCKDYLV
K312 FQELTLHKPTQAVPC
S599 SEVTRLTSGRSGVGV
S602 TRLTSGRSGVGVAVT
K615 VTMEPCRKQIDQQNC
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