UniProtKB - P57790 (KEAP1_RAT)
Kelch-like ECH-associated protein 1
Keap1
Functioni
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 (By similarity).
The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome (By similarity).
By similarityActivity regulationi
: protein ubiquitination Pathwayi
This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.By similarityView all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 151 | Sensor for electrophilic agentsBy similarity | 1 | |
Sitei | 257 | Sensor for electrophilic agentsBy similarity | 1 | |
Sitei | 273 | Sensor for electrophilic agentsBy similarity | 1 | |
Sitei | 288 | Sensor for electrophilic agentsBy similarity | 1 | |
Sitei | 434 | Sensor for electrophilic agentsBy similarity | 1 |
GO - Molecular functioni
- disordered domain specific binding Source: RGD
- identical protein binding Source: RGD
GO - Biological processi
- cellular response to carbohydrate stimulus Source: RGD
- cellular response to interleukin-4 Source: RGD
- cellular response to organic cyclic compound Source: RGD
- cellular response to oxidative stress Source: UniProtKB
- cytoplasmic sequestering of transcription factor Source: RGD
- in utero embryonic development Source: RGD
- negative regulation of gene expression Source: RGD
- protein ubiquitination Source: UniProtKB
- regulation of autophagy Source: UniProtKB
- regulation of epidermal cell differentiation Source: RGD
- regulation of transcription, DNA-templated Source: RGD
- response to immobilization stress Source: RGD
- response to metal ion Source: RGD
- response to thyroid hormone Source: RGD
- selenium compound metabolic process Source: RGD
- ubiquitin-dependent protein catabolic process Source: UniProtKB
Keywordsi
Biological process | Ubl conjugation pathway |
Enzyme and pathway databases
Reactomei | R-RNO-5689880, Ub-specific processing proteases R-RNO-8932339, ROS sensing by NFE2L2 R-RNO-8951664, Neddylation R-RNO-983168, Antigen processing: Ubiquitination & Proteasome degradation |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: Kelch-like ECH-associated protein 1Alternative name(s): Cytosolic inhibitor of Nrf21 Publication Short name: INrf21 Publication |
Gene namesi | |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 621619, Keap1 |
Subcellular locationi
Cytoskeleton
- actin filament Source: RGD
Endoplasmic reticulum
- endoplasmic reticulum Source: RGD
Nucleus
- nucleus Source: RGD
Other locations
- adherens junction Source: RGD
- Cul3-RING ubiquitin ligase complex Source: UniProtKB
- cytoplasm Source: RGD
- focal adhesion Source: RGD
- inclusion body Source: UniProtKB
- midbody Source: RGD
- protein-containing complex Source: RGD
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000119095 | 1 – 624 | Kelch-like ECH-associated protein 1Add BLAST | 624 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 38 | S-(2-succinyl)cysteineBy similarity | 1 | |
Cross-linki | 135 | N5-[4-(S-L-cysteinyl)-5-methyl-1H-imidazol-2-yl]-L-ornithine (Arg-Cys) (interchain with C-151 in KEAP1)By similarity | ||
Modified residuei | 151 | S-(2,3-dicarboxypropyl)cysteine; alternateBy similarity | 1 | |
Modified residuei | 151 | S-(2-succinyl)cysteineBy similarity | 1 | |
Modified residuei | 151 | S-nitrosocysteine; alternateBy similarity | 1 | |
Cross-linki | 151 | N5-[4-(S-L-cysteinyl)-5-methyl-1H-imidazol-2-yl]-L-ornithine (Cys-Arg) (interchain with R-135 in KEAP1)By similarity | ||
Modified residuei | 241 | S-(2-succinyl)cysteineBy similarity | 1 | |
Modified residuei | 257 | S-(2,3-dicarboxypropyl)cysteineBy similarity | 1 | |
Modified residuei | 273 | S-(2,3-dicarboxypropyl)cysteineBy similarity | 1 | |
Modified residuei | 288 | S-(2,3-dicarboxypropyl)cysteine; alternateBy similarity | 1 | |
Modified residuei | 288 | S-(2-succinyl)cysteineBy similarity | 1 | |
Modified residuei | 319 | S-(2-succinyl)cysteineBy similarity | 1 | |
Modified residuei | 434 | S-cGMP-cysteineBy similarity | 1 | |
Modified residuei | 613 | S-(2-succinyl)cysteineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
S-nitrosylation, Thioether bond, Ubl conjugationProteomic databases
PaxDbi | P57790 |
PRIDEi | P57790 |
PTM databases
iPTMneti | P57790 |
PhosphoSitePlusi | P57790 |
Interactioni
Subunit structurei
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 (By similarity).
Forms a ternary complex with NFE2L2/NRF2 and PGAM5 (By similarity).
Interacts with (phosphorylated) SQSTM1/p62; the interaction is direct and inactivates the BCR(KEAP1) complex by sequestering it in inclusion bodies, promoting its degradation (By similarity).
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 (By similarity).
By similarityGO - Molecular functioni
- disordered domain specific binding Source: RGD
- identical protein binding Source: RGD
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000028360 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 77 – 149 | BTBPROSITE-ProRule annotationAdd BLAST | 73 | |
Domaini | 184 – 286 | BACKAdd BLAST | 103 | |
Repeati | 327 – 372 | Kelch 1Add BLAST | 46 | |
Repeati | 373 – 423 | Kelch 2Add BLAST | 51 | |
Repeati | 424 – 470 | Kelch 3Add BLAST | 47 | |
Repeati | 471 – 517 | Kelch 4Add BLAST | 47 | |
Repeati | 519 – 564 | Kelch 5Add BLAST | 46 | |
Repeati | 565 – 611 | Kelch 6Add BLAST | 47 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Kelch repeat, RepeatPhylogenomic databases
eggNOGi | KOG4441, Eukaryota |
InParanoidi | P57790 |
PhylomeDBi | P57790 |
Family and domain databases
Gene3Di | 2.120.10.80, 1 hit 3.30.710.10, 1 hit |
InterProi | View protein in InterPro IPR011705, BACK IPR017096, BTB-kelch_protein IPR000210, BTB/POZ_dom IPR030563, KEAP1 IPR015915, Kelch-typ_b-propeller IPR006652, Kelch_1 IPR011333, SKP1/BTB/POZ_sf |
PANTHERi | PTHR24412:SF162, PTHR24412:SF162, 1 hit |
Pfami | View protein in Pfam PF07707, BACK, 1 hit PF00651, BTB, 1 hit PF01344, Kelch_1, 6 hits |
PIRSFi | PIRSF037037, Kelch-like_protein_gigaxonin, 1 hit |
SMARTi | View protein in SMART SM00875, BACK, 1 hit SM00225, BTB, 1 hit SM00612, Kelch, 6 hits |
SUPFAMi | SSF117281, SSF117281, 1 hit SSF54695, SSF54695, 1 hit |
PROSITEi | View protein in PROSITE PS50097, BTB, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MQPEPKPSGA PRSSQFLPLW SKCPEGAGDA VMYASTECKA EVTPSQDGNR
60 70 80 90 100
TFSYTLEDHT KQAFGIMNEL RLSQQLCDVT LQVKYEDIPA AQFMAHKVVL
110 120 130 140 150
ASSSPVFKAM FTNGLREQGM EVVSIEGIHP KVMERLIEFA YTASISVGEK
160 170 180 190 200
CVLHVMNGAV MYQIDSVVRA CSDFLVQQLD PSNAIGIANF AEQIGCTELH
210 220 230 240 250
QRAREYIYMH FGEVAKQEEF FNLSHCQLAT LISRDDLNVR CESEVFHACI
260 270 280 290 300
DWVKYDCPQR RFYVQALLRA VRCHALTPRF LQTQLQKCEI LQADARCKDY
310 320 330 340 350
LVQIFQELTL HKPTQAVPCR APKVGRLIYT AGGYFRQSLS YLEAYNPSNG
360 370 380 390 400
SWLRLADLQV PRSGLAGCVV GGLLYAVGGR NNSPDGNTDS SALDCYNPMT
410 420 430 440 450
NQWSPCASLS VPRNRSGGGV IDGHIYAVGG SHGCIHHSSV ERYEPDRDEW
460 470 480 490 500
HLVAPMLTRR IGVGVAVLNR LLYAVGGFDG TNRLNSAECY YPERNEWRMI
510 520 530 540 550
TPMNTIRSGA GVCVLHSCIY AAGGYDGQDQ LNSVERYDVE TETWTFVASM
560 570 580 590 600
KHRRSALGIA VHQGRIYVLG GYDGHTFLDS VECYDPDTDT WSEVTRLTSG
610 620
RSGVGVAVTM EPCRKQIDQQ NCTC
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketG3V8U2 | G3V8U2_RAT | Kelch-like ECH-associated protein 1 | Keap1 | 620 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF304364 mRNA Translation: AAG16275.1 |
Genome annotation databases
UCSCi | RGD:621619, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF304364 mRNA Translation: AAG16275.1 |
3D structure databases
SMRi | P57790 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000028360 |
Chemistry databases
ChEMBLi | CHEMBL4523596 |
PTM databases
iPTMneti | P57790 |
PhosphoSitePlusi | P57790 |
Proteomic databases
PaxDbi | P57790 |
PRIDEi | P57790 |
Genome annotation databases
UCSCi | RGD:621619, rat |
Organism-specific databases
RGDi | 621619, Keap1 |
Phylogenomic databases
eggNOGi | KOG4441, Eukaryota |
InParanoidi | P57790 |
PhylomeDBi | P57790 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
Reactomei | R-RNO-5689880, Ub-specific processing proteases R-RNO-8932339, ROS sensing by NFE2L2 R-RNO-8951664, Neddylation R-RNO-983168, Antigen processing: Ubiquitination & Proteasome degradation |
Miscellaneous databases
PROi | PR:P57790 |
Family and domain databases
Gene3Di | 2.120.10.80, 1 hit 3.30.710.10, 1 hit |
InterProi | View protein in InterPro IPR011705, BACK IPR017096, BTB-kelch_protein IPR000210, BTB/POZ_dom IPR030563, KEAP1 IPR015915, Kelch-typ_b-propeller IPR006652, Kelch_1 IPR011333, SKP1/BTB/POZ_sf |
PANTHERi | PTHR24412:SF162, PTHR24412:SF162, 1 hit |
Pfami | View protein in Pfam PF07707, BACK, 1 hit PF00651, BTB, 1 hit PF01344, Kelch_1, 6 hits |
PIRSFi | PIRSF037037, Kelch-like_protein_gigaxonin, 1 hit |
SMARTi | View protein in SMART SM00875, BACK, 1 hit SM00225, BTB, 1 hit SM00612, Kelch, 6 hits |
SUPFAMi | SSF117281, SSF117281, 1 hit SSF54695, SSF54695, 1 hit |
PROSITEi | View protein in PROSITE PS50097, BTB, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | KEAP1_RAT | |
Accessioni | P57790Primary (citable) accession number: P57790 Secondary accession number(s): Q9ERI3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 27, 2001 |
Last sequence update: | April 27, 2001 | |
Last modified: | September 29, 2021 | |
This is version 140 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families