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Protein

Kelch-like ECH-associated protein 1

Gene

Keap1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome (By similarity).By similarity2 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-5689880. Ub-specific processing proteases.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Kelch-like ECH-associated protein 1
Alternative name(s):
Cytosolic inhibitor of Nrf2
Short name:
INrf2
Gene namesi
Name:Keap1
Synonyms:Inrf2, Kiaa0132
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1858732. Keap1.

Subcellular locationi

GO - Cellular componenti

  • actin filament Source: CACAO
  • Cul3-RING ubiquitin ligase complex Source: UniProtKB
  • cytoplasm Source: MGI
  • endoplasmic reticulum Source: MGI
  • microtubule organizing center Source: MGI
  • midbody Source: MGI
  • nucleoplasm Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi599 – 601SGR → AAA: Decreases repression of NFE2L2-dependent gene expression. 1 Publication3
Mutagenesisi602 – 604SGV → AAA: Abolishes repression of NFE2L2-dependent gene expression. 1 Publication3
Mutagenesisi605 – 608GVAV → AAAA: Decreases repression of NFE2L2-dependent gene expression. 1 Publication4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001190941 – 624Kelch-like ECH-associated protein 1Add BLAST624

Post-translational modificationi

Ubiquitinated by the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and is subject to proteasomal-independent degradation. 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 (By similarity).By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ9Z2X8.
MaxQBiQ9Z2X8.
PaxDbiQ9Z2X8.
PeptideAtlasiQ9Z2X8.
PRIDEiQ9Z2X8.

PTM databases

iPTMnetiQ9Z2X8.
PhosphoSitePlusiQ9Z2X8.
SwissPalmiQ9Z2X8.

Expressioni

Gene expression databases

BgeeiENSMUSG00000003308.
CleanExiMM_KEAP1.
GenevisibleiQ9Z2X8. MM.

Interactioni

Subunit structurei

Homodimer. Forms a ternary complex with NFE2L2 and PGAM5. Interacts with the N-terminal regulatory domain of NFE2L2/NRF2. Interacts with BPTF and PTMA. Interacts with CUL3. Part of a complex that contains KEAP1, CUL3 and RBX1 (By similarity). Interacts indirectly with ENC1 (By similarity). Interacts with MAP1LC3B (By similarity). Interacts with SESN1 and SESN2 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Nfe2l2Q6079522EBI-647110,EBI-642563
SQSTM1Q135012EBI-647110,EBI-307104From a different organism.
Sqstm1Q643376EBI-647110,EBI-645025

GO - Molecular functioni

Protein-protein interaction databases

BioGridi206135. 13 interactors.
DIPiDIP-49698N.
IntActiQ9Z2X8. 7 interactors.
MINTiMINT-4111966.
STRINGi10090.ENSMUSP00000062467.

Structurei

Secondary structure

1624
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi328 – 331Combined sources4
Beta strandi334 – 338Combined sources5
Beta strandi342 – 345Combined sources4
Turni347 – 349Combined sources3
Beta strandi352 – 354Combined sources3
Beta strandi366 – 370Combined sources5
Beta strandi373 – 377Combined sources5
Beta strandi380 – 383Combined sources4
Beta strandi386 – 389Combined sources4
Beta strandi393 – 397Combined sources5
Turni398 – 401Combined sources4
Beta strandi402 – 405Combined sources4
Beta strandi417 – 421Combined sources5
Beta strandi424 – 428Combined sources5
Beta strandi440 – 444Combined sources5
Turni445 – 448Combined sources4
Beta strandi449 – 453Combined sources5
Beta strandi464 – 468Combined sources5
Beta strandi471 – 478Combined sources8
Beta strandi483 – 491Combined sources9
Turni492 – 495Combined sources4
Beta strandi496 – 499Combined sources4
Beta strandi511 – 515Combined sources5
Beta strandi518 – 522Combined sources5
Beta strandi527 – 530Combined sources4
Beta strandi534 – 538Combined sources5
Turni539 – 542Combined sources4
Beta strandi543 – 546Combined sources4
Beta strandi558 – 562Combined sources5
Beta strandi565 – 569Combined sources5
Beta strandi574 – 577Combined sources4
Beta strandi581 – 585Combined sources5
Turni586 – 589Combined sources4
Beta strandi590 – 593Combined sources4
Beta strandi605 – 608Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X2JX-ray1.60A309-624[»]
1X2RX-ray1.70A309-624[»]
2DYHX-ray1.90A309-624[»]
2Z32X-ray2.00A309-624[»]
3ADEX-ray2.80A309-624[»]
3WDZX-ray2.60A321-609[»]
3WN7X-ray1.57A/L321-609[»]
4ZY3X-ray1.80A/B321-609[»]
5CGJX-ray3.36A309-624[»]
5FNQX-ray1.91A322-624[»]
5FNRX-ray1.89A322-624[»]
5FNSX-ray1.79A322-624[»]
5FNTX-ray1.79A322-624[»]
5FNUX-ray1.78A322-624[»]
5FZJX-ray2.01A322-624[»]
5FZNX-ray1.97A322-624[»]
ProteinModelPortaliQ9Z2X8.
SMRiQ9Z2X8.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Z2X8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini77 – 149BTBPROSITE-ProRule annotationAdd BLAST73
Domaini184 – 286BACKAdd BLAST103
Repeati327 – 372Kelch 1Add BLAST46
Repeati373 – 423Kelch 2Add BLAST51
Repeati424 – 470Kelch 3Add BLAST47
Repeati471 – 517Kelch 4Add BLAST47
Repeati519 – 564Kelch 5Add BLAST46
Repeati565 – 611Kelch 6Add BLAST47

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi301 – 310Nuclear export signalBy similarity10

Domaini

The Kelch repeats mediate interaction with NF2L2/NRF2, BPTF and PGAM5.By similarity

Sequence similaritiesi

Contains 1 BTB (POZ) domain.PROSITE-ProRule annotation
Contains 6 Kelch repeats.Curated

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441. Eukaryota.
ENOG410XNX8. LUCA.
GeneTreeiENSGT00760000118931.
HOGENOMiHOG000230814.
HOVERGENiHBG014286.
InParanoidiQ9Z2X8.
KOiK10456.
OMAiHTQFLPL.
OrthoDBiEOG091G02T3.
PhylomeDBiQ9Z2X8.
TreeFamiTF329218.

Family and domain databases

Gene3Di2.130.10.80. 1 hit.
InterProiIPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015916. Gal_Oxidase_b-propeller.
IPR030563. KEAP1.
IPR006652. Kelch_1.
IPR011333. SKP1/BTB/POZ.
[Graphical view]
PANTHERiPTHR24412:SF162. PTHR24412:SF162. 1 hit.
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 6 hits.
[Graphical view]
PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTiSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 6 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z2X8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQPEPKLSGA PRSSQFLPLW SKCPEGAGDA VMYASTECKA EVTPSQDGNR
60 70 80 90 100
TFSYTLEDHT KQAFGVMNEL 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
NQWSPCASMS VPRNRIGVGV IDGHIYAVGG SHGCIHHSSV ERYEPERDEW
460 470 480 490 500
HLVAPMLTRR IGVGVAVLNR LLYAVGGFDG TNRLNSAECY YPERNEWRMI
510 520 530 540 550
TPMNTIRSGA GVCVLHNCIY AAGGYDGQDQ LNSVERYDVE TETWTFVAPM
560 570 580 590 600
RHHRSALGIT VHQGKIYVLG GYDGHTFLDS VECYDPDSDT WSEVTRMTSG
610 620
RSGVGVAVTM EPCRKQIDQQ NCTC
Length:624
Mass (Da):69,553
Last modified:May 1, 1999 - v1
Checksum:i4645DB0122FB5F54
GO

Sequence cautioni

The sequence BAC97871 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti43T → A in BAE29559 (PubMed:16141072).Curated1
Sequence conflicti43T → A in BAE30980 (PubMed:16141072).Curated1
Sequence conflicti348S → G in BAC32621 (PubMed:16141072).Curated1
Sequence conflicti361P → T in BAE29559 (PubMed:16141072).Curated1
Sequence conflicti361P → T in BAE30980 (PubMed:16141072).Curated1
Sequence conflicti579D → V in BAE32581 (PubMed:16141072).Curated1
Sequence conflicti579D → V in BAE33299 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020063 mRNA. Translation: BAA34639.1.
AF454353 Genomic DNA. Translation: AAL84711.1.
AK129061 mRNA. Translation: BAC97871.1. Different initiation.
AK046178 mRNA. Translation: BAC32621.1.
AK076234 mRNA. Translation: BAC36267.1.
AK150437 mRNA. Translation: BAE29559.1.
AK150485 mRNA. Translation: BAE29601.1.
AK152142 mRNA. Translation: BAE30980.1.
AK154430 mRNA. Translation: BAE32581.1.
AK155507 mRNA. Translation: BAE33299.1.
AK159858 mRNA. Translation: BAE35433.1.
BC055732 mRNA. Translation: AAH55732.1.
CCDSiCCDS22897.1.
RefSeqiNP_001103775.1. NM_001110305.1.
NP_001103776.1. NM_001110306.1.
NP_001103777.1. NM_001110307.1.
NP_057888.1. NM_016679.4.
UniGeneiMm.248266.

Genome annotation databases

EnsembliENSMUST00000049567; ENSMUSP00000062467; ENSMUSG00000003308.
ENSMUST00000164812; ENSMUSP00000131029; ENSMUSG00000003308.
ENSMUST00000193982; ENSMUSP00000141840; ENSMUSG00000003308.
ENSMUST00000194542; ENSMUSP00000141807; ENSMUSG00000003308.
GeneIDi50868.
KEGGimmu:50868.
UCSCiuc009oko.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020063 mRNA. Translation: BAA34639.1.
AF454353 Genomic DNA. Translation: AAL84711.1.
AK129061 mRNA. Translation: BAC97871.1. Different initiation.
AK046178 mRNA. Translation: BAC32621.1.
AK076234 mRNA. Translation: BAC36267.1.
AK150437 mRNA. Translation: BAE29559.1.
AK150485 mRNA. Translation: BAE29601.1.
AK152142 mRNA. Translation: BAE30980.1.
AK154430 mRNA. Translation: BAE32581.1.
AK155507 mRNA. Translation: BAE33299.1.
AK159858 mRNA. Translation: BAE35433.1.
BC055732 mRNA. Translation: AAH55732.1.
CCDSiCCDS22897.1.
RefSeqiNP_001103775.1. NM_001110305.1.
NP_001103776.1. NM_001110306.1.
NP_001103777.1. NM_001110307.1.
NP_057888.1. NM_016679.4.
UniGeneiMm.248266.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1X2JX-ray1.60A309-624[»]
1X2RX-ray1.70A309-624[»]
2DYHX-ray1.90A309-624[»]
2Z32X-ray2.00A309-624[»]
3ADEX-ray2.80A309-624[»]
3WDZX-ray2.60A321-609[»]
3WN7X-ray1.57A/L321-609[»]
4ZY3X-ray1.80A/B321-609[»]
5CGJX-ray3.36A309-624[»]
5FNQX-ray1.91A322-624[»]
5FNRX-ray1.89A322-624[»]
5FNSX-ray1.79A322-624[»]
5FNTX-ray1.79A322-624[»]
5FNUX-ray1.78A322-624[»]
5FZJX-ray2.01A322-624[»]
5FZNX-ray1.97A322-624[»]
ProteinModelPortaliQ9Z2X8.
SMRiQ9Z2X8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi206135. 13 interactors.
DIPiDIP-49698N.
IntActiQ9Z2X8. 7 interactors.
MINTiMINT-4111966.
STRINGi10090.ENSMUSP00000062467.

PTM databases

iPTMnetiQ9Z2X8.
PhosphoSitePlusiQ9Z2X8.
SwissPalmiQ9Z2X8.

Proteomic databases

EPDiQ9Z2X8.
MaxQBiQ9Z2X8.
PaxDbiQ9Z2X8.
PeptideAtlasiQ9Z2X8.
PRIDEiQ9Z2X8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000049567; ENSMUSP00000062467; ENSMUSG00000003308.
ENSMUST00000164812; ENSMUSP00000131029; ENSMUSG00000003308.
ENSMUST00000193982; ENSMUSP00000141840; ENSMUSG00000003308.
ENSMUST00000194542; ENSMUSP00000141807; ENSMUSG00000003308.
GeneIDi50868.
KEGGimmu:50868.
UCSCiuc009oko.2. mouse.

Organism-specific databases

CTDi9817.
MGIiMGI:1858732. Keap1.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG4441. Eukaryota.
ENOG410XNX8. LUCA.
GeneTreeiENSGT00760000118931.
HOGENOMiHOG000230814.
HOVERGENiHBG014286.
InParanoidiQ9Z2X8.
KOiK10456.
OMAiHTQFLPL.
OrthoDBiEOG091G02T3.
PhylomeDBiQ9Z2X8.
TreeFamiTF329218.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-5689880. Ub-specific processing proteases.

Miscellaneous databases

EvolutionaryTraceiQ9Z2X8.
PROiQ9Z2X8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003308.
CleanExiMM_KEAP1.
GenevisibleiQ9Z2X8. MM.

Family and domain databases

Gene3Di2.130.10.80. 1 hit.
InterProiIPR011705. BACK.
IPR017096. BTB-kelch_protein.
IPR000210. BTB/POZ_dom.
IPR015916. Gal_Oxidase_b-propeller.
IPR030563. KEAP1.
IPR006652. Kelch_1.
IPR011333. SKP1/BTB/POZ.
[Graphical view]
PANTHERiPTHR24412:SF162. PTHR24412:SF162. 1 hit.
PfamiPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 6 hits.
[Graphical view]
PIRSFiPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTiSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 6 hits.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
PROSITEiPS50097. BTB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKEAP1_MOUSE
AccessioniPrimary (citable) accession number: Q9Z2X8
Secondary accession number(s): Q3U243
, Q3U8N7, Q547S3, Q6ZQI6, Q8BQY3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 1999
Last modified: November 2, 2016
This is version 158 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.