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Q9Z2X8 (KEAP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Kelch-like ECH-associated protein 1
Alternative name(s):
Cytosolic inhibitor of Nrf2
Short name=INrf2
Gene names
Name:Keap1
Synonyms:Inrf2, Kiaa0132
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length624 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.6

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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.

Subcellular location

Cytoplasm. Nucleus. Note: Shuttles between cytoplasm and nucleus By similarity. Ref.7

Domain

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

Post-translational modification

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.

Sequence similarities

Contains 1 BACK (BTB/Kelch associated) domain.

Contains 1 BTB (POZ) domain.

Contains 6 Kelch repeats.

Sequence caution

The sequence BAC97871.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   DomainKelch repeat
Repeat
   PTMUbl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to interleukin-4

Inferred from direct assay PubMed 9798653. Source: MGI

in utero embryonic development

Inferred from mutant phenotype PubMed 15087497. Source: MGI

proteasomal ubiquitin-independent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of epidermal cell differentiation

Inferred from mutant phenotype PubMed 15087497. Source: MGI

regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 15087497. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentCul3-RING ubiquitin ligase complex

Inferred from sequence or structural similarity. Source: UniProtKB

centrosome

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from physical interaction PubMed 14517290. Source: MGI

endoplasmic reticulum

Inferred from direct assay PubMed 14517290. Source: MGI

midbody

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 20173742. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SQSTM1Q135012EBI-647110,EBI-307104From a different organism.
Sqstm1Q643376EBI-647110,EBI-645025

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 624624Kelch-like ECH-associated protein 1
PRO_0000119094

Regions

Domain77 – 14973BTB
Domain184 – 286103BACK
Repeat327 – 37246Kelch 1
Repeat373 – 42351Kelch 2
Repeat424 – 47047Kelch 3
Repeat471 – 51747Kelch 4
Repeat519 – 56446Kelch 5
Repeat565 – 61147Kelch 6
Motif301 – 31010Nuclear export signal By similarity

Experimental info

Mutagenesis599 – 6013SGR → AAA: Decreases repression of NFE2L2-dependent gene expression.
Mutagenesis602 – 6043SGV → AAA: Abolishes repression of NFE2L2-dependent gene expression. Ref.8
Mutagenesis605 – 6084GVAV → AAAA: Decreases repression of NFE2L2-dependent gene expression. Ref.8
Sequence conflict431T → A in BAE29559. Ref.4
Sequence conflict431T → A in BAE30980. Ref.4
Sequence conflict3481S → G in BAC32621. Ref.4
Sequence conflict3611P → T in BAE29559. Ref.4
Sequence conflict3611P → T in BAE30980. Ref.4
Sequence conflict5791D → V in BAE32581. Ref.4
Sequence conflict5791D → V in BAE33299. Ref.4

Secondary structure

............................................................. 624
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9Z2X8 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 4645DB0122FB5F54

FASTA62469,553
        10         20         30         40         50         60 
MQPEPKLSGA PRSSQFLPLW SKCPEGAGDA VMYASTECKA EVTPSQDGNR TFSYTLEDHT 

        70         80         90        100        110        120 
KQAFGVMNEL RLSQQLCDVT LQVKYEDIPA AQFMAHKVVL ASSSPVFKAM FTNGLREQGM 

       130        140        150        160        170        180 
EVVSIEGIHP KVMERLIEFA YTASISVGEK CVLHVMNGAV MYQIDSVVRA CSDFLVQQLD 

       190        200        210        220        230        240 
PSNAIGIANF AEQIGCTELH QRAREYIYMH FGEVAKQEEF FNLSHCQLAT LISRDDLNVR 

       250        260        270        280        290        300 
CESEVFHACI DWVKYDCPQR RFYVQALLRA VRCHALTPRF LQTQLQKCEI LQADARCKDY 

       310        320        330        340        350        360 
LVQIFQELTL HKPTQAVPCR APKVGRLIYT AGGYFRQSLS YLEAYNPSNG SWLRLADLQV 

       370        380        390        400        410        420 
PRSGLAGCVV GGLLYAVGGR NNSPDGNTDS SALDCYNPMT NQWSPCASMS VPRNRIGVGV 

       430        440        450        460        470        480 
IDGHIYAVGG SHGCIHHSSV ERYEPERDEW HLVAPMLTRR IGVGVAVLNR LLYAVGGFDG 

       490        500        510        520        530        540 
TNRLNSAECY YPERNEWRMI TPMNTIRSGA GVCVLHNCIY AAGGYDGQDQ LNSVERYDVE 

       550        560        570        580        590        600 
TETWTFVAPM RHHRSALGIT VHQGKIYVLG GYDGHTFLDS VECYDPDSDT WSEVTRMTSG 

       610        620 
RSGVGVAVTM EPCRKQIDQQ NCTC 

« Hide

References

« Hide 'large scale' references
[1]"Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain."
Itoh K., Wakabayashi N., Katoh Y., Ishii T., Igarashi K., Engel J.D., Yamamoto M.
Genes Dev. 13:76-86(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Tissue: Embryo.
[2]"Mouse INrf2 gene structure."
Dhakshinamoorthy S., Jaiswal A.K.
Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: C57BL/6.
[3]"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H.
DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Fetal brain.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Bone marrow, Corpora quadrigemina, Dendritic cell, Liver and Lung.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[6]"Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression."
McMahon M., Itoh K., Yamamoto M., Hayes J.D.
J. Biol. Chem. 278:21592-21600(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Fetal Alz-50 clone 1 interacts with the human orthologue of the Kelch-like Ech-associated protein."
Strachan G.D., Morgan K.L., Otis L.L., Caltagarone J., Gittis A., Bowser R., Jordan-Sciutto K.L.
Biochemistry 43:12113-12122(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[8]"Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer."
Padmanabhan B., Tong K.I., Ohta T., Nakamura Y., Scharlock M., Ohtsuji M., Kang M., Kobayashi A., Yokoyama S., Yamamoto M.
Mol. Cell 21:689-700(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 309-624 IN COMPLEX WITH NFE2L2, MUTAGENESIS OF 599-SER--ARG-601; 602-SER--VAL-604 AND 605-GLY--VAL-608.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS22897.1.
RefSeqNP_001103775.1. NM_001110305.1.
NP_001103776.1. NM_001110306.1.
NP_001103777.1. NM_001110307.1.
NP_057888.1. NM_016679.4.
UniGeneMm.248266.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ9Z2X8.
SMRQ9Z2X8. Positions 59-297, 324-609.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid206135. 14 interactions.
DIPDIP-49698N.
IntActQ9Z2X8. 5 interactions.
MINTMINT-4111966.
STRING10090.ENSMUSP00000062467.

PTM databases

PhosphoSiteQ9Z2X8.

Proteomic databases

MaxQBQ9Z2X8.
PaxDbQ9Z2X8.
PRIDEQ9Z2X8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000049567; ENSMUSP00000062467; ENSMUSG00000003308.
ENSMUST00000164812; ENSMUSP00000131029; ENSMUSG00000003308.
GeneID50868.
KEGGmmu:50868.
UCSCuc009oko.2. mouse.

Organism-specific databases

CTD9817.
MGIMGI:1858732. Keap1.
RougeSearch...

Phylogenomic databases

eggNOGNOG255039.
GeneTreeENSGT00740000115088.
HOGENOMHOG000230814.
HOVERGENHBG014286.
InParanoidQ9Z2X8.
KOK10456.
OMAQIGCTEL.
OrthoDBEOG76739M.
PhylomeDBQ9Z2X8.
TreeFamTF329218.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9Z2X8.
BgeeQ9Z2X8.
CleanExMM_KEAP1.
GenevestigatorQ9Z2X8.

Family and domain databases

Gene3D2.130.10.80. 1 hit.
3.30.710.10. 1 hit.
InterProIPR011705. BACK.
IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR015916. Gal_Oxidase_b-propeller.
IPR017096. Kelch-like_gigaxonin-typ.
IPR006652. Kelch_1.
[Graphical view]
PfamPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 6 hits.
[Graphical view]
PIRSFPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 6 hits.
[Graphical view]
SUPFAMSSF54695. SSF54695. 1 hit.
PROSITEPS50097. BTB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9Z2X8.
NextBio307831.
PROQ9Z2X8.
SOURCESearch...

Entry information

Entry nameKEAP1_MOUSE
AccessionPrimary (citable) accession number: Q9Z2X8
Secondary accession number(s): Q3U243 expand/collapse secondary AC list , Q3U8N7, Q547S3, Q6ZQI6, Q8BQY3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 1999
Last modified: July 9, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot