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P57790 (KEAP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length624 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript 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.

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 By similarity. Nucleus By similarity. Note: Shuttles between cytoplasm and nucleus By similarity.

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.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   DomainKelch repeat
Repeat
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processalkanesulfonate metabolic process

Inferred from expression pattern PubMed 20621739. Source: RGD

cellular response to organic cyclic compound

Inferred from expression pattern Ref.1. Source: RGD

cytoplasmic sequestering of transcription factor

Inferred from mutant phenotype Ref.1. Source: RGD

flavonoid metabolic process

Inferred from expression pattern PubMed 14960151PubMed 22838648. Source: RGD

malate metabolic process

Inferred from expression pattern PubMed 14960151. Source: RGD

negative regulation of gene expression

Inferred from direct assay PubMed 20026152. Source: RGD

proteasomal ubiquitin-independent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

protein oligomerization

Inferred from direct assay PubMed 20026152. Source: RGD

protein ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

response to immobilization stress

Inferred from expression pattern PubMed 17316384. Source: RGD

response to metal ion

Inferred from expression pattern PubMed 22649286. Source: RGD

response to thyroid hormone

Inferred from expression pattern PubMed 22649286. Source: RGD

selenium compound metabolic process

Inferred from expression pattern PubMed 16978024. Source: RGD

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentCul3-RING ubiquitin ligase complex

Inferred from sequence or structural similarity. Source: UniProtKB

cell-cell adherens junction

Inferred from direct assay PubMed 14506708. Source: RGD

cytoplasm

Inferred from direct assay PubMed 16000310. Source: RGD

focal adhesion

Inferred from direct assay PubMed 14506708. Source: RGD

nucleus

Inferred from direct assay PubMed 16000310. Source: RGD

   Molecular_functionprotein binding

Inferred from physical interaction Ref.1. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 624624Kelch-like ECH-associated protein 1
PRO_0000119095

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

Sequences

Sequence LengthMass (Da)Tools
P57790 [UniParc].

Last modified April 27, 2001. Version 1.
Checksum: B5E77B5A72546A79

FASTA62469,399
        10         20         30         40         50         60 
MQPEPKPSGA PRSSQFLPLW SKCPEGAGDA VMYASTECKA EVTPSQDGNR TFSYTLEDHT 

        70         80         90        100        110        120 
KQAFGIMNEL 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 NQWSPCASLS VPRNRSGGGV 

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

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

       550        560        570        580        590        600 
TETWTFVASM KHRRSALGIA VHQGRIYVLG GYDGHTFLDS VECYDPDTDT WSEVTRLTSG 

       610        620 
RSGVGVAVTM EPCRKQIDQQ NCTC 

« Hide

References

[1]"Functional characterization and role of INrf2 in antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene."
Dhakshinamoorthy S., Jaiswal A.K.
Oncogene 20:3906-3917(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF304364 mRNA. Translation: AAG16275.1.
UniGeneRn.23467.

3D structure databases

ProteinModelPortalP57790.
SMRP57790. Positions 324-619.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid250741. 1 interaction.
STRING10116.ENSRNOP00000028360.

PTM databases

PhosphoSiteP57790.

Proteomic databases

PaxDbP57790.
PRIDEP57790.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:621619. rat.

Organism-specific databases

RGD621619. Keap1.

Phylogenomic databases

eggNOGNOG255039.
HOGENOMHOG000230814.
HOVERGENHBG014286.
InParanoidP57790.
PhylomeDBP57790.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

GenevestigatorP57790.

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

NextBio620287.
PROP57790.

Entry information

Entry nameKEAP1_RAT
AccessionPrimary (citable) accession number: P57790
Secondary accession number(s): Q9ERI3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 27, 2001
Last modified: June 11, 2014
This is version 103 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

PATHWAY comments

Index of metabolic and biosynthesis pathways