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Protein

Kelch-like ECH-associated protein 1

Gene

Keap1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 similarity

Pathwayi

GO - Biological processi

  1. alkanesulfonate metabolic process Source: RGD
  2. cellular response to organic cyclic compound Source: RGD
  3. cytoplasmic sequestering of transcription factor Source: RGD
  4. flavonoid metabolic process Source: RGD
  5. malate metabolic process Source: RGD
  6. negative regulation of gene expression Source: RGD
  7. proteasomal ubiquitin-independent protein catabolic process Source: UniProtKB
  8. protein oligomerization Source: RGD
  9. protein ubiquitination Source: UniProtKB
  10. regulation of transcription, DNA-templated Source: UniProtKB-KW
  11. response to immobilization stress Source: RGD
  12. response to metal ion Source: RGD
  13. response to thyroid hormone Source: RGD
  14. selenium compound metabolic process Source: RGD
  15. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation, Ubl conjugation pathway

Enzyme and pathway databases

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi621619. Keap1.

Subcellular locationi

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

GO - Cellular componenti

  1. cell-cell adherens junction Source: RGD
  2. Cul3-RING ubiquitin ligase complex Source: UniProtKB
  3. cytoplasm Source: RGD
  4. focal adhesion Source: RGD
  5. nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 624624Kelch-like ECH-associated protein 1PRO_0000119095Add
BLAST

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

PaxDbiP57790.
PRIDEiP57790.

PTM databases

PhosphoSiteiP57790.

Expressioni

Gene expression databases

GenevestigatoriP57790.

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).By similarity

Protein-protein interaction databases

BioGridi250741. 1 interaction.
STRINGi10116.ENSRNOP00000028360.

Structurei

3D structure databases

ProteinModelPortaliP57790.
SMRiP57790. Positions 324-619.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini77 – 14973BTBPROSITE-ProRule annotationAdd
BLAST
Domaini184 – 286103BACKAdd
BLAST
Repeati327 – 37246Kelch 1Add
BLAST
Repeati373 – 42351Kelch 2Add
BLAST
Repeati424 – 47047Kelch 3Add
BLAST
Repeati471 – 51747Kelch 4Add
BLAST
Repeati519 – 56446Kelch 5Add
BLAST
Repeati565 – 61147Kelch 6Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi301 – 31010Nuclear export signalBy similarity

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

eggNOGiNOG255039.
HOGENOMiHOG000230814.
HOVERGENiHBG014286.
InParanoidiP57790.
PhylomeDBiP57790.

Family and domain databases

Gene3Di2.130.10.80. 1 hit.
InterProiIPR011705. 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]
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.

P57790-1 [UniParc]FASTAAdd to Basket

« Hide

        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
Length:624
Mass (Da):69,399
Last modified:April 27, 2001 - v1
Checksum:iB5E77B5A72546A79
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF304364 mRNA. Translation: AAG16275.1.
UniGeneiRn.23467.

Genome annotation databases

UCSCiRGD:621619. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF304364 mRNA. Translation: AAG16275.1.
UniGeneiRn.23467.

3D structure databases

ProteinModelPortaliP57790.
SMRiP57790. Positions 324-619.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250741. 1 interaction.
STRINGi10116.ENSRNOP00000028360.

PTM databases

PhosphoSiteiP57790.

Proteomic databases

PaxDbiP57790.
PRIDEiP57790.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:621619. rat.

Organism-specific databases

RGDi621619. Keap1.

Phylogenomic databases

eggNOGiNOG255039.
HOGENOMiHOG000230814.
HOVERGENiHBG014286.
InParanoidiP57790.
PhylomeDBiP57790.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

NextBioi620287.
PROiP57790.

Gene expression databases

GenevestigatoriP57790.

Family and domain databases

Gene3Di2.130.10.80. 1 hit.
InterProiIPR011705. 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]
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...

Publicationsi

  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.

Entry informationi

Entry nameiKEAP1_RAT
AccessioniPrimary (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: January 7, 2015
This is version 106 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

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.