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Protein

Kelch-like ECH-associated protein 1

Gene

Keap1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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: 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

  • cellular response to organic cyclic compound Source: RGD
  • cytoplasmic sequestering of transcription factor Source: RGD
  • negative regulation of DNA binding transcription factor activity Source: GO_Central
  • negative regulation of gene expression Source: RGD
  • proteasomal ubiquitin-independent protein catabolic process Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  • protein complex oligomerization Source: RGD
  • protein ubiquitination Source: UniProtKB
  • response to immobilization stress Source: RGD
  • response to metal ion Source: RGD
  • response to thyroid hormone Source: RGD
  • selenium compound metabolic process Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Biological processTranscription, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621619 Keap1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001190951 – 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

PaxDbiP57790
PRIDEiP57790

PTM databases

iPTMnetiP57790
PhosphoSitePlusiP57790

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. Interacts indirectly with ENC1. Interacts with MAP1LC3B. Interacts with SESN1 and SESN2. Interacts with HSP90AA1 and HSP90AB1.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000028360

Structurei

3D structure databases

ProteinModelPortaliP57790
SMRiP57790
ModBaseiSearch...
MobiDBiSearch...

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

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

eggNOGiKOG4441 Eukaryota
ENOG410XNX8 LUCA
HOGENOMiHOG000230814
HOVERGENiHBG014286
InParanoidiP57790
PhylomeDBiP57790

Family and domain databases

Gene3Di2.120.10.80, 1 hit
InterProiView 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
PANTHERiPTHR24412:SF162 PTHR24412:SF162, 1 hit
PfamiView protein in Pfam
PF07707 BACK, 1 hit
PF00651 BTB, 1 hit
PF01344 Kelch_1, 6 hits
PIRSFiPIRSF037037 Kelch-like_protein_gigaxonin, 1 hit
SMARTiView protein in SMART
SM00875 BACK, 1 hit
SM00225 BTB, 1 hit
SM00612 Kelch, 6 hits
SUPFAMiSSF117281 SSF117281, 1 hit
SSF54695 SSF54695, 1 hit
PROSITEiView protein in PROSITE
PS50097 BTB, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiKEAP1_RAT
AccessioniPrimary (citable) accession number: P57790
Secondary accession number(s): Q9ERI3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 27, 2001
Last modified: May 23, 2018
This is version 129 of the entry and version 1 of the sequence. See 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

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