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Protein

Kelch-like ECH-associated protein 1

Gene

Keap1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

  • disordered domain specific binding Source: CAFA
  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: CAFA
  • transcription factor binding Source: MGI

GO - Biological processi

Keywordsi

Biological processTranscription, Transcription regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-5689880 Ub-specific processing proteases
R-MMU-8951664 Neddylation
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1858732 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

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

Chemistry databases

ChEMBLiCHEMBL3562164

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
ExpressionAtlasiQ9Z2X8 baseline and differential
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. Interacts indirectly with ENC1. Interacts with MAP1LC3B. Interacts with SESN1 and SESN2. Interacts with HSP90AA1 and HSP90AB1.By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • disordered domain specific binding Source: CAFA
  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: CAFA
  • transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi206135, 15 interactors
CORUMiQ9Z2X8
DIPiDIP-49698N
ELMiQ9Z2X8
IntActiQ9Z2X8, 8 interactors
MINTiQ9Z2X8
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

Keywords - Domaini

Kelch repeat, Repeat

Phylogenomic databases

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

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.

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

Similar proteinsi

Entry informationi

Entry nameiKEAP1_MOUSE
AccessioniPrimary (citable) accession number: Q9Z2X8
Secondary accession number(s): Q3U243
, Q3U8N7, Q547S3, Q6ZQI6, Q8BQY3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 1999
Last modified: April 25, 2018
This is version 172 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

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

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