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Kelch-like ECH-associated protein 1 (Cytosolic inhibitor of Nrf2) (INrf2)

 KEAP1_PIG               Reviewed;         624 AA.
Q684M4;
01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
11-OCT-2004, sequence version 1.
12-SEP-2018, entry version 93.
RecName: Full=Kelch-like ECH-associated protein 1;
AltName: Full=Cytosolic inhibitor of Nrf2;
Short=INrf2;
Name=KEAP1; Synonyms=INRF2;
Sus scrofa (Pig).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Suina; Suidae;
Sus.
NCBI_TaxID=9823;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=15305063; DOI=10.1159/000079578;
Leeb T., Martins-Wess F., Kuiper H., Lassnig C., Distl O., Mueller M.;
"Molecular characterization of the porcine TYK2 gene on SSC 2q1.3 ->
q2.1.";
Cytogenet. Genome Res. 107:103-107(2004).
-!- 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). {ECO:0000250}.
-!- PATHWAY: Protein modification; protein ubiquitination.
-!- SUBUNIT: 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.
{ECO:0000250|UniProtKB:Q14145}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus
{ECO:0000250}. Note=Shuttles between cytoplasm and nucleus.
{ECO:0000250}.
-!- DOMAIN: The Kelch repeats mediate interaction with NF2L2/NRF2,
BPTF and PGAM5. {ECO:0000250}.
-!- PTM: 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). {ECO:0000250}.
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EMBL; AJ632303; CAG15151.1; -; Genomic_DNA.
RefSeq; NP_001108143.1; NM_001114671.1.
RefSeq; XP_003480844.1; XM_003480796.3.
RefSeq; XP_005654868.1; XM_005654811.2.
RefSeq; XP_005654915.1; XM_005654858.2.
RefSeq; XP_013842850.1; XM_013987396.1.
RefSeq; XP_013842889.1; XM_013987435.1.
UniGene; Ssc.11795; -.
UniGene; Ssc.87184; -.
ProteinModelPortal; Q684M4; -.
SMR; Q684M4; -.
STRING; 9823.ENSSSCP00000014495; -.
PaxDb; Q684M4; -.
PeptideAtlas; Q684M4; -.
PRIDE; Q684M4; -.
Ensembl; ENSSSCT00000014895; ENSSSCP00000014494; ENSSSCG00000023667.
Ensembl; ENSSSCT00000014896; ENSSSCP00000014495; ENSSSCG00000023667.
Ensembl; ENSSSCT00000064933; ENSSSCP00000056325; ENSSSCG00000023667.
GeneID; 100136900; -.
KEGG; ssc:100136900; -.
CTD; 9817; -.
eggNOG; KOG4441; Eukaryota.
eggNOG; ENOG410XNX8; LUCA.
GeneTree; ENSGT00760000118931; -.
HOGENOM; HOG000230814; -.
HOVERGEN; HBG014286; -.
InParanoid; Q684M4; -.
KO; K10456; -.
OMA; EQIGCTE; -.
OrthoDB; EOG091G02T3; -.
TreeFam; TF329218; -.
Reactome; R-SSC-5689880; Ub-specific processing proteases.
Reactome; R-SSC-8951664; Neddylation.
Reactome; R-SSC-983168; Antigen processing: Ubiquitination & Proteasome degradation.
UniPathway; UPA00143; -.
Proteomes; UP000008227; Chromosome 2.
Bgee; ENSSSCG00000013640; Expressed in 5 organ(s), highest expression level in heart.
Genevisible; Q684M4; SS.
GO; GO:0005884; C:actin filament; IEA:Ensembl.
GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISS:UniProtKB.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0005829; C:cytosol; IEA:Ensembl.
GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
GO; GO:0005815; C:microtubule organizing center; IEA:Ensembl.
GO; GO:0030496; C:midbody; IEA:Ensembl.
GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
GO; GO:0097718; F:disordered domain specific binding; IEA:Ensembl.
GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
GO; GO:0008134; F:transcription factor binding; IBA:GO_Central.
GO; GO:0071353; P:cellular response to interleukin-4; IEA:Ensembl.
GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; IBA:GO_Central.
GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IBA:GO_Central.
GO; GO:0010499; P:proteasomal ubiquitin-independent protein catabolic process; ISS:UniProtKB.
GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
GO; GO:0045604; P:regulation of epidermal cell differentiation; IEA:Ensembl.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
Gene3D; 2.120.10.80; -; 1.
InterPro; IPR011705; BACK.
InterPro; IPR017096; BTB-kelch_protein.
InterPro; IPR000210; BTB/POZ_dom.
InterPro; IPR030563; KEAP1.
InterPro; IPR015915; Kelch-typ_b-propeller.
InterPro; IPR006652; Kelch_1.
InterPro; IPR011333; SKP1/BTB/POZ_sf.
PANTHER; PTHR24412:SF162; PTHR24412:SF162; 1.
Pfam; PF07707; BACK; 1.
Pfam; PF00651; BTB; 1.
Pfam; PF01344; Kelch_1; 6.
PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
SMART; SM00875; BACK; 1.
SMART; SM00225; BTB; 1.
SMART; SM00612; Kelch; 6.
SUPFAM; SSF117281; SSF117281; 1.
SUPFAM; SSF54695; SSF54695; 1.
PROSITE; PS50097; BTB; 1.
3: Inferred from homology;
Complete proteome; Cytoplasm; Kelch repeat; Nucleus;
Reference proteome; Repeat; Transcription; Transcription regulation;
Ubl conjugation; Ubl conjugation pathway.
CHAIN 1 624 Kelch-like ECH-associated protein 1.
/FTId=PRO_0000286392.
DOMAIN 77 149 BTB. {ECO:0000255|PROSITE-
ProRule:PRU00037}.
DOMAIN 184 286 BACK.
REPEAT 327 372 Kelch 1.
REPEAT 373 423 Kelch 2.
REPEAT 424 470 Kelch 3.
REPEAT 471 517 Kelch 4.
REPEAT 519 564 Kelch 5.
REPEAT 565 611 Kelch 6.
MOTIF 301 310 Nuclear export signal. {ECO:0000250}.
SEQUENCE 624 AA; 69816 MW; F087ECC342299444 CRC64;
MQPEPRPSGA GAHTQFLPLR SQRPEGAGDT VMYASTECKA EVTPSQHGNR TFSYTLEDHT
KQAFGIMNEL RLSQQLCDVT LQVKYEDAPA AQFMAHKVVL ASSSPVFKAM FTNGLREQGM
EVVSIEGIHP KVMERLIEFA YTASISMGEK CVLHVMNGAV MYQIDSVVRA CSDFLVQQLD
PSNAIGIANF AEQIGCAELH QRAREYIYMH FGEVAKQEEF FNLSHCQLVT LISRDDLNVR
CESEVFHACI NWVKYDCEQR RFYVQALLRA VRCHSLTPHF LQMQLQKCEI LQSDSRCKDY
LVKIFQELTL HKPTQVMPCR APKVGRLIYT AGGYFRQSLS YLEAYNPSDG TWLRLADLQV
PRSGLAGCVV GGLLYAVGGR NNSPDGNTDS SALDCYNPMT NQWSPCAPMS VPRNRIGVGV
IDGHIYAVGG SHGCIHHNSV ERYEPERDEW HLVAPMLTRR IGVGVAVLNR LLYAVGGFDG
TNRLNSAECY YPERNEWRMI TPMNTIRSGA GVCVLHNCIY AAGGYDGQDQ LNSVERYDVE
TETWTFVAPM KHRRSALGIT VHQGRIYVLG GYDGHTFLDS VECYDPDTDT WSEVTRMTSG
RSGVGVAVTM EPCRKQIDQQ NCTC


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