P57790 (KEAP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Kelch-like ECH-associated protein 1

Alternative name(s):
Cytosolic inhibitor of Nrf2
Short name=INrf2

Gene names

Name:	Keap1
Synonyms:	Inrf2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	624 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
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 process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Domain	Kelch repeat Repeat
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	alkanesulfonate 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-dependent 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 stimulus Inferred from expression pattern PubMed 22649286. Source: RGD selenium compound metabolic process Inferred from expression pattern PubMed 16978024. Source: RGD transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Cul3-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
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 624	624	Kelch-like ECH-associated protein 1		PRO_0000119095
Regions
	Domain	77 – 149	73	BTB
	Domain	184 – 286	103	BACK
	Repeat	327 – 372	46	Kelch 1
	Repeat	373 – 423	51	Kelch 2
	Repeat	424 – 470	47	Kelch 3
	Repeat	471 – 517	47	Kelch 4
	Repeat	519 – 564	46	Kelch 5
	Repeat	565 – 611	47	Kelch 6
	Motif	301 – 310	10	Nuclear export signal By similarity

Sequences

	Sequence		Length	Mass (Da)
	P57790 [UniParc]. Last modified April 27, 2001. Version 1. Checksum: B5E77B5A72546A79	FASTA	624	69,399
	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

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.
IPI	IPI00199116.
UniGene	Rn.23467.
3D structure databases
ProteinModelPortal	P57790.
SMR	P57790. Positions 324-619.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000028360.
PTM databases
PhosphoSite	P57790.
Proteomic databases
PaxDb	P57790.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	RGD:621619. rat.
Organism-specific databases
CTD	9817.
RGD	621619. Keap1.
Phylogenomic databases
eggNOG	NOG255039.
HOGENOM	HOG000230814.
HOVERGEN	HBG014286.
InParanoid	P57790.
OrthoDB	EOG4WH8KC.
Enzyme and pathway databases
UniPathway	UPA00143.
Gene expression databases
Genevestigator	P57790.
GermOnline	ENSRNOG00000020878. Rattus norvegicus.
Family and domain databases
Gene3D	2.130.10.80. 1 hit. 3.30.710.10. 1 hit.
InterPro	IPR011705. BACK. IPR000210. BTB/POZ-like. IPR011333. BTB/POZ_fold. IPR013069. BTB_POZ. IPR015916. Gal_Oxidase_b-propeller. IPR017096. Kelch-like_gigaxonin. IPR006652. Kelch_1. [Graphical view]
Pfam	PF07707. BACK. 1 hit. PF00651. BTB. 1 hit. PF01344. Kelch_1. 6 hits. [Graphical view]
PIRSF	PIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMART	SM00875. BACK. 1 hit. SM00225. BTB. 1 hit. SM00612. Kelch. 6 hits. [Graphical view]
SUPFAM	SSF54695. BTB/POZ_fold. 1 hit.
PROSITE	PS50097. BTB. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	620287.

Entry information

Entry name

KEAP1_RAT

Accession

Primary (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:	May 1, 2013
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program