Q9Z2X8 (KEAP1_MOUSE) 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, Kiaa0132

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	624 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. 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. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome By similarity. Ref.1 Ref.6
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.
Subcellular location	Cytoplasm. Nucleus. Note: Shuttles between cytoplasm and nucleus By similarity. Ref.7
Domain	The Kelch repeats mediate interaction with NF2L2/NRF2, BPTF and PGAM5 By similarity.
Post-translational modification	Ubiquitinated and subject to proteasomal degradation By similarity.
Sequence similarities	Contains 1 BACK (BTB/Kelch associated) domain. Contains 1 BTB (POZ) domain. Contains 6 Kelch repeats.
Sequence caution	The sequence BAC97871.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	Kelch repeat Repeat
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	in utero embryonic development Inferred from mutant phenotype. Source: MGI regulation of epidermal cell differentiation Inferred from mutant phenotype. Source: MGI regulation of transcription, DNA-dependent Inferred from mutant phenotype. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from direct assay. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SQSTM1	Q13501	2	EBI-647110,EBI-307104	From a different organism.
Sqstm1	Q64337	6	EBI-647110,EBI-645025

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_0000119094

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

Experimental info

Mutagenesis

599 – 601

3

SGR → AAA: Decreases repression of NFE2L2-dependent gene expression.

Mutagenesis

602 – 604

3

SGV → AAA: Abolishes repression of NFE2L2-dependent gene expression. Ref.8

Mutagenesis

605 – 608

4

GVAV → AAAA: Decreases repression of NFE2L2-dependent gene expression. Ref.8

Sequence conflict

43

1

T → A in BAE29559. Ref.4

Sequence conflict

43

1

T → A in BAE30980. Ref.4

Sequence conflict

348

1

S → G in BAC32621. Ref.4

Sequence conflict

361

1

P → T in BAE29559. Ref.4

Sequence conflict

361

1

P → T in BAE30980. Ref.4

Sequence conflict

579

1

D → V in BAE32581. Ref.4

Sequence conflict

579

1

D → V in BAE33299. Ref.4

Secondary structure

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624

Helix Strand Turn

Details...

Beta strand

326 – 331

6

Beta strand

334 – 338

5

Beta strand

342 – 345

4

Turn

347 – 349

3

Beta strand

352 – 354

3

Beta strand

366 – 370

5

Beta strand

373 – 377

5

Beta strand

380 – 383

4

Beta strand

386 – 389

4

Beta strand

393 – 396

4

Turn

398 – 400

3

Beta strand

403 – 405

3

Beta strand

417 – 421

5

Beta strand

424 – 428

5

Beta strand

440 – 444

5

Turn

445 – 448

4

Beta strand

449 – 452

4

Beta strand

464 – 468

5

Beta strand

471 – 475

5

Beta strand

487 – 491

5

Helix

492 – 494

3

Beta strand

496 – 500

5

Beta strand

511 – 515

5

Beta strand

518 – 522

5

Beta strand

527 – 530

4

Beta strand

534 – 538

5

Turn

539 – 541

3

Beta strand

544 – 546

3

Beta strand

558 – 562

5

Beta strand

565 – 569

5

Beta strand

580 – 585

6

Turn

586 – 589

4

Beta strand

590 – 596

7

Beta strand

605 – 609

5

Sequences

	Sequence		Length	Mass (Da)
	Q9Z2X8 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 4645DB0122FB5F54	FASTA	624	69,553
	10 20 30 40 50 60 MQPEPKLSGA PRSSQFLPLW SKCPEGAGDA VMYASTECKA EVTPSQDGNR TFSYTLEDHT 70 80 90 100 110 120 KQAFGVMNEL 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 NQWSPCASMS VPRNRIGVGV 430 440 450 460 470 480 IDGHIYAVGG SHGCIHHSSV ERYEPERDEW HLVAPMLTRR IGVGVAVLNR LLYAVGGFDG 490 500 510 520 530 540 TNRLNSAECY YPERNEWRMI TPMNTIRSGA GVCVLHNCIY AAGGYDGQDQ LNSVERYDVE 550 560 570 580 590 600 TETWTFVAPM RHHRSALGIT VHQGKIYVLG GYDGHTFLDS VECYDPDSDT WSEVTRMTSG 610 620 RSGVGVAVTM EPCRKQIDQQ NCTC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain." Itoh K., Wakabayashi N., Katoh Y., Ishii T., Igarashi K., Engel J.D., Yamamoto M. Genes Dev. 13:76-86(1999) [PubMed: 9887101] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Embryo.
[2]	"Mouse INrf2 gene structure." Dhakshinamoorthy S., Jaiswal A.K. Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: C57BL/6.
[3]	"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed: 14621295] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Fetal brain.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Bone marrow, Corpora quadrigemina, Dendritic cell, Liver and Lung.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[6]	"Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression." McMahon M., Itoh K., Yamamoto M., Hayes J.D. J. Biol. Chem. 278:21592-21600(2003) [PubMed: 12682069] [Abstract] Cited for: FUNCTION.
[7]	"Fetal Alz-50 clone 1 interacts with the human orthologue of the Kelch-like Ech-associated protein." Strachan G.D., Morgan K.L., Otis L.L., Caltagarone J., Gittis A., Bowser R., Jordan-Sciutto K.L. Biochemistry 43:12113-12122(2004) [PubMed: 15379550] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer." Padmanabhan B., Tong K.I., Ohta T., Nakamura Y., Scharlock M., Ohtsuji M., Kang M., Kobayashi A., Yokoyama S., Yamamoto M. Mol. Cell 21:689-700(2006) [PubMed: 16507366] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 309-624 IN COMPLEX WITH NFE2L2, MUTAGENESIS OF 599-SER--ARG-601; 602-SER--VAL-604 AND 605-GLY--VAL-608.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00131516.

RefSeq

NP_001103775.1. NM_001110305.1.
NP_001103776.1. NM_001110306.1.
NP_001103777.1. NM_001110307.1.
NP_057888.1. NM_016679.4.

UniGene

Mm.248266.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X2J	X-ray	1.60	A	309-624	[»]
1X2R	X-ray	1.70	A	309-624	[»]
2DYH	X-ray	1.90	A	309-624	[»]
2Z32	X-ray	2.00	A	309-624	[»]
3ADE	X-ray	2.80	A	309-624	[»]

ProteinModelPortal

Q9Z2X8.

SMR

Q9Z2X8. Positions 53-292, 324-613.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Z2X8. 4 interactions.

STRING

Q9Z2X8.

PTM databases

PhosphoSite

Q9Z2X8.

Proteomic databases

PRIDE

Q9Z2X8.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000049567; ENSMUSP00000062467; ENSMUSG00000003308.
ENSMUST00000164812; ENSMUSP00000131029; ENSMUSG00000003308.

GeneID

50868.

KEGG

mmu:50868.

UCSC

uc009oko.2. mouse.

Organism-specific databases

CTD

9817.

MGI

MGI:1858732. Keap1.

Rouge

Search...

Phylogenomic databases

GeneTree

ENSGT00570000078759.

HOGENOM

HBG713858.

HOVERGEN

HBG014286.

InParanoid

Q9Z2X8.

OMA

TLQVKYE.

OrthoDB

EOG4WH8KC.

Gene expression databases

ArrayExpress

Q9Z2X8.

Bgee

Q9Z2X8.

CleanEx

MM_KEAP1.

Genevestigator

Q9Z2X8.

GermOnline

ENSMUSG00000003308. Mus musculus.

Family and domain databases

InterPro

IPR011705. BACK.
IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR017096. Kelch-like_gigaxonin.
IPR015915. Kelch-typ_b-propeller.
IPR006652. Kelch_1.
[Graphical view]

Gene3D

G3DSA:3.30.710.10. BTB/POZ_fold. 1 hit.
G3DSA:2.120.10.80. Kelch-typ_b-propeller. 1 hit.

KO

K10456.

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

307831.

SOURCE

Search...

Entry information

Entry name

KEAP1_MOUSE

Accession

Primary (citable) accession number: Q9Z2X8
Secondary accession number(s): Q3U243 , Q3U8N7, Q547S3, Q6ZQI6, Q8BQY3

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	May 1, 1999
Last modified:	December 14, 2011
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program