Q14145 (KEAP1_HUMAN) 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
Kelch-like protein 19

Gene names

Name:	KEAP1
Synonyms:	INRF2, KIAA0132, KLHL19

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	624 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.13
Enzyme regulation	Ubiquitination and subsequent degradation of PGAM5 is inhibited by oxidative stress and sulforaphane. Sulforaphane also inhibits ubiquitination of NFE2L2/NRF2. Ref.10 Ref.13
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. Interacts with NFE2L1. Interacts indirectly with ENC1. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.19
Subcellular location	Cytoplasm. Nucleus. Note: Shuttles between cytoplasm and nucleus. Ref.7 Ref.8 Ref.11 Ref.15
Tissue specificity	Broadly expressed, with highest levels in skeletal muscle. Ref.8
Domain	The Kelch repeats mediate interaction with NF2L2/NRF2, BPTF and PGAM5. Ref.13
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. Ref.9 Ref.10
Sequence similarities	Contains 1 BACK (BTB/Kelch associated) domain. Contains 1 BTB (POZ) domain. Contains 6 Kelch repeats.
Sequence caution	The sequence BAA09481.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
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 electronic annotation. Source: Compara proteasomal ubiquitin-independent protein catabolic process Inferred from direct assay Ref.10. Source: UniProtKB protein ubiquitination Inferred from direct assay Ref.10. Source: UniProtKB regulation of epidermal cell differentiation Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Cul3-RING ubiquitin ligase complex Inferred from direct assay Ref.10. Source: UniProtKB centrosome Inferred from direct assay. Source: HPA cytoplasm Inferred from direct assay Ref.15. Source: UniProtKB endoplasmic reticulum Inferred from electronic annotation. Source: Compara midbody Inferred from direct assay PubMed 15166316. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IKBKB	O14920	6	EBI-751001,EBI-81266
Ikbkb	O88351	2	EBI-751001,EBI-447960	From a different organism.
Irf1	P15314	2	EBI-751001,EBI-6115486	From a different organism.
RELA	Q04206	4	EBI-751001,EBI-73886
SQSTM1	Q13501	8	EBI-751001,EBI-307104
Sqstm1	Q64337	2	EBI-751001,EBI-645025	From a different organism.
TSC22D4	Q9Y3Q8	3	EBI-751001,EBI-739485

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_0000119093

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

518 – 564

47

Kelch 5

Repeat

565 – 611

47

Kelch 6

Motif

301 – 310

10

Nuclear export signal

Natural variations

Natural variant

23

1

C → Y in a breast cancer sample; somatic mutation. Ref.22

VAR_036084

Natural variant

167

1

V → F in a lung adenocarcinoma patient. Ref.21

VAR_032102

Natural variant

236

1

D → H in a NSCLC cell line. Ref.21

VAR_032103

Natural variant

284

1

Q → L in a lung adenocarcinoma patient. Ref.21

VAR_032104

Natural variant

333

1

G → C in a NSCLC cell line; strongly reduces interaction with NFE2L2 and reduces repression of NFE2L2-dependent gene expression. Ref.21

VAR_032105

Natural variant

349

1

D → N. Ref.2
Corresponds to variant rs1048289 [ dbSNP | Ensembl ].

VAR_032106

Natural variant

350

1

G → S in a NSCLC cell line. Ref.21

VAR_032107

Natural variant

364

1

G → C in a lung adenocarcinoma cell line; also in NSCLC cell lines; may be a polymorphism; strongly reduces interaction with NFE2L2 and reduces repression of NFE2L2-dependent gene expression. Ref.20

VAR_032108

Natural variant

430

1

G → C in a lung adenocarcinoma patient; somatic mutation; strongly reduces interaction with NFE2L2 and reduces repression of NFE2L2-dependent gene expression. Ref.20

VAR_032109

Natural variant

522

1

A → V in a breast cancer sample; somatic mutation. Ref.22

VAR_036085

Experimental info

Mutagenesis

125 – 127

3

IEG → AAA: Increases ubiquitination and proteolytic degradation. Ref.9

Mutagenesis

151

1

C → S: Constitutive repression of NFE2L2-dependent gene expression. Promotes increased degradation of NFE2L2. Resistance of ubiquitination of PGAM5 to inhibition by oxidative stress and sulforaphane. Does not prevent its ubiquitination and degradation in response to quinone-induced oxidative stress. Ref.7 Ref.10 Ref.13

Mutagenesis

162 – 164

3

YQI → AAA: Increases ubiquitination and proteolytic degradation. Ref.9

Mutagenesis

273

1

C → S: Abolishes repression of NFE2L2-dependent gene expression. Slows down degradation of NFE2L2. Ref.7

Mutagenesis

288

1

C → S: Abolishes repression of NFE2L2-dependent gene expression. Slows down degradation of NFE2L2. Ref.7

Mutagenesis

308

1

L → A: Loss of export from nucleus; when associated with A-310. Ref.11

Mutagenesis

310

1

L → A: Loss of export from nucleus; when associated with A-308. Ref.11

Mutagenesis

334

1

Y → A: Loss of interaction with NFE2L2. Strongly reduces repression of NFE2L2-dependent gene expression. Loss of interaction with PGAM5. Ref.13 Ref.19

Mutagenesis

380

1

R → A: Loss of interaction with NFE2L2. Abolishes repression of NFE2L2-dependent gene expression. Ref.19

Mutagenesis

382

1

N → A: Loss of interaction with NFE2L2. Strongly reduces repression of NFE2L2-dependent gene expression. Ref.19

Mutagenesis

415

1

R → A: Loss of interaction with NFE2L2. Abolishes repression of NFE2L2-dependent gene expression. Loss of interaction with PGAM5. Ref.13 Ref.19

Mutagenesis

436

1

H → A: Loss of interaction with NFE2L2. Abolishes repression of NFE2L2-dependent gene expression. Ref.19

Mutagenesis

478

1

F → A: Abolishes repression of NFE2L2-dependent gene expression. Ref.19

Mutagenesis

483

1

R → A: Loss of interaction with NFE2L2. Abolishes repression of NFE2L2-dependent gene expression. Loss of interaction with PGAM5. Ref.13 Ref.19

Mutagenesis

525

1

Y → A: Loss of interaction with NFE2L2. Strongly reduces repression of NFE2L2-dependent gene expression. Ref.19

Mutagenesis

572

1

Y → A: Loss of interaction with NFE2L2. Strongly reduces repression of NFE2L2-dependent gene expression. Loss of interaction with PGAM5. Ref.13 Ref.19

Sequence conflict

504

1

N → S in BAG51647. Ref.4

Secondary structure

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624

Helix Strand Turn

Details...

Beta strand

327 – 331

5

Beta strand

334 – 338

5

Beta strand

342 – 345

4

Turn

347 – 349

3

Beta strand

352 – 354

3

Beta strand

362 – 364

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

Turn

492 – 495

4

Beta strand

496 – 499

4

Beta strand

511 – 515

5

Beta strand

518 – 522

5

Beta strand

527 – 530

4

Beta strand

534 – 538

5

Turn

539 – 542

4

Beta strand

543 – 547

5

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)
	Q14145 [UniParc]. Last modified May 1, 2007. Version 2. Checksum: CE180F3897BB8C97	FASTA	624	69,666
	10 20 30 40 50 60 MQPDPRPSGA GACCRFLPLQ SQCPEGAGDA VMYASTECKA EVTPSQHGNR TFSYTLEDHT 70 80 90 100 110 120 KQAFGIMNEL RLSQQLCDVT LQVKYQDAPA AQFMAHKVVL ASSSPVFKAM FTNGLREQGM 130 140 150 160 170 180 EVVSIEGIHP KVMERLIEFA YTASISMGEK CVLHVMNGAV MYQIDSVVRA CSDFLVQQLD 190 200 210 220 230 240 PSNAIGIANF AEQIGCVELH QRAREYIYMH FGEVAKQEEF FNLSHCQLVT LISRDDLNVR 250 260 270 280 290 300 CESEVFHACI NWVKYDCEQR RFYVQALLRA VRCHSLTPNF LQMQLQKCEI LQSDSRCKDY 310 320 330 340 350 360 LVKIFEELTL HKPTQVMPCR APKVGRLIYT AGGYFRQSLS YLEAYNPSDG TWLRLADLQV 370 380 390 400 410 420 PRSGLAGCVV GGLLYAVGGR NNSPDGNTDS SALDCYNPMT NQWSPCAPMS VPRNRIGVGV 430 440 450 460 470 480 IDGHIYAVGG SHGCIHHNSV ERYEPERDEW HLVAPMLTRR IGVGVAVLNR LLYAVGGFDG 490 500 510 520 530 540 TNRLNSAECY YPERNEWRMI TAMNTIRSGA GVCVLHNCIY AAGGYDGQDQ LNSVERYDVE 550 560 570 580 590 600 TETWTFVAPM KHRRSALGIT VHQGRIYVLG GYDGHTFLDS VECYDPDTDT WSEVTRMTSG 610 620 RSGVGVAVTM EPCRKQIDQQ NCTC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human INrf2 gene structure and nucleotide sequence." Dhakshinamoorthy S., Jaiswal A.K. Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N. DNA Res. 2:167-174(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASN-349. Tissue: Bone marrow.
[3]	Ohara O., Nagase T., Kikuno R., Nomura N. Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Skin and Uterus.
[7]	"Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress." Zhang D.D., Hannink M. Mol. Cell. Biol. 23:8137-8151(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-151; CYS-273 AND CYS-288, SUBCELLULAR LOCATION.
[8]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NF2L2/NRF2 AND BPTF, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[9]	"Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex." Zhang D.D., Lo S.-C., Cross J.V., Templeton D.J., Hannink M. Mol. Cell. Biol. 24:10941-10953(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CUL3 AND RBX1, MUTAGENESIS OF 125-ILE--GLY-127 AND 162-TYR--ILE-164, UBIQUITINATION.
[10]	"Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway." Zhang D.D., Lo S.C., Sun Z., Habib G.M., Lieberman M.W., Hannink M. J. Biol. Chem. 280:30091-30099(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH CUL3 AND RBX1, UBIQUITINATION, ENZYME REGULATION, MUTAGENESIS OF CYS-151.
[11]	"Nuclear oncoprotein prothymosin alpha is a partner of Keap1: implications for expression of oxidative stress-protecting genes." Karapetian R.N., Evstafieva A.G., Abaeva I.S., Chichkova N.V., Filonov G.S., Rubtsov Y.P., Sukhacheva E.A., Melnikov S.V., Schneider U., Wanker E.E., Vartapetian A.B. Mol. Cell. Biol. 25:1089-1099(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PTMA, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-308 AND LEU-310.
[12]	"Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal transmembrane domain. Inhibition of nuclear translocation and transacting function." Wang W., Chan J.Y. J. Biol. Chem. 281:19676-19687(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NFE2L1.
[13]	"PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex." Lo S.-C., Hannink M. J. Biol. Chem. 281:37893-37903(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PGAM5, FUNCTION, ENZYME REGULATION, DOMAIN, MUTAGENESIS OF CYS-151; TYR-334; ARG-415; ARG-483 AND TYR-572.
[14]	"PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria." Lo S.-C., Hannink M. Exp. Cell Res. 314:1789-1803(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NFE2L2 AND PGAM5.
[15]	"Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational level." Wang X.J., Zhang D.D. PLoS ONE 4:E5492-E5492(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ENC1, SUBCELLULAR LOCATION.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"Crystallization and initial crystallographic analysis of the Kelch domain from human Keap1." Li X., Zhang D., Hannink M., Beamer L.J. Acta Crystallogr. D 60:2346-2348(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 321-609.
[18]	"Conserved solvent and side-chain interactions in the 1.35 Angstrom structure of the Kelch domain of Keap1." Beamer L.J., Li X., Bottoms C.A., Hannink M. Acta Crystallogr. D 61:1335-1342(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 321-609.
[19]	"Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling." Lo S.-C., Li X., Henzl M.T., Beamer L.J., Hannink M. EMBO J. 25:3605-3617(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 321-609 IN COMPLEX WITH NFE2L2, SUBUNIT, MUTAGENESIS OF TYR-334; ARG-380; ASN-382; ARG-415; HIS-436; PHE-478; ARG-483; TYR-525 AND TYR-572.
[20]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS CYS-364 AND CYS-430, CHARACTERIZATION OF VARIANTS CYS-364 AND CYS-430.
[21]	"Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer." Singh A., Misra V., Thimmulappa R.K., Lee H., Ames S., Hoque M.O., Herman J.G., Baylin S.B., Sidransky D., Gabrielson E., Brock M.V., Biswal S. PLoS Med. 3:1865-1876(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PHE-167; HIS-236; LEU-284; CYS-333 AND SER-350, CHARACTERIZATION OF VARIANTS HIS-236 AND CYS-333.
[22]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] TYR-23 AND VAL-522.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF361892 , AF361888, AF361889, AF361890, AF361891 Genomic DNA. Translation: AAK43722.1.
AF361886 mRNA. Translation: AAK51082.1.
D50922 mRNA. Translation: BAA09481.3. Different initiation.
AK056204 mRNA. Translation: BAG51647.1.
AC011461 Genomic DNA. No translation available.
BC002417 mRNA. Translation: AAH02417.1.
BC002930 mRNA. Translation: AAH02930.1.
BC015945 mRNA. Translation: AAH15945.1.
BC021957 mRNA. Translation: AAH21957.2.

IPI

IPI00106502.

RefSeq

NP_036421.2. NM_012289.3.
NP_987096.1. NM_203500.1.

UniGene

Hs.465870.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1U6D	X-ray	1.85	X	321-609	[»]
1ZGK	X-ray	1.35	A	321-609	[»]
2FLU	X-ray	1.50	X	321-609	[»]
3VNG	X-ray	2.10	A	321-609	[»]
3VNH	X-ray	2.10	A	321-609	[»]

ProteinModelPortal

Q14145.

ModBase

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Protein-protein interaction databases

DIP

DIP-42134N.

IntAct

Q14145. 49 interactions.

MINT

MINT-1197065.

STRING

9606.ENSP00000171111.

PTM databases

PhosphoSite

Q14145.

Polymorphism databases

DMDM

146345444.

Proteomic databases

PaxDb

Q14145.

PRIDE

Q14145.

Protocols and materials databases

DNASU

9817.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000171111; ENSP00000171111; ENSG00000079999.
ENST00000393623; ENSP00000377245; ENSG00000079999.

GeneID

9817.

KEGG

hsa:9817.

UCSC

uc002moq.1. human.

Organism-specific databases

CTD

9817.

GeneCards

GC19M010596.

HGNC

HGNC:23177. KEAP1.

HPA

CAB025337.
HPA005558.

MIM

606016. gene.

neXtProt

NX_Q14145.

PharmGKB

PA134887774.

HUGE

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GenAtlas

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Phylogenomic databases

eggNOG

NOG255039.

HOGENOM

HOG000230814.

HOVERGEN

HBG014286.

InParanoid

Q14145.

KO

K10456.

OMA

TLQVKYE.

OrthoDB

EOG4WH8KC.

PhylomeDB

Q14145.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

Bgee

Q14145.

CleanEx

HS_KEAP1.

Genevestigator

Q14145.

GermOnline

ENSG00000079999. Homo sapiens.

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

EvolutionaryTrace

Q14145.

GenomeRNAi

9817.

NextBio

36968.

SOURCE

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Entry information

Entry name

KEAP1_HUMAN

Accession

Primary (citable) accession number: Q14145
Secondary accession number(s): B3KPD5 , Q6LEP0, Q8WTX1, Q9BPY9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	May 1, 2007
Last modified:	May 1, 2013
This is version 135 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.