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Q14145 (KEAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length624 AA.
Sequence statusComplete.
Protein existenceEvidence 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 and MAP1LC3B. Interacts indirectly with ENC1. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.20

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 processTranscription
Transcription regulation
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainKelch repeat
Repeat
   PTMUbl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to interleukin-4

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentCul3-RING ubiquitin ligase complex

Inferred from direct assay Ref.10. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.15. Source: UniProtKB

endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

microtubule organizing center

Inferred from direct assay. Source: HPA

midbody

Inferred from direct assay PubMed 15166316. Source: UniProtKB

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionprotein binding

Inferred from physical interaction Ref.15Ref.17. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 624624Kelch-like ECH-associated protein 1
PRO_0000119093

Regions

Domain77 – 14973BTB
Domain184 – 286103BACK
Repeat327 – 37246Kelch 1
Repeat373 – 42351Kelch 2
Repeat424 – 47047Kelch 3
Repeat471 – 51747Kelch 4
Repeat518 – 56447Kelch 5
Repeat565 – 61147Kelch 6
Motif301 – 31010Nuclear export signal

Natural variations

Natural variant231C → Y in a breast cancer sample; somatic mutation. Ref.23
VAR_036084
Natural variant1671V → F in a lung adenocarcinoma patient. Ref.22
VAR_032102
Natural variant2361D → H in a NSCLC cell line. Ref.22
VAR_032103
Natural variant2841Q → L in a lung adenocarcinoma patient. Ref.22
VAR_032104
Natural variant3331G → C in a NSCLC cell line; strongly reduces interaction with NFE2L2 and reduces repression of NFE2L2-dependent gene expression. Ref.22
VAR_032105
Natural variant3491D → N. Ref.2
Corresponds to variant rs1048289 [ dbSNP | Ensembl ].
VAR_032106
Natural variant3501G → S in a NSCLC cell line. Ref.22
VAR_032107
Natural variant3641G → 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.21
VAR_032108
Natural variant4301G → C in a lung adenocarcinoma patient; somatic mutation; strongly reduces interaction with NFE2L2 and reduces repression of NFE2L2-dependent gene expression. Ref.21
VAR_032109
Natural variant5221A → V in a breast cancer sample; somatic mutation. Ref.23
VAR_036085

Experimental info

Mutagenesis125 – 1273IEG → AAA: Increases ubiquitination and proteolytic degradation. Ref.9
Mutagenesis1511C → 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
Mutagenesis162 – 1643YQI → AAA: Increases ubiquitination and proteolytic degradation. Ref.9
Mutagenesis2731C → S: Abolishes repression of NFE2L2-dependent gene expression. Slows down degradation of NFE2L2. Ref.7
Mutagenesis2881C → S: Abolishes repression of NFE2L2-dependent gene expression. Slows down degradation of NFE2L2. Ref.7
Mutagenesis3081L → A: Loss of export from nucleus; when associated with A-310. Ref.11
Mutagenesis3101L → A: Loss of export from nucleus; when associated with A-308. Ref.11
Mutagenesis3341Y → A: Loss of interaction with NFE2L2. Strongly reduces repression of NFE2L2-dependent gene expression. Loss of interaction with PGAM5. Ref.13 Ref.20
Mutagenesis3801R → A: Loss of interaction with NFE2L2. Abolishes repression of NFE2L2-dependent gene expression. Ref.20
Mutagenesis3821N → A: Loss of interaction with NFE2L2. Strongly reduces repression of NFE2L2-dependent gene expression. Ref.20
Mutagenesis4151R → A: Loss of interaction with NFE2L2. Abolishes repression of NFE2L2-dependent gene expression. Loss of interaction with PGAM5. Ref.13 Ref.20
Mutagenesis4361H → A: Loss of interaction with NFE2L2. Abolishes repression of NFE2L2-dependent gene expression. Ref.20
Mutagenesis4781F → A: Abolishes repression of NFE2L2-dependent gene expression. Ref.20
Mutagenesis4831R → A: Loss of interaction with NFE2L2. Abolishes repression of NFE2L2-dependent gene expression. Loss of interaction with PGAM5. Ref.13 Ref.20
Mutagenesis5251Y → A: Loss of interaction with NFE2L2. Strongly reduces repression of NFE2L2-dependent gene expression. Ref.20
Mutagenesis5721Y → A: Loss of interaction with NFE2L2. Strongly reduces repression of NFE2L2-dependent gene expression. Loss of interaction with PGAM5. Ref.13 Ref.20
Sequence conflict5041N → S in BAG51647. Ref.4

Secondary structure

................................................................... 624
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q14145 [UniParc].

Last modified May 1, 2007. Version 2.
Checksum: CE180F3897BB8C97

FASTA62469,666
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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]"Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites."
Tang Z., Lin M.G., Stowe T.R., Chen S., Zhu M., Stearns T., Franco B., Zhong Q.
Nature 502:254-257(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP1LC3B.
[18]"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.
[19]"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.
[20]"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.
[21]"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.
[22]"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.
[23]"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. expand/collapse author list , 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 expand/collapse EMBL AC list , 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.
CCDSCCDS12239.1.
RefSeqNP_036421.2. NM_012289.3.
NP_987096.1. NM_203500.1.
XP_005260230.1. XM_005260173.1.
XP_005260231.1. XM_005260174.1.
UniGeneHs.465870.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1U6DX-ray1.85X321-609[»]
1ZGKX-ray1.35A321-609[»]
2FLUX-ray1.50X321-609[»]
3VNGX-ray2.10A321-609[»]
3VNHX-ray2.10A321-609[»]
3ZGCX-ray2.20A/B321-609[»]
3ZGDX-ray1.98A/B321-609[»]
4IFLX-ray1.80X321-609[»]
4IFNX-ray2.40X321-609[»]
4IN4X-ray2.59A/B/C321-609[»]
4IQKX-ray1.97A321-609[»]
4L7BX-ray2.41A/B321-609[»]
4L7CX-ray2.40A/B/C321-609[»]
4L7DX-ray2.25A/B/C321-609[»]
4N1BX-ray2.55A/B/C321-609[»]
ProteinModelPortalQ14145.
SMRQ14145. Positions 59-297, 322-609.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115156. 72 interactions.
DIPDIP-42134N.
IntActQ14145. 51 interactions.
MINTMINT-1197065.
STRING9606.ENSP00000171111.

Chemistry

ChEMBLCHEMBL3038498.

PTM databases

PhosphoSiteQ14145.

Polymorphism databases

DMDM146345444.

Proteomic databases

MaxQBQ14145.
PaxDbQ14145.
PRIDEQ14145.

Protocols and materials databases

DNASU9817.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000171111; ENSP00000171111; ENSG00000079999.
ENST00000393623; ENSP00000377245; ENSG00000079999.
GeneID9817.
KEGGhsa:9817.
UCSCuc002moq.1. human.

Organism-specific databases

CTD9817.
GeneCardsGC19M010596.
HGNCHGNC:23177. KEAP1.
HPACAB025337.
HPA005558.
MIM606016. gene.
neXtProtNX_Q14145.
PharmGKBPA134887774.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG255039.
HOGENOMHOG000230814.
HOVERGENHBG014286.
InParanoidQ14145.
KOK10456.
OMAQIGCTEL.
OrthoDBEOG76739M.
PhylomeDBQ14145.
TreeFamTF329218.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ14145.
BgeeQ14145.
CleanExHS_KEAP1.
GenevestigatorQ14145.

Family and domain databases

Gene3D2.130.10.80. 1 hit.
3.30.710.10. 1 hit.
InterProIPR011705. BACK.
IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR013069. BTB_POZ.
IPR015916. Gal_Oxidase_b-propeller.
IPR017096. Kelch-like_gigaxonin-typ.
IPR006652. Kelch_1.
[Graphical view]
PfamPF07707. BACK. 1 hit.
PF00651. BTB. 1 hit.
PF01344. Kelch_1. 6 hits.
[Graphical view]
PIRSFPIRSF037037. Kelch-like_protein_gigaxonin. 1 hit.
SMARTSM00875. BACK. 1 hit.
SM00225. BTB. 1 hit.
SM00612. Kelch. 6 hits.
[Graphical view]
SUPFAMSSF54695. SSF54695. 1 hit.
PROSITEPS50097. BTB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ14145.
GeneWikiKEAP1.
GenomeRNAi9817.
NextBio36968.
PROQ14145.
SOURCESearch...

Entry information

Entry nameKEAP1_HUMAN
AccessionPrimary (citable) accession number: Q14145
Secondary accession number(s): B3KPD5 expand/collapse secondary AC list , Q6LEP0, Q8WTX1, Q9BPY9
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 2007
Last modified: July 9, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM