KEAP1_HUMAN
ID KEAP1_HUMAN Reviewed; 624 AA.
AC Q14145; B3KPD5; Q6LEP0; Q8WTX1; Q9BPY9;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Kelch-like ECH-associated protein 1 {ECO:0000303|PubMed:14585973};
DE AltName: Full=Cytosolic inhibitor of Nrf2 {ECO:0000303|Ref.1};
DE Short=INrf2 {ECO:0000303|Ref.1};
DE AltName: Full=Kelch-like protein 19 {ECO:0000312|HGNC:HGNC:23177};
GN Name=KEAP1 {ECO:0000303|PubMed:14585973, ECO:0000312|HGNC:HGNC:23177};
GN Synonyms=INRF2 {ECO:0000303|Ref.1}, KIAA0132 {ECO:0000303|PubMed:8590280},
GN KLHL19 {ECO:0000312|HGNC:HGNC:23177};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RA Dhakshinamoorthy S., Jaiswal A.K.;
RT "Human INrf2 gene structure and nucleotide sequence.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-349.
RC TISSUE=Bone marrow;
RX PubMed=8590280; DOI=10.1093/dnares/2.4.167;
RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. IV. The
RT coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of
RT cDNA clones from human cell line KG-1.";
RL DNA Res. 2:167-174(1995).
RN [3]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R., Nomura N.;
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, MUTAGENESIS OF CYS-151; CYS-273 AND CYS-288, AND SUBCELLULAR
RP LOCATION.
RX PubMed=14585973; DOI=10.1128/mcb.23.22.8137-8151.2003;
RA Zhang D.D., Hannink M.;
RT "Distinct cysteine residues in Keap1 are required for Keap1-dependent
RT ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive
RT agents and oxidative stress.";
RL Mol. Cell. Biol. 23:8137-8151(2003).
RN [8]
RP INTERACTION WITH NFE2L2 AND BPTF, FUNCTION, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15379550; DOI=10.1021/bi0494166;
RA Strachan G.D., Morgan K.L., Otis L.L., Caltagarone J., Gittis A.,
RA Bowser R., Jordan-Sciutto K.L.;
RT "Fetal Alz-50 clone 1 interacts with the human orthologue of the Kelch-like
RT Ech-associated protein.";
RL Biochemistry 43:12113-12122(2004).
RN [9]
RP FUNCTION, INTERACTION WITH CUL3 AND RBX1, MUTAGENESIS OF 125-ILE--GLY-127
RP AND 162-TYR--ILE-164, AND UBIQUITINATION.
RX PubMed=15572695; DOI=10.1128/mcb.24.24.10941-10953.2004;
RA Zhang D.D., Lo S.-C., Cross J.V., Templeton D.J., Hannink M.;
RT "Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent
RT ubiquitin ligase complex.";
RL Mol. Cell. Biol. 24:10941-10953(2004).
RN [10]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH CUL3 AND RBX1, UBIQUITINATION,
RP ACTIVITY REGULATION, AND MUTAGENESIS OF CYS-151.
RX PubMed=15983046; DOI=10.1074/jbc.m501279200;
RA Zhang D.D., Lo S.C., Sun Z., Habib G.M., Lieberman M.W., Hannink M.;
RT "Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3,
RT targets Keap1 for degradation by a proteasome-independent pathway.";
RL J. Biol. Chem. 280:30091-30099(2005).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE BCR(KEAP1) COMPLEX,
RP INTERACTION WITH NFE2L2, AND MUTAGENESIS OF 123-VAL--GLY-127 AND
RP 161-MET-TYR-162.
RX PubMed=15601839; DOI=10.1128/mcb.25.1.162-171.2005;
RA Furukawa M., Xiong Y.;
RT "BTB protein Keap1 targets antioxidant transcription factor Nrf2 for
RT ubiquitination by the Cullin 3-Roc1 ligase.";
RL Mol. Cell. Biol. 25:162-171(2005).
RN [12]
RP INTERACTION WITH PTMA, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-308 AND
RP LEU-310.
RX PubMed=15657435; DOI=10.1128/mcb.25.3.1089-1099.2005;
RA Karapetian R.N., Evstafieva A.G., Abaeva I.S., Chichkova N.V.,
RA Filonov G.S., Rubtsov Y.P., Sukhacheva E.A., Melnikov S.V., Schneider U.,
RA Wanker E.E., Vartapetian A.B.;
RT "Nuclear oncoprotein prothymosin alpha is a partner of Keap1: implications
RT for expression of oxidative stress-protecting genes.";
RL Mol. Cell. Biol. 25:1089-1099(2005).
RN [13]
RP FUNCTION, ACTIVITY REGULATION, DOMAIN, AND MUTAGENESIS OF CYS-151.
RX PubMed=19489739; DOI=10.1042/bj20090471;
RA Eggler A.L., Small E., Hannink M., Mesecar A.D.;
RT "Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE)
RT activation are dependent on the partial molar volume at position 151 of
RT Keap1.";
RL Biochem. J. 422:171-180(2009).
RN [14]
RP FUNCTION, AND INTERACTION WITH NFE2L2.
RX PubMed=16006525; DOI=10.1073/pnas.0502402102;
RA Eggler A.L., Liu G., Pezzuto J.M., van Breemen R.B., Mesecar A.D.;
RT "Modifying specific cysteines of the electrophile-sensing human Keap1
RT protein is insufficient to disrupt binding to the Nrf2 domain Neh2.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:10070-10075(2005).
RN [15]
RP INTERACTION WITH NFE2L1.
RX PubMed=16687406; DOI=10.1074/jbc.m602802200;
RA Wang W., Chan J.Y.;
RT "Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal
RT transmembrane domain. Inhibition of nuclear translocation and transacting
RT function.";
RL J. Biol. Chem. 281:19676-19687(2006).
RN [16]
RP INTERACTION WITH PGAM5, FUNCTION, ACTIVITY REGULATION, DOMAIN, AND
RP MUTAGENESIS OF CYS-151; TYR-334; ARG-415; ARG-483 AND TYR-572.
RX PubMed=17046835; DOI=10.1074/jbc.m606539200;
RA Lo S.-C., Hannink M.;
RT "PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-
RT regulated Keap1-dependent ubiquitin ligase complex.";
RL J. Biol. Chem. 281:37893-37903(2006).
RN [17]
RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH CUL3.
RX PubMed=17127771; DOI=10.1074/jbc.m607622200;
RA Gao L., Wang J., Sekhar K.R., Yin H., Yared N.F., Schneider S.N., Sasi S.,
RA Dalton T.P., Anderson M.E., Chan J.Y., Morrow J.D., Freeman M.L.;
RT "Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the
RT association between Keap1 and Cullin3.";
RL J. Biol. Chem. 282:2529-2537(2007).
RN [18]
RP FUNCTION, ACTIVITY REGULATION, DOMAIN, AND MUTAGENESIS OF CYS-151.
RX PubMed=18251510; DOI=10.1021/tx700302s;
RA Rachakonda G., Xiong Y., Sekhar K.R., Stamer S.L., Liebler D.C.,
RA Freeman M.L.;
RT "Covalent modification at Cys151 dissociates the electrophile sensor Keap1
RT from the ubiquitin ligase CUL3.";
RL Chem. Res. Toxicol. 21:705-710(2008).
RN [19]
RP INTERACTION WITH NFE2L2 AND PGAM5.
RX PubMed=18387606; DOI=10.1016/j.yexcr.2008.02.014;
RA Lo S.-C., Hannink M.;
RT "PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to
RT mitochondria.";
RL Exp. Cell Res. 314:1789-1803(2008).
RN [20]
RP INTERACTION WITH ENC1, AND SUBCELLULAR LOCATION.
RX PubMed=19424503; DOI=10.1371/journal.pone.0005492;
RA Wang X.J., Zhang D.D.;
RT "Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational
RT level.";
RL PLoS ONE 4:E5492-E5492(2009).
RN [21]
RP INTERACTION WITH SQSTM1, AND ACTIVITY REGULATION.
RX PubMed=20495340; DOI=10.4161/auto.6.5.12189;
RA Fan W., Tang Z., Chen D., Moughon D., Ding X., Chen S., Zhu M., Zhong Q.;
RT "Keap1 facilitates p62-mediated ubiquitin aggregate clearance via
RT autophagy.";
RL Autophagy 6:614-621(2010).
RN [22]
RP FUNCTION, INTERACTION WITH SQSTM1, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF ARG-380; ASN-382; ARG-415; HIS-436; ARG-483;
RP TYR-525 AND TYR-572.
RX PubMed=20452972; DOI=10.1074/jbc.m110.118976;
RA Jain A., Lamark T., Sjoettem E., Larsen K.B., Awuh J.A., Oevervatn A.,
RA McMahon M., Hayes J.D., Johansen T.;
RT "p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a
RT positive feedback loop by inducing antioxidant response element-driven gene
RT transcription.";
RL J. Biol. Chem. 285:22576-22591(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP INTERACTION WITH SESN1 AND SESN2.
RX PubMed=23274085; DOI=10.1016/j.cmet.2012.12.002;
RA Bae S.H., Sung S.H., Oh S.Y., Lim J.M., Lee S.K., Park Y.N., Lee H.E.,
RA Kang D., Rhee S.G.;
RT "Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation
RT of Keap1 and prevent oxidative liver damage.";
RL Cell Metab. 17:73-84(2013).
RN [25]
RP INTERACTION WITH MAP1LC3B.
RX PubMed=24089205; DOI=10.1038/nature12606;
RA Tang Z., Lin M.G., Stowe T.R., Chen S., Zhu M., Stearns T., Franco B.,
RA Zhong Q.;
RT "Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar
RT satellites.";
RL Nature 502:254-257(2013).
RN [26]
RP INTERACTION WITH HSP90AA1 AND HSP90AB1.
RX PubMed=26517842; DOI=10.1371/journal.pone.0141786;
RA Prince T.L., Kijima T., Tatokoro M., Lee S., Tsutsumi S., Yim K., Rivas C.,
RA Alarcon S., Schwartz H., Khamit-Kush K., Scroggins B.T., Beebe K.,
RA Trepel J.B., Neckers L.;
RT "Client proteins and small molecule inhibitors display distinct binding
RT preferences for constitutive and stress-induced HSP90 isoforms and their
RT conformationally restricted mutants.";
RL PLoS ONE 10:E0141786-E0141786(2015).
RN [27]
RP INTERACTION WITH EBOLAVIRUS PROTEIN VP24 (MICROBIAL INFECTION).
RX PubMed=24630991; DOI=10.1016/j.celrep.2014.01.043;
RA Edwards M.R., Johnson B., Mire C.E., Xu W., Shabman R.S., Speller L.N.,
RA Leung D.W., Geisbert T.W., Amarasinghe G.K., Basler C.F.;
RT "The Marburg virus VP24 protein interacts with Keap1 to activate the
RT cytoprotective antioxidant response pathway.";
RL Cell Rep. 6:1017-1025(2014).
RN [28]
RP FUNCTION.
RX PubMed=28380357; DOI=10.1016/j.celrep.2017.03.030;
RA Lee Y., Chou T.F., Pittman S.K., Keith A.L., Razani B., Weihl C.C.;
RT "Keap1/cullin3 modulates p62/SQSTM1 activity via UBA domain
RT ubiquitination.";
RL Cell Rep. 19:188-202(2017).
RN [29]
RP FUNCTION, ALKYLATION AT CYS-151; CYS-257; CYS-273 AND CYS-288, ACTIVITY
RP REGULATION, DOMAIN, AND MUTAGENESIS OF CYS-151.
RX PubMed=29590092; DOI=10.1038/nature25986;
RA Mills E.L., Ryan D.G., Prag H.A., Dikovskaya D., Menon D., Zaslona Z.,
RA Jedrychowski M.P., Costa A.S.H., Higgins M., Hams E., Szpyt J.,
RA Runtsch M.C., King M.S., McGouran J.F., Fischer R., Kessler B.M.,
RA McGettrick A.F., Hughes M.M., Carroll R.G., Booty L.M., Knatko E.V.,
RA Meakin P.J., Ashford M.L.J., Modis L.K., Brunori G., Sevin D.C.,
RA Fallon P.G., Caldwell S.T., Kunji E.R.S., Chouchani E.T., Frezza C.,
RA Dinkova-Kostova A.T., Hartley R.C., Murphy M.P., O'Neill L.A.;
RT "Itaconate is an anti-inflammatory metabolite that activates Nrf2 via
RT alkylation of KEAP1.";
RL Nature 556:113-117(2018).
RN [30]
RP CROSS-LINK AT ARG-135 AND CYS-151, ACTIVITY REGULATION, DOMAIN, AND
RP MUTAGENESIS OF ARG-15; ARG-135 AND CYS-151.
RX PubMed=30323285; DOI=10.1038/s41586-018-0622-0;
RA Bollong M.J., Lee G., Coukos J.S., Yun H., Zambaldo C., Chang J.W.,
RA Chin E.N., Ahmad I., Chatterjee A.K., Lairson L.L., Schultz P.G.,
RA Moellering R.E.;
RT "A metabolite-derived protein modification integrates glycolysis with
RT KEAP1-NRF2 signalling.";
RL Nature 562:600-604(2018).
RN [31]
RP REVIEW.
RX PubMed=28842501; DOI=10.1074/jbc.r117.800169;
RA Suzuki T., Yamamoto M.;
RT "Stress-sensing mechanisms and the physiological roles of the Keap1-Nrf2
RT system during cellular stress.";
RL J. Biol. Chem. 292:16817-16824(2017).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 321-609.
RX PubMed=15583386; DOI=10.1107/s0907444904024825;
RA Li X., Zhang D., Hannink M., Beamer L.J.;
RT "Crystallization and initial crystallographic analysis of the Kelch domain
RT from human Keap1.";
RL Acta Crystallogr. D 60:2346-2348(2004).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 321-609.
RX PubMed=16204884; DOI=10.1107/s0907444905022626;
RA Beamer L.J., Li X., Bottoms C.A., Hannink M.;
RT "Conserved solvent and side-chain interactions in the 1.35 Angstrom
RT structure of the Kelch domain of Keap1.";
RL Acta Crystallogr. D 61:1335-1342(2005).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 321-609 IN COMPLEX WITH NFE2L2,
RP SUBUNIT, AND MUTAGENESIS OF TYR-334; ARG-380; ASN-382; ARG-415; HIS-436;
RP PHE-478; ARG-483; TYR-525 AND TYR-572.
RX PubMed=16888629; DOI=10.1038/sj.emboj.7601243;
RA Lo S.-C., Li X., Henzl M.T., Beamer L.J., Hannink M.;
RT "Structure of the Keap1:Nrf2 interface provides mechanistic insight into
RT Nrf2 signaling.";
RL EMBO J. 25:3605-3617(2006).
RN [35] {ECO:0007744|PDB:4CXI, ECO:0007744|PDB:4CXJ, ECO:0007744|PDB:4CXT}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 48-180, INTERACTION WITH CUL3,
RP AND MUTAGENESIS OF CYS-151.
RX PubMed=24896564; DOI=10.1371/journal.pone.0098896;
RA Cleasby A., Yon J., Day P.J., Richardson C., Tickle I.J., Williams P.A.,
RA Callahan J.F., Carr R., Concha N., Kerns J.K., Qi H., Sweitzer T., Ward P.,
RA Davies T.G.;
RT "Structure of the BTB domain of Keap1 and its interaction with the
RT triterpenoid antagonist CDDO.";
RL PLoS ONE 9:e98896-e98896(2014).
RN [36]
RP VARIANTS CYS-364 AND CYS-430, AND CHARACTERIZATION OF VARIANTS CYS-364 AND
RP CYS-430.
RX PubMed=16507366; DOI=10.1016/j.molcel.2006.01.013;
RA Padmanabhan B., Tong K.I., Ohta T., Nakamura Y., Scharlock M., Ohtsuji M.,
RA Kang M., Kobayashi A., Yokoyama S., Yamamoto M.;
RT "Structural basis for defects of Keap1 activity provoked by its point
RT mutations in lung cancer.";
RL Mol. Cell 21:689-700(2006).
RN [37]
RP VARIANTS PHE-167; HIS-236; LEU-284; CYS-333 AND SER-350, AND
RP CHARACTERIZATION OF VARIANTS HIS-236 AND CYS-333.
RX PubMed=17020408; DOI=10.1371/journal.pmed.0030420;
RA Singh A., Misra V., Thimmulappa R.K., Lee H., Ames S., Hoque M.O.,
RA Herman J.G., Baylin S.B., Sidransky D., Gabrielson E., Brock M.V.,
RA Biswal S.;
RT "Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer.";
RL PLoS Med. 3:1865-1876(2006).
RN [38]
RP VARIANTS [LARGE SCALE ANALYSIS] TYR-23 AND VAL-522.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3
CC ubiquitin ligase complex that regulates the response to oxidative
CC stress by targeting NFE2L2/NRF2 for ubiquitination (PubMed:14585973,
CC PubMed:15379550, PubMed:15572695, PubMed:15983046, PubMed:15601839).
CC KEAP1 acts as a key sensor of oxidative and electrophilic stress: in
CC normal conditions, the BCR(KEAP1) complex mediates ubiquitination and
CC degradation of NFE2L2/NRF2, a transcription factor regulating
CC expression of many cytoprotective genes (PubMed:15601839,
CC PubMed:16006525). In response to oxidative stress, different
CC electrophile metabolites trigger non-enzymatic covalent modifications
CC of highly reactive cysteine residues in KEAP1, leading to inactivate
CC the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting
CC NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying
CC enzymes (PubMed:19489739, PubMed:16006525, PubMed:17127771,
CC PubMed:18251510, PubMed:29590092). In response to selective autophagy,
CC KEAP1 is sequestered in inclusion bodies following its interaction with
CC SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and
CC activation of NFE2L2/NRF2 (PubMed:20452972). The BCR(KEAP1) complex
CC also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62
CC sequestering activity and degradation (PubMed:28380357). The BCR(KEAP1)
CC complex also targets BPTF and PGAM5 for ubiquitination and degradation
CC by the proteasome (PubMed:15379550, PubMed:17046835).
CC {ECO:0000269|PubMed:14585973, ECO:0000269|PubMed:15379550,
CC ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15601839,
CC ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16006525,
CC ECO:0000269|PubMed:17046835, ECO:0000269|PubMed:17127771,
CC ECO:0000269|PubMed:18251510, ECO:0000269|PubMed:19489739,
CC ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:28380357,
CC ECO:0000269|PubMed:29590092}.
CC -!- ACTIVITY REGULATION: Ubiquitin ligase activity of the BCR(KEAP1)
CC complex is inhibited by oxidative stress and electrophile metabolites
CC such as sulforaphane (PubMed:15983046, PubMed:17046835,
CC PubMed:29590092, PubMed:30323285). Electrophile metabolites react with
CC reactive cysteine residues in KEAP1 and trigger non-enzymatic covalent
CC modifications of these cysteine residues, leading to inactivate the
CC ubiquitin ligase activity of the BCR(KEAP1) complex (PubMed:19489739,
CC PubMed:17127771, PubMed:18251510, PubMed:29590092, PubMed:30323285).
CC Selective autophagy also inactivates the BCR(KEAP1) complex via
CC interaction between KEAP1 and SQSTM1/p62, which sequesters the complex
CC in inclusion bodies and promotes its degradation (PubMed:20495340,
CC PubMed:20452972). {ECO:0000269|PubMed:15983046,
CC ECO:0000269|PubMed:17046835, ECO:0000269|PubMed:17127771,
CC ECO:0000269|PubMed:18251510, ECO:0000269|PubMed:19489739,
CC ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:20495340,
CC ECO:0000269|PubMed:29590092, ECO:0000269|PubMed:30323285}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:14585973, ECO:0000269|PubMed:15379550,
CC ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15601839,
CC ECO:0000269|PubMed:15983046}.
CC -!- SUBUNIT: Component of the BCR(KEAP1) E3 ubiquitin ligase complex, at
CC least composed of 2 molecules of CUL3, 2 molecules of KEAP1, and RBX1
CC (PubMed:15572695, PubMed:15983046, PubMed:15601839, PubMed:17127771,
CC PubMed:18251510, PubMed:24896564). Interacts with NFE2L2/NRF2; the
CC interaction is direct (PubMed:15379550, PubMed:15601839,
CC PubMed:16006525, PubMed:18387606, PubMed:16888629). Forms a ternary
CC complex with NFE2L2/NRF2 and PGAM5 (PubMed:17046835). Interacts with
CC (phosphorylated) SQSTM1/p62; the interaction is direct and inactivates
CC the BCR(KEAP1) complex by sequestering it in inclusion bodies,
CC promoting its degradation (PubMed:20495340, PubMed:20452972). Interacts
CC with NFE2L1 (PubMed:16687406). Interacts with BPTF and PTMA
CC (PubMed:15657435). Interacts with MAP1LC3B (PubMed:24089205). Interacts
CC indirectly with ENC1 (PubMed:19424503). Interacts with SESN1 and SESN2
CC (PubMed:23274085). Interacts with HSP90AA1 and HSP90AB1
CC (PubMed:26517842). {ECO:0000269|PubMed:15379550,
CC ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15601839,
CC ECO:0000269|PubMed:15657435, ECO:0000269|PubMed:15983046,
CC ECO:0000269|PubMed:16006525, ECO:0000269|PubMed:16687406,
CC ECO:0000269|PubMed:16888629, ECO:0000269|PubMed:17046835,
CC ECO:0000269|PubMed:17127771, ECO:0000269|PubMed:18251510,
CC ECO:0000269|PubMed:18387606, ECO:0000269|PubMed:19424503,
CC ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:20495340,
CC ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:24089205,
CC ECO:0000269|PubMed:24896564, ECO:0000269|PubMed:26517842}.
CC -!- SUBUNIT: (Microbial infection) Interacts with ebolavirus protein VP24;
CC this interaction activates transcription factor NFE2L2/NRF2 by blocking
CC its interaction with KEAP1. {ECO:0000269|PubMed:24630991}.
CC -!- INTERACTION:
CC Q14145; Q5JTC6: AMER1; NbExp=2; IntAct=EBI-751001, EBI-6169747;
CC Q14145; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-751001, EBI-11954519;
CC Q14145; P45381: ASPA; NbExp=4; IntAct=EBI-751001, EBI-750475;
CC Q14145; O14525-2: ASTN1; NbExp=4; IntAct=EBI-751001, EBI-21977454;
CC Q14145; Q9Y2D1: ATF5; NbExp=3; IntAct=EBI-751001, EBI-492509;
CC Q14145; A9UGY9: ATG5; NbExp=3; IntAct=EBI-751001, EBI-10175276;
CC Q14145; Q9H1Y0: ATG5; NbExp=3; IntAct=EBI-751001, EBI-1047414;
CC Q14145; Q2NKX9: C2orf68; NbExp=4; IntAct=EBI-751001, EBI-11603468;
CC Q14145; Q9BWT7: CARD10; NbExp=3; IntAct=EBI-751001, EBI-3866279;
CC Q14145; Q9NPC3: CCNB1IP1; NbExp=4; IntAct=EBI-751001, EBI-745269;
CC Q14145; P02452: COL1A1; NbExp=3; IntAct=EBI-751001, EBI-982999;
CC Q14145; P02458-1: COL2A1; NbExp=3; IntAct=EBI-751001, EBI-12375799;
CC Q14145; P68400: CSNK2A1; NbExp=3; IntAct=EBI-751001, EBI-347804;
CC Q14145; Q13618: CUL3; NbExp=5; IntAct=EBI-751001, EBI-456129;
CC Q14145; Q9NX09: DDIT4; NbExp=3; IntAct=EBI-751001, EBI-715104;
CC Q14145; Q9NY33: DPP3; NbExp=8; IntAct=EBI-751001, EBI-718333;
CC Q14145; Q96JC9: EAF1; NbExp=3; IntAct=EBI-751001, EBI-769261;
CC Q14145; Q6P6B1: ERICH5; NbExp=3; IntAct=EBI-751001, EBI-11343491;
CC Q14145; P62495: ETF1; NbExp=8; IntAct=EBI-751001, EBI-750990;
CC Q14145; Q6P1L5: FAM117B; NbExp=6; IntAct=EBI-751001, EBI-3893327;
CC Q14145; Q14440: GPErik; NbExp=3; IntAct=EBI-751001, EBI-10232920;
CC Q14145; Q8TDV0: GPR151; NbExp=3; IntAct=EBI-751001, EBI-11955647;
CC Q14145; P28799: GRN; NbExp=3; IntAct=EBI-751001, EBI-747754;
CC Q14145; A0A0C4DFT7: GYPA; NbExp=3; IntAct=EBI-751001, EBI-12044847;
CC Q14145; B8Q183: GYPA; NbExp=4; IntAct=EBI-751001, EBI-10176190;
CC Q14145; P02724: GYPA; NbExp=4; IntAct=EBI-751001, EBI-702665;
CC Q14145; P05362: ICAM1; NbExp=3; IntAct=EBI-751001, EBI-1035358;
CC Q14145; Q9BYX4: IFIH1; NbExp=3; IntAct=EBI-751001, EBI-6115771;
CC Q14145; O14920: IKBKB; NbExp=6; IntAct=EBI-751001, EBI-81266;
CC Q14145; Q4KMZ1: IQCC; NbExp=3; IntAct=EBI-751001, EBI-12206419;
CC Q14145; P05107: ITGB2; NbExp=3; IntAct=EBI-751001, EBI-300173;
CC Q14145; O95198: KLHL2; NbExp=3; IntAct=EBI-751001, EBI-746999;
CC Q14145; Q6TFL4: KLHL24; NbExp=3; IntAct=EBI-751001, EBI-2510117;
CC Q14145; Q8N4I8: KLHL3; NbExp=3; IntAct=EBI-751001, EBI-10230467;
CC Q14145; Q9UH77: KLHL3; NbExp=3; IntAct=EBI-751001, EBI-8524663;
CC Q14145; P62310: LSM3; NbExp=6; IntAct=EBI-751001, EBI-348239;
CC Q14145; Q13257: MAD2L1; NbExp=8; IntAct=EBI-751001, EBI-78203;
CC Q14145; O60336: MAPKBP1; NbExp=3; IntAct=EBI-751001, EBI-947402;
CC Q14145; Q9BTE3-2: MCMBP; NbExp=3; IntAct=EBI-751001, EBI-9384556;
CC Q14145; Q14494: NFE2L1; NbExp=6; IntAct=EBI-751001, EBI-2804436;
CC Q14145; Q16236: NFE2L2; NbExp=34; IntAct=EBI-751001, EBI-2007911;
CC Q14145; Q96TA1: NIBAN2; NbExp=9; IntAct=EBI-751001, EBI-2514593;
CC Q14145; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-751001, EBI-741158;
CC Q14145; Q9NZJ9: NUDT4; NbExp=3; IntAct=EBI-751001, EBI-4280066;
CC Q14145; Q9UKX7: NUP50; NbExp=3; IntAct=EBI-751001, EBI-2371082;
CC Q14145; Q8N573-5: OXR1; NbExp=3; IntAct=EBI-751001, EBI-10265887;
CC Q14145; Q13153: PAK1; NbExp=3; IntAct=EBI-751001, EBI-1307;
CC Q14145; Q86YC2: PALB2; NbExp=4; IntAct=EBI-751001, EBI-1222653;
CC Q14145; Q15149: PLEC; NbExp=3; IntAct=EBI-751001, EBI-297903;
CC Q14145; Q15149-8: PLEC; NbExp=4; IntAct=EBI-751001, EBI-28998350;
CC Q14145; P54619: PRKAG1; NbExp=6; IntAct=EBI-751001, EBI-1181439;
CC Q14145; P06454-2: PTMA; NbExp=6; IntAct=EBI-751001, EBI-10194874;
CC Q14145; O95997: PTTG1; NbExp=2; IntAct=EBI-751001, EBI-2551072;
CC Q14145; Q6P9E2: RECK; NbExp=6; IntAct=EBI-751001, EBI-10253121;
CC Q14145; Q04206: RELA; NbExp=4; IntAct=EBI-751001, EBI-73886;
CC Q14145; P58004: SESN2; NbExp=3; IntAct=EBI-751001, EBI-3939642;
CC Q14145; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-751001, EBI-358489;
CC Q14145; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-751001, EBI-5235340;
CC Q14145; Q13501: SQSTM1; NbExp=19; IntAct=EBI-751001, EBI-307104;
CC Q14145; Q9UGK3: STAP2; NbExp=3; IntAct=EBI-751001, EBI-1553984;
CC Q14145; Q9P0N9: TBC1D7; NbExp=3; IntAct=EBI-751001, EBI-3258000;
CC Q14145; P54274: TERF1; NbExp=2; IntAct=EBI-751001, EBI-710997;
CC Q14145; Q96PN7: TRERF1; NbExp=2; IntAct=EBI-751001, EBI-3505166;
CC Q14145; Q9Y3Q8: TSC22D4; NbExp=3; IntAct=EBI-751001, EBI-739485;
CC Q14145; Q9BRX9: WDR83; NbExp=7; IntAct=EBI-751001, EBI-7705033;
CC Q14145; O76024: WFS1; NbExp=3; IntAct=EBI-751001, EBI-720609;
CC Q14145; Q9P202: WHRN; NbExp=3; IntAct=EBI-751001, EBI-310886;
CC Q14145; P58317: ZNF121; NbExp=3; IntAct=EBI-751001, EBI-1228269;
CC Q14145; Q9NX65: ZSCAN32; NbExp=3; IntAct=EBI-751001, EBI-739949;
CC Q14145; O88351: Ikbkb; Xeno; NbExp=2; IntAct=EBI-751001, EBI-447960;
CC Q14145; P15314: Irf1; Xeno; NbExp=2; IntAct=EBI-751001, EBI-6115486;
CC Q14145; Q64337: Sqstm1; Xeno; NbExp=2; IntAct=EBI-751001, EBI-645025;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14585973,
CC ECO:0000269|PubMed:15379550, ECO:0000269|PubMed:15601839,
CC ECO:0000269|PubMed:15657435, ECO:0000269|PubMed:19424503}. Nucleus
CC {ECO:0000269|PubMed:15657435}. Note=Mainly cytoplasmic
CC (PubMed:15601839). In response to selective autophagy, relocalizes to
CC inclusion bodies following interaction with SQSTM1/p62
CC (PubMed:20452972). {ECO:0000269|PubMed:15601839,
CC ECO:0000269|PubMed:20452972}.
CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in skeletal
CC muscle. {ECO:0000269|PubMed:15379550}.
CC -!- DOMAIN: KEAP1 contains reactive cysteine residues that act as sensors
CC for endogenously produced and exogenously encountered small molecules,
CC which react with sulfhydryl groups and modify the cysteine sensors,
CC leading to impair ability of the BCR(KEAP1) complex to ubiquitinate
CC target proteins. {ECO:0000269|PubMed:17127771,
CC ECO:0000269|PubMed:18251510, ECO:0000269|PubMed:19489739,
CC ECO:0000269|PubMed:29590092, ECO:0000269|PubMed:30323285}.
CC -!- DOMAIN: The Kelch repeats mediate interaction with NFE2L2/NRF2, BPTF
CC and PGAM5. {ECO:0000269|PubMed:17046835}.
CC -!- PTM: Non-enzymatic covalent modifications of reactive cysteines by
CC electrophile metabolites inactivate the BCR(KEAP1) complex
CC (PubMed:17127771, PubMed:18251510, PubMed:29590092, PubMed:30323285).
CC Accumulation of fumarate promotes the formation of cysteine S-
CC succination (S-(2-succinyl)cysteine), leading to inactivate the
CC BCR(KEAP1) complex and promote NFE2L2/NRF2 nuclear accumulation and
CC activation (By similarity). Nitric oxide-dependent 8-Nitro-cGMP
CC formation promotes cysteine guanylation (S-cGMP-cysteine), leading to
CC NFE2L2/NRF2 nuclear accumulation and activation (By similarity).
CC Itaconate, an anti-inflammatory metabolite generated in response to
CC lipopolysaccharide, alkylates cysteines, activating NFE2L2/NRF2
CC (PubMed:29590092). Methylglyoxal, a reactive metabolite that
CC accumulates when the glycolytic enzyme PGK1 is inhibited, promotes
CC formation of a methylimidazole cross-link between proximal Cys-151 and
CC Arg-135 on another KEAP1 molecule, resulting in an inactive dimer that
CC inactivates the BCR(KEAP1) complex (PubMed:30323285).
CC {ECO:0000250|UniProtKB:Q9Z2X8, ECO:0000269|PubMed:17127771,
CC ECO:0000269|PubMed:18251510, ECO:0000269|PubMed:29590092,
CC ECO:0000269|PubMed:30323285}.
CC -!- PTM: Degraded via a proteasomal-independent process during selective
CC autophagy: interaction with phosphorylated SQSTM1/p62 sequesters KEAP1
CC in inclusion bodies, leading to its degradation.
CC {ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:20452972}.
CC -!- PTM: Auto-ubiquitinated by the BCR(KEAP1) complex (PubMed:15572695,
CC PubMed:15983046). Quinone-induced oxidative stress, but not
CC sulforaphane, increases its ubiquitination (PubMed:15572695,
CC PubMed:15983046). Ubiquitination and subsequent degradation is most
CC pronounced following prolonged exposure of cells to oxidative stress,
CC particularly in glutathione-deficient cells that are highly susceptible
CC to oxidative stress (PubMed:15572695, PubMed:15983046).
CC {ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15983046}.
CC -!- SIMILARITY: Belongs to the KEAP1 family. {ECO:0000305}.
CC -!- CAUTION: The mechanism of inactivation of the BCR(KEAP1) complex by
CC covalent modifications of reactive cysteines is unclear. Covalent
CC modifications were initially thought to disrupt interaction between
CC KEAP1 and NFE2L2/NRF2 (By similarity). Recent publications suggest that
CC cysteine modifications disrupt the interaction between KEAP1 and CUL3
CC without affecting the interaction between KEAP1 and NFE2L2/NRF2
CC (PubMed:16006525, PubMed:17127771, PubMed:18251510, PubMed:24896564).
CC {ECO:0000250|UniProtKB:Q9Z2X8, ECO:0000269|PubMed:16006525,
CC ECO:0000269|PubMed:17127771, ECO:0000269|PubMed:18251510,
CC ECO:0000269|PubMed:24896564}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA09481.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF361892; AAK43722.1; -; Genomic_DNA.
DR EMBL; AF361888; AAK43722.1; JOINED; Genomic_DNA.
DR EMBL; AF361889; AAK43722.1; JOINED; Genomic_DNA.
DR EMBL; AF361890; AAK43722.1; JOINED; Genomic_DNA.
DR EMBL; AF361891; AAK43722.1; JOINED; Genomic_DNA.
DR EMBL; AF361886; AAK51082.1; -; mRNA.
DR EMBL; D50922; BAA09481.3; ALT_INIT; mRNA.
DR EMBL; AK056204; BAG51647.1; -; mRNA.
DR EMBL; AC011461; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002417; AAH02417.1; -; mRNA.
DR EMBL; BC002930; AAH02930.1; -; mRNA.
DR EMBL; BC015945; AAH15945.1; -; mRNA.
DR EMBL; BC021957; AAH21957.2; -; mRNA.
DR CCDS; CCDS12239.1; -.
DR RefSeq; NP_036421.2; NM_012289.3.
DR RefSeq; NP_987096.1; NM_203500.1.
DR RefSeq; XP_005260230.1; XM_005260173.1.
DR RefSeq; XP_005260231.1; XM_005260174.1.
DR RefSeq; XP_011526754.1; XM_011528452.1.
DR PDB; 1U6D; X-ray; 1.85 A; X=321-609.
DR PDB; 1ZGK; X-ray; 1.35 A; A=321-609.
DR PDB; 2FLU; X-ray; 1.50 A; X=321-609.
DR PDB; 3VNG; X-ray; 2.10 A; A=321-609.
DR PDB; 3VNH; X-ray; 2.10 A; A=321-609.
DR PDB; 3ZGC; X-ray; 2.20 A; A/B=321-609.
DR PDB; 3ZGD; X-ray; 1.98 A; A/B=321-609.
DR PDB; 4CXI; X-ray; 2.35 A; A=48-180.
DR PDB; 4CXJ; X-ray; 2.80 A; A=48-180.
DR PDB; 4CXT; X-ray; 2.66 A; A=48-180.
DR PDB; 4IFJ; X-ray; 1.80 A; A=321-609.
DR PDB; 4IFL; X-ray; 1.80 A; X=321-609.
DR PDB; 4IFN; X-ray; 2.40 A; X=321-609.
DR PDB; 4IN4; X-ray; 2.59 A; A/B/C=321-609.
DR PDB; 4IQK; X-ray; 1.97 A; A=321-609.
DR PDB; 4L7B; X-ray; 2.41 A; A/B=321-609.
DR PDB; 4L7C; X-ray; 2.40 A; A/B/C=321-609.
DR PDB; 4L7D; X-ray; 2.25 A; A/B/C=321-609.
DR PDB; 4N1B; X-ray; 2.55 A; A/B/C=321-609.
DR PDB; 4XMB; X-ray; 2.43 A; A=321-609.
DR PDB; 5DAD; X-ray; 2.61 A; A=49-182.
DR PDB; 5DAF; X-ray; 2.37 A; A=49-182.
DR PDB; 5F72; X-ray; 1.85 A; C/K=321-611.
DR PDB; 5GIT; X-ray; 2.19 A; A=48-180.
DR PDB; 5NLB; X-ray; 3.45 A; A=51-204.
DR PDB; 5WFL; X-ray; 1.93 A; A/B=312-624.
DR PDB; 5WFV; X-ray; 1.91 A; A/B=320-612.
DR PDB; 5WG1; X-ray; 2.02 A; A/B=320-612.
DR PDB; 5WHL; X-ray; 2.50 A; A/B=312-624.
DR PDB; 5WHO; X-ray; 2.23 A; A/B=312-624.
DR PDB; 5WIY; X-ray; 2.23 A; A/B=312-624.
DR PDB; 5X54; X-ray; 2.30 A; A/B=321-609.
DR PDB; 6FFM; X-ray; 2.20 A; A=48-180.
DR PDB; 6FMP; X-ray; 2.92 A; A/B=321-609.
DR PDB; 6FMQ; X-ray; 2.10 A; A/B=321-609.
DR PDB; 6HWS; X-ray; 1.75 A; A=321-609.
DR PDB; 6LRZ; X-ray; 1.54 A; A=311-616.
DR PDB; 6ROG; X-ray; 2.16 A; A/X=321-609.
DR PDB; 6SP1; X-ray; 2.57 A; A/B=321-609.
DR PDB; 6SP4; X-ray; 2.59 A; A/B/C/D/E/F=321-609.
DR PDB; 6T7V; X-ray; 2.60 A; A=321-609.
DR PDB; 6T7Z; X-ray; 2.00 A; A=321-609.
DR PDB; 6TG8; X-ray; 2.75 A; AAA=322-609.
DR PDB; 6TYM; X-ray; 1.42 A; A=321-609.
DR PDB; 6TYP; X-ray; 2.50 A; A=321-609.
DR PDB; 6UF0; X-ray; 1.96 A; A/B=321-609.
DR PDB; 6V6Z; X-ray; 1.60 A; A/B/C/D=321-609.
DR PDB; 6W66; X-ray; 3.21 A; C=48-180.
DR PDB; 6W67; X-ray; 2.20 A; A=48-180.
DR PDB; 6W68; X-ray; 2.55 A; A=48-180.
DR PDB; 6W69; X-ray; 2.50 A; A=48-180.
DR PDB; 6WCQ; EM; 8.50 A; C=1-624.
DR PDB; 6Z6A; X-ray; 2.37 A; A/B=321-609.
DR PDB; 7EXI; X-ray; 1.82 A; A=45-180.
DR PDB; 7K28; X-ray; 2.15 A; A/B=325-614.
DR PDB; 7K29; X-ray; 2.20 A; A/B=324-624.
DR PDB; 7K2A; X-ray; 1.90 A; A/B=324-624.
DR PDB; 7K2B; X-ray; 2.31 A; A/B=324-624.
DR PDB; 7K2C; X-ray; 2.11 A; A/B=325-614.
DR PDB; 7K2D; X-ray; 2.21 A; A/B=324-623.
DR PDB; 7K2E; X-ray; 2.03 A; A/B=324-624.
DR PDB; 7K2F; X-ray; 2.37 A; A/X=312-623.
DR PDB; 7K2G; X-ray; 2.15 A; A/B=324-624.
DR PDB; 7K2H; X-ray; 2.09 A; A/B=324-624.
DR PDB; 7K2I; X-ray; 2.42 A; A/B=324-623.
DR PDB; 7K2J; X-ray; 2.52 A; A/B=325-614.
DR PDB; 7K2K; X-ray; 1.98 A; A/B=324-624.
DR PDB; 7K2L; X-ray; 1.98 A; A=326-609, B=326-614.
DR PDB; 7K2M; X-ray; 2.02 A; A/B=326-614.
DR PDB; 7K2N; X-ray; 2.22 A; A/B=324-624.
DR PDB; 7K2O; X-ray; 2.11 A; A/B=324-624.
DR PDB; 7K2P; X-ray; 2.11 A; A/B=324-624.
DR PDB; 7K2Q; X-ray; 2.37 A; A/B=325-614.
DR PDB; 7K2R; X-ray; 2.10 A; A/B=325-614.
DR PDB; 7K2S; X-ray; 2.13 A; A/B=324-624.
DR PDB; 7Q5H; X-ray; 2.31 A; A/B=321-609.
DR PDB; 7Q6Q; X-ray; 2.55 A; A/B=321-609.
DR PDB; 7Q6S; X-ray; 2.14 A; A/B=321-609.
DR PDB; 7Q8R; X-ray; 2.28 A; A/B=321-609.
DR PDB; 7Q96; X-ray; 2.42 A; A/B=321-609.
DR PDBsum; 1U6D; -.
DR PDBsum; 1ZGK; -.
DR PDBsum; 2FLU; -.
DR PDBsum; 3VNG; -.
DR PDBsum; 3VNH; -.
DR PDBsum; 3ZGC; -.
DR PDBsum; 3ZGD; -.
DR PDBsum; 4CXI; -.
DR PDBsum; 4CXJ; -.
DR PDBsum; 4CXT; -.
DR PDBsum; 4IFJ; -.
DR PDBsum; 4IFL; -.
DR PDBsum; 4IFN; -.
DR PDBsum; 4IN4; -.
DR PDBsum; 4IQK; -.
DR PDBsum; 4L7B; -.
DR PDBsum; 4L7C; -.
DR PDBsum; 4L7D; -.
DR PDBsum; 4N1B; -.
DR PDBsum; 4XMB; -.
DR PDBsum; 5DAD; -.
DR PDBsum; 5DAF; -.
DR PDBsum; 5F72; -.
DR PDBsum; 5GIT; -.
DR PDBsum; 5NLB; -.
DR PDBsum; 5WFL; -.
DR PDBsum; 5WFV; -.
DR PDBsum; 5WG1; -.
DR PDBsum; 5WHL; -.
DR PDBsum; 5WHO; -.
DR PDBsum; 5WIY; -.
DR PDBsum; 5X54; -.
DR PDBsum; 6FFM; -.
DR PDBsum; 6FMP; -.
DR PDBsum; 6FMQ; -.
DR PDBsum; 6HWS; -.
DR PDBsum; 6LRZ; -.
DR PDBsum; 6ROG; -.
DR PDBsum; 6SP1; -.
DR PDBsum; 6SP4; -.
DR PDBsum; 6T7V; -.
DR PDBsum; 6T7Z; -.
DR PDBsum; 6TG8; -.
DR PDBsum; 6TYM; -.
DR PDBsum; 6TYP; -.
DR PDBsum; 6UF0; -.
DR PDBsum; 6V6Z; -.
DR PDBsum; 6W66; -.
DR PDBsum; 6W67; -.
DR PDBsum; 6W68; -.
DR PDBsum; 6W69; -.
DR PDBsum; 6WCQ; -.
DR PDBsum; 6Z6A; -.
DR PDBsum; 7EXI; -.
DR PDBsum; 7K28; -.
DR PDBsum; 7K29; -.
DR PDBsum; 7K2A; -.
DR PDBsum; 7K2B; -.
DR PDBsum; 7K2C; -.
DR PDBsum; 7K2D; -.
DR PDBsum; 7K2E; -.
DR PDBsum; 7K2F; -.
DR PDBsum; 7K2G; -.
DR PDBsum; 7K2H; -.
DR PDBsum; 7K2I; -.
DR PDBsum; 7K2J; -.
DR PDBsum; 7K2K; -.
DR PDBsum; 7K2L; -.
DR PDBsum; 7K2M; -.
DR PDBsum; 7K2N; -.
DR PDBsum; 7K2O; -.
DR PDBsum; 7K2P; -.
DR PDBsum; 7K2Q; -.
DR PDBsum; 7K2R; -.
DR PDBsum; 7K2S; -.
DR PDBsum; 7Q5H; -.
DR PDBsum; 7Q6Q; -.
DR PDBsum; 7Q6S; -.
DR PDBsum; 7Q8R; -.
DR PDBsum; 7Q96; -.
DR AlphaFoldDB; Q14145; -.
DR BMRB; Q14145; -.
DR SMR; Q14145; -.
DR BioGRID; 115156; 248.
DR CORUM; Q14145; -.
DR DIP; DIP-42134N; -.
DR ELM; Q14145; -.
DR IntAct; Q14145; 172.
DR MINT; Q14145; -.
DR STRING; 9606.ENSP00000171111; -.
DR BindingDB; Q14145; -.
DR ChEMBL; CHEMBL2069156; -.
DR DrugBank; DB08908; Dimethyl fumarate.
DR DrugCentral; Q14145; -.
DR GuidetoPHARMACOLOGY; 2757; -.
DR GlyGen; Q14145; 11 sites, 1 O-linked glycan (11 sites).
DR iPTMnet; Q14145; -.
DR PhosphoSitePlus; Q14145; -.
DR SwissPalm; Q14145; -.
DR BioMuta; KEAP1; -.
DR DMDM; 146345444; -.
DR EPD; Q14145; -.
DR jPOST; Q14145; -.
DR MassIVE; Q14145; -.
DR MaxQB; Q14145; -.
DR PaxDb; Q14145; -.
DR PeptideAtlas; Q14145; -.
DR PRIDE; Q14145; -.
DR ProteomicsDB; 59849; -.
DR ABCD; Q14145; 5 sequenced antibodies.
DR Antibodypedia; 1418; 714 antibodies from 39 providers.
DR DNASU; 9817; -.
DR Ensembl; ENST00000171111.10; ENSP00000171111.4; ENSG00000079999.14.
DR Ensembl; ENST00000393623.6; ENSP00000377245.1; ENSG00000079999.14.
DR GeneID; 9817; -.
DR KEGG; hsa:9817; -.
DR MANE-Select; ENST00000171111.10; ENSP00000171111.4; NM_203500.2; NP_987096.1.
DR UCSC; uc002moq.2; human.
DR CTD; 9817; -.
DR DisGeNET; 9817; -.
DR GeneCards; KEAP1; -.
DR HGNC; HGNC:23177; KEAP1.
DR HPA; ENSG00000079999; Tissue enhanced (skeletal).
DR MalaCards; KEAP1; -.
DR MIM; 606016; gene.
DR neXtProt; NX_Q14145; -.
DR OpenTargets; ENSG00000079999; -.
DR Orphanet; 276399; Familial multinodular goiter.
DR PharmGKB; PA134887774; -.
DR VEuPathDB; HostDB:ENSG00000079999; -.
DR eggNOG; KOG4441; Eukaryota.
DR GeneTree; ENSGT00940000159543; -.
DR HOGENOM; CLU_004253_14_2_1; -.
DR InParanoid; Q14145; -.
DR OMA; CYHPEND; -.
DR OrthoDB; 746011at2759; -.
DR PhylomeDB; Q14145; -.
DR TreeFam; TF329218; -.
DR PathwayCommons; Q14145; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q14145; -.
DR SIGNOR; Q14145; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 9817; 183 hits in 1142 CRISPR screens.
DR ChiTaRS; KEAP1; human.
DR EvolutionaryTrace; Q14145; -.
DR GeneWiki; KEAP1; -.
DR GenomeRNAi; 9817; -.
DR Pharos; Q14145; Tclin.
DR PRO; PR:Q14145; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q14145; protein.
DR Bgee; ENSG00000079999; Expressed in hindlimb stylopod muscle and 199 other tissues.
DR ExpressionAtlas; Q14145; baseline and differential.
DR Genevisible; Q14145; HS.
DR GO; GO:0005884; C:actin filament; IEA:Ensembl.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0016234; C:inclusion body; IDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0097718; F:disordered domain specific binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0071353; P:cellular response to interleukin-4; IEA:Ensembl.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; TAS:ParkinsonsUK-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; TAS:ParkinsonsUK-UCL.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0045604; P:regulation of epidermal cell differentiation; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 2.120.10.80; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR IDEAL; IID00384; -.
DR InterPro; IPR011705; BACK.
DR InterPro; IPR017096; BTB-kelch_protein.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR030563; KEAP1.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR006652; Kelch_1.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR PANTHER; PTHR24412:SF162; PTHR24412:SF162; 1.
DR Pfam; PF07707; BACK; 1.
DR Pfam; PF00651; BTB; 1.
DR Pfam; PF01344; Kelch_1; 6.
DR PIRSF; PIRSF037037; Kelch-like_protein_gigaxonin; 1.
DR SMART; SM00875; BACK; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00612; Kelch; 6.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Host-virus interaction; Kelch repeat; Nucleus;
KW Reference proteome; Repeat; S-nitrosylation; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..624
FT /note="Kelch-like ECH-associated protein 1"
FT /id="PRO_0000119093"
FT DOMAIN 77..149
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 184..286
FT /note="BACK"
FT REPEAT 327..372
FT /note="Kelch 1"
FT REPEAT 373..423
FT /note="Kelch 2"
FT REPEAT 424..470
FT /note="Kelch 3"
FT REPEAT 471..517
FT /note="Kelch 4"
FT REPEAT 518..564
FT /note="Kelch 5"
FT REPEAT 565..611
FT /note="Kelch 6"
FT SITE 151
FT /note="Sensor for electrophilic agents"
FT /evidence="ECO:0000269|PubMed:18251510,
FT ECO:0000269|PubMed:29590092"
FT SITE 257
FT /note="Sensor for electrophilic agents"
FT /evidence="ECO:0000269|PubMed:29590092"
FT SITE 273
FT /note="Sensor for electrophilic agents"
FT /evidence="ECO:0000269|PubMed:29590092"
FT SITE 288
FT /note="Sensor for electrophilic agents"
FT /evidence="ECO:0000269|PubMed:29590092"
FT SITE 434
FT /note="Sensor for electrophilic agents"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2X8"
FT MOD_RES 38
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2X8"
FT MOD_RES 151
FT /note="S-(2,3-dicarboxypropyl)cysteine; alternate"
FT /evidence="ECO:0000269|PubMed:29590092"
FT MOD_RES 151
FT /note="S-(2-succinyl)cysteine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2X8"
FT MOD_RES 151
FT /note="S-nitrosocysteine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2X8"
FT MOD_RES 241
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2X8"
FT MOD_RES 257
FT /note="S-(2,3-dicarboxypropyl)cysteine"
FT /evidence="ECO:0000269|PubMed:29590092"
FT MOD_RES 273
FT /note="S-(2,3-dicarboxypropyl)cysteine"
FT /evidence="ECO:0000269|PubMed:29590092"
FT MOD_RES 288
FT /note="S-(2,3-dicarboxypropyl)cysteine; alternate"
FT /evidence="ECO:0000269|PubMed:29590092"
FT MOD_RES 288
FT /note="S-(2-succinyl)cysteine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2X8"
FT MOD_RES 319
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2X8"
FT MOD_RES 434
FT /note="S-cGMP-cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2X8"
FT MOD_RES 613
FT /note="S-(2-succinyl)cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2X8"
FT CROSSLNK 135
FT /note="N5-[4-(S-L-cysteinyl)-5-methyl-1H-imidazol-2-yl]-L-
FT ornithine (Arg-Cys) (interchain with C-151 in KEAP1)"
FT /evidence="ECO:0000269|PubMed:30323285"
FT CROSSLNK 151
FT /note="N5-[4-(S-L-cysteinyl)-5-methyl-1H-imidazol-2-yl]-L-
FT ornithine (Cys-Arg) (interchain with R-135 in KEAP1)"
FT /evidence="ECO:0000269|PubMed:30323285"
FT VARIANT 23
FT /note="C -> Y (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036084"
FT VARIANT 167
FT /note="V -> F (in a lung adenocarcinoma patient)"
FT /evidence="ECO:0000269|PubMed:17020408"
FT /id="VAR_032102"
FT VARIANT 236
FT /note="D -> H (in a NSCLC cell line)"
FT /evidence="ECO:0000269|PubMed:17020408"
FT /id="VAR_032103"
FT VARIANT 284
FT /note="Q -> L (in a lung adenocarcinoma patient)"
FT /evidence="ECO:0000269|PubMed:17020408"
FT /id="VAR_032104"
FT VARIANT 333
FT /note="G -> C (in a NSCLC cell line; strongly reduces
FT interaction with NFE2L2/NRF2 and reduces repression of
FT NFE2L2/NRF2-dependent gene expression)"
FT /evidence="ECO:0000269|PubMed:17020408"
FT /id="VAR_032105"
FT VARIANT 349
FT /note="D -> N (in dbSNP:rs1048289)"
FT /evidence="ECO:0000269|PubMed:8590280"
FT /id="VAR_032106"
FT VARIANT 350
FT /note="G -> S (in a NSCLC cell line; dbSNP:rs777308626)"
FT /evidence="ECO:0000269|PubMed:17020408"
FT /id="VAR_032107"
FT VARIANT 364
FT /note="G -> C (in a lung adenocarcinoma cell line; also in
FT NSCLC cell lines; strongly reduces interaction with NFE2L2/
FT NRF2 and reduces repression of NFE2L2/NRF2-dependent gene
FT expression; dbSNP:rs1397945617)"
FT /evidence="ECO:0000269|PubMed:16507366"
FT /id="VAR_032108"
FT VARIANT 430
FT /note="G -> C (in a lung adenocarcinoma patient; somatic
FT mutation; strongly reduces interaction with NFE2L2/NRF2 and
FT reduces repression of NFE2L2/NRF2-dependent gene
FT expression)"
FT /evidence="ECO:0000269|PubMed:16507366"
FT /id="VAR_032109"
FT VARIANT 522
FT /note="A -> V (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036085"
FT MUTAGEN 15
FT /note="R->A: Reduced formation of a high-molecular mass
FT KEAP1 molecule when methylglyoxal accumulates."
FT /evidence="ECO:0000269|PubMed:30323285"
FT MUTAGEN 123..127
FT /note="VSIEG->ASAEA: Abolished interaction with
FT NFE2L2/NRF2; when associated with 161-A-A-162."
FT /evidence="ECO:0000269|PubMed:15601839"
FT MUTAGEN 125..127
FT /note="IEG->AAA: Increases ubiquitination and proteolytic
FT degradation."
FT /evidence="ECO:0000269|PubMed:15572695"
FT MUTAGEN 135
FT /note="R->A: Reduced formation of a high-molecular mass
FT KEAP1 molecule when methylglyoxal accumulates."
FT /evidence="ECO:0000269|PubMed:30323285"
FT MUTAGEN 151
FT /note="C->S,N,D,L: Substitution with a small side chain
FT that prevents covalent modification by an electrophile;
FT promotes constitutive ubiquitination of NFE2L2/NRF2 and
FT subsequent repression of phase 2 detoxifying enzymes.
FT Resistance of ubiquitination of PGAM5 to inhibition by
FT oxidative stress and sulforaphane. Impaired interaction
FT with CUL3. Reduced formation of a high-molecular mass KEAP1
FT molecule when methylglyoxal accumulates."
FT /evidence="ECO:0000269|PubMed:14585973,
FT ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:17046835,
FT ECO:0000269|PubMed:18251510, ECO:0000269|PubMed:19489739,
FT ECO:0000269|PubMed:29590092, ECO:0000269|PubMed:30323285"
FT MUTAGEN 151
FT /note="C->W,Y: Substitution with a bulky side chain that
FT mimicks covalent modification by an electrophile; prevents
FT ubiquitination and degradation of NFE2L2/NRF2, leading to
FT constitutive activation of NFE2L2/NRF2 and subsequent
FT expression of phase 2 detoxifying enzymes."
FT /evidence="ECO:0000269|PubMed:19489739,
FT ECO:0000269|PubMed:24896564"
FT MUTAGEN 161..162
FT /note="MY->AA: Abolished interaction with NFE2L2/NRF2; when
FT associated with 123-A--A-127."
FT /evidence="ECO:0000269|PubMed:15601839"
FT MUTAGEN 162..164
FT /note="YQI->AAA: Increases ubiquitination and proteolytic
FT degradation."
FT /evidence="ECO:0000269|PubMed:15572695"
FT MUTAGEN 273
FT /note="C->S: Abolishes repression of NFE2L2/NRF2-dependent
FT gene expression. Slows down degradation of NFE2L2/NRF2."
FT /evidence="ECO:0000269|PubMed:14585973"
FT MUTAGEN 288
FT /note="C->S: Abolishes repression of NFE2L2/NRF2-dependent
FT gene expression. Slows down degradation of NFE2L2/NRF2."
FT /evidence="ECO:0000269|PubMed:14585973"
FT MUTAGEN 308
FT /note="L->A: Loss of export from nucleus; when associated
FT with A-310."
FT /evidence="ECO:0000269|PubMed:15657435"
FT MUTAGEN 310
FT /note="L->A: Loss of export from nucleus; when associated
FT with A-308."
FT /evidence="ECO:0000269|PubMed:15657435"
FT MUTAGEN 334
FT /note="Y->A: Loss of interaction with NFE2L2/NRF2. Strongly
FT reduces repression of NFE2L2/NRF2-dependent gene
FT expression. Loss of interaction with PGAM5."
FT /evidence="ECO:0000269|PubMed:16888629,
FT ECO:0000269|PubMed:17046835"
FT MUTAGEN 380
FT /note="R->A: Loss of interaction with NFE2L2/NRF2.
FT Abolishes repression of NFE2L2/NRF2-dependent gene
FT expression. Impaired interaction with SQSTM1/p62."
FT /evidence="ECO:0000269|PubMed:16888629,
FT ECO:0000269|PubMed:20452972"
FT MUTAGEN 382
FT /note="N->A: Loss of interaction with NFE2L2/NRF2. Strongly
FT reduces repression of NFE2L2/NRF2-dependent gene
FT expression. Impaired interaction with SQSTM1/p62."
FT /evidence="ECO:0000269|PubMed:16888629,
FT ECO:0000269|PubMed:20452972"
FT MUTAGEN 415
FT /note="R->A: Loss of interaction with NFE2L2/NRF2.
FT Abolishes repression of NFE2L2/NRF2-dependent gene
FT expression. Loss of interaction with PGAM5. Does not affect
FT interaction with SQSTM1/p62."
FT /evidence="ECO:0000269|PubMed:16888629,
FT ECO:0000269|PubMed:17046835, ECO:0000269|PubMed:20452972"
FT MUTAGEN 436
FT /note="H->A: Loss of interaction with NFE2L2/NRF2.
FT Abolishes repression of NFE2L2/NRF2-dependent gene
FT expression. Does not affect interaction with SQSTM1/p62."
FT /evidence="ECO:0000269|PubMed:16888629,
FT ECO:0000269|PubMed:20452972"
FT MUTAGEN 478
FT /note="F->A: Abolishes repression of NFE2L2/NRF2-dependent
FT gene expression."
FT /evidence="ECO:0000269|PubMed:16888629"
FT MUTAGEN 483
FT /note="R->A: Loss of interaction with NFE2L2/NRF2.
FT Abolishes repression of NFE2L2/NRF2-dependent gene
FT expression. Loss of interaction with PGAM5. Does not affect
FT interaction with SQSTM1/p62."
FT /evidence="ECO:0000269|PubMed:16888629,
FT ECO:0000269|PubMed:17046835, ECO:0000269|PubMed:20452972"
FT MUTAGEN 525
FT /note="Y->A: Loss of interaction with NFE2L2/NRF2. Strongly
FT reduces repression of NFE2L2/NRF2-dependent gene
FT expression. Abolishes interaction with SQSTM1/p62."
FT /evidence="ECO:0000269|PubMed:16888629,
FT ECO:0000269|PubMed:20452972"
FT MUTAGEN 572
FT /note="Y->A: Loss of interaction with NFE2L2/NRF2. Strongly
FT reduces repression of NFE2L2/NRF2-dependent gene
FT expression. Loss of interaction with PGAM5. Abolishes
FT interaction with SQSTM1/p62."
FT /evidence="ECO:0000269|PubMed:16888629,
FT ECO:0000269|PubMed:17046835, ECO:0000269|PubMed:20452972"
FT CONFLICT 504
FT /note="N -> S (in Ref. 4; BAG51647)"
FT /evidence="ECO:0000305"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:6W66"
FT HELIX 59..72
FT /evidence="ECO:0007829|PDB:7EXI"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:7EXI"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:5DAD"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:7EXI"
FT HELIX 97..103
FT /evidence="ECO:0007829|PDB:7EXI"
FT HELIX 105..111
FT /evidence="ECO:0007829|PDB:7EXI"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:7EXI"
FT STRAND 121..125
FT /evidence="ECO:0007829|PDB:7EXI"
FT HELIX 130..142
FT /evidence="ECO:0007829|PDB:7EXI"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:6W66"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:7EXI"
FT HELIX 152..161
FT /evidence="ECO:0007829|PDB:7EXI"
FT HELIX 165..177
FT /evidence="ECO:0007829|PDB:7EXI"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:5NLB"
FT HELIX 184..194
FT /evidence="ECO:0007829|PDB:5NLB"
FT HELIX 199..202
FT /evidence="ECO:0007829|PDB:5NLB"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 334..338
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:1ZGK"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:2FLU"
FT STRAND 366..370
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 373..377
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 380..383
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 386..389
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 393..396
FT /evidence="ECO:0007829|PDB:1ZGK"
FT TURN 398..400
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 417..421
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 424..428
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 440..444
FT /evidence="ECO:0007829|PDB:1ZGK"
FT TURN 445..448
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 449..452
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 464..468
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 471..475
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 480..483
FT /evidence="ECO:0007829|PDB:6HWS"
FT STRAND 487..491
FT /evidence="ECO:0007829|PDB:1ZGK"
FT TURN 492..495
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 496..499
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 511..515
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 518..522
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 527..530
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 534..538
FT /evidence="ECO:0007829|PDB:1ZGK"
FT TURN 539..542
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 543..547
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 558..562
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 565..569
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 574..577
FT /evidence="ECO:0007829|PDB:5F72"
FT STRAND 580..585
FT /evidence="ECO:0007829|PDB:1ZGK"
FT TURN 586..589
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 590..596
FT /evidence="ECO:0007829|PDB:1ZGK"
FT STRAND 605..609
FT /evidence="ECO:0007829|PDB:1ZGK"
SQ SEQUENCE 624 AA; 69666 MW; CE180F3897BB8C97 CRC64;
MQPDPRPSGA GACCRFLPLQ SQCPEGAGDA VMYASTECKA EVTPSQHGNR TFSYTLEDHT
KQAFGIMNEL RLSQQLCDVT LQVKYQDAPA AQFMAHKVVL ASSSPVFKAM FTNGLREQGM
EVVSIEGIHP KVMERLIEFA YTASISMGEK CVLHVMNGAV MYQIDSVVRA CSDFLVQQLD
PSNAIGIANF AEQIGCVELH QRAREYIYMH FGEVAKQEEF FNLSHCQLVT LISRDDLNVR
CESEVFHACI NWVKYDCEQR RFYVQALLRA VRCHSLTPNF LQMQLQKCEI LQSDSRCKDY
LVKIFEELTL HKPTQVMPCR APKVGRLIYT AGGYFRQSLS YLEAYNPSDG TWLRLADLQV
PRSGLAGCVV GGLLYAVGGR NNSPDGNTDS SALDCYNPMT NQWSPCAPMS VPRNRIGVGV
IDGHIYAVGG SHGCIHHNSV ERYEPERDEW HLVAPMLTRR IGVGVAVLNR LLYAVGGFDG
TNRLNSAECY YPERNEWRMI TAMNTIRSGA GVCVLHNCIY AAGGYDGQDQ LNSVERYDVE
TETWTFVAPM KHRRSALGIT VHQGRIYVLG GYDGHTFLDS VECYDPDTDT WSEVTRMTSG
RSGVGVAVTM EPCRKQIDQQ NCTC
