IKKB_HUMAN
ID IKKB_HUMAN Reviewed; 756 AA.
AC O14920; B4DZ30; B4E0U4; O75327;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 233.
DE RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit beta;
DE Short=I-kappa-B-kinase beta;
DE Short=IKK-B;
DE Short=IKK-beta;
DE Short=IkBKB;
DE EC=2.7.11.10;
DE AltName: Full=I-kappa-B kinase 2;
DE Short=IKK2;
DE AltName: Full=Nuclear factor NF-kappa-B inhibitor kinase beta;
DE Short=NFKBIKB;
DE AltName: Full=Serine/threonine protein kinase IKBKB;
DE EC=2.7.11.1 {ECO:0000269|PubMed:25326418};
GN Name=IKBKB; Synonyms=IKKB;
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 [MRNA] (ISOFORM 1), AND MUTAGENESIS OF LYS-44; SER-177
RP AND SER-181.
RC TISSUE=Cervix carcinoma;
RX PubMed=9346484; DOI=10.1126/science.278.5339.860;
RA Mercurio F., Zhu H., Murray B.W., Shevchenko A., Bennett B.L., Li J.W.,
RA Young D.B., Barbosa M., Mann M., Manning A., Rao A.;
RT "IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-
RT kappaB activation.";
RL Science 278:860-866(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF LYS-44.
RX PubMed=9346485; DOI=10.1126/science.278.5339.866;
RA Woronicz J.D., Gao X., Cao Z., Rothe M., Goeddel D.V.;
RT "IkappaB kinase-beta: NF-kappaB activation and complex formation with
RT IkappaB kinase-alpha and NIK.";
RL Science 278:866-869(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=9813230; DOI=10.1016/s0378-1119(98)00462-4;
RA Hu M.C.-T., Wang Y.-P.;
RT "IkappaB kinase-alpha and -beta genes are coexpressed in adult and
RT embryonic tissues but localized to different human chromosomes.";
RL Gene 222:31-40(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND GENE MAPPING.
RX PubMed=9763654; DOI=10.1159/000015058;
RA Shindo M., Nakano H., Sakon S., Yagita H., Mihara M., Okumura K.;
RT "Assignment of IkappaB kinase beta (IKBKB) to human chromosome band
RT 8p12-->p11 by in situ hybridization.";
RL Cytogenet. Cell Genet. 82:32-33(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Testis, and Thymus;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TRP-554.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Lung;
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 [9]
RP PROTEIN SEQUENCE OF 170-182 (ISOFORM 1), INACTIVATION BY YERSINIA YOPJ
RP (MICROBIAL INFECTION), ACETYLATION AT THR-180 (MICROBIAL INFECTION), AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17116858; DOI=10.1073/pnas.0608995103;
RA Mittal R., Peak-Chew S.Y., McMahon H.T.;
RT "Acetylation of MEK2 and I kappa B kinase (IKK) activation loop residues by
RT YopJ inhibits signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:18574-18579(2006).
RN [10]
RP IKK PHOSPHORYLATION.
RX PubMed=9819420; DOI=10.1128/mcb.18.12.7336;
RA Nemoto S., DiDonato J.A., Lin A.;
RT "Coordinate regulation of IkappaB kinases by mitogen-activated protein
RT kinase kinase kinase 1 and NF-kappaB-inducing kinase.";
RL Mol. Cell. Biol. 18:7336-7343(1998).
RN [11]
RP IDENTIFICATION IN A COMPLEX WITH CHUK; NFKBIA; RELA; ELP1 AND MAP3K14.
RX PubMed=9751059; DOI=10.1038/26254;
RA Cohen L., Henzel W.J., Baeuerle P.A.;
RT "IKAP is a scaffold protein of the IkappaB kinase complex.";
RL Nature 395:292-296(1998).
RN [12]
RP INTERACTION WITH SQSTM1; PRKCZ AND PRKCI.
RX PubMed=10356400; DOI=10.1093/emboj/18.11.3044;
RA Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J.;
RT "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB
RT activation.";
RL EMBO J. 18:3044-3053(1999).
RN [13]
RP PHOSPHORYLATION AT SER-177 AND SER-181.
RX PubMed=10022904; DOI=10.1128/mcb.19.3.2180;
RA Lallena M.J., Diaz-Meco M.T., Bren G., Paya C.V., Moscat J.;
RT "Activation of IkappaB kinase beta by protein kinase C isoforms.";
RL Mol. Cell. Biol. 19:2180-2188(1999).
RN [14]
RP PHOSPHORYLATION AT SER-177; SER-181; SER-670; SER-672; SER-675; SER-682;
RP SER-689; SER-692; SER-695; SER-697; SER-705; SER-733; SER-740 AND SER-750.
RX PubMed=10195894; DOI=10.1126/science.284.5412.309;
RA Delhase M., Hayakawa M., Chen Y., Karin M.;
RT "Positive and negative regulation of IkappaB kinase activity through
RT IKKbeta subunit phosphorylation.";
RL Science 284:309-313(1999).
RN [15]
RP INTERACTION WITH EIF2AK2.
RX PubMed=10848580; DOI=10.1128/mcb.20.13.4532-4542.2000;
RA Bonnet M.C., Weil R., Dam E., Hovanessian A.G., Meurs E.F.;
RT "PKR stimulates NF-kappaB irrespective of its kinase function by
RT interacting with the IkappaB kinase complex.";
RL Mol. Cell. Biol. 20:4532-4542(2000).
RN [16]
RP PHOSPHORYLATION AT SER-177 AND SER-181 BY TBK1, AND MUTAGENESIS OF
RP 177-SER--SER-181.
RX PubMed=10783893; DOI=10.1038/35008109;
RA Tojima Y., Fujimoto A., Delhase M., Chen Y., Hatakeyama S., Nakayama K.,
RA Kaneko Y., Nimura Y., Motoyama N., Ikeda K., Karin M., Nakanishi M.;
RT "NAK is an IkappaB kinase-activating kinase.";
RL Nature 404:778-782(2000).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF NFKB1.
RX PubMed=11297557; DOI=10.1074/jbc.m101754200;
RA Salmeron A., Janzen J., Soneji Y., Bump N., Kamens J., Allen H., Ley S.C.;
RT "Direct phosphorylation of NF-kappa B1 p105 by the Ikappa B kinase complex
RT on serine 927 is essential for signal-induced p105 proteolysis.";
RL J. Biol. Chem. 276:22215-22222(2001).
RN [18]
RP INTERACTION WITH IKBKG AND TANK.
RX PubMed=12133833; DOI=10.1074/jbc.m205069200;
RA Chariot A., Leonardi A., Muller J., Bonif M., Brown K., Siebenlist U.;
RT "Association of the adaptor TANK with the I kappa B kinase (IKK) regulator
RT NEMO connects IKK complexes with IKK epsilon and TBK1 kinases.";
RL J. Biol. Chem. 277:37029-37036(2002).
RN [19]
RP IDENTIFICATION IN A COMPLEX WITH CREBBP; NCOA2; NCOA3; IKKA AND IKBKG.
RX PubMed=11971985; DOI=10.1128/mcb.22.10.3549-3561.2002;
RA Wu R.-C., Qin J., Hashimoto Y., Wong J., Xu J., Tsai S.Y., Tsai M.-J.,
RA O'Malley B.W.;
RT "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator activity by
RT I kappa B kinase.";
RL Mol. Cell. Biol. 22:3549-3561(2002).
RN [20]
RP COMPOSITION OF THE IKK COMPLEX.
RX PubMed=12612076; DOI=10.1128/mcb.23.6.2029-2041.2003;
RA Tegethoff S., Behlke J., Scheidereit C.;
RT "Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is
RT obligatory for IKK complex activity and NF-kappaB activation.";
RL Mol. Cell. Biol. 23:2029-2041(2003).
RN [21]
RP FUNCTION, AND INTERACTION WITH FOXO3.
RX PubMed=15084260; DOI=10.1016/s0092-8674(04)00302-2;
RA Hu M.C., Lee D.F., Xia W., Golfman L.S., Ou-Yang F., Yang J.Y., Zou Y.,
RA Bao S., Hanada N., Saso H., Kobayashi R., Hung M.C.;
RT "IkappaB kinase promotes tumorigenesis through inhibition of forkhead
RT FOXO3a.";
RL Cell 117:225-237(2004).
RN [22]
RP INTERACTION WITH TICAM1.
RX PubMed=14739303; DOI=10.1074/jbc.m311629200;
RA Han K.J., Su X., Xu L.-G., Bin L.H., Zhang J., Shu H.-B.;
RT "Mechanisms of the TRIF-induced interferon-stimulated response element and
RT NF-kappaB activation and apoptosis pathways.";
RL J. Biol. Chem. 279:15652-15661(2004).
RN [23]
RP INTERACTION WITH NALP2.
RX PubMed=15456791; DOI=10.1074/jbc.m406741200;
RA Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C.,
RA Reed J.C.;
RT "PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-
RT kappaB and caspase-1 activation in macrophages.";
RL J. Biol. Chem. 279:51897-51907(2004).
RN [24]
RP INTERACTION WITH ARRB1 AND ARRB2.
RX PubMed=15173580; DOI=10.1073/pnas.0402851101;
RA Witherow D.S., Garrison T.R., Miller W.E., Lefkowitz R.J.;
RT "beta-Arrestin inhibits NF-kappaB activity by means of its interaction with
RT the NF-kappaB inhibitor IkappaBalpha.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8603-8607(2004).
RN [25]
RP S-NITROSYLATION AT CYS-179.
RX PubMed=15184672; DOI=10.1073/pnas.0400588101;
RA Reynaert N.L., Ckless K., Korn S.H., Vos N., Guala A.S., Wouters E.F.,
RA van der Vliet A., Janssen-Heininger Y.M.;
RT "Nitric oxide represses inhibitory kappaB kinase through S-nitrosylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8945-8950(2004).
RN [26]
RP INTERACTION WITH NIBP.
RX PubMed=15951441; DOI=10.1074/jbc.m501670200;
RA Hu W.-H., Pendergast J.S., Mo X.-M., Brambilla R., Bracchi-Ricard V.,
RA Li F., Walters W.M., Blits B., He L., Schaal S.M., Bethea J.R.;
RT "NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B
RT activation.";
RL J. Biol. Chem. 280:29233-29241(2005).
RN [27]
RP PHOSPHORYLATION AT SER-181 BY PDPK1, AND INTERACTION WITH PDPK1.
RX PubMed=16207722; DOI=10.1074/jbc.m506235200;
RA Tanaka H., Fujita N., Tsuruo T.;
RT "3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinase beta
RT (IkkB) phosphorylation activates NF-kappaB signaling.";
RL J. Biol. Chem. 280:40965-40973(2005).
RN [28]
RP UBIQUITINATION AT LYS-163.
RX PubMed=16267042; DOI=10.1074/jbc.m508656200;
RA Carter R.S., Pennington K.N., Arrate P., Oltz E.M., Ballard D.W.;
RT "Site-specific monoubiquitination of IkappaB kinase IKKbeta regulates its
RT phosphorylation and persistent activation.";
RL J. Biol. Chem. 280:43272-43279(2005).
RN [29]
RP INTERACTION WITH MAVS.
RX PubMed=16177806; DOI=10.1038/nature04193;
RA Meylan E., Curran J., Hofmann K., Moradpour D., Binder M.,
RA Bartenschlager R., Tschopp J.;
RT "Cardif is an adaptor protein in the RIG-I antiviral pathway and is
RT targeted by hepatitis C virus.";
RL Nature 437:1167-1172(2005).
RN [30]
RP HYDROXYLATION AT PRO-191, AND MUTAGENESIS OF PRO-191.
RX PubMed=17114296; DOI=10.1073/pnas.0602235103;
RA Cummins E.P., Berra E., Comerford K.M., Ginouves A., Fitzgerald K.T.,
RA Seeballuck F., Godson C., Nielsen J.E., Moynagh P., Pouyssegur J.,
RA Taylor C.T.;
RT "Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving
RT insight into hypoxia-induced NFkappaB activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:18154-18159(2006).
RN [31]
RP INTERACTION WITH YOPJ (MICROBIAL INFECTION), AND ACETYLATION (MICROBIAL
RP INFECTION).
RX PubMed=16728640; DOI=10.1126/science.1126867;
RA Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J.,
RA Orth K.;
RT "Yersinia YopJ acetylates and inhibits kinase activation by blocking
RT phosphorylation.";
RL Science 312:1211-1214(2006).
RN [32]
RP INTERACTION WITH ATM.
RX PubMed=16497931; DOI=10.1126/science.1121513;
RA Wu Z.H., Shi Y., Tibbetts R.S., Miyamoto S.;
RT "Molecular linkage between the kinase ATM and NF-kappaB signaling in
RT response to genotoxic stimuli.";
RL Science 311:1141-1146(2006).
RN [33]
RP IDENTIFICATION IN A MEMBRANE RAFT COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=17287217; DOI=10.1074/jbc.m609157200;
RA Ohnuma K., Uchiyama M., Yamochi T., Nishibashi K., Hosono O., Takahashi N.,
RA Kina S., Tanaka H., Lin X., Dang N.H., Morimoto C.;
RT "Caveolin-1 triggers T-cell activation via CD26 in association with
RT CARMA1.";
RL J. Biol. Chem. 282:10117-10131(2007).
RN [34]
RP INTERACTION WITH FAF1.
RX PubMed=17684021; DOI=10.1074/jbc.c700106200;
RA Park M.Y., Moon J.H., Lee K.S., Choi H.I., Chung J., Hong H.J., Kim E.;
RT "FAF1 suppresses IkappaB kinase (IKK) activation by disrupting the IKK
RT complex assembly.";
RL J. Biol. Chem. 282:27572-27577(2007).
RN [35]
RP FUNCTION IN PHOSPHORYLATION OF BCL10.
RX PubMed=17213322; DOI=10.1073/pnas.0606982104;
RA Lobry C., Lopez T., Israel A., Weil R.;
RT "Negative feedback loop in T cell activation through IkappaB kinase-induced
RT phosphorylation and degradation of Bcl10.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:908-913(2007).
RN [36]
RP REVIEW.
RX PubMed=10712233; DOI=10.1152/ajpcell.2000.278.3.c451;
RA Jobin C., Sartor R.B.;
RT "The I kappa B/NF-kappa B system: a key determinant of mucosal inflammation
RT and protection.";
RL Am. J. Physiol. 278:C451-C462(2000).
RN [37]
RP REVIEW, AND DOMAIN.
RX PubMed=18626576; DOI=10.1007/s12026-008-8025-1;
RA Solt L.A., May M.J.;
RT "The IkappaB kinase complex: master regulator of NF-kappaB signaling.";
RL Immunol. Res. 42:3-18(2008).
RN [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [41]
RP INTERACTION WITH NAA10, AND FUNCTION IN PHOSPHORYLATION OF NAA10.
RX PubMed=19716809; DOI=10.1016/j.bbrc.2009.08.127;
RA Kuo H.P., Lee D.F., Xia W., Lai C.C., Li L.Y., Hung M.C.;
RT "Phosphorylation of ARD1 by IKKbeta contributes to its destabilization and
RT degradation.";
RL Biochem. Biophys. Res. Commun. 389:156-161(2009).
RN [42]
RP DEPHOSPHORYLATION AT SER-177 AND SER-181, AND INTERACTION WITH PPM1A AND
RP PPM1B.
RX PubMed=18930133; DOI=10.1016/j.cellsig.2008.09.012;
RA Sun W., Yu Y., Dotti G., Shen T., Tan X., Savoldo B., Pass A.K., Chu M.,
RA Zhang D., Lu X., Fu S., Lin X., Yang J.;
RT "PPM1A and PPM1B act as IKKbeta phosphatases to terminate TNFalpha-induced
RT IKKbeta-NF-kappaB activation.";
RL Cell. Signal. 21:95-102(2009).
RN [43]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [44]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [45]
RP FUNCTION, AND INTERACTION WITH NLRC5.
RX PubMed=20434986; DOI=10.1016/j.cell.2010.03.040;
RA Cui J., Zhu L., Xia X., Wang H.Y., Legras X., Hong J., Ji J., Shen P.,
RA Zheng S., Chen Z.J., Wang R.F.;
RT "NLRC5 negatively regulates the NF-kappaB and type I interferon signaling
RT pathways.";
RL Cell 141:483-496(2010).
RN [46]
RP INTERACTION WITH TRIM21, MONOUBIQUITINATION, UBIQUITINATION INACTIVATION BY
RP YERSINIA YOPJ (MICROBIAL INFECTION), AND MUTAGENESIS OF LYS-163; SER-177
RP AND SER-181.
RX PubMed=19675099; DOI=10.1093/jb/mvp127;
RA Wada K., Niida M., Tanaka M., Kamitani T.;
RT "Ro52-mediated monoubiquitination of IKK{beta} down-regulates NF-{kappa}B
RT signalling.";
RL J. Biochem. 146:821-832(2009).
RN [47]
RP FUNCTION IN PHOSPHORYLATION OF RELA.
RX PubMed=20410276; DOI=10.1128/jvi.00142-10;
RA Yoboua F., Martel A., Duval A., Mukawera E., Grandvaux N.;
RT "Respiratory syncytial virus-mediated NF-kappa B p65 phosphorylation at
RT serine 536 is dependent on RIG-I, TRAF6, and IKK beta.";
RL J. Virol. 84:7267-7277(2010).
RN [48]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=20797629; DOI=10.1016/j.molcel.2010.07.030;
RA Tsuchiya Y., Asano T., Nakayama K., Kato T. Jr., Karin M., Kamata H.;
RT "Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and
RT degradation in UV-induced NF-kappaB activation.";
RL Mol. Cell 39:570-582(2010).
RN [49]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [50]
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 [51]
RP FUNCTION, AND PHOSPHORYLATION BY TBK1 AND IKBKE.
RX PubMed=21138416; DOI=10.1042/bj20101701;
RA Clark K., Peggie M., Plater L., Sorcek R.J., Young E.R., Madwed J.B.,
RA Hough J., McIver E.G., Cohen P.;
RT "Novel cross-talk within the IKK family controls innate immunity.";
RL Biochem. J. 434:93-104(2011).
RN [52]
RP INTERACTION WITH ZNF268, AND SUBUNIT.
RX PubMed=23091055; DOI=10.1074/jbc.m112.399923;
RA Wang W., Guo M., Hu L., Cai J., Zeng Y., Luo J., Shu Z., Li W., Huang Z.;
RT "The zinc finger protein ZNF268 is overexpressed in human cervical cancer
RT and contributes to tumorigenesis via enhancing NF-kappaB signaling.";
RL J. Biol. Chem. 287:42856-42866(2012).
RN [53]
RP INTERACTION WITH IKBKE.
RX PubMed=23453969; DOI=10.1016/j.celrep.2013.01.031;
RA Zhou A.Y., Shen R.R., Kim E., Lock Y.J., Xu M., Chen Z.J., Hahn W.C.;
RT "IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination
RT by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex.";
RL Cell Rep. 3:724-733(2013).
RN [54]
RP INTERACTION WITH SASH1.
RX PubMed=23776175; DOI=10.4049/jimmunol.1200583;
RA Dauphinee S.M., Clayton A., Hussainkhel A., Yang C., Park Y.J.,
RA Fuller M.E., Blonder J., Veenstra T.D., Karsan A.;
RT "SASH1 is a scaffold molecule in endothelial TLR4 signaling.";
RL J. Immunol. 191:892-901(2013).
RN [55]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672 AND SER-675, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [56]
RP INTERACTION WITH AKAP13.
RX PubMed=23090968; DOI=10.1128/mcb.00887-12;
RA del Vescovo C.D., Cotecchia S., Diviani D.;
RT "A-kinase-anchoring protein-Lbc anchors IkappaB kinase beta to support
RT interleukin-6-mediated cardiomyocyte hypertrophy.";
RL Mol. Cell. Biol. 33:14-27(2013).
RN [57]
RP INVOLVEMENT IN IMD15B.
RX PubMed=24369075; DOI=10.1056/nejmoa1309199;
RA Pannicke U., Baumann B., Fuchs S., Henneke P., Rensing-Ehl A., Rizzi M.,
RA Janda A., Hese K., Schlesier M., Holzmann K., Borte S., Laux C., Rump E.M.,
RA Rosenberg A., Zelinski T., Schrezenmeier H., Wirth T., Ehl S.,
RA Schroeder M.L., Schwarz K.;
RT "Deficiency of innate and acquired immunity caused by an IKBKB mutation.";
RL N. Engl. J. Med. 369:2504-2514(2013).
RN [58]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-675, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [59]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-166.
RX PubMed=25326418; DOI=10.1073/pnas.1418399111;
RA Lopez-Pelaez M., Lamont D.J., Peggie M., Shpiro N., Gray N.S., Cohen P.;
RT "Protein kinase IKKbeta-catalyzed phosphorylation of IRF5 at Ser462 induces
RT its dimerization and nuclear translocation in myeloid cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:17432-17437(2014).
RN [60]
RP INTERACTION WITH IFIT5.
RX PubMed=26334375; DOI=10.1016/j.cellsig.2015.08.018;
RA Zheng C., Zheng Z., Zhang Z., Meng J., Liu Y., Ke X., Hu Q., Wang H.;
RT "IFIT5 positively regulates NF-kappaB signaling through synergizing the
RT recruitment of IkappaB kinase (IKK) to TGF-beta-activated kinase 1
RT (TAK1).";
RL Cell. Signal. 27:2343-2354(2015).
RN [61]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [62]
RP INTERACTION WITH ARFIP2.
RX PubMed=26296658; DOI=10.1016/j.cellsig.2015.08.012;
RA You D.J., Park C.R., Furlong M., Koo O., Lee C., Ahn C., Seong J.Y.,
RA Hwang J.I.;
RT "Dimer of arfaptin 2 regulates NF-kappaB signaling by interacting with
RT IKKbeta/NEMO and inhibiting IKKbeta kinase activity.";
RL Cell. Signal. 27:2173-2181(2015).
RN [63]
RP INTERACTION WITH FKBP5.
RX PubMed=26101251; DOI=10.1093/nar/gkv615;
RA Romano S., Xiao Y., Nakaya M., D'Angelillo A., Chang M., Jin J., Hausch F.,
RA Masullo M., Feng X., Romano M.F., Sun S.C.;
RT "FKBP51 employs both scaffold and isomerase functions to promote NF-kappaB
RT activation in melanoma.";
RL Nucleic Acids Res. 43:6983-6993(2015).
RN [64]
RP INTERACTION WITH LRRC14.
RX PubMed=27426725; DOI=10.1016/j.yexcr.2016.07.011;
RA Wu C., Yang Y., Ou J., Zhu L., Zhao W., Cui J.;
RT "LRRC14 attenuates Toll-like receptor-mediated NF-kappa-B signaling through
RT disruption of IKK complex.";
RL Exp. Cell Res. 347:65-73(2016).
RN [65]
RP INTERACTION WITH VACCINIA VIRUS PROTEIN B14 (MICROBIAL INFECTION).
RX PubMed=29748387; DOI=10.1074/jbc.ra118.002817;
RA Tang Q., Chakraborty S., Xu G.;
RT "Mechanism of vaccinia viral protein B14 mediated inhibition of IkappaB
RT kinase beta activation.";
RL J. Biol. Chem. 293:10344-10352(2018).
RN [66]
RP FUNCTION, INVOLVEMENT IN IMD15A, VARIANT IMD15A ILE-203, CHARACTERIZATION
RP OF VARIANT IMD15A ILE-203, AND MUTAGENESIS OF LYS-171 AND 272-ARG--SER-756.
RX PubMed=30337470; DOI=10.1084/jem.20180639;
RA Cardinez C., Miraghazadeh B., Tanita K., da Silva E., Hoshino A., Okada S.,
RA Chand R., Asano T., Tsumura M., Yoshida K., Ohnishi H., Kato Z.,
RA Yamazaki M., Okuno Y., Miyano S., Kojima S., Ogawa S., Andrews T.D.,
RA Field M.A., Burgio G., Morio T., Vinuesa C.G., Kanegane H., Cook M.C.;
RT "Gain-of-function IKBKB mutation causes human combined immune deficiency.";
RL J. Exp. Med. 215:2715-2724(2018).
RN [67]
RP INTERACTION WITH FKBP5.
RX PubMed=31434731; DOI=10.1128/jvi.01159-19;
RA DeDiego M.L., Martinez-Sobrido L., Topham D.J.;
RT "Novel Functions of IFI44L as a Feedback Regulator of Host Antiviral
RT Responses.";
RL J. Virol. 93:0-0(2019).
RN [68]
RP IDENTIFICATION IN THE IKK COMPLEX.
RX PubMed=32935379; DOI=10.15252/embj.2020105139;
RA Chathuranga K., Kim T.H., Lee H., Park J.S., Kim J.H., Chathuranga W.A.G.,
RA Ekanayaka P., Choi Y.J., Lee C.H., Kim C.J., Jung J.U., Lee J.S.;
RT "Negative regulation of NEMO signaling by the ubiquitin E3 ligase MARCH2.";
RL EMBO J. 39:e105139-e105139(2020).
RN [69]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 701-742.
RX PubMed=18462684; DOI=10.1016/j.str.2008.02.012;
RA Rushe M., Silvian L., Bixler S., Chen L.L., Cheung A., Bowes S., Cuervo H.,
RA Berkowitz S., Zheng T., Guckian K., Pellegrini M., Lugovskoy A.;
RT "Structure of a NEMO/IKK-associating domain reveals architecture of the
RT interaction site.";
RL Structure 16:798-808(2008).
RN [70]
RP VARIANT [LARGE SCALE ANALYSIS] SER-360.
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).
RN [71]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-360; ARG-369; GLN-526; THR-710 AND
RP LEU-734.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine kinase that plays an essential role in the NF-kappa-B
CC signaling pathway which is activated by multiple stimuli such as
CC inflammatory cytokines, bacterial or viral products, DNA damages or
CC other cellular stresses (PubMed:30337470). Acts as part of the
CC canonical IKK complex in the conventional pathway of NF-kappa-B
CC activation. Phosphorylates inhibitors of NF-kappa-B on 2 critical
CC serine residues. These modifications allow polyubiquitination of the
CC inhibitors and subsequent degradation by the proteasome. In turn, free
CC NF-kappa-B is translocated into the nucleus and activates the
CC transcription of hundreds of genes involved in immune response, growth
CC control, or protection against apoptosis. In addition to the NF-kappa-B
CC inhibitors, phosphorylates several other components of the signaling
CC pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as
CC well as IKK-related kinases TBK1 and IKBKE (PubMed:11297557,
CC PubMed:20410276). IKK-related kinase phosphorylations may prevent the
CC overproduction of inflammatory mediators since they exert a negative
CC regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-
CC dependent inactivation of this pro-apoptotic transcription factor
CC (PubMed:15084260). Also phosphorylates other substrates including
CC NCOA3, BCL10 and IRS1 (PubMed:17213322). Within the nucleus, acts as an
CC adapter protein for NFKBIA degradation in UV-induced NF-kappa-B
CC activation (PubMed:11297557). Phosphorylates RIPK1 at 'Ser-25' which
CC represses its kinase activity and consequently prevents TNF-mediated
CC RIPK1-dependent cell death (By similarity). Phosphorylates the C-
CC terminus of IRF5, stimulating IRF5 homodimerization and translocation
CC into the nucleus (PubMed:25326418). {ECO:0000250|UniProtKB:O88351,
CC ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:15084260,
CC ECO:0000269|PubMed:17213322, ECO:0000269|PubMed:19716809,
CC ECO:0000269|PubMed:20410276, ECO:0000269|PubMed:20434986,
CC ECO:0000269|PubMed:20797629, ECO:0000269|PubMed:21138416,
CC ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:30337470}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[I-kappa-B protein] = ADP + H(+) + O-phospho-L-
CC seryl-[I-kappa-B protein]; Xref=Rhea:RHEA:19073, Rhea:RHEA-
CC COMP:13698, Rhea:RHEA-COMP:13699, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC ChEBI:CHEBI:456216; EC=2.7.11.10;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:25326418};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000305};
CC -!- SUBUNIT: Component of the I-kappa-B-kinase (IKK) core complex
CC consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-
CC beta/IKBKB dimers are associated with four gamma/IKBKG subunits
CC (PubMed:32935379). The IKK core complex seems to associate with
CC regulatory or adapter proteins to form a IKK-signalosome holo-complex
CC (PubMed:12612076). The IKK complex associates with TERF2IP/RAP1,
CC leading to promote IKK-mediated phosphorylation of RELA/p65 (By
CC similarity). Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA,
CC IKBKB, IKBKG and CREBBP (PubMed:11971985). Part of a 70-90 kDa complex
CC at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14
CC (PubMed:9751059). Found in a membrane raft complex, at least composed
CC of BCL10, CARD11, DPP4 and IKBKB (PubMed:17287217). Interacts with
CC SQSTM1 through PRKCZ or PRKCI (PubMed:10356400). Forms an NGF-induced
CC complex with IKBKB, PRKCI and TRAF6 (By similarity). May interact with
CC MAVS/IPS1 (PubMed:16177806). Interacts with NALP2 (PubMed:15456791).
CC Interacts with TICAM1 (PubMed:14739303). Interacts with FAF1; the
CC interaction disrupts the IKK complex formation (PubMed:17684021).
CC Interacts with ATM (PubMed:16497931). Part of a ternary complex
CC consisting of TANK, IKBKB and IKBKG (PubMed:12133833). Interacts with
CC NIBP; the interaction is direct (PubMed:15951441). Interacts with ARRB1
CC and ARRB2 (PubMed:15173580). Interacts with TRIM21 (PubMed:19675099).
CC Interacts with NLRC5; prevents IKBKB phosphorylation and kinase
CC activity (PubMed:20434986). Interacts with PDPK1 (PubMed:16207722).
CC Interacts with EIF2AK2/PKR (PubMed:10848580). The phosphorylated form
CC interacts with PPM1A and PPM1B (PubMed:18930133). Interacts with ZNF268
CC isoform 2; the interaction is further increased in a TNF-alpha-
CC dependent manner (PubMed:23091055). Interacts with IKBKE
CC (PubMed:23453969). Interacts with NAA10, leading to NAA10 degradation
CC (PubMed:19716809). Interacts with FOXO3 (PubMed:15084260). Interacts
CC with AKAP13 (PubMed:23090968). Interacts with IFIT5; the interaction
CC synergizes the recruitment of IKK to MAP3K7 and enhances IKK
CC phosphorylation (PubMed:26334375). Interacts with LRRC14; disrupts
CC IKBKB-IKBKG interaction preventing I-kappa-B-kinase (IKK) core complex
CC formation and leading to a decrease of IKBKB phosphorylation and NF-
CC kappaB activation (PubMed:27426725). Interacts with SASH1
CC (PubMed:23776175). Interacts with ARFIP2 (PubMed:26296658). Interacts
CC with FKBP5 (PubMed:31434731, PubMed:26101251).
CC {ECO:0000250|UniProtKB:O88351, ECO:0000250|UniProtKB:Q9QY78,
CC ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10848580,
CC ECO:0000269|PubMed:11971985, ECO:0000269|PubMed:12133833,
CC ECO:0000269|PubMed:12612076, ECO:0000269|PubMed:14739303,
CC ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:15173580,
CC ECO:0000269|PubMed:15456791, ECO:0000269|PubMed:15951441,
CC ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:16207722,
CC ECO:0000269|PubMed:16497931, ECO:0000269|PubMed:17287217,
CC ECO:0000269|PubMed:17684021, ECO:0000269|PubMed:18930133,
CC ECO:0000269|PubMed:19675099, ECO:0000269|PubMed:19716809,
CC ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:23091055,
CC ECO:0000269|PubMed:23453969, ECO:0000269|PubMed:23776175,
CC ECO:0000269|PubMed:26101251, ECO:0000269|PubMed:26296658,
CC ECO:0000269|PubMed:26334375, ECO:0000269|PubMed:27426725,
CC ECO:0000269|PubMed:31434731, ECO:0000269|PubMed:32935379,
CC ECO:0000269|PubMed:9751059}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Yersinia YopJ.
CC {ECO:0000269|PubMed:16728640}.
CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus protein
CC B14. {ECO:0000269|PubMed:29748387}.
CC -!- INTERACTION:
CC O14920; O14965: AURKA; NbExp=2; IntAct=EBI-81266, EBI-448680;
CC O14920; Q16543: CDC37; NbExp=4; IntAct=EBI-81266, EBI-295634;
CC O14920; O15111: CHUK; NbExp=17; IntAct=EBI-81266, EBI-81249;
CC O14920; O14920: IKBKB; NbExp=8; IntAct=EBI-81266, EBI-81266;
CC O14920; Q9Y6K9: IKBKG; NbExp=36; IntAct=EBI-81266, EBI-81279;
CC O14920; Q14145: KEAP1; NbExp=6; IntAct=EBI-81266, EBI-751001;
CC O14920; Q99558: MAP3K14; NbExp=6; IntAct=EBI-81266, EBI-358011;
CC O14920; O43318: MAP3K7; NbExp=6; IntAct=EBI-81266, EBI-358684;
CC O14920; Q9Y6Q9: NCOA3; NbExp=3; IntAct=EBI-81266, EBI-81196;
CC O14920; P19838: NFKB1; NbExp=3; IntAct=EBI-81266, EBI-300010;
CC O14920; P25963: NFKBIA; NbExp=27; IntAct=EBI-81266, EBI-307386;
CC O14920; P67775: PPP2CA; NbExp=3; IntAct=EBI-81266, EBI-712311;
CC O14920; Q04206: RELA; NbExp=2; IntAct=EBI-81266, EBI-73886;
CC O14920; P23396: RPS3; NbExp=4; IntAct=EBI-81266, EBI-351193;
CC O14920; Q9UGK3: STAP2; NbExp=7; IntAct=EBI-81266, EBI-1553984;
CC O14920; Q9UKE5: TNIK; NbExp=2; IntAct=EBI-81266, EBI-1051794;
CC O14920; P04637: TP53; NbExp=2; IntAct=EBI-81266, EBI-366083;
CC O14920; Q92574: TSC1; NbExp=3; IntAct=EBI-81266, EBI-1047085;
CC O14920; P03230: LMP1; Xeno; NbExp=2; IntAct=EBI-81266, EBI-6973030;
CC O14920; P0DTC9: N; Xeno; NbExp=7; IntAct=EBI-81266, EBI-25475856;
CC O14920; P03409: Tax; Xeno; NbExp=3; IntAct=EBI-81266, EBI-5236464;
CC O14920; P24772: VACWR196; Xeno; NbExp=3; IntAct=EBI-81266, EBI-4291651;
CC O14920; Q5D1E7: Zc3h12a; Xeno; NbExp=4; IntAct=EBI-81266, EBI-5326026;
CC O14920-3; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-25847993, EBI-1055254;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20797629}. Nucleus
CC {ECO:0000269|PubMed:20797629}. Membrane raft
CC {ECO:0000269|PubMed:17287217}. Note=Colocalized with DPP4 in membrane
CC rafts. {ECO:0000269|PubMed:17287217}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O14920-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14920-2; Sequence=VSP_041825;
CC Name=3;
CC IsoId=O14920-3; Sequence=VSP_041826, VSP_041827;
CC Name=4;
CC IsoId=O14920-4; Sequence=VSP_043408;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, placenta, skeletal
CC muscle, kidney, pancreas, spleen, thymus, prostate, testis and
CC peripheral blood.
CC -!- DOMAIN: The kinase domain is located in the N-terminal region. The
CC leucine zipper is important to allow homo- and hetero-dimerization. At
CC the C-terminal region is located the region responsible for the
CC interaction with NEMO/IKBKG. {ECO:0000269|PubMed:18626576}.
CC -!- PTM: Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181
CC by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances
CC activity. Once activated, autophosphorylates on the C-terminal serine
CC cluster; which decreases activity and prevents prolonged activation of
CC the inflammatory response. Phosphorylated by the IKK-related kinases
CC TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB
CC activity and NF-kappa-B-dependent gene transcription. Dephosphorylated
CC at Ser-177 and Ser-181 by PPM1A and PPM1B.
CC {ECO:0000269|PubMed:10022904, ECO:0000269|PubMed:10195894,
CC ECO:0000269|PubMed:10783893, ECO:0000269|PubMed:16207722}.
CC -!- PTM: (Microbial infection) Acetylation of Thr-180 by Yersinia YopJ
CC prevents phosphorylation and activation, thus blocking the I-kappa-B
CC pathway. {ECO:0000269|PubMed:16728640, ECO:0000269|PubMed:17116858}.
CC -!- PTM: Ubiquitinated. Monoubiquitination involves TRIM21 that leads to
CC inhibition of Tax-induced NF-kappa-B signaling. According to
CC PubMed:19675099, 'Ser-163' does not serve as a monoubiquitination site.
CC According to PubMed:16267042, ubiquitination on 'Ser-163' modulates
CC phosphorylation on C-terminal serine residues.
CC {ECO:0000269|PubMed:16267042, ECO:0000269|PubMed:19675099}.
CC -!- PTM: (Microbial infection) Monoubiquitination by TRIM21 is disrupted by
CC Yersinia YopJ. {ECO:0000269|PubMed:19675099}.
CC -!- PTM: Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic
CC conditions results in activation of NF-kappa-B.
CC {ECO:0000269|PubMed:17114296}.
CC -!- DISEASE: Immunodeficiency 15B (IMD15B) [MIM:615592]: An autosomal
CC recessive primary immunodeficiency disorder characterized by onset in
CC infancy of life-threatening bacterial, fungal, and viral infections and
CC failure to thrive. Laboratory studies show hypo- or agammaglobulinemia
CC with relatively normal numbers of B and T-cells, and impaired
CC differentiation and activation of immune cells.
CC {ECO:0000269|PubMed:24369075}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Immunodeficiency 15A (IMD15A) [MIM:618204]: An autosomal
CC dominant primary immunodeficiency disorder characterized by
CC lymphopenia, inflammation and immune activation of both CD4+ and CD8+ T
CC cells. Patients suffer from recurrent respiratory tract infections,
CC oral candidiasis, and otitis media. {ECO:0000269|PubMed:30337470}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. I-kappa-B kinase subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ikbkb/";
CC ---------------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
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DR EMBL; AF029684; AAC51860.1; -; mRNA.
DR EMBL; AF080158; AAD08997.1; -; mRNA.
DR EMBL; AF031416; AAC64675.1; -; mRNA.
DR EMBL; AK302723; BAG63942.1; -; mRNA.
DR EMBL; AK303528; BAG64556.1; -; mRNA.
DR EMBL; AK316418; BAH14789.1; -; mRNA.
DR EMBL; AY663108; AAT65965.1; -; Genomic_DNA.
DR EMBL; AC083973; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006231; AAH06231.1; -; mRNA.
DR CCDS; CCDS56535.1; -. [O14920-4]
DR CCDS; CCDS6128.1; -. [O14920-1]
DR RefSeq; NP_001177649.1; NM_001190720.2.
DR RefSeq; NP_001229707.1; NM_001242778.1. [O14920-4]
DR RefSeq; NP_001547.1; NM_001556.2. [O14920-1]
DR PDB; 3BRT; X-ray; 2.25 A; A/C=701-730.
DR PDB; 3BRV; X-ray; 2.20 A; A/C=701-745.
DR PDB; 4E3C; X-ray; 3.98 A; A/B/C/D/E/F=11-669.
DR PDB; 4KIK; X-ray; 2.83 A; A/B=2-664.
DR PDBsum; 3BRT; -.
DR PDBsum; 3BRV; -.
DR PDBsum; 4E3C; -.
DR PDBsum; 4KIK; -.
DR AlphaFoldDB; O14920; -.
DR SMR; O14920; -.
DR BioGRID; 109767; 208.
DR ComplexPortal; CPX-3269; IkappaB kinase complex.
DR CORUM; O14920; -.
DR DIP; DIP-27527N; -.
DR ELM; O14920; -.
DR IntAct; O14920; 82.
DR MINT; O14920; -.
DR STRING; 9606.ENSP00000430684; -.
DR BindingDB; O14920; -.
DR ChEMBL; CHEMBL1991; -.
DR DrugBank; DB06151; Acetylcysteine.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB01169; Arsenic trioxide.
DR DrugBank; DB00995; Auranofin.
DR DrugBank; DB06521; Ertiprotafib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00244; Mesalazine.
DR DrugBank; DB05183; MLN0415.
DR DrugBank; DB00795; Sulfasalazine.
DR DrugCentral; O14920; -.
DR GuidetoPHARMACOLOGY; 2039; -.
DR GlyConnect; 2884; 1 O-Linked glycan (1 site).
DR GlyGen; O14920; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O14920; -.
DR MetOSite; O14920; -.
DR PhosphoSitePlus; O14920; -.
DR BioMuta; IKBKB; -.
DR EPD; O14920; -.
DR jPOST; O14920; -.
DR MassIVE; O14920; -.
DR MaxQB; O14920; -.
DR PaxDb; O14920; -.
DR PeptideAtlas; O14920; -.
DR PRIDE; O14920; -.
DR ProteomicsDB; 48297; -. [O14920-1]
DR ProteomicsDB; 48298; -. [O14920-2]
DR ProteomicsDB; 48299; -. [O14920-3]
DR ProteomicsDB; 48300; -. [O14920-4]
DR Antibodypedia; 802; 2327 antibodies from 51 providers.
DR DNASU; 3551; -.
DR Ensembl; ENST00000520810.6; ENSP00000430684.1; ENSG00000104365.16. [O14920-1]
DR GeneID; 3551; -.
DR KEGG; hsa:3551; -.
DR MANE-Select; ENST00000520810.6; ENSP00000430684.1; NM_001556.3; NP_001547.1.
DR UCSC; uc003xow.3; human. [O14920-1]
DR CTD; 3551; -.
DR DisGeNET; 3551; -.
DR GeneCards; IKBKB; -.
DR HGNC; HGNC:5960; IKBKB.
DR HPA; ENSG00000104365; Low tissue specificity.
DR MalaCards; IKBKB; -.
DR MIM; 603258; gene.
DR MIM; 615592; phenotype.
DR MIM; 618204; phenotype.
DR neXtProt; NX_O14920; -.
DR OpenTargets; ENSG00000104365; -.
DR Orphanet; 397787; Severe combined immunodeficiency due to IKK2 deficiency.
DR PharmGKB; PA29776; -.
DR VEuPathDB; HostDB:ENSG00000104365; -.
DR eggNOG; KOG4250; Eukaryota.
DR GeneTree; ENSGT00950000182937; -.
DR HOGENOM; CLU_000288_101_2_1; -.
DR InParanoid; O14920; -.
DR OMA; NAMQDTM; -.
DR OrthoDB; 1013139at2759; -.
DR PhylomeDB; O14920; -.
DR TreeFam; TF324269; -.
DR BRENDA; 2.7.11.10; 2681.
DR PathwayCommons; O14920; -.
DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-HSA-168927; TICAM1, RIP1-mediated IKK complex recruitment.
DR Reactome; R-HSA-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-HSA-202424; Downstream TCR signaling.
DR Reactome; R-HSA-209543; p75NTR recruits signalling complexes.
DR Reactome; R-HSA-209560; NF-kB is activated and signals survival.
DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-HSA-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-HSA-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-HSA-5602636; IKBKB deficiency causes SCID.
DR Reactome; R-HSA-5603027; IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR).
DR Reactome; R-HSA-5603029; IkBA variant leads to EDA-ID.
DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-HSA-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation.
DR Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-HSA-933543; NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
DR Reactome; R-HSA-937039; IRAK1 recruits IKK complex.
DR Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR SABIO-RK; O14920; -.
DR SignaLink; O14920; -.
DR SIGNOR; O14920; -.
DR BioGRID-ORCS; 3551; 34 hits in 1114 CRISPR screens.
DR ChiTaRS; IKBKB; human.
DR EvolutionaryTrace; O14920; -.
DR GeneWiki; IKK2; -.
DR GenomeRNAi; 3551; -.
DR Pharos; O14920; Tchem.
DR PRO; PR:O14920; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O14920; protein.
DR Bgee; ENSG00000104365; Expressed in spleen and 195 other tissues.
DR ExpressionAtlas; O14920; baseline and differential.
DR Genevisible; O14920; HS.
DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0008385; C:IkappaB kinase complex; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008384; F:IkappaB kinase activity; TAS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0097110; F:scaffold protein binding; IDA:MGI.
DR GO; GO:1990459; F:transferrin receptor binding; IPI:ARUK-UCL.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; TAS:Reactome.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:UniProtKB.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; IMP:UniProtKB.
DR GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; IMP:UniProtKB.
DR GO; GO:0042325; P:regulation of phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0009615; P:response to virus; TAS:UniProtKB.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome.
DR GO; GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
DR Gene3D; 1.20.1270.250; -; 1.
DR IDEAL; IID00525; -.
DR InterPro; IPR041185; IKBKB_SDD.
DR InterPro; IPR046375; IKBKB_SDD_sf.
DR InterPro; IPR022007; IKKbetaNEMObind.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF18397; IKBKB_SDD; 1.
DR Pfam; PF12179; IKKbetaNEMObind; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM01239; IKKbetaNEMObind; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Disease variant; Host-virus interaction;
KW Hydroxylation; Isopeptide bond; Kinase; Membrane; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; S-nitrosylation; SCID;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..756
FT /note="Inhibitor of nuclear factor kappa-B kinase subunit
FT beta"
FT /id="PRO_0000086013"
FT DOMAIN 15..300
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 458..479
FT /note="Leucine-zipper"
FT REGION 667..706
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 737..742
FT /note="NEMO-binding"
FT COMPBIAS 670..700
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 145
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 21..29
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 177
FT /note="Phosphoserine; by TBK1 and PKC/PRKCZ"
FT /evidence="ECO:0000269|PubMed:10022904,
FT ECO:0000269|PubMed:10195894, ECO:0000269|PubMed:10783893"
FT MOD_RES 179
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000269|PubMed:15184672"
FT MOD_RES 180
FT /note="(Microbial infection) O-acetylthreonine; by Yersinia
FT YopJ"
FT /evidence="ECO:0000269|PubMed:17116858"
FT MOD_RES 181
FT /note="Phosphoserine; by TBK1, PKC/PRKCZ and PDPK1"
FT /evidence="ECO:0000269|PubMed:10022904,
FT ECO:0000269|PubMed:10195894, ECO:0000269|PubMed:10783893,
FT ECO:0000269|PubMed:16207722"
FT MOD_RES 191
FT /note="Hydroxyproline"
FT /evidence="ECO:0000269|PubMed:17114296"
FT MOD_RES 670
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894"
FT MOD_RES 672
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10195894,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 675
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 675
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 682
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894"
FT MOD_RES 689
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894"
FT MOD_RES 692
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894"
FT MOD_RES 695
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894"
FT MOD_RES 697
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894"
FT MOD_RES 705
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894"
FT MOD_RES 733
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894"
FT MOD_RES 740
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894"
FT MOD_RES 750
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:10195894"
FT CROSSLNK 163
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:16267042"
FT VAR_SEQ 1..66
FT /note="MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHNQETGEQIAIKQCRQELSP
FT RNRERWCLEIQIMR -> MSSDGTI (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043408"
FT VAR_SEQ 1..34
FT /note="MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHN -> MFSGGCHSPGFGRP
FT SPAFPAPGSPPPAPRPCR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041825"
FT VAR_SEQ 231..256
FT /note="WHSKVRQKSEVDIVVSEDLNGTVKFS -> CVRMWPGTVAHSCNPSTLGGRG
FT RWIS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041826"
FT VAR_SEQ 257..756
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041827"
FT VARIANT 203
FT /note="V -> I (in IMD15A; gain-of-function mutation
FT resulting in increased activation of NF-kappa-B signaling
FT pathway; dbSNP:rs1563340753)"
FT /evidence="ECO:0000269|PubMed:30337470"
FT /id="VAR_081275"
FT VARIANT 360
FT /note="A -> S (in breast cancer samples; infiltrating
FT ductal carcinoma; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_035626"
FT VARIANT 369
FT /note="Q -> R (in dbSNP:rs56411242)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040567"
FT VARIANT 526
FT /note="R -> Q (in dbSNP:rs2272736)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040568"
FT VARIANT 554
FT /note="R -> W (in dbSNP:rs17875749)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_021124"
FT VARIANT 710
FT /note="A -> T (in dbSNP:rs34309584)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040569"
FT VARIANT 734
FT /note="F -> L (in dbSNP:rs56301637)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040570"
FT VARIANT 736
FT /note="A -> T (in dbSNP:rs17611716)"
FT /id="VAR_051628"
FT MUTAGEN 44
FT /note="K->A: Loss of kinase activity and no effect on
FT binding to NIK."
FT /evidence="ECO:0000269|PubMed:9346484,
FT ECO:0000269|PubMed:9346485"
FT MUTAGEN 163
FT /note="K->R: Monoubiquitinated; when associated with E-177
FT and E-181."
FT /evidence="ECO:0000269|PubMed:19675099"
FT MUTAGEN 166
FT /note="D->A: Loss of protein kinase activity."
FT /evidence="ECO:0000269|PubMed:25326418"
FT MUTAGEN 171
FT /note="K->E: Increased activation of NF-kappa-B signaling."
FT /evidence="ECO:0000269|PubMed:30337470"
FT MUTAGEN 177..181
FT /note="SLCTS->ALCTA: COmplete loss of TBK1-mediated
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:10783893"
FT MUTAGEN 177
FT /note="S->A: Decrease of activity."
FT /evidence="ECO:0000269|PubMed:19675099,
FT ECO:0000269|PubMed:9346484"
FT MUTAGEN 177
FT /note="S->E: Full activation. Interaction with TRIM21 is
FT enhanced; when associated with E-181. Monoubiquitinated;
FT when associated with R-163 and E-181. Strongly promoted NF-
FT kappa-B gene expression; when associated with E-181."
FT /evidence="ECO:0000269|PubMed:19675099,
FT ECO:0000269|PubMed:9346484"
FT MUTAGEN 181
FT /note="S->A: Decrease of activity."
FT /evidence="ECO:0000269|PubMed:19675099,
FT ECO:0000269|PubMed:9346484"
FT MUTAGEN 181
FT /note="S->E: Full activation. Interaction with TRIM21 is
FT enhanced; when associated with E-177. Monoubiquitinated;
FT when associated with R-163 and E-177. Strongly promoted NF-
FT kappa-B gene expression; when associated with E-177."
FT /evidence="ECO:0000269|PubMed:19675099,
FT ECO:0000269|PubMed:9346484"
FT MUTAGEN 191
FT /note="P->A: Loss of hypoxic inducibility."
FT /evidence="ECO:0000269|PubMed:17114296"
FT MUTAGEN 272..756
FT /note="Missing: Loss of activation of NF-kappa-B
FT signaling."
FT /evidence="ECO:0000269|PubMed:30337470"
FT CONFLICT 259
FT /note="L -> S (in Ref. 5; BAG63942/BAH14789)"
FT /evidence="ECO:0000305"
FT STRAND 15..22
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:4KIK"
FT TURN 35..37
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 40..44
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 52..67
FT /evidence="ECO:0007829|PDB:4KIK"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 87..91
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 104..109
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 119..138
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 157..164
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:4KIK"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 191..195
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 202..217
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 228..235
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 267..280
FT /evidence="ECO:0007829|PDB:4KIK"
FT TURN 285..289
FT /evidence="ECO:0007829|PDB:4KIK"
FT TURN 292..294
FT /evidence="ECO:0007829|PDB:4KIK"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 299..307
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 310..316
FT /evidence="ECO:0007829|PDB:4KIK"
FT TURN 317..320
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 321..327
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 333..344
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 353..355
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 367..370
FT /evidence="ECO:0007829|PDB:4KIK"
FT TURN 382..385
FT /evidence="ECO:0007829|PDB:4KIK"
FT STRAND 386..389
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 408..415
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 423..499
FT /evidence="ECO:0007829|PDB:4KIK"
FT TURN 500..504
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 509..520
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 527..548
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 559..575
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 579..581
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 588..661
FT /evidence="ECO:0007829|PDB:4KIK"
FT HELIX 706..729
FT /evidence="ECO:0007829|PDB:3BRV"
FT HELIX 734..736
FT /evidence="ECO:0007829|PDB:3BRV"
FT HELIX 740..742
FT /evidence="ECO:0007829|PDB:3BRV"
SQ SEQUENCE 756 AA; 86564 MW; F9CADF671AE9E14E CRC64;
MSWSPSLTTQ TCGAWEMKER LGTGGFGNVI RWHNQETGEQ IAIKQCRQEL SPRNRERWCL
EIQIMRRLTH PNVVAARDVP EGMQNLAPND LPLLAMEYCQ GGDLRKYLNQ FENCCGLREG
AILTLLSDIA SALRYLHENR IIHRDLKPEN IVLQQGEQRL IHKIIDLGYA KELDQGSLCT
SFVGTLQYLA PELLEQQKYT VTVDYWSFGT LAFECITGFR PFLPNWQPVQ WHSKVRQKSE
VDIVVSEDLN GTVKFSSSLP YPNNLNSVLA ERLEKWLQLM LMWHPRQRGT DPTYGPNGCF
KALDDILNLK LVHILNMVTG TIHTYPVTED ESLQSLKARI QQDTGIPEED QELLQEAGLA
LIPDKPATQC ISDGKLNEGH TLDMDLVFLF DNSKITYETQ ISPRPQPESV SCILQEPKRN
LAFFQLRKVW GQVWHSIQTL KEDCNRLQQG QRAAMMNLLR NNSCLSKMKN SMASMSQQLK
AKLDFFKTSI QIDLEKYSEQ TEFGITSDKL LLAWREMEQA VELCGRENEV KLLVERMMAL
QTDIVDLQRS PMGRKQGGTL DDLEEQAREL YRRLREKPRD QRTEGDSQEM VRLLLQAIQS
FEKKVRVIYT QLSKTVVCKQ KALELLPKVE EVVSLMNEDE KTVVRLQEKR QKELWNLLKI
ACSKVRGPVS GSPDSMNASR LSQPGQLMSQ PSTASNSLPE PAKKSEELVA EAHNLCTLLE
NAIQDTVREQ DQSFTALDWS WLQTEEEEHS CLEQAS
