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 27-MAR-2024, entry version 242. 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 {ECO:0000269|PubMed:9346484}; DE AltName: Full=I-kappa-B kinase 2 {ECO:0000303|PubMed:9346484}; DE Short=IKK-2 {ECO:0000303|PubMed:9346484}; DE Short=IKK2 {ECO:0000303|PubMed:9346484}; 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), FUNCTION, CATALYTIC ACTIVITY, AND RP MUTAGENESIS OF LYS-44; SER-177 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 PHOSPHORYLATION. RX PubMed=11460167; DOI=10.1038/35085597; RA Wang C., Deng L., Hong M., Akkaraju G.R., Inoue J., Chen Z.J.; RT "TAK1 is a ubiquitin-dependent kinase of MKK and IKK."; RL Nature 412:346-351(2001). RN [19] 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 [20] 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 [21] 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 [22] 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 [23] 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 [24] 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 [25] RP FUNCTION. RX PubMed=14673179; DOI=10.1128/mcb.24.1.475-486.2004; RA Cohen S., Achbert-Weiner H., Ciechanover A.; RT "Dual effects of IkappaB kinase beta-mediated phosphorylation on p105 fate: RT SCF(beta-TrCP)-dependent degradation and SCF(beta-TrCP)-independent RT processing."; RL Mol. Cell. Biol. 24:475-486(2004). RN [26] 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 [27] 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 [28] 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 [29] 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 [30] 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 [31] 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 [32] 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 [33] 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 [34] 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 [35] 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 [36] 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 [37] 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 [38] 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 [39] 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 [40] 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 [41] 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 [42] 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 [43] RP 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 [44] 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 [45] 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 [46] 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 [47] 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 [48] 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 [49] 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 [50] 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 [51] 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 [52] 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 [53] 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 [54] 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 [55] 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 [56] 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 [57] 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 [58] 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 [59] 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 [60] 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 [61] 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 [62] 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 [63] 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 [64] 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 [65] 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 [66] 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 [67] 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 [68] 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 [69] 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 [70] 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 [71] 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 [72] 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 [73] 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:20434986, PubMed:20797629, CC PubMed:21138416, PubMed:9346484, PubMed:30337470). Acts as a part of CC the canonical IKK complex in the conventional pathway of NF-kappa-B CC activation (PubMed:9346484). Phosphorylates inhibitors of NF-kappa-B on CC 2 critical serine residues (PubMed:9346484, PubMed:20434986, CC PubMed:20797629, PubMed:21138416). These modifications allow CC polyubiquitination of the inhibitors and subsequent degradation by the CC proteasome (PubMed:9346484, PubMed:20434986, PubMed:20797629, CC PubMed:21138416). In turn, free NF-kappa-B is translocated into the CC nucleus and activates the transcription of hundreds of genes involved CC in immune response, growth control, or protection against apoptosis CC (PubMed:9346484, PubMed:20434986, PubMed:20797629, PubMed:21138416). In CC addition to the NF-kappa-B inhibitors, phosphorylates several other CC components of the signaling pathway including NEMO/IKBKG, NF-kappa-B CC subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE CC (PubMed:11297557, PubMed:14673179, PubMed:20410276, PubMed:21138416). CC IKK-related kinase phosphorylations may prevent the overproduction of CC inflammatory mediators since they exert a negative regulation on CC canonical IKKs (PubMed:11297557, PubMed:20410276, PubMed:21138416). CC Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this CC pro-apoptotic transcription factor (PubMed:15084260). Also CC phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 CC (PubMed:19716809, PubMed:17213322). Phosphorylates RIPK1 at 'Ser-25' CC which represses its kinase activity and consequently prevents TNF- CC mediated RIPK1-dependent cell death (By similarity). Phosphorylates the CC C-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:14673179, CC ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17213322, CC ECO:0000269|PubMed:19716809, ECO:0000269|PubMed:20410276, CC ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20797629, CC ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:25326418, CC ECO:0000269|PubMed:30337470, ECO:0000269|PubMed:9346484}. 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 Evidence={ECO:0000269|PubMed:9346484}; 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 AKAP13 (PubMed:23090968). Interacts CC with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 CC and enhances IKK phosphorylation (PubMed:26334375). Interacts with CC LRRC14; disrupts IKBKB-IKBKG interaction preventing I-kappa-B-kinase CC (IKK) core complex formation and leading to a decrease of IKBKB CC phosphorylation and NF-kappaB activation (PubMed:27426725). Interacts CC with SASH1 (PubMed:23776175). Interacts with ARFIP2 (PubMed:26296658). CC Interacts 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:15173580, ECO:0000269|PubMed:15456791, CC ECO:0000269|PubMed:15951441, ECO:0000269|PubMed:16177806, CC ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16497931, CC ECO:0000269|PubMed:17287217, ECO:0000269|PubMed:17684021, CC ECO:0000269|PubMed:18930133, ECO:0000269|PubMed:19675099, 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; P24772: OPG200; Xeno; NbExp=3; IntAct=EBI-81266, EBI-4291651; CC O14920; P03409: Tax; Xeno; NbExp=3; IntAct=EBI-81266, EBI-5236464; 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 (PubMed:10022904, PubMed:16207722). Phosphorylated by CC MAP3K7/TAK1 in response to NOD1 and NOD2 signaling, promoting CC activation and phosphorylation of NF-kappa-B inhibitors, leading to NF- CC kappa-B activation (PubMed:11460167). Once activated, CC autophosphorylates on the C-terminal serine cluster; which decreases CC activity and prevents prolonged activation of the inflammatory response CC (PubMed:10195894). Phosphorylated by the IKK-related kinases TBK1 and CC IKBKE, which is associated with reduced CHUK/IKKA and IKBKB activity CC and NF-kappa-B-dependent gene transcription (PubMed:10783893). CC Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B CC (PubMed:18930133). {ECO:0000269|PubMed:10022904, CC ECO:0000269|PubMed:10195894, ECO:0000269|PubMed:10783893, CC ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:16207722, CC ECO:0000269|PubMed:18930133}. 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 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; 236. 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 DrugCentral; O14920; -. DR GuidetoPHARMACOLOGY; 2039; -. DR GlyConnect; 2884; 1 O-GlcNAc glycan (1 site). DR GlyCosmos; O14920; 1 site, 1 glycan. DR GlyGen; O14920; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O14920; -. DR MetOSite; O14920; -. DR PhosphoSitePlus; O14920; -. DR BioMuta; IKBKB; -. DR CPTAC; CPTAC-3081; -. DR CPTAC; CPTAC-3082; -. DR EPD; O14920; -. DR jPOST; O14920; -. DR MassIVE; O14920; -. DR MaxQB; O14920; -. DR PaxDb; 9606-ENSP00000430684; -. DR PeptideAtlas; O14920; -. DR ProteomicsDB; 48297; -. [O14920-1] DR ProteomicsDB; 48298; -. [O14920-2] DR ProteomicsDB; 48299; -. [O14920-3] DR ProteomicsDB; 48300; -. [O14920-4] DR Pumba; O14920; -. DR Antibodypedia; 802; 2609 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 AGR; HGNC:5960; -. 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; SLMALDW; -. DR OrthoDB; 3949542at2759; -. 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 NF-kappa-B 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 Reactome; R-HSA-9758274; Regulation of NF-kappa B signaling. DR Reactome; R-HSA-9833482; PKR-mediated signaling. DR SABIO-RK; O14920; -. DR SignaLink; O14920; -. DR SIGNOR; O14920; -. DR BioGRID-ORCS; 3551; 36 hits in 1199 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 197 other cell types or tissues. DR ExpressionAtlas; O14920; baseline and differential. DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProt. 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; IDA: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:0007249; P:canonical NF-kappaB signal transduction; IDA:UniProtKB. 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: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:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome. 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 canonical NF-kappaB signal transduction; IDA:UniProt. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; NAS: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:0072659; P:protein localization to plasma membrane; IMP:UniProtKB. DR GO; GO:0051604; P:protein maturation; IDA:UniProt. 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:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome. DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB. DR CDD; cd14038; STKc_IKK_beta; 1. DR CDD; cd17046; Ubl_IKKA_like; 1. DR Gene3D; 1.20.1270.250; -; 1. DR Gene3D; 6.10.250.2110; -; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR22969; IKB KINASE; 1. DR PANTHER; PTHR22969:SF7; INHIBITOR OF NUCLEAR FACTOR KAPPA-B KINASE SUBUNIT BETA; 1. 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; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; O14920; HS. 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 /evidence="ECO:0000269|PubMed:12133833" 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 FT NF-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 FT NF-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 //