ID IKKA_HUMAN Reviewed; 745 AA. AC O15111; O14666; Q13132; Q5W0I4; Q92467; DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 2. DT 24-JAN-2024, entry version 238. DE RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit alpha; DE Short=I-kappa-B kinase alpha; DE Short=IKK-A; DE Short=IKK-alpha; DE Short=IkBKA; DE Short=IkappaB kinase; DE EC=2.7.11.10 {ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, ECO:0000269|PubMed:9346484}; DE AltName: Full=Conserved helix-loop-helix ubiquitous kinase; DE AltName: Full=I-kappa-B kinase 1 {ECO:0000303|PubMed:9346484}; DE Short=IKK-1 {ECO:0000303|PubMed:9346484}; DE Short=IKK1 {ECO:0000303|PubMed:9346484}; DE AltName: Full=Nuclear factor NF-kappa-B inhibitor kinase alpha; DE Short=NFKBIKA; DE AltName: Full=Transcription factor 16; DE Short=TCF-16; GN Name=CHUK; Synonyms=IKKA, TCF16; 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], FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF RP LYS-44, AND VARIANT ILE-268. RC TISSUE=T-cell; RX PubMed=9244310; DOI=10.1016/s0092-8674(00)80344-x; RA Regnier C.H., Song H.Y., Gao X., Goeddel D.V., Cao Z., Rothe M.; RT "Identification and characterization of an IkappaB kinase."; RL Cell 90:373-383(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC RP ACTIVITY, AND VARIANT ILE-268. RX PubMed=9252186; DOI=10.1038/41493; RA DiDonato J.A., Hayakawa M., Rothwarf D.M., Zandi E., Karin M.; RT "A cytokine-responsive IkappaB kinase that activates the transcription RT factor NF-kappaB."; RL Nature 388:548-554(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC RP ACTIVITY, AND MUTAGENESIS OF LYS-44 AND SER-176. 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-268. 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 [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-268. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-745, AND VARIANT ILE-268. RC TISSUE=Cervix carcinoma; RX PubMed=8777433; RA Connelly M.A., Marcu K.B.; RT "CHUK, a new member of the helix-loop-helix and leucine zipper families of RT interacting proteins, contains a serine-threonine kinase catalytic RT domain."; RL Cell. Mol. Biol. Res. 41:537-549(1995). RN [8] RP PROTEIN SEQUENCE OF 169-181, INACTIVATION BY YERSINIA YOPJ (MICROBIAL RP INFECTION), ACETYLATION AT THR-179 (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 [9] RP IDENTIFICATION IN A COMPLEX WITH IKBKB; 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 [10] RP PHOSPHORYLATION AT SER-176, AND MUTAGENESIS OF SER-176; THR-179 AND RP SER-180. RX PubMed=9520446; DOI=10.1073/pnas.95.7.3792; RA Ling L., Cao Z., Goeddel D.V.; RT "NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser- RT 176."; RL Proc. Natl. Acad. Sci. U.S.A. 95:3792-3797(1998). RN [11] RP PHOSPHORYLATION AT THR-23, AND MUTAGENESIS OF THR-23. RX PubMed=10485710; DOI=10.1038/43466; RA Ozes O.N., Mayo L.D., Gustin J.A., Pfeffer S.R., Pfeffer L.M., Donner D.B.; RT "NF-kappaB activation by tumour necrosis factor requires the Akt serine- RT threonine kinase."; RL Nature 401:82-85(1999). RN [12] RP INTERACTION WITH IKBKB. 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 [13] 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 [14] 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 [15] RP SUBUNIT OF A COMPLEX CONTAINING CREBBP; NCOA2; NCOA3; IKBKB 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 [16] 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 [17] RP SUBCELLULAR LOCATION, AND FUNCTION IN PHOSPHORYLATION OF HISTONE H3. RX PubMed=12789342; DOI=10.1038/nature01576; RA Yamamoto Y., Verma U.N., Prajapati S., Kwak Y.T., Gaynor R.B.; RT "Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced RT gene expression."; RL Nature 423:655-659(2003). RN [18] 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 [19] 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 [20] 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 [21] 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 [22] RP INTERACTION WITH PIAS1. RX PubMed=17540171; DOI=10.1016/j.cell.2007.03.056; RA Liu B., Yang Y., Chernishof V., Loo R.R., Jang H., Tahk S., Yang R., RA Mink S., Shultz D., Bellone C.J., Loo J.A., Shuai K.; RT "Proinflammatory stimuli induce IKKalpha-mediated phosphorylation of PIAS1 RT to restrict inflammation and immunity."; RL Cell 129:903-914(2007). RN [23] RP FUNCTION IN PHOSPHORYLATION OF CREBBP. RX PubMed=17434128; DOI=10.1016/j.molcel.2007.02.019; RA Huang W.C., Ju T.K., Hung M.C., Chen C.C.; RT "Phosphorylation of CBP by IKKalpha promotes cell growth by switching the RT binding preference of CBP from p53 to NF-kappaB."; RL Mol. Cell 26:75-87(2007). RN [24] 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 [25] RP PHOSPHORYLATION AT THR-23 AND SER-180 BY SGK1. RX PubMed=19088076; DOI=10.1074/jbc.m805055200; RA Tai D.J., Su C.C., Ma Y.L., Lee E.H.; RT "SGK1 phosphorylation of IkappaB Kinase alpha and p300 Up-regulates NF- RT kappaB activity and increases N-Methyl-D-aspartate receptor NR2A and NR2B RT expression."; RL J. Biol. Chem. 284:4073-4089(2009). RN [26] RP INTERACTION WITH TRAF2. RX PubMed=19150425; DOI=10.1016/j.molcel.2008.11.023; RA Li S., Wang L., Dorf M.E.; RT "PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63- RT linked polyubiquitination."; RL Mol. Cell 33:30-42(2009). RN [27] 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 [28] RP INTERACTION WITH L.MONOCYTOGENES INLC (MICROBIAL INFECTION). RX PubMed=20855622; DOI=10.1073/pnas.1007765107; RA Gouin E., Adib-Conquy M., Balestrino D., Nahori M.A., Villiers V., RA Colland F., Dramsi S., Dussurget O., Cossart P.; RT "The Listeria monocytogenes InlC protein interferes with innate immune RT responses by targeting the I{kappa}B kinase subunit IKK{alpha}."; RL Proc. Natl. Acad. Sci. U.S.A. 107:17333-17338(2010). RN [29] RP INVOLVEMENT IN COCOS. RX PubMed=20961246; DOI=10.1056/nejmoa0911698; RA Lahtela J., Nousiainen H.O., Stefanovic V., Tallila J., Viskari H., RA Karikoski R., Gentile M., Saloranta C., Varilo T., Salonen R., Kestila M.; RT "Mutant CHUK and severe fetal encasement malformation."; RL N. Engl. J. Med. 363:1631-1637(2010). RN [30] RP FUNCTION IN MAP3K14 PHOSPHORYLATION. RX PubMed=20501937; DOI=10.1126/scisignal.2000778; RA Razani B., Zarnegar B., Ytterberg A.J., Shiba T., Dempsey P.W., Ware C.F., RA Loo J.A., Cheng G.; RT "Negative feedback in noncanonical NF-kappaB signaling modulates NIK RT stability through IKKalpha-mediated phosphorylation."; RL Sci. Signal. 3:RA41-RA41(2010). RN [31] 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 [32] RP FUNCTION IN PHOSPHORYLATION OF TAX1BP1. RX PubMed=21765415; DOI=10.1038/ni.2066; RA Shembade N., Pujari R., Harhaj N.S., Abbott D.W., Harhaj E.W.; RT "The kinase IKKalpha inhibits activation of the transcription factor NF- RT kappaB by phosphorylating the regulatory molecule TAX1BP1."; RL Nat. Immunol. 12:834-843(2011). RN [33] 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 [34] 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 [35] 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 [36] 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 [37] RP INTERACTION WITH DDX3X, AND SUBCELLULAR LOCATION. RX PubMed=30341167; DOI=10.1042/bcj20180163; RA Fullam A., Gu L., Hoehn Y., Schroeder M.; RT "DDX3 directly facilitates IKKalpha activation and regulates downstream RT signalling pathways."; RL Biochem. J. 475:3595-3607(2018). RN [38] RP FUNCTION. RX PubMed=30217973; DOI=10.1038/s41467-018-05722-3; RA Di Rita A., Peschiaroli A., D'Acunzo P., Strobbe D., Hu Z., Gruber J., RA Nygaard M., Lambrughi M., Melino G., Papaleo E., Dengjel J., El Alaoui S., RA Campanella M., Doetsch V., Rogov V.V., Strappazzon F., Cecconi F.; RT "HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating RT AMBRA1 activation via IKKalpha."; RL Nat. Commun. 9:3755-3755(2018). RN [39] 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 [40] RP FUNCTION, AND UBIQUITINATION BY TRIM56. RX PubMed=35952808; DOI=10.1016/j.ijbiomac.2022.08.019; RA Liu Y., Chen Y., Ding C., Zhu X., Song X., Ren Y., Wang Q., Zhang Y., RA Sun X.; RT "TRIM56 positively regulates TNFalpha-induced NF-kappaB signaling by RT enhancing the ubiquitination of TAK1."; RL Int. J. Biol. Macromol. 219:571-578(2022). RN [41] RP INVOLVEMENT IN BPS2. RX PubMed=25691407; DOI=10.1002/ajmg.a.36896; RA Leslie E.J., O'Sullivan J., Cunningham M.L., Singh A., Goudy S.L., RA Ababneh F., Alsubaie L., Ch'ng G.S., van der Laar I.M., Hoogeboom A.J., RA Dunnwald M., Kapoor S., Jiramongkolchai P., Standley J., Manak J.R., RA Murray J.C., Dixon M.J.; RT "Expanding the genetic and phenotypic spectrum of popliteal pterygium RT disorders."; RL Am. J. Med. Genet. A 167A:545-552(2015). RN [42] RP VARIANTS [LARGE SCALE ANALYSIS] CYS-126; ALA-155 AND ILE-268. 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). RN [43] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 732-745. 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). 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:9244310, PubMed:9252186, CC PubMed:9346484, PubMed:18626576). Acts as a part of the canonical IKK CC complex in the conventional pathway of NF-kappa-B activation and CC phosphorylates inhibitors of NF-kappa-B on serine residues CC (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576, CC PubMed:35952808). These modifications allow polyubiquitination of the CC inhibitors and subsequent degradation by the proteasome CC (PubMed:9244310, PubMed:9252186, PubMed:9346484, PubMed:18626576). In CC turn, free NF-kappa-B is translocated into the nucleus and activates CC the transcription of hundreds of genes involved in immune response, CC growth control, or protection against apoptosis (PubMed:9244310, CC PubMed:9252186, PubMed:9346484, PubMed:18626576). Negatively regulates CC the pathway by phosphorylating the scaffold protein TAXBP1 and thus CC promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex CC (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11) CC (PubMed:21765415). Therefore, CHUK plays a key role in the negative CC feedback of NF-kappa-B canonical signaling to limit inflammatory gene CC activation. As part of the non-canonical pathway of NF-kappa-B CC activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates CC NFKB2/p100 associated with RelB, inducing its proteolytic processing to CC NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes CC (PubMed:20501937). In turn, these complexes regulate genes encoding CC molecules involved in B-cell survival and lymphoid organogenesis. CC Participates also in the negative feedback of the non-canonical NF- CC kappa-B signaling pathway by phosphorylating and destabilizing CC MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently CC increases both its transcriptional and histone acetyltransferase CC activities (PubMed:17434128). Modulates chromatin accessibility at NF- CC kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' CC that are subsequently acetylated at 'Lys-14' by CREBBP CC (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting CC protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro- CC apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 CC at 'Ser-25' which represses its kinase activity and consequently CC prevents TNF-mediated RIPK1-dependent cell death (By similarity). CC Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 CC interaction with ATG8 family proteins and its mitophagic activity CC (PubMed:30217973). {ECO:0000250|UniProtKB:Q60680, CC ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:15084260, CC ECO:0000269|PubMed:17434128, ECO:0000269|PubMed:20434986, CC ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:21765415, CC ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35952808, CC ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, CC ECO:0000269|PubMed:9346484, ECO:0000303|PubMed:18626576}. 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:9244310, ECO:0000269|PubMed:9252186, CC ECO:0000269|PubMed:9346484}; CC -!- ACTIVITY REGULATION: Activated when phosphorylated and inactivated when CC dephosphorylated. 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:10195894, PubMed:12612076). The IKK complex associates with CC TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of CC RELA/p65 (By similarity). Part of a complex composed of NCOA2, NCOA3, CC CHUK/IKKA, IKBKB, IKBKG and CREBBP (PubMed:11971985). Part of a 70-90 CC kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, ELP1 CC and MAP3K14 (PubMed:9751059). Directly interacts with TRPC4AP (By CC similarity). May interact with TRAF2 (PubMed:19150425). Interacts with CC NALP2 (PubMed:15456791). May interact with MAVS/IPS1 (PubMed:16177806). CC Interacts with ARRB1 and ARRB2 (PubMed:15173580). Interacts with NLRC5; CC prevents CHUK phosphorylation and kinase activity (PubMed:20434986). CC Interacts with PIAS1; this interaction induces PIAS1 phosphorylation CC (PubMed:17540171). Interacts with ZNF268 isoform 2; the interaction is CC further increased in a TNF-alpha-dependent manner (PubMed:23091055). CC Interacts with FOXO3 (PubMed:15084260). Interacts with IFIT5; the CC interaction synergizes the recruitment of IKK to MAP3K7 and enhances CC IKK phosphorylation (PubMed:26334375). Interacts with LRRC14 CC (PubMed:27426725). Interacts with SASH1 (PubMed:23776175). Directly CC interacts with DDX3X after the physiological activation of the TLR7 and CC TLR8 pathways; this interaction enhances CHUK autophosphorylation CC (PubMed:30341167). {ECO:0000250|UniProtKB:Q60680, CC ECO:0000269|PubMed:10195894, ECO:0000269|PubMed:11971985, CC ECO:0000269|PubMed:12612076, ECO:0000269|PubMed:15084260, CC ECO:0000269|PubMed:15173580, ECO:0000269|PubMed:15456791, CC ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:17540171, CC ECO:0000269|PubMed:19150425, ECO:0000269|PubMed:20434986, CC ECO:0000269|PubMed:23091055, ECO:0000269|PubMed:23776175, CC ECO:0000269|PubMed:26334375, ECO:0000269|PubMed:27426725, CC ECO:0000269|PubMed:30341167, ECO:0000269|PubMed:32935379, CC ECO:0000269|PubMed:9751059}. CC -!- SUBUNIT: (Microbial infection) Interacts with InlC of Listeria CC monocytogenes. {ECO:0000269|PubMed:20855622}. CC -!- INTERACTION: CC O15111; Q16543: CDC37; NbExp=5; IntAct=EBI-81249, EBI-295634; CC O15111; P46527: CDKN1B; NbExp=4; IntAct=EBI-81249, EBI-519280; CC O15111; Q13451: FKBP5; NbExp=2; IntAct=EBI-81249, EBI-306914; CC O15111; P07900: HSP90AA1; NbExp=3; IntAct=EBI-81249, EBI-296047; CC O15111; O14920: IKBKB; NbExp=17; IntAct=EBI-81249, EBI-81266; CC O15111; Q9Y6K9: IKBKG; NbExp=27; IntAct=EBI-81249, EBI-81279; CC O15111; Q92985: IRF7; NbExp=4; IntAct=EBI-81249, EBI-968267; CC O15111; Q99558: MAP3K14; NbExp=12; IntAct=EBI-81249, EBI-358011; CC O15111; Q5TCX8: MAP3K21; NbExp=2; IntAct=EBI-81249, EBI-1057380; CC O15111; P01106: MYC; NbExp=3; IntAct=EBI-81249, EBI-447544; CC O15111; P19838: NFKB1; NbExp=3; IntAct=EBI-81249, EBI-300010; CC O15111; P25963: NFKBIA; NbExp=15; IntAct=EBI-81249, EBI-307386; CC O15111; Q04206: RELA; NbExp=2; IntAct=EBI-81249, EBI-73886; CC O15111; Q15796: SMAD2; NbExp=2; IntAct=EBI-81249, EBI-1040141; CC O15111; Q86VP1: TAX1BP1; NbExp=2; IntAct=EBI-81249, EBI-529518; CC O15111; P03129: E7; Xeno; NbExp=2; IntAct=EBI-81249, EBI-866453; CC O15111; Q07857: E7; Xeno; NbExp=2; IntAct=EBI-81249, EBI-9690349; CC O15111; Q6TY28: E7; Xeno; NbExp=2; IntAct=EBI-81249, EBI-9690312; CC O15111; Q6TY35: E7; Xeno; NbExp=2; IntAct=EBI-81249, EBI-9690239; CC O15111; Q80901: E7; Xeno; NbExp=2; IntAct=EBI-81249, EBI-9690278; CC O15111; Q8B5B5: E7; Xeno; NbExp=2; IntAct=EBI-81249, EBI-9690330; CC O15111; P71451: inlC; Xeno; NbExp=3; IntAct=EBI-81249, EBI-21019720; CC O15111; P24772: OPG200; Xeno; NbExp=3; IntAct=EBI-81249, EBI-4291651; CC O15111; Q77M19: P; Xeno; NbExp=2; IntAct=EBI-81249, EBI-6149376; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12789342, CC ECO:0000269|PubMed:30341167}. Nucleus {ECO:0000269|PubMed:12789342}. CC Note=Shuttles between the cytoplasm and the nucleus. CC -!- TISSUE SPECIFICITY: Widely expressed. 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: Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by CC MEKK1, and dephosphorylated by PP2A. Autophosphorylated. CC -!- PTM: Ubiquitinated by TRIM56 via 'Lys-63'-linked ubiquitination, CC promoting activation of CHUK/IKKA. {ECO:0000269|PubMed:35952808}. CC -!- PTM: (Microbial infection) Acetylation of Thr-179 by Yersinia YopJ CC prevents phosphorylation and activation, thus blocking the I-kappa-B CC signaling pathway. {ECO:0000269|PubMed:17116858}. CC -!- DISEASE: Cocoon syndrome (COCOS) [MIM:613630]: A lethal syndrome CC characterized by multiple fetal malformations including defective face CC and seemingly absent limbs, which are bound to the trunk and encased CC under the skin. {ECO:0000269|PubMed:20961246}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Bartsocas-Papas syndrome 2 (BPS2) [MIM:619339]: An autosomal CC recessive, severe form of popliteal pterygium syndrome. Popliteal CC pterygia syndromes have considerable variability in severity and in the CC associated phenotypic features but they are all characterized by CC cutaneous webbing across one or more major joints, cleft lip and/or CC palate, syndactyly, and genital malformations. CC {ECO:0000269|PubMed:25691407}. Note=The disease may be caused by CC variants affecting the gene represented 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/chuk/"; 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; AF012890; AAC51662.1; -; mRNA. DR EMBL; AF009225; AAC51671.1; -; mRNA. DR EMBL; AF080157; AAD08996.1; -; mRNA. DR EMBL; AY652653; AAT49098.1; -; Genomic_DNA. DR EMBL; AL138921; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U22512; AAC50713.1; -; mRNA. DR CCDS; CCDS7488.1; -. DR RefSeq; NP_001269.3; NM_001278.4. DR PDB; 3BRT; X-ray; 2.25 A; A/C=732-745. DR PDB; 5EBZ; X-ray; 4.50 A; A/B/C/D/E/F/G/H/I/J/K/L=10-660. DR PDB; 5TQW; EM; 5.60 A; A/B=10-660. DR PDB; 5TQX; EM; 5.40 A; A/B=10-660. DR PDB; 5TQY; EM; 5.20 A; A/B=10-660. DR PDBsum; 3BRT; -. DR PDBsum; 5EBZ; -. DR PDBsum; 5TQW; -. DR PDBsum; 5TQX; -. DR PDBsum; 5TQY; -. DR AlphaFoldDB; O15111; -. DR EMDB; EMD-8436; -. DR EMDB; EMD-8437; -. DR EMDB; EMD-8438; -. DR EMDB; EMD-8439; -. DR SMR; O15111; -. DR BioGRID; 107569; 223. DR ComplexPortal; CPX-3269; IkappaB kinase complex. DR CORUM; O15111; -. DR DIP; DIP-27526N; -. DR ELM; O15111; -. DR IntAct; O15111; 86. DR MINT; O15111; -. DR STRING; 9606.ENSP00000359424; -. DR BindingDB; O15111; -. DR ChEMBL; CHEMBL3476; -. DR DrugBank; DB06151; Acetylcysteine. DR DrugBank; DB00233; Aminosalicylic acid. DR DrugBank; DB00244; Mesalazine. DR DrugCentral; O15111; -. DR GuidetoPHARMACOLOGY; 1989; -. DR GlyGen; O15111; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O15111; -. DR PhosphoSitePlus; O15111; -. DR BioMuta; CHUK; -. DR CPTAC; CPTAC-1220; -. DR CPTAC; CPTAC-1221; -. DR CPTAC; CPTAC-2837; -. DR CPTAC; CPTAC-3087; -. DR EPD; O15111; -. DR jPOST; O15111; -. DR MassIVE; O15111; -. DR MaxQB; O15111; -. DR PaxDb; 9606-ENSP00000359424; -. DR PeptideAtlas; O15111; -. DR ProteomicsDB; 48449; -. DR Pumba; O15111; -. DR Antibodypedia; 801; 1722 antibodies from 52 providers. DR DNASU; 1147; -. DR Ensembl; ENST00000370397.8; ENSP00000359424.6; ENSG00000213341.11. DR GeneID; 1147; -. DR KEGG; hsa:1147; -. DR MANE-Select; ENST00000370397.8; ENSP00000359424.6; NM_001278.5; NP_001269.3. DR UCSC; uc001kqp.4; human. DR AGR; HGNC:1974; -. DR CTD; 1147; -. DR DisGeNET; 1147; -. DR GeneCards; CHUK; -. DR HGNC; HGNC:1974; CHUK. DR HPA; ENSG00000213341; Low tissue specificity. DR MalaCards; CHUK; -. DR MIM; 600664; gene. DR MIM; 613630; phenotype. DR MIM; 619339; phenotype. DR neXtProt; NX_O15111; -. DR OpenTargets; ENSG00000213341; -. DR Orphanet; 465824; Fetal encasement syndrome. DR PharmGKB; PA26510; -. DR VEuPathDB; HostDB:ENSG00000213341; -. DR eggNOG; KOG4250; Eukaryota. DR GeneTree; ENSGT00950000182937; -. DR HOGENOM; CLU_000288_101_2_1; -. DR InParanoid; O15111; -. DR OMA; MQPFTWH; -. DR OrthoDB; 3949542at2759; -. DR PhylomeDB; O15111; -. DR TreeFam; TF324269; -. DR BRENDA; 2.7.11.10; 2681. DR PathwayCommons; O15111; -. 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-198323; AKT phosphorylates targets in the cytosol. DR Reactome; R-HSA-202424; Downstream TCR signaling. 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-5607761; Dectin-1 mediated noncanonical NF-kB signaling. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer. DR Reactome; R-HSA-5676590; NIK-->noncanonical NF-kB 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; O15111; -. DR SignaLink; O15111; -. DR SIGNOR; O15111; -. DR BioGRID-ORCS; 1147; 43 hits in 1198 CRISPR screens. DR ChiTaRS; CHUK; human. DR EvolutionaryTrace; O15111; -. DR GeneWiki; CHUK; -. DR GenomeRNAi; 1147; -. DR Pharos; O15111; Tchem. DR PRO; PR:O15111; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; O15111; Protein. DR Bgee; ENSG00000213341; Expressed in secondary oocyte and 197 other cell types or tissues. DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. 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:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. 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:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0097110; F:scaffold protein binding; IDA:MGI. DR GO; GO:1990459; F:transferrin receptor binding; IPI:ARUK-UCL. DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc. DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:0071276; P:cellular response to cadmium ion; IMP:CAFA. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:CAFA. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB. DR GO; GO:0098586; P:cellular response to virus; IMP:CAFA. DR GO; GO:0007252; P:I-kappaB phosphorylation; TAS:ProtInc. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB. DR GO; GO:0045087; P:innate immune response; TAS:UniProtKB. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0038061; P:non-canonical NF-kappaB signal transduction; IDA:UniProt. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:ARUK-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:CAFA. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IMP:CAFA. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0010034; P:response to acetate; IEA:Ensembl. DR GO; GO:0043200; P:response to amino acid; IEA:Ensembl. DR GO; GO:0061847; P:response to cholecystokinin; IEA:Ensembl. DR GO; GO:0033194; P:response to hydroperoxide; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0009615; P:response to virus; TAS:UniProtKB. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0007266; P:Rho protein signal transduction; IEA:Ensembl. DR GO; GO:0003009; P:skeletal muscle contraction; IEA:Ensembl. DR GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl. DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IDA:UniProt. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IBA:GO_Central. DR CDD; cd14039; STKc_IKK_alpha; 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; IID00526; -. 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; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR22969; IKB KINASE; 1. DR PANTHER; PTHR22969:SF13; INHIBITOR OF NUCLEAR FACTOR KAPPA-B KINASE SUBUNIT ALPHA; 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 PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; O15111; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Cytoplasm; KW Direct protein sequencing; Kinase; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; KW Transferase; Ubl conjugation. FT CHAIN 1..745 FT /note="Inhibitor of nuclear factor kappa-B kinase subunit FT alpha" FT /id="PRO_0000086011" FT DOMAIN 15..302 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 455..476 FT /note="Leucine-zipper" FT REGION 738..743 FT /note="NEMO-binding" FT ACT_SITE 144 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 23 FT /note="Phosphothreonine; by PKB/AKT1 and SGK1" FT /evidence="ECO:0000269|PubMed:10485710, FT ECO:0000269|PubMed:19088076" FT MOD_RES 176 FT /note="Phosphoserine; by MAP3K14" FT /evidence="ECO:0000269|PubMed:9520446" FT MOD_RES 179 FT /note="(Microbial infection) O-acetylthreonine; by Yersinia FT YopJ" FT /evidence="ECO:0000269|PubMed:17116858" FT MOD_RES 180 FT /note="Phosphoserine; by SGK1" FT /evidence="ECO:0000269|PubMed:19088076" FT VARIANT 126 FT /note="S -> C (in dbSNP:rs34427437)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040565" FT VARIANT 155 FT /note="V -> A (in dbSNP:rs2230803)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040566" FT VARIANT 268 FT /note="V -> I (in dbSNP:rs2230804)" FT /evidence="ECO:0000269|PubMed:15164054, FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:8777433, FT ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, FT ECO:0000269|PubMed:9813230" FT /id="VAR_021359" FT MUTAGEN 23 FT /note="T->A: Loss of phosphorylation and decrease of kinase FT activity." FT /evidence="ECO:0000269|PubMed:10485710" FT MUTAGEN 44 FT /note="K->A: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:9244310, FT ECO:0000269|PubMed:9346484" FT MUTAGEN 44 FT /note="K->M: Loss of autophosphorylation." FT /evidence="ECO:0000269|PubMed:9244310, FT ECO:0000269|PubMed:9346484" FT MUTAGEN 176 FT /note="S->A: Loss of phosphorylation and of activity." FT /evidence="ECO:0000269|PubMed:9346484, FT ECO:0000269|PubMed:9520446" FT MUTAGEN 176 FT /note="S->E: Full activation." FT /evidence="ECO:0000269|PubMed:9346484, FT ECO:0000269|PubMed:9520446" FT MUTAGEN 179 FT /note="T->A: No change in phosphorylation." FT /evidence="ECO:0000269|PubMed:9520446" FT MUTAGEN 180 FT /note="S->A: No change in phosphorylation." FT /evidence="ECO:0000269|PubMed:9520446" FT CONFLICT 543 FT /note="E -> G (in Ref. 2; AAC51671)" FT /evidence="ECO:0000305" FT CONFLICT 604 FT /note="L -> R (in Ref. 7; AAC50713)" FT /evidence="ECO:0000305" FT CONFLICT 679..680 FT /note="TS -> AY (in Ref. 7; AAC50713)" FT /evidence="ECO:0000305" FT CONFLICT 684 FT /note="P -> A (in Ref. 3; no nucleotide entry and 7; FT AAC50713)" FT /evidence="ECO:0000305" FT CONFLICT 686..687 FT /note="TS -> DL (in Ref. 7; AAC50713)" FT /evidence="ECO:0000305" FT HELIX 735..737 FT /evidence="ECO:0007829|PDB:3BRT" FT HELIX 741..743 FT /evidence="ECO:0007829|PDB:3BRT" SQ SEQUENCE 745 AA; 84640 MW; 4EA55C6FFC66FA16 CRC64; MERPPGLRPG AGGPWEMRER LGTGGFGNVC LYQHRELDLK IAIKSCRLEL STKNRERWCH EIQIMKKLNH ANVVKACDVP EELNILIHDV PLLAMEYCSG GDLRKLLNKP ENCCGLKESQ ILSLLSDIGS GIRYLHENKI IHRDLKPENI VLQDVGGKII HKIIDLGYAK DVDQGSLCTS FVGTLQYLAP ELFENKPYTA TVDYWSFGTM VFECIAGYRP FLHHLQPFTW HEKIKKKDPK CIFACEEMSG EVRFSSHLPQ PNSLCSLVVE PMENWLQLML NWDPQQRGGP VDLTLKQPRC FVLMDHILNL KIVHILNMTS AKIISFLLPP DESLHSLQSR IERETGINTG SQELLSETGI SLDPRKPASQ CVLDGVRGCD SYMVYLFDKS KTVYEGPFAS RSLSDCVNYI VQDSKIQLPI IQLRKVWAEA VHYVSGLKED YSRLFQGQRA AMLSLLRYNA NLTKMKNTLI SASQQLKAKL EFFHKSIQLD LERYSEQMTY GISSEKMLKA WKEMEEKAIH YAEVGVIGYL EDQIMSLHAE IMELQKSPYG RRQGDLMESL EQRAIDLYKQ LKHRPSDHSY SDSTEMVKII VHTVQSQDRV LKELFGHLSK LLGCKQKIID LLPKVEVALS NIKEADNTVM FMQGKRQKEI WHLLKIACTQ SSARSLVGSS LEGAVTPQTS AWLPPTSAEH DHSLSCVVTP QDGETSAQMI EENLNCLGHL STIIHEANEE QGNSMMNLDW SWLTE //