IKKA_MOUSE
ID IKKA_MOUSE Reviewed; 745 AA.
AC Q60680; Q80VU2; Q9D2X3;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 199.
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;
DE AltName: Full=Conserved helix-loop-helix ubiquitous kinase;
DE AltName: Full=I-kappa-B kinase 1;
DE Short=IKK1;
DE AltName: Full=Nuclear factor NF-kappa-B inhibitor kinase alpha;
DE Short=NFKBIKA;
GN Name=Chuk; Synonyms=Ikka;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ;
RX PubMed=7558004; DOI=10.1006/geno.1995.1054;
RA Mock B.A., Connelly M.A., McBride O.W., Kozak C.A., Marcu K.B.;
RT "CHUK, a conserved helix-loop-helix ubiquitous kinase, maps to human
RT chromosome 10 and mouse chromosome 19.";
RL Genomics 27:348-351(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J; TISSUE=Colon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Eye;
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 [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=10195895; DOI=10.1126/science.284.5412.313;
RA Takeda K., Takeuchi O., Tsujimura T., Itami S., Adachi O., Kawai T.,
RA Sanjo H., Yoshikawa K., Terada N., Akira S.;
RT "Limb and skin abnormalities in mice lacking IKKalpha.";
RL Science 284:313-316(1999).
RN [6]
RP ALTERNATIVE SPLICING.
RX PubMed=10733566; DOI=10.1128/mcb.20.8.2635-2649.2000;
RA McKenzie F.R., Connelly M.A., Balzarano D., Mueller J.R., Geleziunas R.,
RA Marcu K.B.;
RT "Functional isoforms of IkappaB kinase alpha (IKKalpha) lacking leucine
RT zipper and helix-loop-helix domains reveal that IKKalpha and IKKbeta have
RT different activation requirements.";
RL Mol. Cell. Biol. 20:2635-2649(2000).
RN [7]
RP PHOSPHORYLATION BY MAP3K14/NIK.
RX PubMed=9520401; DOI=10.1073/pnas.95.7.3537;
RA Nakano H., Shindo M., Sakon S., Nishinaka S., Mihara M., Yagita H.,
RA Okumura K.;
RT "Differential regulation of IkappaB kinase alpha and beta by two upstream
RT kinases, NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK
RT kinase kinase-1.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:3537-3542(1998).
RN [8]
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 [9]
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 [10]
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 [11]
RP INTERACTION WITH TRPC4AP.
RX PubMed=14585990; DOI=10.1128/mcb.23.22.8334-8344.2003;
RA Soond S.M., Terry J.L., Colbert J.D., Riches D.W.H.;
RT "TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that
RT mediates activation of the transcription factor NF-kappaB.";
RL Mol. Cell. Biol. 23:8334-8344(2003).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [13]
RP INTERACTION WITH ARRB2.
RX PubMed=18194271; DOI=10.1111/j.1365-2567.2007.02781.x;
RA Kizaki T., Izawa T., Sakurai T., Haga S., Taniguchi N., Tajiri H.,
RA Watanabe K., Day N.K., Toba K., Ohno H.;
RT "Beta2-adrenergic receptor regulates Toll-like receptor-4-induced nuclear
RT factor-kappaB activation through beta-arrestin 2.";
RL Immunology 124:348-356(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [15]
RP INTERACTION WITH TERF2IP.
RX PubMed=20622870; DOI=10.1038/ncb2080;
RA Teo H., Ghosh S., Luesch H., Ghosh A., Wong E.T., Malik N., Orth A.,
RA de Jesus P., Perry A.S., Oliver J.D., Tran N.L., Speiser L.J., Wong M.,
RA Saez E., Schultz P., Chanda S.K., Verma I.M., Tergaonkar V.;
RT "Telomere-independent Rap1 is an IKK adaptor and regulates NF-kappaB-
RT dependent gene expression.";
RL Nat. Cell Biol. 12:758-767(2010).
RN [16]
RP FUNCTION.
RX PubMed=30988283; DOI=10.1038/s41467-019-09690-0;
RA Dondelinger Y., Delanghe T., Priem D., Wynosky-Dolfi M.A., Sorobetea D.,
RA Rojas-Rivera D., Giansanti P., Roelandt R., Gropengiesser J.,
RA Ruckdeschel K., Savvides S.N., Heck A.J.R., Vandenabeele P., Brodsky I.E.,
RA Bertrand M.J.M.;
RT "Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in
RT models of infection and inflammation.";
RL Nat. Commun. 10:1729-1729(2019).
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. Acts as part of the canonical IKK complex in
CC the conventional pathway of NF-kappa-B activation and phosphorylates
CC inhibitors of NF-kappa-B on serine residues. These modifications allow
CC polyubiquitination of the inhibitors and subsequent degradation by the
CC proteasome. In turn, free NF-kappa-B is translocated into the nucleus
CC and activates the transcription of hundreds of genes involved in immune
CC response, growth control, or protection against apoptosis. Negatively
CC regulates the pathway by phosphorylating the scaffold protein TAXBP1
CC and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing
CC complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and
CC RNF11). Therefore, CHUK plays a key role in the negative feedback of
CC NF-kappa-B canonical signaling to limit inflammatory gene activation.
CC As part of the non-canonical pathway of NF-kappa-B activation, the
CC MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100
CC associated with RelB, inducing its proteolytic processing to NFKB2/p52
CC and the formation of NF-kappa-B RelB-p52 complexes. In turn, these
CC complexes regulate genes encoding molecules involved in B-cell survival
CC and lymphoid organogenesis. Participates also in the negative feedback
CC of the non-canonical NF-kappa-B signaling pathway by phosphorylating
CC and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates
CC CREBBP and consequently increases both its transcriptional and histone
CC acetyltransferase activities. 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. Phosphorylates RIPK1 at 'Ser-25' which
CC represses its kinase activity and consequently prevents TNF-mediated
CC RIPK1-dependent cell death (PubMed:30988283). Phosphorylates AMBRA1
CC following mitophagy induction, promoting AMBRA1 interaction with ATG8
CC family proteins and its mitophagic activity (By similarity).
CC {ECO:0000250|UniProtKB:O15111, ECO:0000269|PubMed:12789342,
CC ECO:0000269|PubMed:30988283}.
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 -!- 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. The
CC IKK core complex seems to associate with regulatory or adapter proteins
CC to form a IKK-signalosome holo-complex (PubMed:10195894). The IKK
CC complex associates with TERF2IP/RAP1, leading to promote IKK-mediated
CC phosphorylation of RELA/p65 (PubMed:20622870). Part of a complex
CC composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a
CC 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA,
CC RELA, ELP1 and MAP3K14 (By similarity). Directly interacts with TRPC4AP
CC (PubMed:14585990). May interact with TRAF2. Interacts with NALP2. May
CC interact with MAVS/IPS1 (By similarity). Interacts with ARRB1 and ARRB2
CC (PubMed:18194271). Interacts with NLRC5; prevents CHUK phosphorylation
CC and kinase activity. Interacts with PIAS1; this interaction induces
CC PIAS1 phosphorylation. Interacts with ZNF268 isoform 2; the interaction
CC is further increased in a TNF-alpha-dependent manner (By similarity).
CC Interacts with LRRC14 (By similarity). Interacts with SASH1 (By
CC similarity). Directly interacts with DDX3X after the physiological
CC activation of the TLR7 and TLR8 pathways; this interaction enhances
CC CHUK autophosphorylation (By similarity).
CC {ECO:0000250|UniProtKB:O15111, ECO:0000269|PubMed:10195894,
CC ECO:0000269|PubMed:14585990, ECO:0000269|PubMed:18194271,
CC ECO:0000269|PubMed:20622870}.
CC -!- INTERACTION:
CC Q60680; O88351: Ikbkb; NbExp=4; IntAct=EBI-646245, EBI-447960;
CC Q60680; O88522: Ikbkg; NbExp=6; IntAct=EBI-646245, EBI-998011;
CC Q60680; P70434: Irf7; NbExp=3; IntAct=EBI-646245, EBI-997907;
CC Q60680; Q77M19: P; Xeno; NbExp=3; IntAct=EBI-646245, EBI-6149376;
CC Q60680; P04862: P/V/C; Xeno; NbExp=2; IntAct=EBI-646245, EBI-8848010;
CC Q60680; P06164: P/V/C; Xeno; NbExp=2; IntAct=EBI-646245, EBI-8848117;
CC Q60680; P0C1C7: P/V/C; Xeno; NbExp=2; IntAct=EBI-646245, EBI-6151115;
CC Q60680; P35977: P/V/C; Xeno; NbExp=2; IntAct=EBI-646245, EBI-8848155;
CC Q60680-1; Q8BP22: Fam92a; NbExp=4; IntAct=EBI-646260, EBI-646638;
CC Q60680-1; P02535: Krt10; NbExp=6; IntAct=EBI-646260, EBI-646288;
CC Q60680-1; B7ZNY0: Pde4dip; NbExp=4; IntAct=EBI-646260, EBI-659248;
CC Q60680-2; Q99558: MAP3K14; Xeno; NbExp=3; IntAct=EBI-646264, EBI-358011;
CC Q60680-2; P25963: NFKBIA; Xeno; NbExp=2; IntAct=EBI-646264, EBI-307386;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12789342}. Nucleus
CC {ECO:0000269|PubMed:12789342}. Note=Shuttles between the cytoplasm and
CC the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q60680-1; Sequence=Displayed;
CC Name=2; Synonyms=Delta LH;
CC IsoId=Q60680-2; Sequence=VSP_004866, VSP_004867;
CC Name=3; Synonyms=Delta H;
CC IsoId=Q60680-3; Sequence=VSP_004868, VSP_004869;
CC -!- TISSUE SPECIFICITY: Ubiquitous only for isoform 1, isoforms 2 and 3 are
CC expressed predominantly in brain and T-lymphocytes.
CC -!- DEVELOPMENTAL STAGE: Maximally expressed at 7 dpc followed by 11 dpc,
CC 15 dpc and 17 dpc. In the limb development, its expression predominates
CC in the limb buds at 12.5 dpc.
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.
CC -!- PTM: Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by
CC MEKK1, and dephosphorylated by PP2A. Autophosphorylated.
CC {ECO:0000269|PubMed:9520401}.
CC -!- DISRUPTION PHENOTYPE: Mice show abnormal appearance and die within 4
CC hours after birth. The epidermal cells are highly proliferative with
CC dysregulated epidermal differentiation. {ECO:0000269|PubMed:10195895}.
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}.
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DR EMBL; U12473; AAC52589.1; -; mRNA.
DR EMBL; AK018671; BAB31335.1; -; mRNA.
DR EMBL; BC018243; AAH18243.1; -; mRNA.
DR CCDS; CCDS29843.1; -. [Q60680-1]
DR PIR; I49101; I49101.
DR AlphaFoldDB; Q60680; -.
DR SMR; Q60680; -.
DR BioGRID; 198709; 24.
DR ComplexPortal; CPX-3270; IkappaB kinase complex.
DR CORUM; Q60680; -.
DR DIP; DIP-29719N; -.
DR IntAct; Q60680; 33.
DR MINT; Q60680; -.
DR STRING; 10090.ENSMUSP00000026217; -.
DR ChEMBL; CHEMBL5380; -.
DR iPTMnet; Q60680; -.
DR PhosphoSitePlus; Q60680; -.
DR EPD; Q60680; -.
DR MaxQB; Q60680; -.
DR PaxDb; Q60680; -.
DR PeptideAtlas; Q60680; -.
DR PRIDE; Q60680; -.
DR ProteomicsDB; 267113; -. [Q60680-1]
DR ProteomicsDB; 267114; -. [Q60680-2]
DR ProteomicsDB; 267115; -. [Q60680-3]
DR UCSC; uc008hpi.2; mouse. [Q60680-3]
DR MGI; MGI:99484; Chuk.
DR eggNOG; KOG4250; Eukaryota.
DR InParanoid; Q60680; -.
DR PhylomeDB; Q60680; -.
DR BRENDA; 2.7.11.10; 3474.
DR Reactome; R-MMU-1169091; Activation of NF-kappaB in B cells.
DR Reactome; R-MMU-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-MMU-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-MMU-202424; Downstream TCR signaling.
DR Reactome; R-MMU-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-MMU-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-MMU-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-MMU-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation.
DR Reactome; R-MMU-9020702; Interleukin-1 signaling.
DR Reactome; R-MMU-933542; TRAF6 mediated NF-kB activation.
DR Reactome; R-MMU-937039; IRAK1 recruits IKK complex.
DR Reactome; R-MMU-937041; IKK complex recruitment mediated by RIP1.
DR Reactome; R-MMU-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
DR ChiTaRS; Chuk; mouse.
DR PRO; PR:Q60680; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q60680; protein.
DR GO; GO:0035631; C:CD40 receptor complex; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0008385; C:IkappaB kinase complex; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008384; F:IkappaB kinase activity; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:1990459; F:transferrin receptor binding; ISO:MGI.
DR GO; GO:0071276; P:cellular response to cadmium ion; ISO:MGI.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0098586; P:cellular response to virus; IMP:CAFA.
DR GO; GO:0051607; P:defense response to virus; IMP:CAFA.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:MGI.
DR GO; GO:0007252; P:I-kappaB phosphorylation; TAS:MGI.
DR GO; GO:0007595; P:lactation; IMP:MGI.
DR GO; GO:0060749; P:mammary gland alveolus development; IMP:MGI.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IMP:MGI.
DR GO; GO:0002011; P:morphogenesis of an epithelial sheet; IMP:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IMP:MGI.
DR GO; GO:0030316; P:osteoclast differentiation; IMP:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:MGI.
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; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0061847; P:response to cholecystokinin; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:MGI.
DR GO; GO:0035994; P:response to muscle stretch; IMP:MGI.
DR GO; GO:0010033; P:response to organic substance; ISO:MGI.
DR GO; GO:0007266; P:Rho protein signal transduction; ISO:MGI.
DR GO; GO:0051146; P:striated muscle cell differentiation; ISO:MGI.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IBA:GO_Central.
DR Gene3D; 1.20.1270.250; -; 1.
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 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; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..745
FT /note="Inhibitor of nuclear factor kappa-B kinase subunit
FT alpha"
FT /id="PRO_0000086012"
FT DOMAIN 15..300
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:0000250|UniProtKB:O15111"
FT MOD_RES 176
FT /note="Phosphoserine; by MAP3K14"
FT /evidence="ECO:0000250|UniProtKB:O15111"
FT MOD_RES 180
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000250|UniProtKB:O15111"
FT VAR_SEQ 452..471
FT /note="MLSLLRYNANLTKMKNTLIS -> IFRKNVKSMERNGRKGHSLF (in
FT isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004866"
FT VAR_SEQ 472..745
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004867"
FT VAR_SEQ 577..584
FT /note="DHLYSDST -> GKTLQSQY (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_004868"
FT VAR_SEQ 585..745
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_004869"
FT CONFLICT 236
FT /note="K -> E (in Ref. 3; BAB31335)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="S -> Y (in Ref. 3; BAB31335)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 745 AA; 84729 MW; 3FEF5582AFF92233 CRC64;
MERPPGLRPG AGGPWEMRER LGTGGFGNVS LYQHRELDLK IAIKSCRLEL SSKNRERWCH
EIQIMKKLDH ANVVKACDVP EELNFLINDV PLLAMEYCSG GDLRKLLNKP ENCCGLKESQ
ILSLLSDIGS GIRYLHENKI IHRDLKPENI VLQDVGGKTI HKIIDLGYAK DVDQGSLCTS
FVGTLQYLAP ELFENKPYTA TVDYWSFGTM VFECIAGYRP FLHHLQPFTW HEKIKKKDPK
CIFACEEMTG EVRFSSHLPQ PNSLCSLIVE PMESWLQLML NWDPQQRGGP IDLTLKQPRC
FALMDHILNL KIVHILNMTS AKIISFLLPC DESLHSLQSR IERETGINTG SQELLSETGI
SLDPRKPASQ CVLDGVRGCD SYMVYLFDKS KTVYEGPFAS RSLSDCVNYI VQDSKIQLPI
IQLRKVWAEA VHYVSGLKED YSRLFQGQRA AMLSLLRYNA NLTKMKNTLI SASQQLKAKL
EFFRKSIQLD LERYSEQMTY GISSEKMLKA WKEMEEKAIH YSEVGVIGYL EDQIMSLHTE
IMELQKSPYG RRQGDLMESL EQRAIDLYKQ LKHRPPDHLY SDSTEMVKII VHTVQSQDRV
LKELFGHLSK LLGCKQKIID LLPKVEVALS NIKEADNTVM FMQGKRQKEI WHLLKIACTQ
SSARSLVGSS LEGTVTPPVS AWLPPTLADR EHPLTCVVTP QDGETLAQMI EENLNCLGHL
STIIREANED QSSSLMSLDW SWLAE
