IKKB_MOUSE
ID IKKB_MOUSE Reviewed; 757 AA.
AC O88351; Q9R1J6;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit beta;
DE Short=I-kappa-B-kinase beta;
DE Short=IKK-B;
DE Short=IKK-beta;
DE Short=IkBKB;
DE EC=2.7.11.10;
DE AltName: Full=I-kappa-B kinase 2;
DE Short=IKK2;
DE AltName: Full=Nuclear factor NF-kappa-B inhibitor kinase beta;
DE Short=NFKBIKB;
DE AltName: Full=Serine/threonine protein kinase IKBKB;
DE EC=2.7.11.1 {ECO:0000269|PubMed:25326420, ECO:0000269|PubMed:30988283};
GN Name=Ikbkb; Synonyms=Ikkb;
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], AND PHOSPHORYLATION BY MEKK1.
RC STRAIN=C57BL/6J; TISSUE=Spleen;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hu M.C.-T., Wang Y.-P., Mikhail A., Qiu W.R.;
RT "Murine IkB kinase-B, a developmentally regulated protein kinase that
RT constitutively phosphorylates serine residues of IkB.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=10229185; DOI=10.1016/s1074-7613(00)80042-4;
RA Tanaka M., Fuentes M.E., Yamaguchi K., Durnin M.H., Dalrymple S.A.,
RA Hardy K.L., Goeddel D.V.;
RT "Embryonic lethality, liver degeneration, and impaired NF-kappa B
RT activation in IKK-beta-deficient mice.";
RL Immunity 10:421-429(1999).
RN [4]
RP DEVELOPMENTAL STAGE.
RX PubMed=10523828; DOI=10.1038/sj.onc.1202740;
RA Hu M.C.-T., Wang Y.-P., Qiu W.R., Mikhail A., Meyer C.F., Tan T.-H.;
RT "Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway
RT activates IkappaB kinases (IKK-alpha/beta) and IKK-beta is a
RT developmentally regulated protein kinase.";
RL Oncogene 18:5514-5524(1999).
RN [5]
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 [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=10195897; DOI=10.1126/science.284.5412.321;
RA Li Q., Van Antwerp D., Mercurio F., Lee K.F., Verma I.M.;
RT "Severe liver degeneration in mice lacking the IkappaB kinase 2 gene.";
RL Science 284:321-325(1999).
RN [7]
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 [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-672, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Lung, Pancreas, 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 [10]
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 [11]
RP INTERACTION WITH ZC3H12A.
RX PubMed=22037600; DOI=10.1038/ni.2137;
RA Iwasaki H., Takeuchi O., Teraguchi S., Matsushita K., Uehata T.,
RA Kuniyoshi K., Satoh T., Saitoh T., Matsushita M., Standley D.M., Akira S.;
RT "The IkappaB kinase complex regulates the stability of cytokine-encoding
RT mRNA induced by TLR-IL-1R by controlling degradation of regnase-1.";
RL Nat. Immunol. 12:1167-1175(2011).
RN [12]
RP INTERACTION WITH AKAP13, IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE
RP SPECIFICITY.
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 [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25326420; DOI=10.1073/pnas.1418516111;
RA Ren J., Chen X., Chen Z.J.;
RT "IKKbeta is an IRF5 kinase that instigates inflammation.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:17438-17443(2014).
RN [14]
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 2 critical serine residues. These
CC modifications allow polyubiquitination of the inhibitors and subsequent
CC degradation by the proteasome. In turn, free NF-kappa-B is translocated
CC into the nucleus and activates the transcription of hundreds of genes
CC involved in immune response, growth control, or protection against
CC apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates
CC several other components of the signaling pathway including NEMO/IKBKG,
CC NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1
CC and IKBKE. IKK-related kinase phosphorylations may prevent the
CC overproduction of inflammatory mediators since they exert a negative
CC regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-
CC dependent inactivation of this pro-apoptotic transcription factor. Also
CC phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within
CC the nucleus, acts as an adapter protein for NFKBIA degradation in UV-
CC induced NF-kappa-B activation (By similarity). Phosphorylates RIPK1 at
CC 'Ser-25' which represses its kinase activity and consequently prevents
CC TNF-mediated RIPK1-dependent cell death (PubMed:30988283).
CC Phosphorylates the C-terminus of IRF5, stimulating IRF5
CC homodimerization and translocation into the nucleus (PubMed:25326420).
CC {ECO:0000250|UniProtKB:O14920, ECO:0000269|PubMed:25326420,
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 -!- 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:25326420, ECO:0000269|PubMed:30988283};
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. The
CC IKK core complex seems to associate with regulatory or adapter proteins
CC to form a IKK-signalosome holo-complex (By similarity). The IKK complex
CC 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. Found in a membrane raft complex, at least
CC composed of BCL10, CARD11, DPP4 and IKBKB. Interacts with SQSTM1
CC through PRKCZ or PRKCI. Forms an NGF-induced complex with IKBKB, PRKCI
CC and TRAF6. May interact with MAVS/IPS1. Interacts with NALP2. Interacts
CC with TICAM1. Interacts with FAF1; the interaction disrupts the IKK
CC complex formation. Interacts with ATM. Part of a ternary complex
CC consisting of TANK, IKBKB and IKBKG. Interacts with NIBP; the
CC interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with
CC TRIM21. Interacts with NLRC5; prevents IKBKB phosphorylation and kinase
CC activity. Interacts with PDPK1 (By similarity). Interacts with
CC EIF2AK2/PKR (PubMed:10848580). The phosphorylated form interacts with
CC PPM1A and PPM1B. Interacts with ZNF268 isoform 2; the interaction is
CC further increased in a TNF-alpha-dependent manner. Interacts with
CC IKBKE. Interacts with NAA10, leading to NAA10 degradation. Interacts
CC with FOXO3 (By similarity). Interacts with ZC3H12A (PubMed:22037600).
CC Interacts with AKAP13 (PubMed:23090968). Interacts with LRRC14;
CC disrupts IKBKB-IKBKG interaction preventing I-kappa-B-kinase (IKK) core
CC complex formation and leading to a decrease of IKBKB phosphorylation
CC and NF-kappaB activation (By similarity). Interacts with SASH1 (By
CC similarity). Interacts with ARFIP2 (By similarity). Interacts with
CC FKBP5 (By similarity). {ECO:0000250|UniProtKB:O14920,
CC ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:20622870,
CC ECO:0000269|PubMed:22037600}.
CC -!- INTERACTION:
CC O88351; Q60680: Chuk; NbExp=4; IntAct=EBI-447960, EBI-646245;
CC O88351; O88522: Ikbkg; NbExp=8; IntAct=EBI-447960, EBI-998011;
CC O88351; P68040: Rack1; NbExp=4; IntAct=EBI-447960, EBI-296749;
CC O88351; Q14145: KEAP1; Xeno; NbExp=2; IntAct=EBI-447960, EBI-751001;
CC O88351; P01375: TNF; Xeno; NbExp=3; IntAct=EBI-447960, EBI-359977;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O14920}. Nucleus
CC {ECO:0000250|UniProtKB:O14920}. Membrane raft
CC {ECO:0000250|UniProtKB:O14920}. Note=Colocalized with DPP4 in membrane
CC rafts. {ECO:0000250|UniProtKB:O14920}.
CC -!- TISSUE SPECIFICITY: Detected in heart (at protein level)
CC (PubMed:23090968). Expressed in liver, kidney and spleen.
CC {ECO:0000269|PubMed:23090968}.
CC -!- DEVELOPMENTAL STAGE: While it is expressed ubiquitously throughout the
CC mouse embryo, at 9.5 dpc its expression begins to be localized to the
CC brain, neural ganglia, neural tube, and in liver at 12.5 dpc. At 15.5
CC dpc, the expression is further restricted to specific tissues of the
CC embryo. {ECO:0000269|PubMed:10523828}.
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 (By similarity). {ECO:0000250}.
CC -!- PTM: Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181
CC by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances
CC activity. Once activated, autophosphorylates on the C-terminal serine
CC cluster; which decreases activity and prevents prolonged activation of
CC the inflammatory response. Phosphorylated by the IKK-related kinases
CC TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB
CC activity and NF-kappa-B-dependent gene transcription. Dephosphorylated
CC at Ser-177 and Ser-181 by PPM1A and PPM1B.
CC {ECO:0000250|UniProtKB:O14920}.
CC -!- PTM: Ubiquitinated. Monoubiquitination involves TRIM21 that leads to
CC inhibition of Tax-induced NF-kappa-B signaling. 'Ser-163' may not serve
CC as a monoubiquitination site. Ubiquitination on 'Ser-163' may modulate
CC phosphorylation on C-terminal serine residues.
CC {ECO:0000250|UniProtKB:O14920}.
CC -!- PTM: Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic
CC conditions results in activation of NF-kappa-B.
CC {ECO:0000250|UniProtKB:O14920}.
CC -!- DISRUPTION PHENOTYPE: Mice present extensive liver damage from
CC apoptosis and die as embryos. They show a marked reduction in TNF-alpha
CC and IL1-alpha-induced NF-kappa-B activity.
CC {ECO:0000269|PubMed:10195897, ECO:0000269|PubMed:10229185}.
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; AF026524; AAC23557.1; -; mRNA.
DR EMBL; AF088910; AAD52095.1; -; mRNA.
DR CCDS; CCDS52522.1; -.
DR RefSeq; NP_034676.1; NM_010546.2.
DR AlphaFoldDB; O88351; -.
DR SMR; O88351; -.
DR BioGRID; 200601; 31.
DR ComplexPortal; CPX-3270; IkappaB kinase complex.
DR CORUM; O88351; -.
DR DIP; DIP-29813N; -.
DR IntAct; O88351; 27.
DR MINT; O88351; -.
DR STRING; 10090.ENSMUSP00000033939; -.
DR BindingDB; O88351; -.
DR ChEMBL; CHEMBL6012; -.
DR iPTMnet; O88351; -.
DR PhosphoSitePlus; O88351; -.
DR EPD; O88351; -.
DR jPOST; O88351; -.
DR MaxQB; O88351; -.
DR PaxDb; O88351; -.
DR PeptideAtlas; O88351; -.
DR PRIDE; O88351; -.
DR ProteomicsDB; 266962; -.
DR DNASU; 16150; -.
DR GeneID; 16150; -.
DR KEGG; mmu:16150; -.
DR CTD; 3551; -.
DR MGI; MGI:1338071; Ikbkb.
DR eggNOG; KOG4250; Eukaryota.
DR InParanoid; O88351; -.
DR PhylomeDB; O88351; -.
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-202424; Downstream TCR signaling.
DR Reactome; R-MMU-209543; p75NTR recruits signalling complexes.
DR Reactome; R-MMU-209560; NF-kB is activated and signals survival.
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-5607764; CLEC7A (Dectin-1) 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 BioGRID-ORCS; 16150; 18 hits in 78 CRISPR screens.
DR ChiTaRS; Ikbkb; mouse.
DR PRO; PR:O88351; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O88351; protein.
DR GO; GO:0035631; C:CD40 receptor complex; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008384; F:IkappaB kinase activity; IDA: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:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:ARUK-UCL.
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: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:0001782; P:B cell homeostasis; IMP:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0007252; P:I-kappaB phosphorylation; TAS:MGI.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISO:MGI.
DR GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; ISO:MGI.
DR GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; ISO:MGI.
DR GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:2001259; P:positive regulation of cation channel activity; IGI:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; ISO:MGI.
DR GO; GO:0042325; P:regulation of phosphorylation; ISO:MGI.
DR GO; GO:0061847; P:response to cholecystokinin; ISO:MGI.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
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; 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; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Hydroxylation; Isopeptide bond; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW S-nitrosylation; Serine/threonine-protein kinase; Transferase;
KW Ubl conjugation.
FT CHAIN 1..757
FT /note="Inhibitor of nuclear factor kappa-B kinase subunit
FT beta"
FT /id="PRO_0000086014"
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 683..703
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 737..742
FT /note="NEMO-binding"
FT COMPBIAS 683..698
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:0000250|UniProtKB:O14920"
FT MOD_RES 179
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 181
FT /note="Phosphoserine; by TBK1, PKC/PRKCZ and PDPK1"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 191
FT /note="Hydroxyproline"
FT /evidence="ECO:0000250"
FT MOD_RES 670
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 672
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 675
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 682
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 689
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 692
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 697
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 705
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 733
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT MOD_RES 740
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT CROSSLNK 163
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O14920"
FT CONFLICT 56
FT /note="N -> D (in Ref. 2; AAD52095)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="N -> D (in Ref. 2; AAD52095)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="K -> E (in Ref. 2; AAD52095)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="L -> F (in Ref. 2; AAD52095)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="P -> Q (in Ref. 2; AAD52095)"
FT /evidence="ECO:0000305"
FT CONFLICT 573
FT /note="K -> R (in Ref. 2; AAD52095)"
FT /evidence="ECO:0000305"
FT CONFLICT 736..757
FT /note="TLDWSWLQMEDEERCSLEQACD -> VTA (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 757 AA; 86690 MW; FED962F095449C5E CRC64;
MSWSPSLPTQ TCGAWEMKER LGTGGFGNVI RWHNQATGEQ IAIKQCRQEL SPKNRNRWCL
EIQIMRRLNH PNVVAARDVP EGMQNLAPND LPLLAMEYCQ GGDLRRYLNQ FENCCGLREG
AVLTLLSDIA SALRYLHENR IIHRDLKPEN IVLQQGEKRL IHKIIDLGYA KELDQGSLCT
SFVGTLQYLA PELLEQQKYT VTVDYWSFGT LAFECITGFR PFLPNWQPVQ WHSKVRQKSE
VDIVVSEDLN GAVKFSSSLP FPNNLNSVLA ERLEKWLQLM LMWHPRQRGT DPQYGPNGCF
RALDDILNLK LVHVLNMVTG TVHTYPVTED ESLQSLKTRI QENTGILETD QELLQKAGLV
LLPDKPATQC ISDSKTNEGL TLDMDLVFLL DNSKINYETQ ITPRPPPESV SCILQEPKRN
LSFFQLRKVW GQVWHSIQTL KEDCNRLQQG QRAAMMSLLR NNSCLSKMKN AMASTAQQLK
AKLDFFKTSI QIDLEKYKEQ TEFGITSDKL LLAWREMEQA VEQCGRENDV KHLVERMMAL
QTDIVDLQRS PMGRKQGGTL DDLEEQAREL YRKLREKPRD QRTEGDSQEM VRLLLQAIQS
FEKKVRVIYT QLSKTVVCKQ KALELLPKVE EVVSLMNEDE RTVVRLQEKR QKELWNLLKI
ACSKVRGPVS GSPDSMNVSR LSHPGQLMSQ PSSACDSLPE SDKKSEELVA EAHALCSRLE
SALQDTVKEQ DRSFTTLDWS WLQMEDEERC SLEQACD