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 24-JAN-2024, entry version 203. 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:0000250|UniProtKB:O14920}; 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 RC 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 (By similarity). Acts as a part of the CC canonical IKK complex in the conventional pathway of NF-kappa-B CC activation (By similarity). Phosphorylates inhibitors of NF-kappa-B on CC 2 critical serine residues (By similarity). These modifications allow CC polyubiquitination of the inhibitors and subsequent degradation by the CC proteasome (By similarity). 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 (By similarity). In addition to the NF-kappa-B inhibitors, CC phosphorylates several other components of the signaling pathway CC including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as CC IKK-related kinases TBK1 and IKBKE (By similarity). IKK-related kinase CC phosphorylations may prevent the overproduction of inflammatory CC mediators since they exert a negative regulation on canonical IKKs (By CC similarity). Phosphorylates FOXO3, mediating the TNF-dependent CC inactivation of this pro-apoptotic transcription factor (By CC similarity). Also phosphorylates other substrates including NAA10, CC NCOA3, BCL10 and IRS1 (By similarity). Phosphorylates RIPK1 at 'Ser-25' CC which represses its kinase activity and consequently prevents TNF- CC mediated RIPK1-dependent cell death (PubMed:30988283). Phosphorylates CC the C-terminus of IRF5, stimulating IRF5 homodimerization and CC 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 Evidence={ECO:0000250|UniProtKB:O14920}; 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 ZC3H12A (PubMed:22037600). Interacts with AKAP13 CC (PubMed:23090968). Interacts with LRRC14; disrupts IKBKB-IKBKG CC interaction preventing I-kappa-B-kinase (IKK) core complex formation CC and leading to a decrease of IKBKB phosphorylation and NF-kappaB CC activation (By similarity). Interacts with SASH1 (By similarity). CC Interacts with ARFIP2 (By similarity). Interacts with FKBP5 (By CC 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. {ECO:0000250|UniProtKB:O14920}. 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. Phosphorylated by MAP3K7/TAK1 in response to NOD1 and NOD2 CC signaling, promoting activation and phosphorylation of NF-kappa-B CC inhibitors, leading to NF-kappa-B activation. Once activated, CC autophosphorylates on the C-terminal serine cluster; which decreases CC activity and prevents prolonged activation of the inflammatory CC response. Phosphorylated by the IKK-related kinases TBK1 and IKBKE, CC which is associated with reduced CHUK/IKKA and IKBKB activity and NF- CC kappa-B-dependent gene transcription. Dephosphorylated at Ser-177 and CC Ser-181 by PPM1A and PPM1B. {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}. 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; 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; 34. 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 GlyGen; O88351; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O88351; -. DR PhosphoSitePlus; O88351; -. DR SwissPalm; O88351; -. DR EPD; O88351; -. DR jPOST; O88351; -. DR MaxQB; O88351; -. DR PaxDb; 10090-ENSMUSP00000033939; -. DR PeptideAtlas; O88351; -. DR ProteomicsDB; 266962; -. DR Pumba; O88351; -. DR DNASU; 16150; -. DR GeneID; 16150; -. DR KEGG; mmu:16150; -. DR AGR; MGI:1338071; -. DR CTD; 3551; -. DR MGI; MGI:1338071; Ikbkb. DR eggNOG; KOG4250; Eukaryota. DR InParanoid; O88351; -. DR OrthoDB; 3949542at2759; -. 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 NF-kappa-B 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 Reactome; R-MMU-9758274; Regulation of NF-kappa B signaling. DR Reactome; R-MMU-9833482; PKR-mediated signaling. DR BioGRID-ORCS; 16150; 19 hits in 83 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; 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; IDA: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:0007249; P:canonical NF-kappaB signal transduction; 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: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:0031175; P:neuron projection development; ISO:MGI. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISO:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI. DR GO; GO:0010976; P:positive regulation of neuron projection development; 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:0051604; P:protein maturation; ISO:MGI. 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 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 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 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 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 /evidence="ECO:0000250|UniProtKB:O14920" 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 //