ID:IKKB_HUMAN DESCRIPTION: RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit beta; Short=I-kappa-B-kinase beta; Short=IKK-B; Short=IKK-beta; Short=IkBKB; EC=2.7.11.10; AltName: Full=I-kappa-B kinase 2; Short=IKK2; AltName: Full=Nuclear factor NF-kappa-B inhibitor kinase beta; Short=NFKBIKB; FUNCTION: Serine kinase that plays an essential role in the NF- kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation. CATALYTIC ACTIVITY: ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein]. SUBUNIT: Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK- beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, IKBKAP and MAP3K14. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Interacts with SQSTM1 through PRKCZ or PRKCI. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6. May interact with MAVS/IPS1. Interacts with NALP2. Interacts with TICAM1. Interacts with Yersinia yopJ. Interacts with FAF1; the interaction disrupts the IKK complex formation. Interacts with ATM. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with TRIM21. Interacts with NLRC5; prevents IKBKB phosphorylation and kinase activity. Interacts with PDPK1. INTERACTION: O15111:CHUK; NbExp=7; IntAct=EBI-81266, EBI-81249; Q9Y6K9:IKBKG; NbExp=14; IntAct=EBI-81266, EBI-81279; Q14145:KEAP1; NbExp=6; IntAct=EBI-81266, EBI-751001; Q99558:MAP3K14; NbExp=2; IntAct=EBI-81266, EBI-358011; Q9Y6Q9:NCOA3; NbExp=3; IntAct=EBI-81266, EBI-81196; P25963:NFKBIA; NbExp=9; IntAct=EBI-81266, EBI-307386; P23396:RPS3; NbExp=4; IntAct=EBI-81266, EBI-351193; Q9UGK3:STAP2; NbExp=7; IntAct=EBI-81266, EBI-1553984; Q92574:TSC1; NbExp=3; IntAct=EBI-81266, EBI-1047085; P24772:VACWR196 (xeno); NbExp=3; IntAct=EBI-81266, EBI-4291651; Q5D1E7:Zc3h12a (xeno); NbExp=4; IntAct=EBI-81266, EBI-5326026; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Membrane raft. Note=Colocalized with DPP4 in membrane rafts. TISSUE SPECIFICITY: Highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis and peripheral blood. DOMAIN: The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero- dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG. PTM: Upon cytokine stimulation, phosphorylated on Ser-177 and Ser- 181 by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances activity. Once activated, autophosphorylates on the C- terminal serine cluster; which decreases activity and prevents prolonged activation of the inflammatory response. Phosphorylated by the IKK-related kinases TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB activity and NF-kappa-B-dependent gene transcription. PTM: Acetylation of Thr-180 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway. PTM: Ubiquitinated. Monoubiquitination involves TRIM21 that leads to inhibition of Tax-induced NF-kappa-B signaling. According to PubMed:19675099, 'Ser-163' does not serve as a monoubiquitination site. According to PubMed:16267042, ubiquitination on 'Ser-163' modulates phosphorylation on C-terminal serine residues. Monoubiquitination by TRIM21 is dirupted by Yersinia yopJ. SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/ikbkb/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14920
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
