Summary

Name IKBKB
Full Name Inhibitor of nuclear factor kappa-B kinase subunit beta
Synonyms I-kappa-B-kinase beta, IKK-B, IKK-beta, IkBKB, I-kappa-B kinase 2, IKK2, Nuclear factor NF-kappa-B inhibitor kinase beta, NFKBIKB | IKKB
Primary ID O14920
Links - -
Type protein
Relations 124
Pathways FLT3-ITD signaling
Inhibitors N-(6-Chloro-7-methoxy-9H-pyrido[3,4-b]indol-8-yl)-2-methylnicotinamide; N'-(1,8-dimethyl-4-imidazo[1,2-a]quinoxalinyl)ethane-1,2-diamine
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 (PubMed:30337470). Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation. 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 (PubMed:11297557, PubMed:20410276). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NCOA3, BCL10 and IRS1 (PubMed:17213322). Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation (PubMed:11297557). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates img/direct_inhibition.png cleavage IKBKB 0.377
Publications: 4 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png cleavage IKBKB 0.377
Publications: 4 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation YWHAB 0.377
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation IKBKB 0.413
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation IKBKB 0.259
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation IKBKB 0.413
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation IKBKB 0.49
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation IKBKB 0.647
Publications: 2 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation IKBKB 0.74
Publications: 3 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation IKBKB 0.314
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation IKBKB 0.314
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation IKBKB 0.262
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation COPS5 0.336
Publications: 2 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation TMIGD2 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation IRS1 0.642
Publications: 10 Organism: In Vitro
+ img/unknown.png phosphorylation IKBKG 0.962
Publications: 4 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ASB8 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation NFKBIA 0.919
Publications: 2
Pathways:FLT3-ITD signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation CYLD 0.527
Publications: 6 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation CYLD 0.527
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation DOK1 0.254
Publications: 4 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation RELA 0.881
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation TSC1 0.625
Publications: 4 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation FOXO 0.674
Publications: 2 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ down-regulates img/direct_inhibition.png phosphorylation FOXO3 0.674
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation IKBKB 0.2
Publications: 14 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ down-regulates activity img/direct_inhibition.png phosphorylation IKBKG 0.962
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation IKBKB 0.349
Publications: 3 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CDKN2A 0.406
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation NFKB1 0.848
Publications: 3 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation NFKB1 0.848
Publications: 3 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation IKBKB 0.37
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation IKBKB 0.37
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding IKK-complex 0.804
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates activity img/direct-activation.png binding IKBKB 0.962
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation NFKBIA 0.919
Publications: 1 Organism: Mus Musculus
Pathways:FLT3-ITD signaling
+ down-regulates img/direct_inhibition.png phosphorylation NfKb-p65/p50 0.864
Publications: 2 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination IKBKB 0.555
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination IKBKB 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation BAD 0.266
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ img/unknown.png phosphorylation NfKb-p65/p50 0.864
Publications: 2 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ down-regulates quantity by destabilization img/direct_inhibition.png binding IKBKB 0.413
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation IKBKB 0.695
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding IKBKB 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png chemical inhibition IKBKB 0.8
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png binding IKBKB 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation HES1 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination IKBKB 0.437
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation COMT 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding IKBKB 0.507
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation IKBKB 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png chemical inhibition IKBKB 0.8
Publications: 1 Organism: In Vitro
+ down-regulates img/direct_inhibition.png phosphorylation NFKBIB 0.757
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding IKBKB 0.413
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation NCOA3 0.385
Publications: 1 Organism: Homo Sapiens