inhibitor of nuclear factor kappa-B kinase subunit beta; I-kappa-B-kinase beta; IkBKB; IKK-beta; IKK-B; I-kappa-B kinase 2; IKK2; nuclear factor NF-kappa-B inhibitor kinase beta; NFKBIKB (IKBKB, IKKB)
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Function
- component of the IKK complex in the conventional pathway of NF-kappa-B activation
- phosphorylates inhibitors of NF-kappa-B thus leading to dissociation of the inhibitor/NF-kappa-B complex & ultimately the degradation of the inhibitor
- IKK-beta is required for TNF-alpha induction of NF-kappa B
- also phosphorylates NCOA3
- part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG & CREBBP
- part of a 70-90 kD complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, IKBKAP & MAP3K14
- interacts with SQSTM1 through PRKCZ or PRKCI
- forms an NGF-induced complex with IKBKB, PRKCI & 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
- interacts with NIK
- part of a ternary complex consisting of TANK, IKBKB & IKBKG
- interacts with NIBP; the interaction is direct upon cytokine stimulation
- phosphorylated on Ser-177 & Ser-181 by MEKK1 &/or MAP3K14/NIK; which enhances activity
- once activated, autophosphorylates on the C-terminal Ser cluster which decreases activity & prevents prolonged activation of the inflammatory response
- ubiquitination on Ser-163 modulates phosphorylation on C-terminal Ser
Structure
- can exist as homodimer or heterodimer[2]
- belongs to the protein kinase superfamily, Ser/Thr protein kinase family, I-kappa-B kinase subfamily
- contains canonical MAP kinase kinase activation loop motif SXXXS
- contains 1 protein kinase domain
Compartment
Expression
- highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis & peripheral blood
Pathology
- Yersinia yopJ may acetylate Ser/Thr residues, preventing phosphorylation & activation, which blocks the I-kappa-B signaling pathway
- implicated in aspirin-sensitive insulin resistance; aspirin or sodium salicylate attenuates IKK-beta mediated insulin resistance
More general terms
Component of
References
- ↑ Mercurio F et al IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science 278:860-6, 1997 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9346484
- ↑ 2.0 2.1 Woronicz JD et al. IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. Science 278:866-9,
- ↑ Peters RT et al IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex. Molecular Cell 5:513-22, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10882136
- ↑ Journal Watch 21(19):157, 2001 Yuan M et al Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293:1673, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11533494
- ↑ UniProt http://www.uniprot.org/uniprot/O14920.html
- ↑ SeattleSNPs http://pga.gs.washington.edu/data/ikbkb/