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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)

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: cytoplasm 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

Interactions

molecular events

General

serine/threonine kinase

Properties

SIZE: entity length = 756 aa MW = 87 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: kinase domain SITE: 15-300 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 21-29 Thr phosphorylation site {T23} ATP-binding site NAME: ATP-binding site SITE: 44-44 aspartate residue {D145} Ser phosphorylation site {S177} Ser phosphorylation site {S181} leucine zipper SITE: 458-479 FOR-BINDING-VIA: leucine zipper Ser phosphorylation site {S670} Ser phosphorylation site {S672} Ser phosphorylation site {S675} Ser phosphorylation site {S682} Ser phosphorylation site {S689} Ser phosphorylation site {S692} Ser phosphorylation site {S695} Ser phosphorylation site {S697} Ser phosphorylation site {S705} Ser phosphorylation site {S733} binding site SITE: 737-742 FOR-BINDING-OF: NF-kappa-B essential modulator MOTIF: Ser phosphorylation site {S740} Ser phosphorylation site {S750}

Database Correlations

OMIM 603258 UniProt O14920 PFAM correlations Entrez Gene 3551 KEGG correlations ENZYME 2.7.11.10

References

  1. Mercurio F et al IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation. Science 278:860-6, 1997 PMID: 9346484
  2. Woronicz JD et al. IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. Science 278:866-9,
  3. Peters RT et al IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex. Molecular Cell 5:513-22, 2000 PMID: 10882136
  4. 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: 11533494
  5. UniProt :accession O14920
  6. SeattleSNPs http://pga.gs.washington.edu/data/ikbkb/

Component-of

IkB kinase complex