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IkB kinase complex

Function: - activates NF kappa B through phosphorylation of IkB - activated by TNF-alpha & interleukin-1 - IkB kinase phosphorylates I kappa B (IkB) alpha on Ser-32 & Ser-36 which targets it to the ubiquitin proteasome pathway * see figure Structure: - subunits: IKK-alpha, IKK-beta & IKK-gamma, IKAP & possibly other components - activity requires ubiquitin activating enzyme E1, ubiquitin carrier protein E2 & ubiquitin [1] - MAP kinase kinase 1 (MEKK1) & a protein reacting with antibody to MAP kinase phosphatase-1 (MKP-1) copurifying with IkB kinase activity [2] Notes: - another complex includes IKK-epsilon & is inducible by phorbol esters (PMA) & activated by T-cell receptor [4]

Related

adapter protein CIKS; connection to IKK & SAPK/JNK; TRAF3-interacting protein 2; nuclear factor NF-kappa-B activator 1; ACT1 (TRAF3IP2, C6orf2, C6orf4, C6orf5, C6orf6) dual specificity protein phosphatase 1, MAP kinase phosphatase 1 or CL100 phosphatase IKB protein IKK-epsilon; inhibitor of nuclear factor kappa-B kinase subunit epsilon; I kappa-B kinase epsilon; IkBKE; IKK-E; inducible I kappa-B kinase; IKK-i (IKBKE, IKKE, IKKI, KIAA0151) mitogen-activated protein kinase kinase kinase 1 (MAP3K1, MAPK/ERK kinase kinase 1, MEKK1, MAPKKK1, MEKK)

General

multisubunit protein

Properties

SIZE: MW = 700 kD SUBUNITS: elongator complex protein 1 COMPARTMENT: cytoplasm cell nucleus MOTIF: Ser phosphorylation site {S471} Ser phosphorylation site {S867} Ser phosphorylation site {S1171} Ser phosphorylation site {S1174} inhibitor of nuclear factor kappa-B kinase subunit alpha STATE: active state MOTIF: kinase domain SITE: 15-302 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 {D144} Ser phosphorylation site {S176} leucine zipper SITE: 455-476 FOR-BINDING-VIA: leucine zipper binding site SITE: 738-743 FOR-BINDING-OF: NF-kappa-B essential modulator inhibitor of nuclear factor kappa-B kinase subunit beta 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} NF-kappa-B essential modulator MOTIF: Ser phosphorylation site {S31} Ser phosphorylation site {S43} CHUK/IKBKB interaction {44-111} coiled coil {49-356} MOTIF: cysteine residue {C54} MODIFICATION: cysteine residue {C-INTERCHAIN} Ser phosphorylation site {S68} Ser phosphorylation site {S85} Self-association {246-365} MOTIF: leucine zipper SITE: 322-343 FOR-BINDING-VIA: leucine zipper cysteine residue {C347} MODIFICATION: cysteine residue {C-INTERCHAIN} Ser phosphorylation site {S376} Ser phosphorylation site {S377} CYLD interaction {382-419} MOTIF: Ser phosphorylation site {S387} Zn finger C2HC-type SITE: 396-417 EFFECTOR-BOUND: Zn+2

References

  1. Chen ZJ et al Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity. Cell 84:853-62, 1996 PMID: 8601309
  2. 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
  3. Stancovski I & Baltimore D NF-kappaB activation: the I kappaB kinase revealed? Cell 91:299-302, 1997 PMID: 9363938
  4. Peters RT et al IKKepsilon is part of a novel PMA-inducible IkappaB kinase complex. Molecular Cell 5:513-22, 2000 PMID: 10882136
  5. Peters RT & Maniatis T A new family of IKK-related kinases may function as I kappa B kinase kinases. Biochim Biophys Acta 1471:M57-M62, 2001 PMID: 11342184

Components

elongator complex protein 1; ELP1; IkappaB kinase complex-associated protein; IKK complex-associated protein; p150 (IKBKAP, ELP1, IKAP, DYS) inhibitor of nuclear factor kappa-B kinase subunit alpha; I kappa-B kinase alpha; IkBKA; IKK-alpha; IKK-A; IkappaB kinase; I-kappa-B kinase 1; IKK1; conserved helix-loop-helix ubiquitous kinase; nuclear factor NF-kappa-B inhibitor kinase alpha; NFKBIKA (CHUK, IKKA, TCF16) 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) NF-kappa-B essential modulator; NEMO; NF-kappa-B essential modifier; inhibitor of nuclear factor kappa-B kinase subunit gamma; IkB kinase subunit gamma; I-kappa-B kinase gamma; IKK-gamma; IKKG; IkB kinase-associated protein 1; IKKAP1;FIP-3 (IKBKG, FIP3, NEMO)

Databases & Figures

Kegg hsa/hsa04210 Figures/diagrams/slides/tables related to IkB kinase