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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)

Function: - acts as part 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 - as part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 & the formation of NF-kappa-B RelB-p52 complexes - in targeted gene disruption in mice, IKK1 (CHUK) was not required for cytokine dependent activation of NF kappa B but played a role in keratinocyte differentiation - also phosphorylates NCOA3 - phosphorylates Ser-10 of histone H3 at NF-kappa-B regulated promoters during inflammatory responses triggered by cytokines - component of IKK core complex - 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 - directly interacts with IKK-gamma/NEMO & TRPC4AP (putative) - may interact with TRAF2 - interacts with NALP2 - may interact with MAVS/IPS1 - interacts with NIK [2] - activated when phosphorylated & inactivated when dephosphorylated - phosphorylated by MAP3K14/NIK, AKT & to a lesser extent by MEKK1 - dephosphorylated by PP2A - autophosphorylated Structure: - exists as homodimers & heterodimers - belongs to the protein kinase superfamily, Ser/Thr protein kinase family, I-kappa-B kinase subfamily - contains 1 protein kinase domain - contains canonical MAP kinase kinase activation loop motif SXXXS Compartment: - cytoplasm. nucleus - shuttles between cytoplasm & nucleus Expression: widely expressed

Interactions

molecular events

General

serine/threonine kinase

Properties

SIZE: entity length = 745 aa MW = 85 kD COMPARTMENT: cytoplasm cell nucleus 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

Database Correlations

OMIM 600664 UniProt O15111 Pfam PF00069 Entrez Gene 1147 KEGG correlations ENZYME

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, 1997 PMID: 9346485
  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. UniProt :accession O15111
  5. SeattleSNPs http://pga.gs.washington.edu/data/chuk/

Component-of

IkB kinase complex