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)

^[1]^[2]^[3]^[4]^[5]

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

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

widely expressed

↑ 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, 1997 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9346485
↑ 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
↑ UniProt http://www.uniprot.org/uniprot/O15111.html
↑ SeattleSNPs http://pga.gs.washington.edu/data/chuk/