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Inhibitor of nuclear factor kappa-B kinase subunit alpha

FUNCTION: Acts as part of the IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF- kappa-B complex and 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 and the formation of NF-kappa-B RelB-p52 complexes. Also phosphorylates NCOA3. Phosphorylates 'Ser-10' of histone H3 at NF- kappa-B-regulated promoters during inflammatory responses triggered by cytokines. CATALYTIC ACTIVITY: ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein]. more...

ENZYME REGULATION: Activated when phosphorylated and inactivated when dephosphorylated.

SUBUNIT: Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK- beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, IKBKAP and MAP3K14. Directly interacts with IKK-gamma/NEMO and TRPC4AP (By similarity). May interact with TRAF2. Interacts with NALP2. May interact with MAVS/IPS1. Interacts with ARRB1 and ARRB2. Interacts with NLRC5; prevents CHUK phosphorylation and kinase activity.

SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and the nucleus.

TISSUE SPECIFICITY: Widely expressed.

PTM: Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated.

PTM: Acetylation of Thr-179 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B signaling pathway.

DISEASE: Defects in CHUK are the cause of cocoon syndrome (COCOS) [MIM:613630]; also known as fetal encasement syndrome. COCOS is a lethal syndrome characterized by multiple fetal malformations including defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin.

SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.

SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=SeattleSNPs; URL="";


COPYRIGHT: Protein annotation is derived from the UniProt Consortium ( Distributed under the Creative Commons Attribution-NoDerivs License.



  • Homo sapiens

Gene Symbol:

  • CHUK


  • I-kappa-B kinase alpha
  • Conserved helix-loop-helix ubiquitous kinase
  • IkappaB kinase
  • Nuclear factor NF-kappa-B inhibitor kinase alpha
  • IKK-alpha
  • Transcription factor 16
  • IKK1
  • I-kappa-B kinase 1
  • TCF-16
  • IkBKA
  • IKK-A

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