IKKA: a kinase of the IKK family. Phosphorylates inhibitors of NF-kappa-B, leading to their dissociation from NF-kappa-B and ultimately to their degradation. Phosphorylated and activated downstream of growth factor receptors, IL1R, and TNFR by NAK, IRAK and NIK, respectively. Preferentially found as a heterodimer with IKK-beta but also as an homodimer. Directly interacts with IKK-gamma/NEMO and TRPC4AP. Heterodimers form the active complex. The tripartite complex can also bind to MAP3K14/NIK, MEKK1, IKAP and IKB-alpha-p65-p50 complex. Inhibitors are under development to treat arthritis, inflammation, and apoptotic aspects of cancer. Aspirin (sodium salicylate) selectively binds IKK and reduces inflammation. Misexpression and inhibitors show involvement in insulin sensitization in obese rodents. Mutations in IKK-gamma are found in several immune deficiencies: hyper IgM syndrome, incontinentia pigmenti [embryonic lethal in males, defects in skin, hair, teeth in females] and hypohidrotic ectodermal dysplasia; recurrent infections and defects in teeth, hair, and sweat glands]. Inhibitors: CHS 828, NBD peptide, BMS-345541.
Protein type: EC 2.7.11.10; IKK family; Kinase, protein; Other group; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor)
Chromosomal Location of Human Ortholog: 10q24.31
Cellular Component: cytoplasm; cytosol; IkappaB kinase complex; internal side of plasma membrane; intracellular membrane-bound organelle; nucleoplasm
Molecular Function: IkappaB kinase activity; protein binding; protein heterodimerization activity; protein homodimerization activity; protein kinase activity
Biological Process: activation of NF-kappaB transcription factor; anatomical structure morphogenesis; I-kappaB kinase/NF-kappaB cascade; I-kappaB phosphorylation; immune response; inflammatory response; innate immune response; peptidyl-serine phosphorylation; positive regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of transcription from RNA polymerase II promoter; protein amino acid phosphorylation; response to virus; stimulatory C-type lectin receptor signaling pathway; stress-activated MAPK cascade; T cell receptor signaling pathway; tumor necrosis factor-mediated signaling pathway
Disease: Cocoon Syndrome
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