IKKA Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. 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. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily. Widely expressed. Note: This description may include information from UniProtKB.
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:  CD40 receptor complex; cytoplasm; cytoplasmic side of plasma membrane; cytosol; IkappaB kinase complex; intracellular membrane-bounded organelle; nucleoplasm
Molecular Function:  ATP binding; IkappaB kinase activity; protein binding; protein heterodimerization activity; protein homodimerization activity; protein kinase activity; scaffold protein binding
Biological Process:  anatomical structure morphogenesis; antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; cellular response to cadmium ion; cellular response to reactive oxygen species; cellular response to tumor necrosis factor; cellular response to virus; Fc-epsilon receptor signaling pathway; I-kappaB kinase/NF-kappaB signaling; I-kappaB phosphorylation; immune response; inflammatory response; innate immune response; interleukin-1-mediated signaling pathway; MyD88-independent toll-like receptor signaling pathway; negative regulation of NF-kappaB transcription factor activity; NIK/NF-kappaB signaling; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of interferon-alpha secretion; positive regulation of NF-kappaB transcription factor activity; positive regulation of transcription by RNA polymerase II; positive regulation of transcription, DNA-templated; protein phosphorylation; regulation of tumor necrosis factor-mediated signaling pathway; response to acetate; response to amino acid; response to cholecystokinin; response to drug; response to hydroperoxide; response to lipopolysaccharide; response to toxic substance; response to virus; Rho protein signal transduction; skeletal muscle contraction; stimulatory C-type lectin receptor signaling pathway; stress-activated MAPK cascade; striated muscle cell differentiation; T cell receptor signaling pathway; TRIF-dependent toll-like receptor signaling pathway
Disease: Cocoon Syndrome
Reference #:  O15111 (UniProtKB)
Alt. Names/Synonyms: CHUK; conserved helix-loop ubiquitous kinase; Conserved helix-loop-helix ubiquitous kinase; I-kappa-B kinase 1; I-kappa-B kinase alpha; I-kappa-B kinase-alpha; IkappaB kinase; IkB kinase alpha subunit; IkBKA; IKK-A; IKK-a kinase; IKK-alpha; IKK1; IKKA; Inhibitor of nuclear factor kappa-B kinase subunit alpha; NFKBIKA; Nuclear factor NF-kappa-B inhibitor kinase alpha; Nuclear factor NFkappaB inhibitor kinase alpha; TCF-16; TCF16; Transcription factor 16
Gene Symbols: CHUK
Molecular weight: 84,640 Da
Basal Isoelectric point: 6.27  Predict pI for various phosphorylation states
CST Pathways:  Apoptosis Regulation  |  B Cell Receptor Signaling  |  Death Receptor Signaling  |  Inhibition of Apoptosis  |  Insulin Receptor Signaling  |  NF-kB Signaling  |  PI3K/Akt Signaling  |  T Cell Receptor Signaling  |  Toll-Like Receptor Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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IKKA

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Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene