CHUK
Entrez ID: 1147
Full name: component of inhibitor of nuclear factor kappa B kinase complex
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: Other: IKK
Chromosomal location: 10q24.31
Substructure location: Gatekeeper: A-loop: G-loop: αC-helix:
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CHUK
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...
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 (PubMed:12789342, PubMed:15084260, PubMed:17434128, PubMed:20434986, PubMed:20501937, PubMed:21765415). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity).
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GO - Biological processes (BP):
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 rece...
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, peptidyl-serine phosphorylation, 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, DNA-templated, positive regulation of transcription by RNA polymerase II, 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, tumor necrosis factor-mediated signaling pathway
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GO - Molecular function (MF):
ATP binding, IkappaB kinase activity, protein-containing complex binding, protein heterodimerization activity, protein homodimerization activity, protein kinase activity, protein serine/threonine kinase activity, scaffold protein binding, transferrin receptor binding...
ATP binding, IkappaB kinase activity, protein-containing complex binding, protein heterodimerization activity, protein homodimerization activity, protein kinase activity, protein serine/threonine kinase activity, scaffold protein binding, transferrin receptor binding
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GO - Cellular component (CC):
cytosol, IkappaB kinase complex, nucleoplasm, CD40 receptor complex, cytoplasmic side of plasma membrane, cytoplasm, intracellular membrane-bounded organelle...
cytosol, IkappaB kinase complex, nucleoplasm, CD40 receptor complex, cytoplasmic side of plasma membrane, cytoplasm, intracellular membrane-bounded organelle
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component of inhibitor of nuclear factor kappa B kinase complex
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Gatekeeper
A-loop
G-loop
αC-helix
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A-loop
G-loop
αC-helix
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Minimum 10 samples
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Kaplan plot for CHUK in
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*NOTE: the Kaplan plots were collected from OncoLnc