Aliases for CHUK Gene
External Ids for CHUK Gene
Previous Symbols for CHUK Gene
This gene encodes a member of the serine/threonine protein kinase family. The encoded protein, a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex, phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor. [provided by RefSeq, Jul 2008]
GeneCards Summary for CHUK Gene
CHUK (Conserved Helix-Loop-Helix Ubiquitous Kinase) is a Protein Coding gene. Diseases associated with CHUK include cocoon syndrome and skin papilloma. Among its related pathways are PI3K-Akt signaling pathway and PI-3K cascade. GO annotations related to this gene include protein homodimerization activity and protein heterodimerization activity. An important paralog of this gene is IKBKB.
UniProtKB/Swiss-Prot for CHUK Gene
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.
IkappaB Kinase (IKK) is an enzyme complex that forms part of the NF-kappaB signaling pathway. The complex is comprised of three subunits (IKKalpha (IKK1), IKKbeta (IKK2) and IKKgamma (NEMO)), the alpha- and beta-subunits are catalytically active whereas the gamma-subunit serves a regulatory function. Activation of NF-kappaB occurs via degradation of IkappaB, a process that is initiated by its phosphorylation by IkappaB kinase (IKK). Phosphorylated IkappaB becomes dissociated from NF-kappaB, unmasking the NLS. Phosphorylation also results in IkappaB ubiquitination and targeting to the proteasome. NF-kappaB can now enter the nucleus and regulate gene expression.