Description: Homo sapiens conserved helix-loop-helix ubiquitous kinase (CHUK), mRNA. RefSeq Summary (NM_001278): 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]. Transcript (Including UTRs) Position: hg19 chr10:101,948,124-101,989,344 Size: 41,221 Total Exon Count: 21 Strand: - Coding Region Position: hg19 chr10:101,949,355-101,989,289 Size: 39,935 Coding Exon Count: 21
ID:IKKA_HUMAN DESCRIPTION: RecName: Full=Inhibitor of nuclear factor kappa-B kinase subunit alpha; Short=I-kappa-B kinase alpha; Short=IKK-A; Short=IKK-alpha; Short=IkBKA; Short=IkappaB kinase; EC=2.7.11.10; AltName: Full=Conserved helix-loop-helix ubiquitous kinase; AltName: Full=I-kappa-B kinase 1; Short=IKK1; AltName: Full=Nuclear factor NF-kappa-B inhibitor kinase alpha; Short=NFKBIKA; AltName: Full=Transcription factor 16; Short=TCF-16; FUNCTION: 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. CATALYTIC ACTIVITY: ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein]. 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. Interacts with PIAS1; this interaction induces PIAS1 phosphorylation. INTERACTION: O14920:IKBKB; NbExp=7; IntAct=EBI-81249, EBI-81266; Q9Y6K9:IKBKG; NbExp=12; IntAct=EBI-81249, EBI-81279; Q99558:MAP3K14; NbExp=4; IntAct=EBI-81249, EBI-358011; P01106:MYC; NbExp=3; IntAct=EBI-81249, EBI-447544; P25963:NFKBIA; NbExp=6; IntAct=EBI-81249, EBI-307386; Q04206:RELA; NbExp=2; IntAct=EBI-81249, EBI-73886; Q86VP1:TAX1BP1; NbExp=2; IntAct=EBI-81249, EBI-529518; P24772:VACWR196 (xeno); NbExp=3; IntAct=EBI-81249, EBI-4291651; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and the nucleus. TISSUE SPECIFICITY: Widely expressed. DOMAIN: The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero- dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG. 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="http://pga.gs.washington.edu/data/chuk/";
Arthritis, Rheumatoid|Rheumatoid Arthritis|Anti-TNF Response Potter C et al. 2010, Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NF{kappa}B signalling pathways., Annals of the rheumatic diseases 69(7) : 1315-20 2010.
[PubMed 20448286]
Several SNPs mapping to the TLR and NFkappaB signalling systems demonstrated association with anti-TNF response as a whole and, in particular, with response to etanercept. Validation of these findings in an independent cohort is now warranted.
plasma levels of liver enzymes Yuan ,et al. 2008, Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes, American journal of human genetics 2008 83- 4 : 520-8.
[PubMed 18940312]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O15111
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
