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General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.
Gene namei
Official gene symbol, which is typically a short form of the gene name, according to HGNC.
Component of inhibitor of nuclear factor kappa B kinase complex
Protein classi
Assigned HPA protein class(es) for the encoded protein(s).
Disease related genes Enzymes Human disease related genes Potential drug targets RAS pathway related proteins
Predicted locationi
All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.
Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.
Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).
The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.
Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.
Chromosome
10
Cytoband
q24.31
Chromosome location (bp)
100188300 - 100229596
Number of transcriptsi
Number of protein-coding transcripts from the gene as defined by Ensembl.
Useful information about the protein provided by UniProt.
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 1,2,3,4. Acts as a 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 5,6,7,8,9. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome 10,11,12,13. 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 14,15,16,17. 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) 18. 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 19. 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 20. 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 21. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor 22. Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity 23....show less
Molecular function (UniProt)i
Keywords assigned by UniProt to proteins due to their particular molecular function.
Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.
ATP-binding, Nucleotide-binding
Gene summary (Entrez)i
Useful information about the gene from Entrez
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]...show less
PROTEIN INFORMATIONi
The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.
The Splice variant identifier links to the Ensembl website protein summary for the selected splice variant. The data in the Swissprot and TrEMBL columns links to corresponding pages in the UniProt database.
The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.
The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide and number of predicted transmembrane region(s) according to in-house majority decision methods based on sets of predictors are also reported.
Enzymes ENZYME proteins Transferases Kinases MEMSAT-SVM predicted membrane proteins SPOCTOPUS predicted membrane proteins Predicted intracellular proteins Intracellular proteins predicted by MDM and MDSEC RAS pathway related proteins Disease related genes Potential drug targets Human disease related genes Congenital malformations Other congenital malformations Mapped to neXtProt neXtProt - Evidence at protein level Protein evidence (Kim et al 2014) Protein evidence (Ezkurdia et al 2014)
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GO:0000166[nucleotide binding] GO:0004672[protein kinase activity] GO:0004674[protein serine/threonine kinase activity] GO:0005515[protein binding] GO:0005524[ATP binding] GO:0005634[nucleus] GO:0005654[nucleoplasm] GO:0005737[cytoplasm] GO:0005829[cytosol] GO:0006468[protein phosphorylation] GO:0006954[inflammatory response] GO:0006955[immune response] GO:0007249[I-kappaB kinase/NF-kappaB signaling] GO:0007252[I-kappaB phosphorylation] GO:0008384[IkappaB kinase activity] GO:0008385[IkappaB kinase complex] GO:0009615[response to virus] GO:0009653[anatomical structure morphogenesis] GO:0009898[cytoplasmic side of plasma membrane] GO:0016301[kinase activity] GO:0016310[phosphorylation] GO:0016740[transferase activity] GO:0018105[peptidyl-serine phosphorylation] GO:0032088[negative regulation of NF-kappaB transcription factor activity] GO:0032727[positive regulation of interferon-alpha production] GO:0033209[tumor necrosis factor-mediated signaling pathway] GO:0034614[cellular response to reactive oxygen species] GO:0035631[CD40 receptor complex] GO:0038061[NIK/NF-kappaB signaling] GO:0042803[protein homodimerization activity] GO:0043123[positive regulation of I-kappaB kinase/NF-kappaB signaling] GO:0045087[innate immune response] GO:0045893[positive regulation of DNA-templated transcription] GO:0045944[positive regulation of transcription by RNA polymerase II] GO:0046982[protein heterodimerization activity] GO:0050896[response to stimulus] GO:0051092[positive regulation of NF-kappaB transcription factor activity] GO:0071276[cellular response to cadmium ion] GO:0071356[cellular response to tumor necrosis factor] GO:0097110[scaffold protein binding] GO:0098586[cellular response to virus] GO:1990459[transferrin receptor binding]