CHUK [The Human Chemical-Genetic Interaction Map Project]

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======= CHUK =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CHUK
  * **<color #00a2e8>Official Name</color>**: component of inhibitor of nuclear factor kappa B kinase complex
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1147|1147]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O15111|O15111]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CHUK&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CHUK|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/600664|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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:15084260). {ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17434128, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:21765415}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase Tyr|
|Pkinase|
|IKKbetaNEMObind|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|response to acetate|
|response to cholecystokinin|
|IkappaB kinase activity|
|IkappaB kinase complex|
|regulation of interferon-alpha secretion|
|positive regulation of interferon-alpha secretion|
|CD40 receptor complex|
|I-kappaB phosphorylation|
|response to hydroperoxide|
|positive regulation of interferon-alpha production|
|regulation of interferon-alpha production|
|TRIF-dependent toll-like receptor signaling pathway|
|skeletal muscle contraction|
|MyD88-independent toll-like receptor signaling pathway|
|cellular response to virus|
|cellular response to cadmium ion|
|musculoskeletal movement|
|multicellular organismal movement|
|cytoplasmic side of plasma membrane|
|regulation of tumor necrosis factor-mediated signaling pathway|
|scaffold protein binding|
|response to cadmium ion|
|I-kappaB kinase/NF-kappaB signaling|
|antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent|
|positive regulation of type I interferon production|
|Rho protein signal transduction|
|antigen processing and presentation of exogenous peptide antigen via MHC class I|
|NIK/NF-kappaB signaling|
|negative regulation of NF-kappaB transcription factor activity|
|interleukin-1-mediated signaling pathway|
|antigen processing and presentation of peptide antigen via MHC class I|
|toll-like receptor signaling pathway|
|stress-activated MAPK cascade|
|striated muscle contraction|
|stimulatory C-type lectin receptor signaling pathway|
|response to amino acid|
|innate immune response activating cell surface receptor signaling pathway|
|tumor necrosis factor-mediated signaling pathway|
|regulation of type I interferon production|
|pattern recognition receptor signaling pathway|
|cellular response to reactive oxygen species|
|positive regulation of cytokine secretion|
|stress-activated protein kinase signaling cascade|
|positive regulation of NF-kappaB transcription factor activity|
|negative regulation of DNA-binding transcription factor activity|
|regulation of cytokine-mediated signaling pathway|
|Fc-epsilon receptor signaling pathway|
|cellular response to interleukin-1|
|peptidyl-serine phosphorylation|
|T cell receptor signaling pathway|
|regulation of response to cytokine stimulus|
|antigen processing and presentation of exogenous peptide antigen|
|antigen processing and presentation of exogenous antigen|
|positive regulation of I-kappaB kinase/NF-kappaB signaling|
|antigen processing and presentation of peptide antigen|
|cellular response to metal ion|
|response to reactive oxygen species|
|response to interleukin-1|
|peptidyl-serine modification|
|striated muscle cell differentiation|
|regulation of cytokine secretion|
|antigen processing and presentation|
|cellular response to inorganic substance|
|innate immune response-activating signal transduction|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|protein kinase activity|
|cellular response to tumor necrosis factor|
|cellular response to oxidative stress|
|Fc receptor signaling pathway|
|muscle cell differentiation|
|Ras protein signal transduction|
|muscle contraction|
|activation of innate immune response|
|positive regulation of DNA-binding transcription factor activity|
|response to tumor necrosis factor|
|positive regulation of protein secretion|
|response to virus|
|positive regulation of peptide secretion|
|antigen receptor-mediated signaling pathway|
|muscle system process|
|response to antibiotic|
|response to lipopolysaccharide|
|small GTPase mediated signal transduction|
|response to molecule of bacterial origin|
|positive regulation of innate immune response|
|response to acid chemical|
|positive regulation of response to biotic stimulus|
|protein serine/threonine kinase activity|
|response to metal ion|
|MAPK cascade|
|response to oxidative stress|
|response to peptide hormone|
|signal transduction by protein phosphorylation|
|positive regulation of secretion by cell|
|positive regulation of protein transport|
|regulation of DNA-binding transcription factor activity|
|positive regulation of secretion|
|immune response-activating cell surface receptor signaling pathway|
|positive regulation of cytokine production|
|regulation of innate immune response|
|positive regulation of establishment of protein localization|
|regulation of protein secretion|
|response to peptide|
|positive regulation of defense response|
|muscle structure development|
|immune response-regulating cell surface receptor signaling pathway|
|protein heterodimerization activity|
|regulation of peptide secretion|
|inflammatory response|
|response to toxic substance|
|positive regulation of multi-organism process|
|regulation of response to biotic stimulus|
|response to inorganic substance|
|immune response-activating signal transduction|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|activation of immune response|
|cytokine-mediated signaling pathway|
|intracellular membrane-bounded organelle|
|response to bacterium|
|regulation of cytokine production|
|regulation of protein transport|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of defense response|
|innate immune response|
|regulation of multi-organism process|
|regulation of secretion|
|response to lipid|
|positive regulation of immune response|
|protein homodimerization activity|
|peptidyl-amino acid modification|
|response to hormone|
|defense response to other organism|
|protein phosphorylation|
|positive regulation of transport|
|response to organonitrogen compound|
|cellular response to cytokine stimulus|
|positive regulation of intracellular signal transduction|
|response to drug|
|regulation of protein localization|
|cellular response to oxygen-containing compound|
|response to nitrogen compound|
|regulation of response to external stimulus|
|response to cytokine|
|negative regulation of molecular function|
|regulation of immune response|
|positive regulation of immune system process|
|positive regulation of transcription by RNA polymerase II|
|phosphorylation|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|positive regulation of transcription, DNA-templated|
|response to oxygen-containing compound|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|positive regulation of signal transduction|
|regulation of immune system process|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of transport|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|system process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp95|BI-2536 0.0042μM R03 exp95]]|-1.71|
|[[:results:exp334|All-trans-Retinoic-Acid 40μM R07 exp334]]|1.86|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 3/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|2/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|1/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 10261
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.26 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CHUK Expression in NALM6 Cells: 6.26'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>