======= TBK1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: TBK1
  * **<color #00a2e8>Official Name</color>**: TANK binding kinase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=29110|29110]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9UHD2|Q9UHD2]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=TBK1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20TBK1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/604834|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. [provided by RefSeq, Oct 2010]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser- 177', thus enhancing LC3 binding affinity and antibacterial autophagy (PubMed:21617041). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (PubMed:27103069). Phosphorylates and activates AKT1 (PubMed:21464307). Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C (PubMed:21270402). Phosphorylates Borna disease virus (BDV) P protein (PubMed:16155125). {ECO:0000269|PubMed:10581243, ECO:0000269|PubMed:10783893, ECO:0000269|PubMed:11839743, ECO:0000269|PubMed:12692549, ECO:0000269|PubMed:12702806, ECO:0000269|PubMed:14703513, ECO:0000269|PubMed:15367631, ECO:0000269|PubMed:15485837, ECO:0000269|PubMed:15489227, ECO:0000269|PubMed:16155125, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21270402, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:21931631, ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:23453972, ECO:0000269|PubMed:23746807, ECO:0000269|PubMed:26611359, ECO:0000269|PubMed:27103069}.

<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|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|dendritic cell proliferation|
|positive regulation of xenophagy|
|regulation of xenophagy|
|positive regulation of interferon-beta biosynthetic process|
|type I interferon production|
|regulation of interferon-beta biosynthetic process|
|positive regulation of type I interferon-mediated signaling pathway|
|positive regulation of interferon-alpha production|
|TRIF-dependent toll-like receptor signaling pathway|
|regulation of interferon-alpha production|
|positive regulation of interferon-beta production|
|MyD88-independent toll-like receptor signaling pathway|
|regulation of type I interferon-mediated signaling pathway|
|phosphoprotein binding|
|aggresome|
|negative regulation of type I interferon production|
|regulation of interferon-beta production|
|positive regulation of cytokine-mediated signaling pathway|
|positive regulation of response to cytokine stimulus|
|positive regulation of macroautophagy|
|positive regulation of cytokine biosynthetic process|
|I-kappaB kinase/NF-kappaB signaling|
|positive regulation of type I interferon production|
|peptidyl-threonine phosphorylation|
|lymphocyte proliferation|
|protein phosphatase binding|
|mononuclear cell proliferation|
|peptidyl-threonine modification|
|defense response to Gram-positive bacterium|
|leukocyte proliferation|
|toll-like receptor signaling pathway|
|regulation of cytokine biosynthetic process|
|positive regulation of peptidyl-serine phosphorylation|
|positive regulation of autophagy|
|regulation of type I interferon production|
|pattern recognition receptor signaling pathway|
|regulation of peptidyl-serine phosphorylation|
|cytokine production|
|regulation of cytokine-mediated signaling pathway|
|regulation of macroautophagy|
|peptidyl-serine phosphorylation|
|regulation of response to cytokine stimulus|
|positive regulation of I-kappaB kinase/NF-kappaB signaling|
|defense response to virus|
|nucleic acid binding|
|peptidyl-serine modification|
|endosome membrane|
|innate immune response-activating signal transduction|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|protein kinase activity|
|activation of innate immune response|
|negative regulation of cytokine production|
|response to virus|
|regulation of neuron death|
|defense response to bacterium|
|regulation of autophagy|
|positive regulation of innate immune response|
|positive regulation of response to biotic stimulus|
|protein serine/threonine kinase activity|
|positive regulation of cellular catabolic process|
|lymphocyte activation|
|positive regulation of catabolic process|
|positive regulation of cytokine production|
|regulation of innate immune response|
|positive regulation of defense response|
|inflammatory response|
|positive regulation of multi-organism process|
|regulation of response to biotic stimulus|
|cell population proliferation|
|immune response-activating signal transduction|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|activation of immune response|
|response to bacterium|
|regulation of cytokine production|
|viral process|
|regulation of defense response|
|innate immune response|
|regulation of multi-organism process|
|symbiotic process|
|interspecies interaction between organisms|
|regulation of cellular catabolic process|
|positive regulation of immune response|
|peptidyl-amino acid modification|
|leukocyte activation|
|defense response to other organism|
|protein phosphorylation|
|regulation of catabolic process|
|cellular response to cytokine stimulus|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|positive regulation of phosphorylation|
|identical protein binding|
|cell activation|
|immune effector process|
|regulation of response to external stimulus|
|response to cytokine|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|positive regulation of immune system process|
|regulation of immune response|
|negative regulation of multicellular organismal process|
|positive regulation of transcription by RNA polymerase II|
|positive regulation of protein modification process|
|phosphorylation|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|regulation of protein phosphorylation|
|regulation of response to stress|
|ATP binding|
|positive regulation of transcription, DNA-templated|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic 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:exp85|UM0129480 7μM R02 exp85]]|-2.45|
|[[:results:exp234|Ethanol 0.01 R05 exp234]]|-2.07|
|[[:results:exp239|PFI-2 4μM R05 exp239]]|-2.04|
|[[:results:exp227|Cryptotanshinone 12μM R05 exp227]]|-1.97|
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|-1.97|
|[[:results:exp473|Cincreasin 100μM R08 exp473]]|-1.9|
|[[:results:exp449|Arsenic trioxide 60μM R08 exp449]]|-1.88|
|[[:results:exp243|S-trityl-L-cysteine 0.5μM R05 exp243]]|-1.83|
|[[:results:exp241|QNZ 0.01μM R05 exp241]]|-1.77|
</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: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 18777
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.36 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='TBK1 Expression in NALM6 Cells: 5.36'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>