Browse TBK1

Summary
SymbolTBK1
NameTANK-binding kinase 1
Aliases NAK; T2K; NF-kB-activating kinase; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1
Chromosomal Location12q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Note=Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2.
Domain PF00069 Protein kinase domain
Function

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).

> Gene Ontology
 
Biological Process GO:0001818 negative regulation of cytokine production
GO:0001819 positive regulation of cytokine production
GO:0002218 activation of innate immune response
GO:0002221 pattern recognition receptor signaling pathway
GO:0002224 toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0002757 immune response-activating signal transduction
GO:0002758 innate immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002831 regulation of response to biotic stimulus
GO:0002833 positive regulation of response to biotic stimulus
GO:0006914 autophagy
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0009615 response to virus
GO:0010506 regulation of autophagy
GO:0010508 positive regulation of autophagy
GO:0016236 macroautophagy
GO:0016239 positive regulation of macroautophagy
GO:0016241 regulation of macroautophagy
GO:0018105 peptidyl-serine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0031349 positive regulation of defense response
GO:0032103 positive regulation of response to external stimulus
GO:0032479 regulation of type I interferon production
GO:0032480 negative regulation of type I interferon production
GO:0032481 positive regulation of type I interferon production
GO:0032606 type I interferon production
GO:0032607 interferon-alpha production
GO:0032608 interferon-beta production
GO:0032647 regulation of interferon-alpha production
GO:0032648 regulation of interferon-beta production
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0032943 mononuclear cell proliferation
GO:0033135 regulation of peptidyl-serine phosphorylation
GO:0033138 positive regulation of peptidyl-serine phosphorylation
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0042035 regulation of cytokine biosynthetic process
GO:0042089 cytokine biosynthetic process
GO:0042107 cytokine metabolic process
GO:0042108 positive regulation of cytokine biosynthetic process
GO:0042742 defense response to bacterium
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043900 regulation of multi-organism process
GO:0043902 positive regulation of multi-organism process
GO:0044565 dendritic cell proliferation
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045350 interferon-beta biosynthetic process
GO:0045351 type I interferon biosynthetic process
GO:0045357 regulation of interferon-beta biosynthetic process
GO:0045359 positive regulation of interferon-beta biosynthetic process
GO:0046651 lymphocyte proliferation
GO:0050830 defense response to Gram-positive bacterium
GO:0051607 defense response to virus
GO:0070661 leukocyte proliferation
GO:0070997 neuron death
GO:0098542 defense response to other organism
GO:0098792 xenophagy
GO:1901214 regulation of neuron death
GO:1904415 regulation of xenophagy
GO:1904417 positive regulation of xenophagy
Molecular Function GO:0004674 protein serine/threonine kinase activity
GO:0051219 phosphoprotein binding
Cellular Component GO:0010008 endosome membrane
GO:0044440 endosomal part
> KEGG and Reactome Pathway
 
KEGG hsa04014 Ras signaling pathway
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04623 Cytosolic DNA-sensing pathway
Reactome R-HSA-166054: Activated TLR4 signalling
R-HSA-936964: Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-HSA-1834949: Cytosolic sensors of pathogen-associated DNA
R-HSA-1606341: IRF3 mediated activation of type 1 IFN
R-HSA-3270619: IRF3-mediated induction of type I IFN
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-166166: MyD88-independent TLR3/TLR4 cascade
R-HSA-936440: Negative regulators of RIG-I/MDA5 signaling
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-3134975: Regulation of innate immune responses to cytosolic DNA
R-HSA-3249367: STAT6-mediated induction of chemokines
R-HSA-1834941: STING mediated induction of host immune responses
R-HSA-918233: TRAF3-dependent IRF activation pathway
R-HSA-933541: TRAF6 mediated IRF7 activation
R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling
R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168898: Toll-Like Receptors Cascades
R-HSA-1606322: ZBP1(DAI) mediated induction of type I IFNs
Summary
SymbolTBK1
NameTANK-binding kinase 1
Aliases NAK; T2K; NF-kB-activating kinase; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1
Chromosomal Location12q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TBK1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between TBK1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28356390MelanomaInhibit immunityDC-specific deletion of Tbk1 causes T cell activation and autoimmune symptoms and also enhances antitumor immunity in animal models of cancer immunotherapy. The TBK1-deficient DCs have up-regulated expression of co-stimulatory molecules and increased T cell-priming activity.
24449872Breast CarcinomaInhibit immunity; Resistant to immunotherapyHere, we report that an important innate immune response kinase, the IκB kinase-related TANK-binding kinase 1 (TBK1), is a crucial determinant of resistance to tamoxifen therapies. We show that TBK1 increases ERα transcriptional activity through phosphorylation modification of ERα at the Ser-305 site. Notably, patients with tumors highly expressing TBK1 respond poorly to tamoxifen treatment and show high potential for relapse.
29721392Hepatocellular CarcinomaResistant to immunotherapyInhibitor for TBK1 but not NF-κB suppressed poly (I:C)-inspired migration and invasion, which was further supported by using TBK1 deficient (Tbk1-/- ) cells. Our data suggest that bufalin can suppress the metastasis of HCC cells in poly (I:C) therapy by impairing TBK1 activation, indicating that bufalin may be used in combination with poly (I:C) therapy in HCC treatment for the sake of reversing poly (I:C)-triggered metastasis of HCC cells.
Summary
SymbolTBK1
NameTANK-binding kinase 1
Aliases NAK; T2K; NF-kB-activating kinase; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1
Chromosomal Location12q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of TBK1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: -2.58; FDR: 0.04630 Resistant to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 STARS Score: 6.07; FDR: 0.000 Resistant to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX STARS Score: 4.35; FDR: 0.013 Resistant to T cell-mediated killing
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolTBK1
NameTANK-binding kinase 1
Aliases NAK; T2K; NF-kB-activating kinase; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1
Chromosomal Location12q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of TBK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0850.74
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1630.922
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2620.823
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.0770.84
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1850.916
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.0560.979
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0810.816
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.1220.939
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0730.966
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.3860.72
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.5940.727
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.1140.0907
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TBK1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86016.7-16.70.429
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.305.30.507
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolTBK1
NameTANK-binding kinase 1
Aliases NAK; T2K; NF-kB-activating kinase; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1
Chromosomal Location12q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TBK1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolTBK1
NameTANK-binding kinase 1
Aliases NAK; T2K; NF-kB-activating kinase; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1
Chromosomal Location12q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TBK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TBK1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTBK1
NameTANK-binding kinase 1
Aliases NAK; T2K; NF-kB-activating kinase; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1
Chromosomal Location12q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TBK1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTBK1
NameTANK-binding kinase 1
Aliases NAK; T2K; NF-kB-activating kinase; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1
Chromosomal Location12q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TBK1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTBK1
NameTANK-binding kinase 1
Aliases NAK; T2K; NF-kB-activating kinase; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1
Chromosomal Location12q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TBK1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTBK1
NameTANK-binding kinase 1
Aliases NAK; T2K; NF-kB-activating kinase; NF-kappa-B-activating kinase; Serine/threonine-protein kinase TBK1
Chromosomal Location12q14.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TBK1 collected from DrugBank database.
> Drugs from DrugBank database
 

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