Version 5.4
Mus musculus Gene: Tbk1
Summary
InnateDB Gene IDBG-192882.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Tbk1
Gene Name TANK-binding kinase 1
Synonyms 1200008B05Rik; AI462036; AW048562
Species Mus musculus
Ensembl Gene ENSMUSG00000020115
Encoded Proteins
IDBP-192884
TANK-binding kinase 1
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
PMID 21820332
Tbk1 is involved in the innate immune recognition of Plasmodium falciparum AT-rich DNA and in the subsequent induction of type I IFNs. Mice lacking Tbk1 are resistant to otherwise lethal cerebral malaria.
PMID 22921120
Tbk1 is a key regulator of immunological autophagy and is responsible for autophagosome maturation into bactericidal organelles.
PMID 26363053
Ppp4c, a serine/threonine phosphatase, directly binds to Tbk1 upon virus infection to dephosphorylate Tbk1 and inhibit Tbk1 activation, and subsequently restrain Irf3 activation, resulting in suppressed production of type I IFN and IFN-stimulated genes.
InnateDB Annotation from Orthologs
Summary
PMID 18977754
[Homo sapiens] TBK1 alternative splicing negatively regulates virus-triggered IFN-beta signalling pathway by disrupting DDX58 and MAVS, and inhibiting IFN-beta signalling pathways.
PMID 16286919
[Homo sapiens] TBK1 and IKBKE (IKKi) kinases are required for innate immune activation by B-DNA, which may be important in antiviral innate immunity and other DNA-associated immune disorders.
PMID 12692549
[Homo sapiens] TBK1 and IKBKE have a pivotal role in coordinating the activation of IRF3 and NF-kappaB in the innate immune response.
PMID 21820332
[Homo sapiens] TBK1 is involved in the innate immune recognition of Plasmodium falciparum AT-rich DNA and in the subsequent induction of type I IFNs. Mice lacking Tbk1 are resistant to otherwise lethal cerebral malaria. (Demonstrated in mouse)
PMID 22921120
[Homo sapiens] TBK1 is a key regulator of immunological autophagy and is responsible for autophagosome maturation into bactericidal organelles. (Demonstrated in mouse)
PMID 23986588
[Homo sapiens] Herpes simplex virus 1 protein, UL36 ubiquitin-specific protease (UL36USP), deubiquitinates TRAF3 and inhibits recruitment of TBK1 and counteracts the IFNB pathway
PMID 25070846
[Homo sapiens] USP2 deubiquitinates K63-linked polyubiquitin chains from TBK1 to terminate TBK1 activation and negatively regulate IFNB1 signalling and antiviral immune response.
PMID 26082489
[Homo sapiens] Endotoxin tolerance re-programs TLR4 signalling via suppression of PELI1, a positive regulator of MyD88- and TIR domain-containing adapter inducing IFN-β (TRIF)-dependent signalling that promotes K63-linked polyubiquitination of IRAK1, TBK1, and TAK1.
PMID 25855743
[Homo sapiens] HIV-1 accessory proteins Vpr and Vif bind to TBK1, inhibit its autophosphorylation, and prevent induction of type I and III interferon in myeloid cells.
PMID 26199418
[Homo sapiens] Viral interferon regulatory factor 1 (vIRF1), targets TMEM173 by preventing it from interacting with TBK1, thereby inhibiting TMEM173's phosphorylation and concomitant activation, resulting in an inhibition of the DNA sensing pathway.
Entrez Gene
Summary This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000183735:
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]
Gene Information
Type Protein coding
Genomic Location Chromosome 10:121546455-121586794
Strand Reverse strand
Band D2
Transcripts
ENSMUST00000020316 ENSMUSP00000020316
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 56 experimentally validated interaction(s) in this database.
They are also associated with 132 interaction(s) predicted by orthology.
Experimentally validated
Total 56 [view]
Protein-Protein 56 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 132 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003676 nucleic acid binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0051219 phosphoprotein binding
Biological Process
GO:0002218 activation of innate immune response
GO:0006468 protein phosphorylation
GO:0010629 negative regulation of gene expression
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0044565 dendritic cell proliferation
GO:0045087 innate immune response (InnateDB)
GO:0045359 positive regulation of interferon-beta biosynthetic process
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0050830 defense response to Gram-positive bacterium
GO:0051607 defense response to virus
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
Orthologs
Species
Homo sapiens
Bos taurus
Gene ID
Gene Order
ENSG00000183735
View Gene Order
ENSBTAG00000017401
Not yet available
Pathways
NETPATH
REACTOME
REACT_263316
Toll Like Receptor 3 (TLR3) Cascade pathway
REACT_239142
Innate Immune System pathway
REACT_198980
IRF3 mediated activation of type 1 IFN pathway
REACT_198532
Negative regulators of RIG-I/MDA5 signaling pathway
REACT_227400
STAT6-mediated induction of chemokines pathway
REACT_215863
ZBP1(DAI) mediated induction of type I IFNs pathway
REACT_230745
Immune System pathway
REACT_198521
TRAF6 mediated IRF7 activation pathway
REACT_196447
IRF3-mediated induction of type I IFN pathway
REACT_251547
Toll-Like Receptors Cascades pathway
REACT_218897
Cytosolic sensors of pathogen-associated DNA pathway
REACT_196457
STING mediated induction of host immune responses pathway
REACT_196519
Regulation of innate immune responses to cytosolic DNA pathway
REACT_262462
Activated TLR4 signalling pathway
REACT_241786
MyD88-independent cascade pathway
REACT_219118
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
REACT_238546
TRIF-mediated TLR3/TLR4 signaling pathway
REACT_231481
TRAF3-dependent IRF activation pathway pathway
REACT_225463
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
REACT_246719
Toll Like Receptor 4 (TLR4) Cascade pathway
KEGG
mmu04620
Toll-like receptor signaling pathway pathway
mmu04622
RIG-I-like receptor signaling pathway pathway
mmu04623
Cytosolic DNA-sensing pathway pathway
mmu05160
Hepatitis C pathway
INOH
PID NCI
Pathway Predictions based on Human Orthology Data
NETPATH
NetPath_9
TNFalpha pathway
REACTOME
REACT_118811
IRF3 mediated activation of type 1 IFN pathway
REACT_118764
ZBP1(DAI) mediated induction of type I IFNs pathway
REACT_147841
STING mediated induction of host immune responses pathway
REACT_24938
TRAF6 mediated IRF7 activation pathway
REACT_25271
Negative regulators of RIG-I/MDA5 signaling pathway
REACT_25026
TRAF3-dependent IRF activation pathway pathway
REACT_25359
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
REACT_25148
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
REACT_6809
MyD88-independent cascade pathway
REACT_6783
Toll Like Receptor 3 (TLR3) Cascade pathway
REACT_6894
Toll Like Receptor 4 (TLR4) Cascade pathway
REACT_163993
IRF3-mediated induction of type I IFN pathway
REACT_6802
Innate Immune System pathway
REACT_6966
Toll-Like Receptors Cascades pathway
REACT_163977
Regulation of innate immune responses to cytosolic DNA pathway
REACT_6900
Immune System pathway
REACT_6890
Activated TLR4 signalling pathway
REACT_25281
TRIF-mediated TLR3/TLR4 signaling pathway
REACT_118823
Cytosolic sensors of pathogen-associated DNA pathway
REACT_163734
STAT6-mediated induction of chemokines pathway
KEGG
hsa04620
Toll-like receptor signaling pathway pathway
hsa04622
RIG-I-like receptor signaling pathway pathway
hsa04623
Cytosolic DNA-sensing pathway pathway
hsa05160
Hepatitis C pathway
INOH
PID NCI
Cross-References
SwissProt Q9WUN2
TrEMBL A1L361 Q3THP3
UniProt Splice Variant
Entrez Gene 56480
UniGene Mm.34580
RefSeq NM_019786
OMIM
CCDS CCDS24212
HPRD
IMGT
MGI ID MGI:1929658
MGI Symbol Tbk1
EMBL AF145705 AF191839 AK004269 AK004649 AK168193 BC129910 BC129911 CH466578
GenPept AAD34590 AAF05990 AAI29911 AAI29912 BAB23244 BAB23440 BAE40153 EDL24420
RNA Seq Atlas 56480

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca