InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: TBK1

Summary

InnateDB Gene

IDBG-44993.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TBK1

Gene Name

TANK-binding kinase 1

Synonyms

Species

Homo sapiens

Ensembl Gene

ENSG00000183735

Encoded Proteins

IDBP-44995

TANK-binding kinase 1

IDBP-588310

TANK-binding kinase 1

IDBP-594932

TANK-binding kinase 1

IDBP-587331

TANK-binding kinase 1

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 18977754

TBK1 alternative splicing negatively regulates virus-triggered IFN-beta signalling pathway by disrupting DDX58 and MAVS, and inhibiting IFN-beta signalling pathways.

PMID 16286919

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

TBK1 and IKBKE have a pivotal role in coordinating the activation of IRF3 and NF-kappaB in the innate immune response.

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. (Demonstrated in mouse)

PMID 22921120

TBK1 is a key regulator of immunological autophagy and is responsible for autophagosome maturation into bactericidal organelles. (Demonstrated in mouse)

PMID 23986588

Herpes simplex virus 1 protein, UL36 ubiquitin-specific protease (UL36USP), deubiquitinates TRAF3 and inhibits recruitment of TBK1 and counteracts the IFNB pathway

PMID 25070846

USP2 deubiquitinates K63-linked polyubiquitin chains from TBK1 to terminate TBK1 activation and negatively regulate IFNB1 signalling and antiviral immune response.

PMID 26082489

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

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

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.

InnateDB Annotation from Orthologs

Summary

PMID 21820332

[Mus musculus] 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

[Mus musculus] Tbk1 is a key regulator of immunological autophagy and is responsible for autophagosome maturation into bactericidal organelles.

PMID 26363053

[Mus musculus] 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.

Entrez Gene

Summary

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 12:64451880-64502108

Strand

Forward strand

Band

q14.2

Transcripts

ENST00000331710	ENSP00000329967
ENST00000538890	ENSP00000445834
ENST00000540417	ENSP00000445628
ENST00000539810	ENSP00000444428
ENST00000545025
ENST00000536906
ENST00000541805
ENST00000545392

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 195 experimentally validated interaction(s) in this database.
They are also associated with 27 interaction(s) predicted by orthology.

Experimentally validated
Total	195 [view]
Protein-Protein	195 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	27 [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:0002224	toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006468	protein phosphorylation
GO:0006954	inflammatory response
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0009615	response to virus
GO:0010629	negative regulation of gene expression
GO:0016032	viral process
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:0032727	positive regulation of interferon-alpha production
GO:0032728	positive regulation of interferon-beta production
GO:0033138	positive regulation of peptidyl-serine phosphorylation
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
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