InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TBK1

Summary

InnateDB Protein

IDBP-44995.5

Last Modified

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

Gene Symbol

TBK1

Protein Name

TANK-binding kinase 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000329967

InnateDB Gene

IDBG-44993 (TBK1)

Protein Structure

UniProt Annotation

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. Phosphorylates and activates AKT1. 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. Phosphorylates Borna disease virus (BDV) P protein. {ECO:0000269PubMed:10581243, ECO:0000269PubMed:10783893, ECO:0000269PubMed:11839743, ECO:0000269PubMed:12692549, ECO:0000269PubMed:12702806, ECO:0000269PubMed:14703513, ECO:0000269PubMed:15367631, ECO:0000269PubMed:15485837, ECO:0000269PubMed:15489227, ECO:0000269PubMed:18583960, ECO:0000269PubMed:21138416, ECO:0000269PubMed:21270402, ECO:0000269PubMed:21464307, ECO:0000269PubMed:21617041, ECO:0000269PubMed:21931631, ECO:0000269PubMed:23453971, ECO:0000269PubMed:23453972, ECO:0000269PubMed:23746807}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:15485837, ECO:0000269PubMed:21813773}. Note=Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2.

Disease Associations

Glaucoma 1, open angle, P (GLC1P) [MIM:177700]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. GLC1P is characterized by early onset, thin central corneas and low intraocular pressure. {ECO:0000269PubMed:21447600, ECO:0000269PubMed:22306015}. Note=The disease may be caused by mutations affecting the gene represented in this entry. A copy number variation on chromosome 12q14 consisting of a 300 kb duplication that includes TBK1, XPOT, RASSF3 and GNS has been found in individuals affected by glaucoma. TBK1 is the most likely candidate for the disorder (PubMed:21447600). {ECO:0000269PubMed:21447600}.

Tissue Specificity

Ubiquitous with higher expression in testis. Expressed in the ganglion cells, nerve fiber layer and microvasculature of the retina. {ECO:0000269PubMed:10783893, ECO:0000269PubMed:21447600}.

Comments

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

Cellular Component

GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0010008	endosome membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR029071 Ubiquitin-related domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt