Tchem TBK1 Serine/threonine-protein kinase TBK1

Protein Summary

Description

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). Plays an essential role in the TLR3- and IFN-dependent control of herpes virus HSV-1 and HSV-2 infections in the central nervous system (PubMed:22851595). 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]

Uniprot Accession IDs

• Q9UHD2
• A8K4S4
• Q8IYV3
• Q9NUJ5

Gene Name

• TBK1

Ensembl ID

• ENST00000331710
• ENSP00000329967
• ENSG00000183735

Symbol

• NAK
• NAK
• T2K
• IIAE8
• FTDALS4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
disease perturbation	0.99
biological process	0.95
molecular function	0.94
histone modification site profile	0.89

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Serine/threonine-protein Kinase Tbk1

DTO Classes

Protein / Kinase / Protein Kinase / Other Group / Ikk Family / Serine/threonine-protein Kinase Tbk1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 762.15   (req: < 5)

Gene RIFs: 244   (req: <= 3)

Antibodies: 571   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 762.15   (req: >= 5)

Gene RIFs: 244   (req: > 3)

Antibodies: 571   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 34

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 118

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2