serine/threonine protein kinase TBK1; TANK-binding kinase 1; T2K; NF-kappa-B-activating kinase (TBK1, NAK)

Function

• serine/threonine protein
• activated by phorbol esters & growth factors
• role in signaling cascade converging to the activation of the transcription factor NF-kappa-B
• may function as an IKK kinase, playing an essential role in transcription of a subset of TNF-alpha induced genes
• can phosphorylate IkB-alpha on Ser 32
• also mediates production of RANTES/CCL5 & IFN-beta/IFNB1
• role in the innate immune response
• phosphorylates Borna disease virus (BDV) P protein
• phosphorylates & activates IRF3 & IRF7 & allows their nuclear localization; this leads to production of IFN alpha/betas & the development of a cellular antiviral state
• role induction of the antiviral interferon response (putative)
• catalytically inactive TBK1 inhibits activation of NF kappa B by protein kinase C-epsilon but not PKC-alpha or PKC-delta
• interacts with TIRAP, TANK & TRAF2
• part of a ternary complex consisting of TANK, TRAF2 & TBK1
• interacts with AZI2
• interacts with SIKE
• interacts with TICAM1/TRIF, IRF3 & DDX58/RIG-I; interactions are disrupted by the interaction between TBK1 & SIKE

Structure

• belongs to the protein kinase superfamily, Ser/Thr protein kinase family, I-kappa-B kinase subfamily
• contains 1 protein kinase domain

Compartment

cytoplasm

Expression

ubiquitous with higher expression in testis

Pathology

• inhibition of its interaction with IRF3, due to binding of viral proteins may inhibit the innate immune response
  • hepatitis C virus (HCV) NS3 binding
  • Borna disease virus (BDV) P protein binding

More general terms

• serine/threonine kinase

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=29110
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:29110
• OMIM: https://mirror.omim.org/entry/604834
• UniProt: http://www.uniprot.org/uniprot/Q9UHD2.html