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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
a) hepatitis C virus (HCV) NS3 binding
b) Borna disease virus (BDV) P protein binding
General
serine/threonine kinase
Properties
SIZE: entity length = 729 aa
MW = 84 kD
COMPARTMENT: cytoplasm
STATE: active state
MOTIF: kinase domain
SITE: 9-310
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 15-23
ATP-binding site
NAME: ATP-binding site
SITE: 38-38
aspartate residue {D135}
Ser phosphorylation site {S172}
coiled coil {626-713}
Ser phosphorylation site {S716}
Database Correlations
OMIM 604834
UniProt Q9UHD2
Pfam PF00069
Entrez Gene 29110
Kegg hsa:29110
ENZYME 2.7.11.1
References
- Tojima Y, Fujimoto A, Delhase M, Chen Y, Hatakeyama S,
Nakayama K, Kaneko Y, Nimura Y, Motoyama N, Ikeda K, Karin M,
Nakanishi M.
NAK is an IkappaB kinase-activating kinase.
Nature. 2000 Apr 13;404(6779):778-82.
PMID: 10783893
- Pomerantz JL, Baltimore D.
NF-kappaB activation by a signaling complex containing TRAF2,
TANK and TBK1, a novel IKK-related kinase.
EMBO J. 1999 Dec 1;18(23):6694-704.
PMID: 10581243
- UniProt :accession Q9UHD2