Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007405
UniProt IDQ9UHD2
Primary gene name(s)TBK1
Synonym gene name(s)NAK
Protein nameSerine/threonine-protein kinase TBK1
Protein functionSerine/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:0000269|PubMed:10581243, ECO:0000269|PubMed:10783893, ECO:0000269|PubMed:11839743, ECO:0000269|PubMed:12692549, ECO:0000269|PubMed:12702806, ECO:0000269|PubMed:14703513, ECO:0000269|PubMed:15367631, ECO:0000269|PubMed:15485837, ECO:0000269|PubMed:15489227, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21270402, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:21931631, ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:23453972, ECO:0000269|PubMed:23746807}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:15485837, ECO:0000269|PubMed:21813773}. Note=Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9UHD2
Gene Ontology
(Biological Process)
Complete annatation
defense response to Gram-positive bacterium [GO:0050830];
defense response to virus [GO:0051607];
dendritic cell proliferation [GO:0044565];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
inflammatory response [GO:0006954];
innate immune response [GO:0045087];
negative regulation of gene expression [GO:0010629];
negative regulation of type I interferon production [GO:0032480];
peptidyl-serine phosphorylation [GO:0018105];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of interferon-alpha production [GO:0032727];
positive regulation of interferon-beta biosynthetic process [GO:0045359];
positive regulation of interferon-beta production [GO:0032728];
positive regulation of peptidyl-serine phosphorylation [GO:0033138];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of type I interferon production [GO:0032481];
positive regulation of xenophagy [GO:1904417];
regulation of neuron death [GO:1901214];
response to virus [GO:0009615];
TRIF-dependent toll-like receptor signaling pathway [GO:0035666];
type I interferon production [GO:0032606]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
nucleic acid binding [GO:0003676];
phosphoprotein binding [GO:0051219];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endosome membrane [GO:0010008]
Protein-protein interaction118878
Phylogenetic treeQ9UHD2
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.2521453298850.5035160466054170.62026921572839
AZA vs. DISU0.6112603914028660.01613416529956250.307467013559551
AZA vs. IL70.08327404916177780.6660243770671510.999311006273513
AZA vs. SAHA-0.1367847654787590.5758975618467420.859561599164171
DISU vs. CD30.3454134763370220.3700624560205660.50414111722133
DISU vs. IL7-0.5367697147207180.03368791988170640.239323936011651
DISU vs. SAHA-0.7468083922334650.01084553530699260.109155471956195
DMSO vs. AZA-0.09519100597479230.5721832888906321
DMSO vs. CD3-0.3580208206486210.3418671829133880.455933880186808
DMSO vs. DISU-0.7080921823191620.003896530589705630.13460446509991
DMSO vs. IL70.1854894718629040.3043445881981240.7882514137706
DMSO vs. SAHA-0.04895543827004590.835887211856870.955395312907465
HIV vs. Mock in Activation-0.1230508776232920.8876680258170360.999983755607037
HIV vs. Mock in Latency0.1275626795587320.4415790067152220.999834320637052
IL7 vs. CD3-0.1601926372855270.6762854073518580.778833046931685
SAHA vs. CD3-0.4139176365508270.2730716333045030.385281295187609
SAHA vs. IL7-0.2239837525419710.3587567324172110.609340730643047
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.224585 0.12079
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.952 1.017 1.143 1.15 1.078
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
4EFO X-ray 1.7Å A/B=302-383.
4EUT X-ray 2.6Å A/B=2-385.
4EUU X-ray 1.8Å A/B=2-308.
4IM0 X-ray 2.4Å A=1-657.
4IM2 X-ray 2.5Å A=1-657.
4IM3 X-ray 3.3Å A=1-657.
4IW0 X-ray 4.0Å A=2-657.
4IWO X-ray 2.6Å A=2-657.
4IWP X-ray 3.0Å A=2-657.
4IWQ X-ray 3.0Å A=2-657.
5EOA X-ray 2.5Å C/D=677-729.
5EOF X-ray 2.0Å C/D=677-729.
5EP6 X-ray 1.4Å B/D=677-729.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Vpr interacts with 25855743
Vif interacts with 25855743

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)
hsa04623 Cytosolic DNA-sensing pathway - Homo sapiens (human)
hsa04657 IL-17 signaling pathway - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)