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Aliases for TBK1 Gene

Aliases for TBK1 Gene

  • TANK-Binding Kinase 1 2 3 4
  • NAK 3 4 6
  • NF-Kappa-B-Activating Kinase 3 4
  • T2K 3 4
  • Serine/Threonine-Protein Kinase TBK1 3
  • NF-KB-Activating Kinase 3
  • EC 2.7.11.1 4
  • EC 2.7.11 63

External Ids for TBK1 Gene

Previous GeneCards Identifiers for TBK1 Gene

  • GC00U990677
  • GC13U900006
  • GC12P064562
  • GC12P063132
  • GC12P064845
  • GC12P061898

Summaries for TBK1 Gene

Entrez Gene Summary for TBK1 Gene

  • 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]

GeneCards Summary for TBK1 Gene

TBK1 (TANK-Binding Kinase 1) is a Protein Coding gene. Diseases associated with TBK1 include borna disease and herpes simplex encephalitis. Among its related pathways are Ras signaling pathway and Epstein-Barr virus infection. GO annotations related to this gene include identical protein binding and nucleic acid binding. An important paralog of this gene is CHUK.

UniProtKB/Swiss-Prot for TBK1 Gene

  • 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.

Gene Wiki entry for TBK1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TBK1 Gene

Genomics for TBK1 Gene

Regulatory Elements for TBK1 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for TBK1 Gene

Start:
64,451,880 bp from pter
End:
64,502,119 bp from pter
Size:
50,240 bases
Orientation:
Plus strand

Genomic View for TBK1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for TBK1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TBK1 Gene

Proteins for TBK1 Gene

  • Protein details for TBK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UHD2-TBK1_HUMAN
    Recommended name:
    Serine/threonine-protein kinase TBK1
    Protein Accession:
    Q9UHD2
    Secondary Accessions:
    • A8K4S4
    • Q8IYV3
    • Q9NUJ5

    Protein attributes for TBK1 Gene

    Size:
    729 amino acids
    Molecular mass:
    83642 Da
    Quaternary structure:
    • Homodimer. Interacts with DDX3X, TIRAP and TRAF2. Part of a ternary complex consisting of TANK, TRAF2 and TBK1. Interacts with AZI2, TANK and TBKBP1; these interactions are mutually exclusive and mediate TBK1 activation. Interacts with GSK3B; this interaction promotes TBK1 self-association and autophosphorylation. Interacts with SIKE1; SIKE1 is associated with TBK1 under physiological condition and dissociated from TBK1 upon viral infection or TLR3 stimulation. Interacts with TICAM1/TRIF, IRF3 and DDX58/RIG-I. Interacts with CYLD. Interacts with OPTN and TRAF3. Interacts with SRC. Interacts with the exocyst complex subunit SEC5/EXOC2; this interaction is sufficient to trigger TBK1 activity. Interacts with TMEM173/MITA. Interacts with IFIT3 (via N-terminus). Interacts with MAVS only in the presence of IFIT3. Interacts with HCV NS3, Ebola virus VP35 and Borna disease virus protein P; these interactions lead to inhibition of cellular antiviral response by blocking necessary interactions between the TBK1 and its substrates IRF3 and IRF7.
    Miscellaneous:
    • In cancer cells, pathological TBK1 activation promotes oncogenic transformation by suppressing programmed cell death. Mechanistically, the RALB-SEC5/EXOC2-TBK1 signaling cascade seems to participate in both innate immune signaling and cell transformation. Additionally, TBK1 supports oncogenesis by directly phosphorylating and activating AKT1 at the exocyst (PubMed:21042276).
    SequenceCaution:
    • Sequence=BAA92129.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TBK1 Gene

neXtProt entry for TBK1 Gene

Proteomics data for TBK1 Gene at MOPED

Selected DME Specific Peptides for TBK1 Gene

Post-translational modifications for TBK1 Gene

  • Autophosphorylation at Ser-172 activates the kinase, and is an essential step for virus-triggered signaling. Phosphorylated by IKBKB/IKKB at Ser-172. Phosphorylation requires homodimerization and ubiquitination at Lys-30 and Lys-401. Dephosphorylated at Ser-172 by PPM1B and this negatively regulates its role in mediating antiviral response.
  • Lys-63-linked polyubiquitination by MIB1 after RNA virus infection, or by NRDP1 after LPS stimulation at Lys-30 and Lys-401, participates in kinase activation. Lys-48-linked polyubiquitination at Lys-670 by DTX4 leads to proteasomal degradation. Lys-48-linked polyubiquitination by TRAIP also leads to proteasomal degradation.
  • Ubiquitination at Lys154 and Lys670
  • Modification sites at PhosphoSitePlus

Other Protein References for TBK1 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for TBK1 (TBK1)

Domains for TBK1 Gene

Gene Families for TBK1 Gene

Protein Domains for TBK1 Gene

Suggested Antigen Peptide Sequences for TBK1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9UHD2

UniProtKB/Swiss-Prot:

TBK1_HUMAN :
  • Q9UHD2
Domain:
  • Comprises A N-terminal kinase domain, a ubiquitin-like domain and a C-terminal coiled-coil region mediating homodimerization.
  • Contains 1 protein kinase domain.
  • Contains 1 ubiquitin-like domain.
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.
genes like me logo Genes that share domains with TBK1: view

Function for TBK1 Gene

Molecular function for TBK1 Gene

UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for TBK1 Gene

Gene Ontology (GO) - Molecular Function for TBK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0004672 protein kinase activity NAS 10581243
GO:0004674 protein serine/threonine kinase activity TAS 21042276
GO:0004713 protein tyrosine kinase activity --
GO:0005515 protein binding IPI 14743216
genes like me logo Genes that share ontologies with TBK1: view
genes like me logo Genes that share phenotypes with TBK1: view

Animal Models for TBK1 Gene

MGI Knock Outs for TBK1:

Animal Model Products

CRISPR Products

miRNA for TBK1 Gene

miRTarBase miRNAs that target TBK1

No data available for Transcription Factor Targeting and HOMER Transcription for TBK1 Gene

Localization for TBK1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TBK1 Gene

Cytoplasm. Note=Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TBK1 Gene COMPARTMENTS Subcellular localization image for TBK1 gene
Compartment Confidence
cytosol 4
endosome 4
nucleus 2
plasma membrane 2
cytoskeleton 1
endoplasmic reticulum 1
extracellular 1
mitochondrion 1
peroxisome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for TBK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 21813773
GO:0005829 cytosol TAS --
GO:0010008 endosome membrane TAS --
genes like me logo Genes that share ontologies with TBK1: view

Pathways for TBK1 Gene

genes like me logo Genes that share pathways with TBK1: view

PCR Array Products

Gene Ontology (GO) - Biological Process for TBK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002218 activation of innate immune response --
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS --
GO:0006468 protein phosphorylation IEA --
GO:0006954 inflammatory response TAS 21042276
genes like me logo Genes that share ontologies with TBK1: view

Compounds for TBK1 Gene

(2) HMDB Compounds for TBK1 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(6) Novoseek inferred chemical compound relationships for TBK1 Gene

Compound -log(P) Hits PubMed IDs
poly(i-c) 73.9 1
rantes 61.5 3
serine 39.7 9
inosine monophosphate 38.7 1
threonine 38.2 6
genes like me logo Genes that share compounds with TBK1: view

Transcripts for TBK1 Gene

mRNA/cDNA for TBK1 Gene

(6) Additional mRNA sequences :
(3) Selected AceView cDNA sequences:
(3) REFSEQ mRNAs :
(8) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for TBK1 Gene

TANK-binding kinase 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TBK1

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for TBK1 Gene

No ASD Table

Relevant External Links for TBK1 Gene

GeneLoc Exon Structure for
TBK1
ECgene alternative splicing isoforms for
TBK1

Expression for TBK1 Gene

mRNA expression in normal human tissues for TBK1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for TBK1 Gene

SOURCE GeneReport for Unigene cluster for TBK1 Gene Hs.505874

mRNA Expression by UniProt/SwissProt for TBK1 Gene

Q9UHD2-TBK1_HUMAN
Tissue specificity: Ubiquitous with higher expression in testis. Expressed in the ganglion cells, nerve fiber layer and microvasculature of the retina.
genes like me logo Genes that share expressions with TBK1: view

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for TBK1 Gene

Orthologs for TBK1 Gene

This gene was present in the common ancestor of animals.

Orthologs for TBK1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TBK1 35
  • 99.73 (n)
  • 99.59 (a)
TBK1 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia TBK1 35
  • 94.74 (n)
  • 97.12 (a)
TBK1 36
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TBK1 35
  • 94.6 (n)
  • 96.71 (a)
TBK1 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tbk1 35
  • 86.37 (n)
  • 94.1 (a)
Tbk1 16
Tbk1 36
  • 94 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TBK1 36
  • 91 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tbk1 35
  • 86.88 (n)
  • 94.51 (a)
chicken
(Gallus gallus)
Aves TBK1 35
  • 80.29 (n)
  • 86.56 (a)
TBK1 36
  • 86 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TBK1 36
  • 82 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.14920 35
tropical clawed frog
(Silurana tropicalis)
Amphibia tbk1 35
  • 71.31 (n)
  • 75.59 (a)
zebrafish
(Danio rerio)
Actinopterygii tbk1 35
  • 63.49 (n)
  • 71.59 (a)
tbk1 36
  • 72 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009565 35
  • 46.21 (n)
  • 41.32 (a)
fruit fly
(Drosophila melanogaster)
Insecta ik2 35
  • 47.99 (n)
  • 41.55 (a)
ik2 36
  • 37 (a)
OneToMany
ik2 37
  • 38 (a)
worm
(Caenorhabditis elegans)
Secernentea ikke-1 36
  • 14 (a)
ManyToMany
Y39G8B.5 36
  • 17 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 35 (a)
OneToMany
Species with no ortholog for TBK1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TBK1 Gene

ENSEMBL:
Gene Tree for TBK1 (if available)
TreeFam:
Gene Tree for TBK1 (if available)

Paralogs for TBK1 Gene

Paralogs for TBK1 Gene

Selected SIMAP similar genes for TBK1 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with TBK1: view

Variants for TBK1 Gene

Sequence variations from dbSNP and Humsavar for TBK1 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type MAF
rs14090 -- 64,501,773(-) ACAAA(C/T)GTGTC utr-variant-3-prime
rs4075093 -- 64,483,446(-) ATAAA(A/T)CTAGG intron-variant
rs4075094 -- 64,483,273(-) AAATG(A/T)ATATA intron-variant
rs6581568 -- 64,487,773(+) TTACA(A/G)TCTTT intron-variant
rs6581569 -- 64,492,779(+) gtgca(A/G)tggcg intron-variant

Structural Variations from Database of Genomic Variants (DGV) for TBK1 Gene

Variant ID Type Subtype PubMed ID
nsv832443 CNV Loss 17160897

Relevant External Links for TBK1 Gene

HapMap Linkage Disequilibrium report
TBK1
Human Gene Mutation Database (HGMD)
TBK1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TBK1 Gene

Disorders for TBK1 Gene

MalaCards: The human disease database

MalaCards: The human disease database. (3) Diseases for TBK1 Gene including...

Search for TBK1 Gene in MalaCards »

UniProtKB/Swiss-Prot

TBK1_HUMAN
  • 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:0000269 PubMed:21447600, ECO:0000269 PubMed: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:0000269 PubMed:21447600}.

(5) Novoseek inferred disease relationships for TBK1 Gene

Disease -log(P) Hits PubMed IDs
virus infection 55.8 8
vesicular stomatitis 46.8 2
necrosis 16.7 3
immunodeficiency 16.6 5
tumors 0 4

Relevant External Links for TBK1

Genetic Association Database (GAD)
TBK1
Human Genome Epidemiology (HuGE) Navigator
TBK1
genes like me logo Genes that share disorders with TBK1: view

Publications for TBK1 Gene

  1. NF-kB activation by a signaling complex containing TRAF2, TANK, and TBK1, a novel IKK-related kinase. (PMID: 10581243) Pomerantz J.L. … Baltimore D. (EMBO J. 1999) 2 3 4 23
  2. NAK is an IkappaB kinase-activating kinase. (PMID: 10783893) Tojima Y. … Nakanishi M. (Nature 2000) 2 3 4 23
  3. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. (PMID: 12692549) Fitzgerald K.A. … Maniatis T. (Nat. Immunol. 2003) 3 4 23
  4. Triggering the interferon antiviral response through an IKK-related pathway. (PMID: 12702806) Sharma S. … Hiscott J. (Science 2003) 3 4 23
  5. Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling. (PMID: 14530355) Sato S. … Akira S. (J. Immunol. 2003) 3 4 23

Products for TBK1 Gene

  • Addgene plasmids for TBK1

Sources for TBK1 Gene

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