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TBK1 Gene

protein-coding   GIFtS: 68
GCID: GC12P064845

TANK-Binding Kinase 1

Microbiology & Infectious Diseases Congress
  See related diseases
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
TANK-Binding Kinase 11 2 3     NF-KB-Activating Kinase2
NAK2 3 5     Serine/Threonine-Protein Kinase TBK12
T2K2 3     EC 2.7.11.13
NF-Kappa-B-Activating Kinase2 3     EC 2.7.118

External Ids:    HGNC: 115841   Entrez Gene: 291102   Ensembl: ENSG000001837357   OMIM: 6048345   UniProtKB: Q9UHD23   

Export aliases for TBK1 gene to outside databases

Previous GC identifers: GC00U990677 GC13U900006 GC12P064562 GC12P063132 GC12P061898


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 hantavirus pulmonary syndrome. GO annotations related to this gene include identical protein binding and nucleic acid binding. An important paralog of this gene is IKBKB.

UniProtKB/Swiss-Prot: TBK1_HUMAN, Q9UHD2
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

Gene Wiki entry for TBK1 (TANK-binding kinase 1) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000012.12  NT_029419.13  NC_018923.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the TBK1 gene promoter:
         AREB6   AP-1   ATF-2   c-Jun   Nkx2-5   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidTBK1 promoter sequence
   Search Chromatin IP Primers for TBK1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TBK1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12q14.1   Ensembl cytogenetic band:  12q14.2   HGNC cytogenetic band: 12q14.2

TBK1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TBK1 gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12P064845:  view genomic region     (about GC identifiers)

Start:
64,845,660 bp from pter      End:
64,895,899 bp from pter
Size:
50,240 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: TBK1_HUMAN, Q9UHD2 (See protein sequence)
Recommended Name: Serine/threonine-protein kinase TBK1  
Size: 729 amino acids; 83642 Da
Subunit: 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)
Sequence caution: Sequence=BAA92129.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Selected PDB 3D structures from and Proteopedia for TBK1 (see all 10):
4EFO (3D)        4EUT (3D)        4EUU (3D)        4IM0 (3D)        4IM2 (3D)        4IM3 (3D)    
Secondary accessions: A8K4S4 Q8IYV3 Q9NUJ5

Explore the universe of human proteins at neXtProt for TBK1: NX_Q9UHD2

Explore proteomics data for TBK1 at MOPED

Post-translational modifications: 

  • 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
    response1
  • '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 degradation1
  • Ubiquitination2 at Lys154, Lys670
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for TBK1 (Q9UHD2) (see all 5)
     GPRRNKE  HRDIKPGN  YNEEQIHK  YHAATGSLPF 


    See TBK1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_037386.1  
    ENSEMBL proteins: 
     ENSP00000329967   ENSP00000445834   ENSP00000445628   ENSP00000444428  
    Reactome Protein details: Q9UHD2

    TBK1 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant TBK1 Protein
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for TBK1
    OriGene Protein Over-expression Lysate for TBK1
    OriGene MassSpec for TBK1
    OriGene Custom Protein Services for TBK1
    GenScript Custom Purified and Recombinant Proteins Services for TBK1
    Novus Biologicals TBK1 Proteins
    Novus Biologicals TBK1 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for TBK1

    TBK1 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of TBK1
    Browse R&D Systems for Antibodies
    Cell Signaling Technology (CST) Antibodies for TBK1 
    OriGene Antibodies for TBK1
    OriGene Custom Antibody Services for TBK1
    Novus Biologicals TBK1 Antibodies
    Search for Antibodies for TBK1 at Abcam
    Cloud-Clone Corp. Antibodies for TBK1
    ThermoFisher Antibody for TBK1
    LSBio Antibodies in human, mouse, rat for TBK1

    TBK1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    GenScript Custom Assay Services for TBK1
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for TBK1
    Cloud-Clone Corp. CLIAs for TBK1


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: TANK-binding kinase 1
    IKK family

    3 InterPro protein domains:
     IPR017441 Protein_kinase_ATP_BS
     IPR011009 Kinase-like_dom
     IPR000719 Prot_kinase_dom

    Graphical View of Domain Structure for InterPro Entry Q9UHD2

    ProtoNet protein and cluster: Q9UHD2

    UniProtKB/Swiss-Prot: TBK1_HUMAN, Q9UHD2
    Domain: Comprises A N-terminal kinase domain, a ubiquitin-like domain and a C-terminal leucine-zipper
    Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily
    Similarity: Contains 1 protein kinase domain
    Similarity: Contains 1 ubiquitin-like domain


    TBK1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TBK1_HUMAN, Q9UHD2
    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
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein

         Enzyme Numbers (IUBMB): EC 2.7.112 EC 2.7.11.11

         Gene Ontology (GO): Selected molecular function terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003676nucleic acid binding IEA--
    GO:0004672protein kinase activity NAS10581243
    GO:0004674protein serine/threonine kinase activity TAS--
    GO:0004713protein tyrosine kinase activity ----
    GO:0005515protein binding IPI14743216
         
    TBK1 for ontologies           About GeneDecksing


    Phenotypes:
         5 GenomeRNAi human phenotypes for TBK1:
     Decreased Hepatitis C virus re  Decreased focal adhesion (FA)   Increased Salmonella enterica   Increased Salmonella enterica  
     Increased colony dispersion (i 

         9 MGI mutant phenotypes (inferred from 6 alleles(MGI details for Tbk1):
     cardiovascular system  hematopoietic system  homeostasis/metabolism  immune system  integument 
     liver/biliary system  mortality/aging  no phenotypic analysis  renal/urinary system 

    TBK1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for TBK1: Tbk1tm1Yeh Tbk1tm1.1Lex Tbk1tm1Aki

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TBK1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for TBK1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TBK1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TBK1

    miRNA
    Products:
        
    miRTarBase miRNAs that target TBK1:
    hsa-mir-200c-3p (MIRT006971), hsa-mir-221-3p (MIRT003360)

    Block miRNA regulation of human, mouse, rat TBK1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TBK1 (see all 18):
    hsa-miR-539 hsa-miR-429 hsa-miR-578 hsa-miR-373* hsa-miR-219-2-3p hsa-miR-200b hsa-miR-365 hsa-miR-203
    SwitchGear 3'UTR luciferase reporter plasmidTBK1 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for TBK1
    Predesigned siRNA for gene silencing in human, mouse, rat TBK1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for TBK1

    Clone
    Products:
         
    OriGene clones in human, mouse for TBK1 (see all 7)
    OriGene ORF clones in mouse, rat for TBK1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: TBK1 (NM_013254)
    Sino Biological Human cDNA Clone for TBK1
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TBK1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TBK1

    Cell Line
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    GenScript Custom overexpressing Cell Line Services for TBK1
    Browse ESI BIO Cell Lines and PureStem Progenitors for TBK1 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TBK1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TBK1_HUMAN, Q9UHD2: Cytoplasm. Note=Upon mitogen stimulation or triggering of the immune system, TBK1 is
    recruited to the exocyst by EXOC2
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    endosome4
    nucleus2
    plasma membrane2
    cytoskeleton1
    endoplasmic reticulum1
    extracellular1
    mitochondrion1
    peroxisome1
    vacuole1

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm IDA--
    GO:0005829cytosol TAS--
    GO:0010008endosome membrane TAS--

    TBK1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for TBK1 About   (see all 18)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Cytosolic sensors of pathogen-associated DNA
    ZBP1(DAI) mediated induction of type I IFNs0.81
    Regulation of innate immune responses to cytosolic DNA0.00
    Cytosolic sensors of pathogen-associated DNA0.38
    STING mediated induction of host immune responses0.00
    Cytosolic DNA-sensing pathway0.33
    STAT6-mediated induction of chemokines0.00
    IRF3 mediated activation of type 1 IFN0.00
    IRF3-mediated induction of type I IFN0.00
    2RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
    RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways0.47
    TRAF6 mediated IRF7 activation0.40
    RIG-I-like receptor signaling pathway0.47
    TRAF3-dependent IRF activation pathway0.00
    Negative regulators of RIG-I/MDA5 signaling0.42
    3Toll-like receptor signaling pathway
    Toll-like receptor signaling pathway0.94
    Regulation of toll-like receptor signaling pathway0.93
    Toll-like receptor signaling pathway0.94
    Hepatitis B0.31
    4Influenza A
    Influenza A0.34
    Herpes simplex infection0.33
    Measles0.34
    5Toll Like Receptor 7/8 (TLR7/8) Cascade
    MyD88-independent cascade0.69
    Toll Like Receptor 3 (TLR3) Cascade0.69

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for TBK1
        Toll-Like receptor Signaling Pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for TBK1
        Toll-Like Receptors Pathway
    TNFR2 Pathway

    3 Cell Signaling Technology (CST) Pathways for TBK1
        Lymphocyte Signaling
    TGF-beta/Smad Signaling
    NF-kappaB Signaling

    3 BioSystems Pathways for TBK1
        Toll-like receptor signaling pathway
    TNF-alpha/NF-kB Signaling Pathway
    Regulation of toll-like receptor signaling pathway

    2 Sino Biological Pathways for TBK1
        Notch Signaling Pathway
    NF-kB (NFkB) Pathway

    Selected Reactome Pathways for TBK1 (see all 8)
        TRAF3-dependent IRF activation pathway
    TRAF6 mediated IRF7 activation
    Regulation of innate immune responses to cytosolic DNA
    Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
    Negative regulators of RIG-I/MDA5 signaling


    Selected Kegg Pathways  (Kegg details for TBK1) (see all 10):
        Ras signaling pathway
    Toll-like receptor signaling pathway
    RIG-I-like receptor signaling pathway
    Cytosolic DNA-sensing pathway
    Hepatitis C


    TBK1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TBK1: 
              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              NFKB Signaling Pathway in human mouse rat
              Apoptosis 384HT in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for TBK1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for TBK1 (Q9UHD21, 2, 3 ENSP000003299674) via UniProtKB, MINT, STRING, and/or I2D (see all 162)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TANKQ928441, 2, 3, ENSP000002590754EBI-356402,EBI-356349 MINT-5114997 MINT-8144259 MINT-49268 MINT-49290 MINT-48040 MINT-6492446 MINT-8151323 MINT-48264 I2D: score=8 STRING: ENSP00000259075
    OPTNQ96CV91, 2, 3, ENSP000002630364EBI-356402,EBI-748974 MINT-6492491 MINT-6492320 MINT-6492337 MINT-6492467 MINT-6492519 MINT-6492427 MINT-6492303 MINT-6492355 I2D: score=4 STRING: ENSP00000263036
    TBKBP1A7MCY61, 2, 3, ENSP000003547774STRING: ENSP00000354777 EBI-356402,EBI-359969 MINT-5114931 MINT-5114886 MINT-49254 MINT-48041 MINT-5114907 MINT-5115080 I2D: score=6 
    IRF7Q929851, 2, 3, ENSP000003294114EBI-356402,EBI-968267 MINT-5208589 MINT-5208568 I2D: score=2 STRING: ENSP00000329411
    ENSG00000183311P074372, 3MINT-49276 I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 25):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002218activation of innate immune response ----
    GO:0002224toll-like receptor signaling pathway TAS--
    GO:0002756MyD88-independent toll-like receptor signaling pathway TAS--
    GO:0006468protein phosphorylation ----
    GO:0006954inflammatory response TAS--

    TBK1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
    About This Section

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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for TBK1

    2 HMDB Compounds for TBK1    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    6 Novoseek inferred chemical compound relationships for TBK1 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    poly(i-c) 73.9 1 16849320 (1)
    rantes 61.5 4 17599067 (1), 19656901 (1), 18282411 (1)
    serine 39.7 9 14679297 (1), 9621042 (1), 9418906 (1), 9792838 (1) (see all 9)
    inosine monophosphate 38.7 1 17157040 (1)
    threonine 38.2 6 9621042 (1), 9418906 (1), 9792838 (1), 11070003 (1) (see all 6)
    tyrosine 0 1 17056502 (1)



    TBK1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for TBK1 gene: 
    NM_013254.3  

    Unigene Cluster for TBK1:

    TANK-binding kinase 1
    Hs.505874  [show with all ESTs]
    Unigene Representative Sequence: NM_013254
    8 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000331710(uc001ssc.2) ENST00000538890 ENST00000540417 ENST00000539810
    ENST00000545025 ENST00000536906 ENST00000541805 ENST00000545392
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    Block miRNA regulation of human, mouse, rat TBK1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TBK1 (see all 18):
    hsa-miR-539 hsa-miR-429 hsa-miR-578 hsa-miR-373* hsa-miR-219-2-3p hsa-miR-200b hsa-miR-365 hsa-miR-203
    SwitchGear 3'UTR luciferase reporter plasmidTBK1 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat TBK1
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    Additional mRNA sequence: 

    AF174536.1 AF191838.1 AK002192.1 AK291039.1 AK303683.1 BC034950.2 

    6 DOTS entries:

    DT.215961  DT.100748957  DT.40280149  DT.75155342  DT.75175835  DT.95080140 

    3 AceView cDNA sequences:

    CB528778 BC009864 AI972136 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    TBK1 expression in normal human tissues (normalized intensities)      TBK1 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GAAAAAAATA
    TBK1 Expression
    About this image


    TBK1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Lung (Respiratory System)
             Stem Bronchi
     
     Kidney (Urinary System)
             Metanephros
     
     Neural Tube (Nervous System)
             Telencephalon
     
     Brain (Nervous System)
             Cerebral Cortex
    TBK1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TBK1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.505874

    UniProtKB/Swiss-Prot: TBK1_HUMAN, Q9UHD2
    Tissue specificity: Ubiquitous with higher expression in testis. Expressed in the ganglion cells, nerve fiber
    layer and microvasculature of the retina

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TBK1: 
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              Apoptosis 384HT in human mouse rat

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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for TBK1 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Tbk11 , 5 TANK-binding kinase 11, 5 86.37(n)1
    94.1(a)1
      10 (69.84 cM)5
    564801  NM_019786.41  NP_062760.31 
     1215464555 
    chicken
    (Gallus gallus)
    Aves TBK11 TANK-binding kinase 1 80.29(n)
    86.56(a)
      417825  NM_001199558.1  NP_001186487.1 
    lizard
    (Anolis carolinensis)
    Reptilia TBK16
    TANK-binding kinase 1
    82(a)
    1 ↔ 1
    5(50456954-50477532)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.149202 Xenopus laevis transcribed sequence with weak similarity more 75.57(n)    CD327798.1 
    zebrafish
    (Danio rerio)
    Actinopterygii tbk11 TANK-binding kinase 1 63.49(n)
    71.59(a)
      692289  NM_001044748.2  NP_001038213.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta ik21 , 3 defense response protein kinase3
    IkappaB kinase-like 21
    38(a)3
    47.99(n)1
    41.55(a)1
      38D43
    353291  NM_136204.31  NP_610048.21 
    worm
    (Caenorhabditis elegans)
    Secernentea Y39G8B.56
    ikke-16
    Protein IKKE-1, isoform c
    17(a)
    14(a)
    many ↔ many
    many ↔ many
    II(13987616-13991838) WBGene00012726
    III(9046011-9050693) WBGene00011299


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TBK1 gene
    IKBKB2  IKBKE2  CHUK2  
    8 SIMAP similar genes for TBK1 using alignment to 4 protein entries:     TBK1_HUMAN (see all proteins):
    IKBKE    MAP4K4    MYO3B    PRKACA    ULK3    AURKB
    MARK2    JAK2

    TBK1 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for TBK1 (see all 1006)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0412104
    A breast pleomorphic lobular carcinoma sample4--see VAR_0412102 D H mis40--------
    VAR_0412114
    A colorectal adenocarcinoma sample4--see VAR_0412112 G R mis40--------
    rs1902400741,2
    --64843862(+) ACATAA/CAGACT 1 -- us2k10--------
    rs1162822791,2
    F--64843891(+) ATGCTA/GTCTCA 1 -- us2k11Minor allele frequency- G:0.05WA 118
    rs2013051291,2
    C--64843929(+) TCACT-/AATACT 1 -- us2k10--------
    rs1821718721,2
    --64844080(+) GTGTGC/TACCAC 1 -- us2k10--------
    rs1129406811,2
    C--64844095(+) CCCAGT/CTACAT 1 -- us2k11Minor allele frequency- C:0.00CSA 1
    rs123134491,2
    C,F--64844129(+) TCACTA/GTGTTA 1 -- us2k18Minor allele frequency- G:0.42NA WA EA 252
    rs1880421731,2
    --64844294(+) CAGAAG/TATTTA 1 -- us2k10--------
    rs123676401,2
    C--64844712(+) GCTCAG/ATTAAT 1 -- us2k1 tfbs32Minor allele frequency- A:0.00NA 4

    HapMap Linkage Disequilibrium report for TBK1 (64845660 - 64895899 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for TBK1:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv832443CNV Loss17160897

    Human Gene Mutation Database (HGMD): TBK1
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing TBK1
    DNA2.0 Custom Variant and Variant Library Synthesis for TBK1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 604834    OMIM disorders: --

    UniProtKB/Swiss-Prot: TBK1_HUMAN, Q9UHD2
  • 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. 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)

  • Selected diseases for TBK1 (see all 36):    About MalaCards
    borna disease    hantavirus pulmonary syndrome    herpes simplex encephalitis 1    herpes simplex encephalitis
    stomatitis    primary open angle glaucoma    open-angle glaucoma    dengue hemorrhagic fever
    herpes simplex    cytomegalovirus infection    glaucoma    kawasaki disease
    hemorrhagic fever    encephalitis    measles    medulloblastoma
    kaposi's sarcoma    esophageal squamous cell carcinoma    hepatitis c virus    intellectual disability


    TBK1 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014

    5 Novoseek inferred disease relationships for TBK1 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    virus infection 55.8 12 17376932 (1), 15210742 (1), 16281057 (1), 19307177 (1) (see all 8)
    vesicular stomatitis 46.8 2 15367631 (2)
    necrosis 16.7 7 19307177 (2), 18450748 (1)
    immunodeficiency 16.6 7 10713183 (1), 10607567 (1), 11070003 (1), 9371615 (1) (see all 5)
    tumors 0 8 19307177 (2), 18450748 (1), 11745462 (1)

    Genetic Association Database (GAD): TBK1
    Human Genome Epidemiology (HuGE) Navigator: TBK1 (6 documents)

    Export disorders for TBK1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for TBK1 gene, integrated from 10 sources (see all 216):
    (articles sorted by number of sources associating them with TBK1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. NAK is an IkappaB kinase-activating kinase. (PubMed id 10783893)1, 2, 3, 9 Tojima Y....Nakanishi M. (Nature 2000)
    2. NF-kB activation by a signaling complex containing TRAF2, TANK, and TBK1, a novel IKK-related kinase. (PubMed id 10581243)1, 2, 3, 9 Pomerantz J.L. and Baltimore D. (EMBO J. 1999)
    3. The DEAD-box helicase DDX3X is a critical component of the TANK- binding kinase 1-dependent innate immune response. (PubMed id 18583960)1, 2, 9 Soulat D....Superti-Furga G. (EMBO J. 2008)
    4. Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity. (PubMed id 15367631)1, 2, 9 tenOever B.R.... Hiscott J. (J. Virol. 2004)
    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. (PubMed id 14530355)1, 2, 9 Sato S....Akira S. (J. Immunol. 2003)
    6. Involvement of the ubiquitin-like domain of TBK1/IKK-i kinases in regulation of IFN-inducible genes. (PubMed id 17599067)1, 2, 9 Ikeda F.... Dikic I. (EMBO J. 2007)
    7. SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus- triggered IRF-3 activation pathways. (PubMed id 16281057)1, 2, 9 Huang J.... Shu H.-B. (EMBO J. 2005)
    8. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. (PubMed id 12692549)1, 2, 9 Fitzgerald K.A.... Maniatis T. (Nat. Immunol. 2003)
    9. IKK-i and TBK-1 are enzymatically distinct from the homologous enzyme IKK-2: comparative analysis of recombinant human IKK-i, TBK-1, and IKK-2. (PubMed id 11839743)1, 2, 9 Kishore N.... Tripp C.S. (J. Biol. Chem. 2002)
    10. Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. (PubMed id 15489227)1, 2, 9 Buss H.... Kracht M. (J. Biol. Chem. 2004)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 29110 HGNC: 11584 AceView: TBK1.1 Ensembl:ENSG00000183735 euGenes: HUgn29110
    ECgene: TBK1 Kegg: 29110 H-InvDB: TBK1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for TBK1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TBK1 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for TBK1 gene:
    Search GeneIP for patents involving TBK1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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