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    TBK1 TANK binding kinase 1 [ Homo sapiens (human) ]

    Gene ID: 29110, updated on 12-Nov-2024

    Summary

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    Official Symbol
    TBK1provided by HGNC
    Official Full Name
    TANK binding kinase 1provided by HGNC
    Primary source
    HGNC:HGNC:11584
    See related
    Ensembl:ENSG00000183735 MIM:604834; AllianceGenome:HGNC:11584
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NAK; T2K; AIARV; IIAE8; FTDALS4
    Summary
    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. The protein is also an important kinase for antiviral innate immunity response. [provided by RefSeq, Sep 2021]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
    Expression
    Ubiquitous expression in testis (RPKM 15.8), bone marrow (RPKM 10.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TBK1 in Genome Data Viewer
    Location:
    12q14.2
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (64452120..64502114)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (64430747..64480735)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (64845900..64895894)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6592 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4619 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4620 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:64798894-64799770 Neighboring gene ribosomal protein S11 pseudogene 6 Neighboring gene exportin for tRNA Neighboring gene MPRA-validated peak1761 silencer Neighboring gene mitochondrial ribosomal protein S25 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4621 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6593 Neighboring gene uncharacterized LOC105369803 Neighboring gene Ras association domain family member 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6594 Neighboring gene small nucleolar RNA SNORD83

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. TBK1 participates in glutaminolysis by mediating the phosphorylation of RIPK3 to promote endotoxin tolerance. Pan L, et al. Mol Immunol, 2022 Jul. PMID 35533409
    2. TBK1 mutations in Italian patients with amyotrophic lateral sclerosis: genetic and functional characterisation. Pozzi L, et al. J Neurol Neurosurg Psychiatry, 2017 Oct. PMID 28822984, Free PMC Article
    3. Familial primary lateral sclerosis or dementia associated with Arg573Gly TBK1 mutation. Gómez-Tortosa E, et al. J Neurol Neurosurg Psychiatry, 2017 Nov. PMID 28365590
    4. TBK1 haploinsufficiency results in changes in the K63-ubiquitination profiles in brain and fibroblasts from affected and presymptomatic mutation carriers. Khoshnood B, et al. J Neurol, 2022 Jun. PMID 34800171, Free PMC Article
    5. Transgenic TBK1 mice have features of normal tension glaucoma. Fingert JH, et al. Hum Mol Genet, 2017 Jan 1. PMID 28025332, Free PMC Article

    See all (527) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TBK1 adaptor AZI2/NAP1 regulates NDP52-driven mitochondrial autophagy.
      Title: TBK1 adaptor AZI2/NAP1 regulates NDP52-driven mitochondrial autophagy.
    2. A TBK1-independent primordial function of STING in lysosomal biogenesis.
      Title: A TBK1-independent primordial function of STING in lysosomal biogenesis.
    3. Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition.
      Title: Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition.
    4. A human commensal-pathogenic fungus suppresses host immunity via targeting TBK1.
      Title: A human commensal-pathogenic fungus suppresses host immunity via targeting TBK1.
    5. MARCH1 negatively regulates TBK1-mTOR signaling pathway by ubiquitinating TBK1.
      Title: MARCH1 negatively regulates TBK1-mTOR signaling pathway by ubiquitinating TBK1.
    6. TBK1 is ubiquitinated by TRIM5alpha to assemble mitophagy machinery.
      Title: TBK1 is ubiquitinated by TRIM5α to assemble mitophagy machinery.
    7. cGAS-STING-TBK1 Signaling Promotes Valproic Acid-Responsive Human Cytomegalovirus Immediate-Early Transcription during Infection of Incompletely Differentiated Myeloid Cells.
      Title: cGAS-STING-TBK1 Signaling Promotes Valproic Acid-Responsive Human Cytomegalovirus Immediate-Early Transcription during Infection of Incompletely Differentiated Myeloid Cells.
    8. Suppression of smooth muscle cell inflammation by myocardin-related transcription factors involves inactivation of TANK-binding kinase 1.
      Title: Suppression of smooth muscle cell inflammation by myocardin-related transcription factors involves inactivation of TANK-binding kinase 1.
    9. Genetic and clinical landscape of Chinese frontotemporal dementia: dominance of TBK1 and OPTN mutations.
      Title: Genetic and clinical landscape of Chinese frontotemporal dementia: dominance of TBK1 and OPTN mutations.
    10. The Ca[2+]-dependent phosphatase calcineurin dephosphorylates TBK1 to suppress antiviral innate immunity.
      Title: The Ca(2+)-dependent phosphatase calcineurin dephosphorylates TBK1 to suppress antiviral innate immunity.
    Submit: New GeneRIF Correction See all GeneRIFs (259)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif HIV-1 Vif co-immunoprecipitates with TBK1 suggesting an interaction between Vif and TBK1 PubMed
    Vpr vpr HIV-1 Vpr co-immunoprecipitates with TBK1 suggesting an interaction between Vpr and TBK1 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ11330

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AS1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables nucleic acid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phosphoprotein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein phosphatase binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein serine/threonine kinase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in activation of innate immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in activation of innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in antiviral innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cGAS/STING signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in canonical NF-kappaB signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cytoplasmic pattern recognition receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in defense response to Gram-positive bacterium IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in defense response to virus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in dendritic cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in inflammatory response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in innate immune response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in macroautophagy TAS
    Traceable Author Statement
    more info
    		  
    involved_in negative regulation of TORC1 signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in peptidyl-threonine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of TORC1 signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of autophagy IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of canonical NF-kappaB signal transduction IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in positive regulation of interferon-alpha production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of interferon-beta production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of macroautophagy IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of peptidyl-serine phosphorylation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of type I interferon production IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of type I interferon production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of type I interferon production TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of type I interferon-mediated signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of xenophagy IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of type I interferon production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to virus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in toll-like receptor 4 signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in type I interferon-mediated signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    part_of serine/threonine protein kinase complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    serine/threonine-protein kinase TBK1
    Names
    NF-kB-activating kinase
    NF-kappa-B-activating kinase
    NP_037386.1
    XP_005268866.1
    XP_005268867.1
    XP_054227832.1
    XP_054227833.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_046906.1 RefSeqGene

      Range
      5061..55055
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1306

    mRNA and Protein(s)

    1. NM_013254.4 → NP_037386.1  serine/threonine-protein kinase TBK1

      See identical proteins and their annotated locations for NP_037386.1

      Status: REVIEWED

      Source sequence(s)
      AA970899, AC135279, AC136977, BC034950
      Consensus CDS
      CCDS8968.1
      UniProtKB/Swiss-Prot
      A8K4S4, Q8IYV3, Q9NUJ5, Q9UHD2
      UniProtKB/TrEMBL
      A0A7I2V646
      Related
      ENSP00000329967.5, ENST00000331710.10
      Conserved Domains (3) summary
      smart00220
      Location:9 → 242
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd12219
      Location:297 → 385
      UBL_TBK1_like; Ubiquitin-Like Domain Of Human Tbk1 and similar proteins
      cd13988
      Location:15 → 330
      STKc_TBK1; Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      64452120..64502114
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005268810.2 → XP_005268867.1  serine/threonine-protein kinase TBK1 isoform X1

      See identical proteins and their annotated locations for XP_005268867.1

      UniProtKB/Swiss-Prot
      A8K4S4, Q8IYV3, Q9NUJ5, Q9UHD2
      UniProtKB/TrEMBL
      A0A7I2V646
      Conserved Domains (3) summary
      smart00220
      Location:9 → 242
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd12219
      Location:297 → 385
      UBL_TBK1_like; Ubiquitin-Like Domain Of Human Tbk1 and similar proteins
      cd13988
      Location:15 → 330
      STKc_TBK1; Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1

    2. XM_005268809.2 → XP_005268866.1  serine/threonine-protein kinase TBK1 isoform X1

      See identical proteins and their annotated locations for XP_005268866.1

      UniProtKB/Swiss-Prot
      A8K4S4, Q8IYV3, Q9NUJ5, Q9UHD2
      UniProtKB/TrEMBL
      A0A7I2V646
      Conserved Domains (3) summary
      smart00220
      Location:9 → 242
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd12219
      Location:297 → 385
      UBL_TBK1_like; Ubiquitin-Like Domain Of Human Tbk1 and similar proteins
      cd13988
      Location:15 → 330
      STKc_TBK1; Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1

    RNA

    1. XR_007063071.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      64430747..64480735
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371858.1 → XP_054227833.1  serine/threonine-protein kinase TBK1 isoform X1

      UniProtKB/Swiss-Prot
      A8K4S4, Q8IYV3, Q9NUJ5, Q9UHD2

    2. XM_054371857.1 → XP_054227832.1  serine/threonine-protein kinase TBK1 isoform X1

      UniProtKB/Swiss-Prot
      A8K4S4, Q8IYV3, Q9NUJ5, Q9UHD2

    RNA

    1. XR_008488571.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UHD2.1 GenPept UniProtKB/Swiss-Prot:Q9UHD2

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
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