Serine/threonine-protein kinase TBK1

Details

Name
Serine/threonine-protein kinase TBK1
Synonyms
  • 2.7.11.1
  • NAK
  • NF-kappa-B-activating kinase
  • T2K
  • TANK-binding kinase 1
Gene Name
TBK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051666|Serine/threonine-protein kinase TBK1
MQSTSNHLWLLSDILGQGATANVFRGRHKKTGDLFAIKVFNNISFLRPVDVQMREFEVLK
KLNHKNIVKLFAIEEETTTRHKVLIMEFCPCGSLYTVLEEPSNAYGLPESEFLIVLRDVV
GGMNHLRENGIVHRDIKPGNIMRVIGEDGQSVYKLTDFGAARELEDDEQFVSLYGTEEYL
HPDMYERAVLRKDHQKKYGATVDLWSIGVTFYHAATGSLPFRPFEGPRRNKEVMYKIITG
KPSGAISGVQKAENGPIDWSGDMPVSCSLSRGLQVLLTPVLANILEADQEKCWGFDQFFA
ETSDILHRMVIHVFSLQQMTAHKIYIHSYNTATIFHELVYKQTKIISSNQELIYEGRRLV
LEPGRLAQHFPKTTEENPIFVVSREPLNTIGLIYEKISLPKVHPRYDLDGDASMAKAITG
VVCYACRIASTLLLYQELMRKGIRWLIELIKDDYNETVHKKTEVVITLDFCIRNIEKTVK
VYEKLMKINLEAAELGEISDIHTKLLRLSSSQGTIETSLQDIDSRLSPGGSLADAWAHQE
GTHPKDRNVEKLQVLLNCMTEIYYQFKKDKAERRLAYNEEQIHKFDKQKLYYHATKAMTH
FTDECVKKYEAFLNKSEEWIRKMLHLRKQLLSLTNQCFDIEEEVSKYQEYTNELQETLPQ
KMFTASSGIKHTMTPIYPSSNTLVEMTLGMKKLKEEMEGVVKELAENNHILERFGSLTMD
GGLRNVDCL
Number of residues
729
Molecular Weight
83641.51
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / identical protein binding / nucleic acid binding / phosphoprotein binding / protein kinase activity / protein serine/threonine kinase activity
Processes
cellular response to cytokine stimulus / defense response to Gram-positive bacterium / defense response to virus / dendritic cell proliferation / I-kappaB kinase/NF-kappaB signaling / inflammatory response / innate immune response / negative regulation of gene expression / negative regulation of type I interferon production / peptidyl-serine phosphorylation / peptidyl-threonine phosphorylation / positive regulation of I-kappaB kinase/NF-kappaB signaling / positive regulation of interferon-alpha production / positive regulation of interferon-beta biosynthetic process / positive regulation of interferon-beta production / positive regulation of macroautophagy / positive regulation of peptidyl-serine phosphorylation / positive regulation of transcription by RNA polymerase II / positive regulation of type I interferon production / positive regulation of xenophagy / protein phosphorylation / regulation of neuron death / regulation of type I interferon production / response to virus / TRIF-dependent toll-like receptor signaling pathway / type I interferon production / viral process
Components
aggresome / cytoplasm / cytosol / endosome membrane / nucleoplasm
General 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 (PubMed:21617041). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (PubMed:27103069). Phosphorylates and activates AKT1 (PubMed:21464307). 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 (PubMed:21270402). Phosphorylates Borna disease virus (BDV) P protein (PubMed:16155125).
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051667|Serine/threonine-protein kinase TBK1 (TBK1)
ATGCAGAGCACTTCTAATCATCTGTGGCTTTTATCTGATATTTTAGGCCAAGGAGCTACT
GCAAATGTCTTTCGTGGAAGACATAAGAAAACTGGTGATTTATTTGCTATCAAAGTATTT
AATAACATAAGCTTCCTTCGTCCAGTGGATGTTCAAATGAGAGAATTTGAAGTGTTGAAA
AAACTCAATCACAAAAATATTGTCAAATTATTTGCTATTGAAGAGGAGACAACAACAAGA
CATAAAGTACTTATTATGGAATTTTGTCCATGTGGGAGTTTATACACTGTTTTAGAAGAA
CCTTCTAATGCCTATGGACTACCAGAATCTGAATTCTTAATTGTTTTGCGAGATGTGGTG
GGTGGAATGAATCATCTACGAGAGAATGGTATAGTGCACCGTGATATCAAGCCAGGAAAT
ATCATGCGTGTTATAGGGGAAGATGGACAGTCTGTGTACAAACTCACAGATTTTGGTGCA
GCTAGAGAATTAGAAGATGATGAGCAGTTTGTTTCTCTGTATGGCACAGAAGAATATTTG
CACCCTGATATGTATGAGAGAGCAGTGCTAAGAAAAGATCATCAGAAGAAATATGGAGCA
ACAGTTGATCTTTGGAGCATTGGGGTAACATTTTACCATGCAGCTACTGGATCACTGCCA
TTTAGACCCTTTGAAGGGCCTCGTAGGAATAAAGAAGTGATGTATAAAATAATTACAGGA
AAGCCTTCTGGTGCAATATCTGGAGTACAGAAAGCAGAAAATGGACCAATTGACTGGAGT
GGAGACATGCCTGTTTCTTGCAGTCTTTCTCGGGGTCTTCAGGTTCTACTTACCCCTGTT
CTTGCAAACATCCTTGAAGCAGATCAGGAAAAGTGTTGGGGTTTTGACCAGTTTTTTGCA
GAAACTAGTGATATACTTCACCGAATGGTAATTCATGTTTTTTCGCTACAACAAATGACA
GCTCATAAGATTTATATTCATAGCTATAATACTGCTACTATATTTCATGAACTGGTATAT
AAACAAACCAAAATTATTTCTTCAAATCAAGAACTTATCTACGAAGGGCGACGCTTAGTC
TTAGAACCTGGAAGGCTGGCACAACATTTCCCTAAAACTACTGAGGAAAACCCTATATTT
GTAGTAAGCCGGGAACCTCTGAATACCATAGGATTAATATATGAAAAAATTTCCCTCCCT
AAAGTACATCCACGTTATGATTTAGACGGGGATGCTAGCATGGCTAAGGCAATAACAGGG
GTTGTGTGTTATGCCTGCAGAATTGCCAGTACCTTACTGCTTTATCAGGAATTAATGCGA
AAGGGGATACGATGGCTGATTGAATTAATTAAAGATGATTACAATGAAACTGTTCACAAA
AAGACAGAAGTTGTGATCACATTGGATTTCTGTATCAGAAACATTGAAAAAACTGTGAAA
GTATATGAAAAGTTGATGAAGATCAACCTGGAAGCGGCAGAGTTAGGTGAAATTTCAGAC
ATACACACCAAATTGTTGAGACTTTCCAGTTCTCAGGGAACAATAGAAACCAGTCTTCAG
GATATCGACAGCAGATTATCTCCAGGTGGATCACTGGCAGACGCATGGGCACATCAAGAA
GGCACTCATCCGAAAGACAGAAATGTAGAAAAACTACAAGTCCTGTTAAATTGCATGACA
GAGATTTACTATCAGTTCAAAAAAGACAAAGCAGAACGTAGATTAGCTTATAATGAAGAA
CAAATCCACAAATTTGATAAGCAAAAACTGTATTACCATGCCACAAAAGCTATGACGCAC
TTTACAGATGAATGTGTTAAAAAGTATGAGGCATTTTTGAATAAGTCAGAAGAATGGATA
AGAAAGATGCTTCATCTTAGGAAACAGTTATTATCGCTGACTAATCAGTGTTTTGATATT
GAAGAAGAAGTATCAAAATATCAAGAATATACTAATGAGTTACAAGAAACTCTGCCTCAG
AAAATGTTTACAGCTTCCAGTGGAATCAAACATACCATGACCCCAATTTATCCAAGTTCT
AACACATTAGTAGAAATGACTCTTGGTATGAAGAAATTAAAGGAAGAGATGGAAGGGGTG
GTTAAAGAACTTGCTGAAAATAACCACATTTTAGAAAGGTTTGGCTCTTTAACCATGGAT
GGTGGCCTTCGCAACGTTGACTGTCTTTAG
Chromosome Location
12
Locus
12q14.2
External Identifiers
ResourceLink
UniProtKB IDQ9UHD2
UniProtKB Entry NameTBK1_HUMAN
HGNC IDHGNC:11584
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails