CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-022934
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase TBK1 
Protein Synonyms/Alias
 NF-kappa-B-activating kinase; T2K; TANK-binding kinase 1 
Gene Name
 TBK1 
Gene Synonyms/Alias
 NAK 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
137GIVHRDIKPGNIMRVubiquitination[1]
154EDGQSVYKLTDFGAAubiquitination[1, 2, 3, 4, 5, 6]
231FEGPRRNKEVMYKIIubiquitination[4]
241MYKIITGKPSGAISGubiquitination[1, 4]
251GAISGVQKAENGPIDubiquitination[4]
344ELVYKQTKIISSNQEubiquitination[1]
372RLAQHFPKTTEENPIubiquitination[4]
396TIGLIYEKISLPKVHubiquitination[1, 2, 4, 5]
416DGDASMAKAITGVVCubiquitination[4]
484KTVKVYEKLMKINLEubiquitination[4]
504EISDIHTKLLRLSSSubiquitination[1, 2, 4, 5]
584YNEEQIHKFDKQKLYacetylation[7]
584YNEEQIHKFDKQKLYubiquitination[1]
661LQETLPQKMFTASSGubiquitination[1, 5]
670FTASSGIKHTMTPIYubiquitination[8]
692EMTLGMKKLKEEMEGubiquitination[4]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [3] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [7] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [8] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 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 IFN- alpha and IFN-beta. 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 or 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. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates and activates AKT1. Phosphorylates Borna disease virus (BDV) P protein. 
Sequence Annotation
 DOMAIN 9 310 Protein kinase.
 DOMAIN 309 385 Ubiquitin-like.
 NP_BIND 15 23 ATP (By similarity).
 ACT_SITE 135 135 Proton acceptor (By similarity).
 BINDING 38 38 ATP (By similarity).
 MOD_RES 172 172 Phosphoserine; by autocatalysis and IKKB.
 CROSSLNK 670 670 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Antiviral defense; ATP-binding; Coiled coil; Complete proteome; Cytoplasm; Host-virus interaction; Immunity; Innate immunity; Isopeptide bond; Kinase; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 729 AA 
Protein Sequence
MQSTSNHLWL LSDILGQGAT ANVFRGRHKK TGDLFAIKVF NNISFLRPVD VQMREFEVLK 60
KLNHKNIVKL FAIEEETTTR HKVLIMEFCP CGSLYTVLEE PSNAYGLPES EFLIVLRDVV 120
GGMNHLRENG IVHRDIKPGN IMRVIGEDGQ SVYKLTDFGA ARELEDDEQF VSLYGTEEYL 180
HPDMYERAVL RKDHQKKYGA TVDLWSIGVT FYHAATGSLP FRPFEGPRRN KEVMYKIITG 240
KPSGAISGVQ KAENGPIDWS GDMPVSCSLS RGLQVLLTPV LANILEADQE KCWGFDQFFA 300
ETSDILHRMV IHVFSLQQMT AHKIYIHSYN TATIFHELVY KQTKIISSNQ ELIYEGRRLV 360
LEPGRLAQHF PKTTEENPIF VVSREPLNTI GLIYEKISLP KVHPRYDLDG DASMAKAITG 420
VVCYACRIAS TLLLYQELMR KGIRWLIELI KDDYNETVHK KTEVVITLDF CIRNIEKTVK 480
VYEKLMKINL EAAELGEISD IHTKLLRLSS SQGTIETSLQ DIDSRLSPGG SLADAWAHQE 540
GTHPKDRNVE KLQVLLNCMT EIYYQFKKDK AERRLAYNEE QIHKFDKQKL YYHATKAMTH 600
FTDECVKKYE AFLNKSEEWI RKMLHLRKQL LSLTNQCFDI EEEVSKYQEY TNELQETLPQ 660
KMFTASSGIK HTMTPIYPSS NTLVEMTLGM KKLKEEMEGV VKELAENNHI LERFGSLTMD 720
GGLRNVDCL 729 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0010008; C:endosome membrane; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003676; F:nucleic acid binding; IEA:Compara.
 GO:0004674; F:protein serine/threonine kinase activity; TAS:UniProtKB.
 GO:0050830; P:defense response to Gram-positive bacterium; IEA:Compara.
 GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
 GO:0007249; P:I-kappaB kinase/NF-kappaB cascade; TAS:UniProtKB.
 GO:0006954; P:inflammatory response; TAS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:UniProtKB.
 GO:0010629; P:negative regulation of gene expression; IEA:Compara.
 GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
 GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEP:UniProtKB.
 GO:0032727; P:positive regulation of interferon-alpha production; IDA:BHF-UCL.
 GO:0045359; P:positive regulation of interferon-beta biosynthetic process; IEA:Compara.
 GO:0032728; P:positive regulation of interferon-beta production; IDA:BHF-UCL.
 GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; NAS:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0009615; P:response to virus; TAS:UniProtKB.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0032606; P:type I interferon production; TAS:UniProtKB.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS. 
Pfam
 PF00069; Pkinase 
SMART
  
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS00299; UBIQUITIN_1
 PS50053; UBIQUITIN_2 
PRINTS