EKS-HOS-00300

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00300

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
Other/IKK	442.0	4.6E-132	9	293	285

Status

Reviewed

Ensembl Protein

ENSP00000329967

UniProt Accession

Q9UHD2; A8K4S4; Q8IYV3; Q9NUJ5;

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

TBK1; NAK;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000183735	ENSP00000445834	ENST00000538890
ENSG00000183735	ENSP00000444428	ENST00000539810
ENSG00000183735	ENSP00000445628	ENST00000540417
ENSG00000183735	ENSP00000329967	ENST00000331710

Organism

Homo sapiens

Functional Description

Serine/threonine kinase that plays an essential role inregulating 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.

Protein Length

729

Protein Sequence
(FASTA)

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

Nucleotide Sequence
(FASTA)

ATGCAGAGCA CTTCTAATCA TCTGTGGCTT TTATCTGATA TTTTAGGCCA AGGAGCTACT 60

GCAAATGTCT TTCGTGGAAG ACATAAGAAA ACTGGTGATT TATTTGCTAT CAAAGTATTT 120

AATAACATAA GCTTCCTTCG TCCAGTGGAT GTTCAAATGA GAGAATTTGA AGTGTTGAAA 180

AAACTCAATC ACAAAAATAT TGTCAAATTA TTTGCTATTG AAGAGGAGAC AACAACAAGA 240

CATAAAGTAC TTATTATGGA ATTTTGTCCA TGTGGGAGTT TATACACTGT TTTAGAAGAA 300

CCTTCTAATG CCTATGGACT ACCAGAATCT GAATTCTTAA TTGTTTTGCG AGATGTGGTG 360

GGTGGAATGA ATCATCTACG AGAGAATGGT ATAGTGCACC GTGATATCAA GCCAGGAAAT 420

ATCATGCGTG TTATAGGGGA AGATGGACAG TCTGTGTACA AACTCACAGA TTTTGGTGCA 480

GCTAGAGAAT TAGAAGATGA TGAGCAGTTT GTTTCTCTGT ATGGCACAGA AGAATATTTG 540

CACCCTGATA TGTATGAGAG AGCAGTGCTA AGAAAAGATC ATCAGAAGAA ATATGGAGCA 600

ACAGTTGATC TTTGGAGCAT TGGGGTAACA TTTTACCATG CAGCTACTGG ATCACTGCCA 660

TTTAGACCCT TTGAAGGGCC TCGTAGGAAT AAAGAAGTGA TGTATAAAAT AATTACAGGA 720

AAGCCTTCTG GTGCAATATC TGGAGTACAG AAAGCAGAAA ATGGACCAAT TGACTGGAGT 780

GGAGACATGC CTGTTTCTTG CAGTCTTTCT CGGGGTCTTC AGGTTCTACT TACCCCTGTT 840

CTTGCAAACA TCCTTGAAGC AGATCAGGAA AAGTGTTGGG GTTTTGACCA GTTTTTTGCA 900

GAAACTAGTG ATATACTTCA CCGAATGGTA ATTCATGTTT TTTCGCTACA ACAAATGACA 960

GCTCATAAGA TTTATATTCA TAGCTATAAT ACTGCTACTA TATTTCATGA ACTGGTATAT 1020

AAACAAACCA AAATTATTTC TTCAAATCAA GAACTTATCT ACGAAGGGCG ACGCTTAGTC 1080

TTAGAACCTG GAAGGCTGGC ACAACATTTC CCTAAAACTA CTGAGGAAAA CCCTATATTT 1140

GTAGTAAGCC GGGAACCTCT GAATACCATA GGATTAATAT ATGAAAAAAT TTCCCTCCCT 1200

AAAGTACATC CACGTTATGA TTTAGACGGG GATGCTAGCA TGGCTAAGGC AATAACAGGG 1260

GTTGTGTGTT ATGCCTGCAG AATTGCCAGT ACCTTACTGC TTTATCAGGA ATTAATGCGA 1320

AAGGGGATAC GATGGCTGAT TGAATTAATT AAAGATGATT ACAATGAAAC TGTTCACAAA 1380

AAGACAGAAG TTGTGATCAC ATTGGATTTC TGTATCAGAA ACATTGAAAA AACTGTGAAA 1440

GTATATGAAA AGTTGATGAA GATCAACCTG GAAGCGGCAG AGTTAGGTGA AATTTCAGAC 1500

ATACACACCA AATTGTTGAG ACTTTCCAGT TCTCAGGGAA CAATAGAAAC CAGTCTTCAG 1560

GATATCGACA GCAGATTATC TCCAGGTGGA TCACTGGCAG ACGCATGGGC ACATCAAGAA 1620

GGCACTCATC CGAAAGACAG AAATGTAGAA AAACTACAAG TCCTGTTAAA TTGCATGACA 1680

GAGATTTACT ATCAGTTCAA AAAAGACAAA GCAGAACGTA GATTAGCTTA TAATGAAGAA 1740

CAAATCCACA AATTTGATAA GCAAAAACTG TATTACCATG CCACAAAAGC TATGACGCAC 1800

TTTACAGATG AATGTGTTAA AAAGTATGAG GCATTTTTGA ATAAGTCAGA AGAATGGATA 1860

AGAAAGATGC TTCATCTTAG GAAACAGTTA TTATCGCTGA CTAATCAGTG TTTTGATATT 1920

GAAGAAGAAG TATCAAAATA TCAAGAATAT ACTAATGAGT TACAAGAAAC TCTGCCTCAG 1980

AAAATGTTTA CAGCTTCCAG TGGAATCAAA CATACCATGA CCCCAATTTA TCCAAGTTCT 2040

AACACATTAG TAGAAATGAC TCTTGGTATG AAGAAATTAA AGGAAGAGAT GGAAGGGGTG 2100

GTTAAAGAAC TTGCTGAAAA TAACCACATT TTAGAAAGGT TTGGCTCTTT AACCATGGAT 2160

GGTGGCCTTC GCAACGTTGA CTGTCTTTAG 2190

Domain Profile

S: 1     WelkelLGeGafgnvikarnkktgekiavkvikeesslrprevqvrelevlrklnhkniv  60

         W l+++LG+Ga++nv+++r+kktg+ +a+kv++++s+lrp++vq+re+evl+klnhkniv

Q: 9     WLLSDILGQGATANVFRGRHKKTGDLFAIKVFNNISFLRPVDVQMREFEVLKKLNHKNIV  68

         999*********************************************************

S: 61    klvdveeelnlasarlkvlvleyCsgGdlrkvLeepenayGLkesevlvvLsdvvaglry  120

         kl+++eee   +++r+kvl++e+C +G+l++vLeep+nayGL+ese+l+vL+dvv g+++

Q: 69    KLFAIEEE---TTTRHKVLIMEFCPCGSLYTVLEEPSNAYGLPESEFLIVLRDVVGGMNH  125

         ********...*************************************************

S: 121   LrenkivhRDlkPenivllkgedgksiykltDlGaareldddekvvslvGteeYlaPely  180

         Lren+ivhRD+kP+ni++++gedg+s+ykltD+Gaarel+dde++vsl+GteeYl+P++y

Q: 126   LRENGIVHRDIKPGNIMRVIGEDGQSVYKLTDFGAARELEDDEQFVSLYGTEEYLHPDMY  185

         ************************************************************

S: 181   e........qkkytatvDlWsiGvllyeaitGslPflpfegprr....lykkitkkpaka  228

         e        qkky+atvDlWsiGv++y+a+tGslPf+pfegprr    +yk+it kp++a

Q: 186   EravlrkdhQKKYGATVDLWSIGVTFYHAATGSLPFRPFEGPRRnkevMYKIITGKPSGA  245

         ************************************************************

S: 229   iagteka.ngevefssslPlsaslssglqeklekllanllevdeekrw  275

         i+g++ka ng++++s ++P+s+sls+glq  l+++lan+le+d+ek+w

Q: 246   ISGVQKAeNGPIDWSGDMPVSCSLSRGLQVLLTPVLANILEADQEKCW  293

         *******9***************************************9

Domain Sequence
(FASTA)

WLLSDILGQG ATANVFRGRH KKTGDLFAIK VFNNISFLRP VDVQMREFEV LKKLNHKNIV 60

KLFAIEEETT TRHKVLIMEF CPCGSLYTVL EEPSNAYGLP ESEFLIVLRD VVGGMNHLRE 120

NGIVHRDIKP GNIMRVIGED GQSVYKLTDF GAARELEDDE QFVSLYGTEE YLHPDMYERA 180

VLRKDHQKKY GATVDLWSIG VTFYHAATGS LPFRPFEGPR RNKEVMYKII TGKPSGAISG 240

VQKAENGPID WSGDMPVSCS LSRGLQVLLT PVLANILEAD QEKCW 285

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

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Taeniopygia guttata"; ?>Tetraodon nigroviridis"; ?>Vicugna pacos"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0010008	; C:endosome membrane
GO:0005524	; F:ATP binding
GO:0003676	; F:nucleic acid binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0050830	; P:defense response to Gram-positive bacterium
GO:0051607	; P:defense response to virus
GO:0007249	; P:I-kappaB kinase/NF-kappaB cascade
GO:0006954	; P:inflammatory response
GO:0045087	; P:innate immune response
GO:0010629	; P:negative regulation of gene expression
GO:0032480	; P:negative regulation of type I interferon production
GO:0043123	; P:positive regulation of I-kappaB kinase/NF-kappaB cascade
GO:0032727	; P:positive regulation of interferon-alpha production
GO:0045359	; P:positive regulation of interferon-beta biosynthetic process
GO:0032728	; P:positive regulation of interferon-beta production
GO:0045944	; P:positive regulation of transcription from RNA polymerase II promoter
GO:0009615	; P:response to virus
GO:0008063	; P:Toll signaling pathway
GO:0034138	; P:toll-like receptor 3 signaling pathway
GO:0034142	; P:toll-like receptor 4 signaling pathway
GO:0035666	; P:TRIF-dependent toll-like receptor signaling pathway
GO:0032606	; P:type I interferon production
GO:0019048	; P:virus-host interaction

KEGG

hsa:29110

;

InterPros

IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.

Pfam

PF00069

; Pkinase; 1.

SMARTs

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; FALSE_NEG.
PS00299	; UBIQUITIN_1; FALSE_NEG.
PS50053	; UBIQUITIN_2; FALSE_NEG.

Prints

Created Date

20-Feb-2013