TBKB1_HUMAN
ID TBKB1_HUMAN Reviewed; 615 AA.
AC A7MCY6; B2RZG6; O94873; Q14DW3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=TANK-binding kinase 1-binding protein 1;
DE Short=TBK1-binding protein 1;
GN Name=TBKBP1 {ECO:0000312|EMBL:AAI11419.1};
GN Synonyms=KIAA0775 {ECO:0000312|EMBL:BAA34495.2}, SINTBAD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAA34495.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain {ECO:0000312|EMBL:BAA34495.2};
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [2]
RP SEQUENCE REVISION.
RA Ohara O., Suyama M., Nagase T., Ishikawa K., Kikuno R.;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAI11419.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION.
RX PubMed=14743216; DOI=10.1038/ncb1086;
RA Bouwmeester T., Bauch A., Ruffner H., Angrand P.-O., Bergamini G.,
RA Croughton K., Cruciat C., Eberhard D., Gagneur J., Ghidelli S., Hopf C.,
RA Huhse B., Mangano R., Michon A.-M., Schirle M., Schlegl J., Schwab M.,
RA Stein M.A., Bauer A., Casari G., Drewes G., Gavin A.-C., Jackson D.B.,
RA Joberty G., Neubauer G., Rick J., Kuster B., Superti-Furga G.;
RT "A physical and functional map of the human TNF-alpha/NF-kappa B signal
RT transduction pathway.";
RL Nat. Cell Biol. 6:97-105(2004).
RN [5]
RP INTERACTION WITH IKBKE, AND TISSUE SPECIFICITY.
RX PubMed=17568778; DOI=10.1038/sj.emboj.7601743;
RA Ryzhakov G., Randow F.;
RT "SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-
RT binding domain with NAP1 and TANK.";
RL EMBO J. 26:3180-3190(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184; SER-365; SER-372;
RP SER-379; SER-385; SER-400; SER-415; SER-504 AND SER-534, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [8]
RP FUNCTION, AND INTERACTION WITH TBK1.
RX PubMed=21931631; DOI=10.1371/journal.pone.0023971;
RA Goncalves A., Burckstummer T., Dixit E., Scheicher R., Gorna M.W.,
RA Karayel E., Sugar C., Stukalov A., Berg T., Kralovics R., Planyavsky M.,
RA Bennett K.L., Colinge J., Superti-Furga G.;
RT "Functional dissection of the TBK1 molecular network.";
RL PLoS ONE 6:E23971-E23971(2011).
RN [9]
RP INTERACTION WITH VACCINIA VIRUS PROTEIN C6.
RX PubMed=21931555; DOI=10.1371/journal.ppat.1002247;
RA Unterholzner L., Sumner R.P., Baran M., Ren H., Mansur D.S., Bourke N.M.,
RA Randow F., Smith G.L., Bowie A.G.;
RT "Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor
RT proteins and inhibits activation of IRF3 and IRF7.";
RL PLoS Pathog. 7:E1002247-E1002247(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-504, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-400, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP INTERACTION WITH DDX3X.
RX PubMed=27980081; DOI=10.1042/bcj20160956;
RA Gu L., Fullam A., McCormack N., Hoehn Y., Schroeder M.;
RT "DDX3 directly regulates TRAF3 ubiquitination and acts as a scaffold to co-
RT ordinate assembly of signalling complexes downstream from MAVS.";
RL Biochem. J. 474:571-587(2017).
CC -!- FUNCTION: Adapter protein which constitutively binds TBK1 and IKBKE
CC playing a role in antiviral innate immunity.
CC {ECO:0000269|PubMed:21931631}.
CC -!- SUBUNIT: Homodimer. May form a heterodimer with NAP1. Interacts with
CC TKB1 and IKBKE. Weakly interacts with DDX3X (PubMed:27980081).
CC {ECO:0000269|PubMed:17568778, ECO:0000269|PubMed:21931631,
CC ECO:0000269|PubMed:27980081}.
CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus protein C6
CC (PubMed:21931555). {ECO:0000269|PubMed:21931555}.
CC -!- INTERACTION:
CC A7MCY6; Q9UKV8: AGO2; NbExp=2; IntAct=EBI-359969, EBI-528269;
CC A7MCY6; O96018: APBA3; NbExp=2; IntAct=EBI-359969, EBI-6115839;
CC A7MCY6; Q14164: IKBKE; NbExp=4; IntAct=EBI-359969, EBI-307369;
CC A7MCY6; Q8TDY2: RB1CC1; NbExp=2; IntAct=EBI-359969, EBI-1047793;
CC A7MCY6; Q9UHD2: TBK1; NbExp=9; IntAct=EBI-359969, EBI-356402;
CC A7MCY6; P17362: VACWR022; Xeno; NbExp=2; IntAct=EBI-359969, EBI-9519257;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9872452};
CC IsoId=A7MCY6-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334};
CC IsoId=A7MCY6-2; Sequence=VSP_052714, VSP_052715;
CC -!- TISSUE SPECIFICITY: Detected in leukocytes, lung, placenta, small
CC intestine, liver, kidney, spleen, muscle, heart, brain and at low
CC levels in thymus. {ECO:0000269|PubMed:17568778}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA34495.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB018318; BAA34495.2; ALT_INIT; mRNA.
DR EMBL; BC111418; AAI11419.1; -; mRNA.
DR EMBL; BC152407; AAI52408.1; -; mRNA.
DR EMBL; BC167150; AAI67150.1; -; mRNA.
DR CCDS; CCDS45722.1; -. [A7MCY6-1]
DR RefSeq; NP_055541.1; NM_014726.2. [A7MCY6-1]
DR RefSeq; XP_005257916.1; XM_005257859.4. [A7MCY6-1]
DR RefSeq; XP_005257917.1; XM_005257860.4. [A7MCY6-1]
DR RefSeq; XP_005257918.1; XM_005257861.4. [A7MCY6-1]
DR RefSeq; XP_005257919.1; XM_005257862.3. [A7MCY6-1]
DR AlphaFoldDB; A7MCY6; -.
DR SMR; A7MCY6; -.
DR BioGRID; 115103; 61.
DR ComplexPortal; CPX-6090; TBK1-IKKepsilon-SINTBAD complex.
DR CORUM; A7MCY6; -.
DR DIP; DIP-27604N; -.
DR IntAct; A7MCY6; 16.
DR MINT; A7MCY6; -.
DR STRING; 9606.ENSP00000354777; -.
DR ChEMBL; CHEMBL4523108; -.
DR iPTMnet; A7MCY6; -.
DR PhosphoSitePlus; A7MCY6; -.
DR BioMuta; TBKBP1; -.
DR EPD; A7MCY6; -.
DR jPOST; A7MCY6; -.
DR MassIVE; A7MCY6; -.
DR MaxQB; A7MCY6; -.
DR PaxDb; A7MCY6; -.
DR PeptideAtlas; A7MCY6; -.
DR PRIDE; A7MCY6; -.
DR ProteomicsDB; 1810; -. [A7MCY6-1]
DR ProteomicsDB; 1811; -. [A7MCY6-2]
DR Antibodypedia; 30174; 159 antibodies from 27 providers.
DR DNASU; 9755; -.
DR Ensembl; ENST00000361722.7; ENSP00000354777.3; ENSG00000198933.10. [A7MCY6-1]
DR Ensembl; ENST00000578982.6; ENSP00000462339.2; ENSG00000198933.10. [A7MCY6-1]
DR Ensembl; ENST00000622396.1; ENSP00000484395.1; ENSG00000198933.10. [A7MCY6-2]
DR GeneID; 9755; -.
DR KEGG; hsa:9755; -.
DR MANE-Select; ENST00000578982.6; ENSP00000462339.2; NM_001394755.1; NP_001381684.1.
DR UCSC; uc002ilu.4; human. [A7MCY6-1]
DR CTD; 9755; -.
DR DisGeNET; 9755; -.
DR GeneCards; TBKBP1; -.
DR HGNC; HGNC:30140; TBKBP1.
DR HPA; ENSG00000198933; Low tissue specificity.
DR MIM; 608476; gene.
DR neXtProt; NX_A7MCY6; -.
DR OpenTargets; ENSG00000198933; -.
DR PharmGKB; PA142670830; -.
DR VEuPathDB; HostDB:ENSG00000198933; -.
DR eggNOG; ENOG502QVP4; Eukaryota.
DR GeneTree; ENSGT00940000153704; -.
DR HOGENOM; CLU_029090_0_0_1; -.
DR InParanoid; A7MCY6; -.
DR OMA; QRHSPIQ; -.
DR OrthoDB; 621943at2759; -.
DR PhylomeDB; A7MCY6; -.
DR TreeFam; TF331289; -.
DR PathwayCommons; A7MCY6; -.
DR SignaLink; A7MCY6; -.
DR BioGRID-ORCS; 9755; 24 hits in 1084 CRISPR screens.
DR GenomeRNAi; 9755; -.
DR Pharos; A7MCY6; Tbio.
DR PRO; PR:A7MCY6; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; A7MCY6; protein.
DR Bgee; ENSG00000198933; Expressed in cingulate cortex and 119 other tissues.
DR ExpressionAtlas; A7MCY6; baseline and differential.
DR Genevisible; A7MCY6; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:1902554; C:serine/threonine protein kinase complex; IC:ComplexPortal.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051607; P:defense response to virus; IC:ComplexPortal.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0060337; P:type I interferon signaling pathway; IC:ComplexPortal.
DR InterPro; IPR041641; CALCOCO1/2_Zn_UBZ1.
DR InterPro; IPR024581; TBD.
DR Pfam; PF12845; TBD; 1.
DR PROSITE; PS51905; ZF_UBZ1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Host-virus interaction; Immunity;
KW Innate immunity; Metal-binding; Phosphoprotein; Reference proteome; Zinc;
KW Zinc-finger.
FT CHAIN 1..615
FT /note="TANK-binding kinase 1-binding protein 1"
FT /id="PRO_0000324654"
FT ZN_FING 583..609
FT /note="UBZ1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT REGION 1..279
FT /note="Homodimerization"
FT /evidence="ECO:0000250"
FT REGION 280..329
FT /note="Interaction with TBK1 and IKBKE"
FT /evidence="ECO:0000250"
FT REGION 326..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 48..162
FT /evidence="ECO:0000255"
FT COILED 221..276
FT /evidence="ECO:0000255"
FT COMPBIAS 326..342
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 343..437
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 586
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT BINDING 589
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT BINDING 605
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT BINDING 609
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 365
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 379
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 385
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 400
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 504
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 534
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT VAR_SEQ 186..222
FT /note="PPAPAPPCTDLDLHYLALRGGSGLSHAGWPGSTPSVS -> RRARAVLAVHQ
FT LADGDGGLRHPQLPPLPAGFPCRVPG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052714"
FT VAR_SEQ 223..615
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052715"
SQ SEQUENCE 615 AA; 67702 MW; C8F42919164A554E CRC64;
MESMFEDDIS ILTQEALGPS EVWLDSPGDP SLGGDMCSAS HFALITAYGD IKERLGGLER
ENATLRRRLK VYEIKYPLIS DFGEEHGFSL YEIKDGSLLE VEKVSLQQRL NQFQHELQKN
KEQEEQLGEM IQAYEKLCVE KSDLETELRE MRALVETHLR QICGLEQQLR QQQGLQDAAF
SNLSPPPAPA PPCTDLDLHY LALRGGSGLS HAGWPGSTPS VSDLERRRLE EALEAAQGEA
RGAQLREEQL QAECERLQGE LKQLQETRAQ DLASNQSERD MAWVKRVGDD QVNLALAYTE
LTEELGRLRE LSSLQGRILR TLLQEQARSG GQRHSPLSQR HSPAPQCPSP SPPARAAPPC
PPCQSPVPQR RSPVPPCPSP QQRRSPASPS CPSPVPQRRS PVPPSCQSPS PQRRSPVPPS
CPAPQPRPPP PPPPGERTLA ERAYAKPPSH HVKAGFQGRR SYSELAEGAA YAGASPPWLQ
AEAATLPKPR AYGSELYGPG RPLSPRRAFE GIRLRFEKQP SEEDEWAVPT SPPSPEVGTI
RCASFCAGFP IPESPAATAY AHAEHAQSWP SINLLMETVG SDIRSCPLCQ LGFPVGYPDD
ALIKHIDSHL ENSKI
