ID TANK_HUMAN Reviewed; 425 AA.
AC Q92844; D3DPB5; Q7Z4J6; Q92885;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 27-MAR-2024, entry version 214.
DE RecName: Full=TRAF family member-associated NF-kappa-B activator;
DE AltName: Full=TRAF-interacting protein;
DE Short=I-TRAF;
GN Name=TANK; Synonyms=ITRAF, TRAF2;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=8710854; DOI=10.1073/pnas.93.16.8241;
RA Rothe M., Xiong J., Shu H.-B., Williamson K., Goddard A., Goeddel D.V.;
RT "I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated
RT signal transduction.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:8241-8246(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=8855313; DOI=10.1073/pnas.93.20.11085;
RA Kaye K.M., Devergne O., Harada J.N., Izumi K.M., Yalamanchili R., Kieff E.,
RA Mosialos G.;
RT "Tumor necrosis factor receptor associated factor 2 is a mediator of NF-
RT kappa B activation by latent infection membrane protein 1, the Epstein-Barr
RT virus transforming protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:11085-11090(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT).
RC TISSUE=Placenta;
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 [7]
RP INTERACTION WITH TBK1.
RC TISSUE=Spleen;
RX PubMed=10581243; DOI=10.1093/emboj/18.23.6694;
RA Pomerantz J.L., Baltimore D.;
RT "NF-kB activation by a signaling complex containing TRAF2, TANK, and TBK1,
RT a novel IKK-related kinase.";
RL EMBO J. 18:6694-6704(1999).
RN [8]
RP INTERACTION WITH TRAF2, AND PHOSPHORYLATION BY IKBKE.
RX PubMed=10759890; DOI=10.1046/j.1365-2443.2000.00315.x;
RA Nomura F., Kawai T., Nakanishi K., Akira S.;
RT "NF-kappaB activation through IKK-i-dependent I-TRAF/TANK
RT phosphorylation.";
RL Genes Cells 5:191-202(2000).
RN [9]
RP FUNCTION, AND INTERACTION WITH IKBKG AND IKBKB.
RX PubMed=12133833; DOI=10.1074/jbc.m205069200;
RA Chariot A., Leonardi A., Muller J., Bonif M., Brown K., Siebenlist U.;
RT "Association of the adaptor TANK with the I kappa B kinase (IKK) regulator
RT NEMO connects IKK complexes with IKK epsilon and TBK1 kinases.";
RL J. Biol. Chem. 277:37029-37036(2002).
RN [10]
RP INTERACTION WITH IKBKE.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129 AND SER-357, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126; SER-129; SER-341;
RP SER-354 AND SER-357, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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 [16]
RP INTERACTION WITH VACCINIA VIRUS PROTEIN C6 (MICROBIAL INFECTION).
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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126; SER-129; SER-208;
RP THR-213; SER-225 AND SER-228, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126; SER-178 AND SER-208, AND
RP IDENTIFICATION BY 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 [20]
RP FUNCTION, IDENTIFICATION IN A DEUBIQUITINATION COMPLEX WITH USP10 AND
RP ZC3H12A, AND INTERACTION WITH IKBKG; TRAF6; USP10 AND ZC3H12A.
RX PubMed=25861989; DOI=10.1074/jbc.m115.643767;
RA Wang W., Huang X., Xin H.B., Fu M., Xue A., Wu Z.H.;
RT "TRAF family member-associated NF-kappaB activator (TANK) inhibits
RT genotoxic nuclear factor kappaB activation by facilitating deubiquitinase
RT USP10-dependent deubiquitination of TRAF6 ligase.";
RL J. Biol. Chem. 290:13372-13385(2015).
RN [21]
RP PROTEOLYTIC CLEAVAGE BY ENCEPHALOMYOCARDITIS VIRUS PROTEASE 3C (MICROBIAL
RP INFECTION).
RX PubMed=26363073; DOI=10.1074/jbc.m115.660761;
RA Huang L., Liu Q., Zhang L., Zhang Q., Hu L., Li C., Wang S., Li J.,
RA Zhang Y., Yu H., Wang Y., Zhong Z., Xiong T., Xia X., Wang X., Yu L.,
RA Deng G., Cai X., Cui S., Weng C.;
RT "Encephalomyocarditis Virus 3C Protease Relieves TRAF Family Member-
RT associated NF-kappaB Activator (TANK) Inhibitory Effect on TRAF6-mediated
RT NF-kappaB Signaling through Cleavage of TANK.";
RL J. Biol. Chem. 290:27618-27632(2015).
RN [22]
RP PROTEOLYTIC CLEAVAGE BY ENCEPHALOMYOCARDITIS VIRUS PROTEASE 3C (MICROBIAL
RP INFECTION).
RX PubMed=28487378; DOI=10.1042/bcj20161037;
RA Huang L., Xiong T., Yu H., Zhang Q., Zhang K., Li C., Hu L., Zhang Y.,
RA Zhang L., Liu Q., Wang S., He X., Bu Z., Cai X., Cui S., Li J., Weng C.;
RT "Encephalomyocarditis virus 3C protease attenuates type I interferon
RT production through disrupting the TANK-TBK1-IKKepsilon-IRF3 complex.";
RL Biochem. J. 474:2051-2065(2017).
RN [23]
RP INTERACTION WITH SENECA VALLEY VIRUS PROTEASE 3C (MICROBIAL INFECTION),
RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION), AND MUTAGENESIS OF GLN-197;
RP HIS-247; GLU-251; GLU-262; GLN-266; GLU-267; GLU-272 AND GLN-291.
RX PubMed=28566380; DOI=10.1128/jvi.00823-17;
RA Qian S., Fan W., Liu T., Wu M., Zhang H., Cui X., Zhou Y., Hu J., Wei S.,
RA Chen H., Li X., Qian P.;
RT "Seneca Valley virus suppresses host type I interferon production by
RT targeting adaptor proteins MAVS, TRIF, and TANK for cleavage.";
RL J. Virol. 91:0-0(2017).
RN [24]
RP INTERACTION WITH TBK1.
RX PubMed=29251827; DOI=10.1002/pmic.201700403;
RA Shang J., Xia T., Han Q.Q., Zhao X., Hu M.M., Shu H.B., Guo L.;
RT "Quantitative Proteomics Identified TTC4 as a TBK1 Interactor and a
RT Positive Regulator of SeV-Induced Innate Immunity.";
RL Proteomics 18:0-0(2018).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 174-194 IN COMPLEX WITH TRAF3, AND
RP MUTAGENESIS OF GLN-182; THR-184; ASP-185; ASP-188 AND PHE-194.
RX PubMed=12005438; DOI=10.1016/s0969-2126(02)00733-5;
RA Li C., Ni C.Z., Havert M.L., Cabezas E., He J., Kaiser D., Reed J.C.,
RA Satterthwait A.C., Cheng G., Ely K.R.;
RT "Downstream regulator TANK binds to the CD40 recognition site on TRAF3.";
RL Structure 10:403-411(2002).
CC -!- FUNCTION: Adapter protein involved in I-kappa-B-kinase (IKK) regulation
CC which constitutively binds TBK1 and IKBKE playing a role in antiviral
CC innate immunity. Acts as a regulator of TRAF function by maintaining
CC them in a latent state. Blocks TRAF2 binding to LMP1 and inhibits LMP1-
CC mediated NF-kappa-B activation. Negatively regulates NF-kappaB
CC signaling and cell survival upon DNA damage (PubMed:25861989). Plays a
CC role as an adapter to assemble ZC3H12A, USP10 in a deubiquitination
CC complex which plays a negative feedback response to attenuate NF-kappaB
CC activation through the deubiquitination of IKBKG or TRAF6 in response
CC to interleukin-1-beta (IL1B) stimulation or upon DNA damage
CC (PubMed:25861989). Promotes UBP10-induced deubiquitination of TRAF6 in
CC response to DNA damage (PubMed:25861989). May control negatively TRAF2-
CC mediated NF-kappa-B activation signaled by CD40, TNFR1 and TNFR2.
CC {ECO:0000269|PubMed:12133833, ECO:0000269|PubMed:21931631,
CC ECO:0000269|PubMed:25861989}.
CC -!- SUBUNIT: Homodimer. Found in a deubiquitination complex with TANK,
CC USP10 and ZC3H12A; this complex inhibits genotoxic stress- or
CC interleukin-1-beta-mediated NF-kappaB activation by promoting IKBKG or
CC TRAF6 deubiquitination (PubMed:25861989). Interacts with IKBKG; this
CC interaction increases in response to DNA damage (PubMed:25861989).
CC Interacts with TRAF6; this interaction increases in response to DNA
CC damage and recruits USP10 to the ubiquitinated TRAF6 (PubMed:25861989).
CC Interacts with USP10; this interaction increases in response to DNA
CC damage (PubMed:25861989). Interacts with ZC3H12A; this interaction
CC increases in response to DNA damage (PubMed:25861989). Interacts with
CC TBK1 (PubMed:10581243, PubMed:21931631, PubMed:29251827). Interacts
CC with IKBKE (PubMed:17568778). Interacts also with TRAF1, TRAF2, and
CC TRAF3 by binding to their TRAF-C domains; the interaction with TRAF2 is
CC disrupted by the phosphorylation of TANK by IKBKE (PubMed:10759890,
CC PubMed:12005438). Interacts more strongly with TRAF1 and TRAF2 than
CC TRAF3 (PubMed:10759890, PubMed:12005438). Interacts with IKBKG; the
CC interaction is enhanced by IKBKE and TBK1 (PubMed:12133833). Part of a
CC ternary complex consisting of TANK, IKBKB and IKBKG (PubMed:12133833).
CC {ECO:0000269|PubMed:10581243, ECO:0000269|PubMed:10759890,
CC ECO:0000269|PubMed:12005438, ECO:0000269|PubMed:12133833,
CC ECO:0000269|PubMed:17568778, ECO:0000269|PubMed:21931631,
CC ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:29251827}.
CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus protein C6
CC (PubMed:21931555). {ECO:0000269|PubMed:21931555}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Seneca Valley virus
CC protease 3C; this interaction allows the cleavage of TANK and
CC subsequent suppression of host innate immunity.
CC {ECO:0000269|PubMed:28566380}.
CC -!- INTERACTION:
CC Q92844; O96018: APBA3; NbExp=2; IntAct=EBI-356349, EBI-6115839;
CC Q92844; Q96MT8: CEP63; NbExp=4; IntAct=EBI-356349, EBI-741977;
CC Q92844; P42858: HTT; NbExp=3; IntAct=EBI-356349, EBI-466029;
CC Q92844; Q14164: IKBKE; NbExp=4; IntAct=EBI-356349, EBI-307369;
CC Q92844; Q9Y6K9: IKBKG; NbExp=5; IntAct=EBI-356349, EBI-81279;
CC Q92844; P53350: PLK1; NbExp=3; IntAct=EBI-356349, EBI-476768;
CC Q92844; Q05519: SRSF11; NbExp=3; IntAct=EBI-356349, EBI-1051785;
CC Q92844; P63165: SUMO1; NbExp=8; IntAct=EBI-356349, EBI-80140;
CC Q92844; P61956: SUMO2; NbExp=3; IntAct=EBI-356349, EBI-473220;
CC Q92844; Q9UHD2: TBK1; NbExp=13; IntAct=EBI-356349, EBI-356402;
CC Q92844; Q13625-3: TP53BP2; NbExp=3; IntAct=EBI-356349, EBI-10175039;
CC Q92844; Q12933: TRAF2; NbExp=8; IntAct=EBI-356349, EBI-355744;
CC Q92844; Q13114: TRAF3; NbExp=7; IntAct=EBI-356349, EBI-357631;
CC Q92844; Q92574: TSC1; NbExp=3; IntAct=EBI-356349, EBI-1047085;
CC Q92844; P03495: NS; Xeno; NbExp=2; IntAct=EBI-356349, EBI-2548993;
CC Q92844; P17362: OPG029; Xeno; NbExp=2; IntAct=EBI-356349, EBI-9519257;
CC Q92844-3; P42858: HTT; NbExp=3; IntAct=EBI-25967460, EBI-466029;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Long;
CC IsoId=Q92844-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q92844-2; Sequence=VSP_004442, VSP_004443;
CC Name=3;
CC IsoId=Q92844-3; Sequence=VSP_043702, VSP_043703;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Phosphorylated by IKBKE. {ECO:0000269|PubMed:10759890}.
CC -!- PTM: (Microbial infection) Cleaved by encephalomyocarditis virus (EMCV)
CC protease 3C (PubMed:26363073). This cleavage allows the virus to
CC disrupt the TANK-TBK1-IKKepsilon-IRF3 complex, thereby inhibiting the
CC induction of the IFN-beta signal pathway (PubMed:28487378).
CC {ECO:0000269|PubMed:26363073, ECO:0000269|PubMed:28487378}.
CC -!- PTM: (Microbial infection) Cleaved by Seneca Valley virus protease 3C
CC allowing the virus to suppress interferon type-I through both RIG-I and
CC Toll-like receptor-dependent pathways. {ECO:0000269|PubMed:28566380}.
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DR EMBL; U59863; AAC50681.1; -; mRNA.
DR EMBL; U63830; AAC50770.1; -; mRNA.
DR EMBL; BT009855; AAP88857.1; -; mRNA.
DR EMBL; AC009299; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC009313; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471058; EAX11374.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11375.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11377.1; -; Genomic_DNA.
DR EMBL; BC003388; AAH03388.1; -; mRNA.
DR CCDS; CCDS2215.1; -. [Q92844-1]
DR CCDS; CCDS46436.1; -. [Q92844-3]
DR RefSeq; NP_001186064.1; NM_001199135.1. [Q92844-1]
DR RefSeq; NP_004171.2; NM_004180.2. [Q92844-1]
DR RefSeq; NP_597841.1; NM_133484.1. [Q92844-3]
DR RefSeq; XP_016858585.1; XM_017003096.1.
DR RefSeq; XP_016858586.1; XM_017003097.1.
DR PDB; 1KZZ; X-ray; 3.50 A; B=177-187.
DR PDB; 1L0A; X-ray; 2.90 A; B=178-195.
DR PDB; 5H10; X-ray; 3.21 A; D/E/F=178-185.
DR PDBsum; 1KZZ; -.
DR PDBsum; 1L0A; -.
DR PDBsum; 5H10; -.
DR AlphaFoldDB; Q92844; -.
DR SMR; Q92844; -.
DR BioGRID; 115328; 218.
DR ComplexPortal; CPX-6089; TBK1-IKKepsilon-TANK complex.
DR CORUM; Q92844; -.
DR DIP; DIP-27516N; -.
DR IntAct; Q92844; 192.
DR MINT; Q92844; -.
DR STRING; 9606.ENSP00000259075; -.
DR ChEMBL; CHEMBL4523420; -.
DR GlyCosmos; Q92844; 2 sites, 1 glycan.
DR GlyGen; Q92844; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q92844; -.
DR PhosphoSitePlus; Q92844; -.
DR BioMuta; TANK; -.
DR DMDM; 143811466; -.
DR EPD; Q92844; -.
DR jPOST; Q92844; -.
DR MassIVE; Q92844; -.
DR MaxQB; Q92844; -.
DR PaxDb; 9606-ENSP00000376505; -.
DR PeptideAtlas; Q92844; -.
DR ProteomicsDB; 75537; -. [Q92844-1]
DR ProteomicsDB; 75538; -. [Q92844-2]
DR ProteomicsDB; 75539; -. [Q92844-3]
DR Pumba; Q92844; -.
DR Antibodypedia; 4155; 501 antibodies from 38 providers.
DR DNASU; 10010; -.
DR Ensembl; ENST00000259075.6; ENSP00000259075.2; ENSG00000136560.14. [Q92844-1]
DR Ensembl; ENST00000392749.7; ENSP00000376505.2; ENSG00000136560.14. [Q92844-1]
DR Ensembl; ENST00000403609.1; ENSP00000385983.1; ENSG00000136560.14. [Q92844-3]
DR GeneID; 10010; -.
DR KEGG; hsa:10010; -.
DR MANE-Select; ENST00000392749.7; ENSP00000376505.2; NM_001199135.3; NP_001186064.1.
DR UCSC; uc002ubr.3; human. [Q92844-1]
DR AGR; HGNC:11562; -.
DR CTD; 10010; -.
DR DisGeNET; 10010; -.
DR GeneCards; TANK; -.
DR HGNC; HGNC:11562; TANK.
DR HPA; ENSG00000136560; Low tissue specificity.
DR MIM; 603893; gene.
DR neXtProt; NX_Q92844; -.
DR OpenTargets; ENSG00000136560; -.
DR PharmGKB; PA36330; -.
DR VEuPathDB; HostDB:ENSG00000136560; -.
DR eggNOG; ENOG502QRM3; Eukaryota.
DR GeneTree; ENSGT00390000008712; -.
DR HOGENOM; CLU_053153_0_0_1; -.
DR InParanoid; Q92844; -.
DR OMA; IWQPQDN; -.
DR OrthoDB; 5358337at2759; -.
DR PhylomeDB; Q92844; -.
DR TreeFam; TF336453; -.
DR PathwayCommons; Q92844; -.
DR Reactome; R-HSA-9013973; TICAM1-dependent activation of IRF3/IRF7.
DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation.
DR Reactome; R-HSA-936964; Activation of IRF3, IRF7 mediated by TBK1, IKBKE.
DR SignaLink; Q92844; -.
DR SIGNOR; Q92844; -.
DR BioGRID-ORCS; 10010; 22 hits in 1158 CRISPR screens.
DR ChiTaRS; TANK; human.
DR EvolutionaryTrace; Q92844; -.
DR GeneWiki; TANK_(gene); -.
DR GenomeRNAi; 10010; -.
DR Pharos; Q92844; Tbio.
DR PRO; PR:Q92844; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q92844; Protein.
DR Bgee; ENSG00000136560; Expressed in monocyte and 205 other cell types or tissues.
DR ExpressionAtlas; Q92844; baseline and differential.
DR Genevisible; Q92844; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProt.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:1902554; C:serine/threonine protein kinase complex; NAS:ComplexPortal.
DR GO; GO:0035800; F:deubiquitinase activator activity; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt.
DR GO; GO:0140678; F:molecular function inhibitor activity; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; IBA:GO_Central.
DR GO; GO:0071347; P:cellular response to interleukin-1; IMP:UniProtKB.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; NAS:ComplexPortal.
DR GO; GO:0006974; P:DNA damage response; IMP:UniProtKB.
DR GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; IMP:UniProtKB.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:1903003; P:positive regulation of protein deubiquitination; IMP:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IDA:UniProt.
DR GO; GO:2000158; P:positive regulation of ubiquitin-specific protease activity; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; NAS:ComplexPortal.
DR InterPro; IPR041641; CALCOCO1/2_Zn_UBZ1.
DR InterPro; IPR039669; TANK.
DR InterPro; IPR024581; TBD.
DR PANTHER; PTHR15249; TRAF FAMILY MEMBER-ASSOCIATED NF-KAPPA-B ACTIVATOR; 1.
DR PANTHER; PTHR15249:SF0; TRAF FAMILY MEMBER-ASSOCIATED NF-KAPPA-B ACTIVATOR; 1.
DR Pfam; PF12845; TBD; 1.
DR PROSITE; PS51905; ZF_UBZ1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Coiled coil; Cytoplasm;
KW DNA damage; Host-virus interaction; Metal-binding; Phosphoprotein;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..425
FT /note="TRAF family member-associated NF-kappa-B activator"
FT /id="PRO_0000072427"
FT ZN_FING 393..420
FT /note="UBZ1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT REGION 1..31
FT /note="Necessary for interaction with ZC3H12A"
FT /evidence="ECO:0000269|PubMed:25861989"
FT REGION 70..191
FT /note="Necessary for interaction with TRAF6"
FT /evidence="ECO:0000269|PubMed:25861989"
FT REGION 133..172
FT /note="Interaction with TBK1 and IKBKE"
FT /evidence="ECO:0000250"
FT REGION 172..191
FT /note="TRAF family member interaction"
FT COILED 22..62
FT /evidence="ECO:0000255"
FT BINDING 396
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT BINDING 399
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT BINDING 416
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT BINDING 420
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01253"
FT SITE 197
FT /note="Cleavage by EMCV protease 3C"
FT /evidence="ECO:0000269|PubMed:26363073"
FT SITE 272..273
FT /note="(Microbial infection) Cleavage; by viral Seneca
FT Valley virus protease 3C"
FT /evidence="ECO:0000269|PubMed:28566380"
FT SITE 291..292
FT /note="(Microbial infection) Cleavage; by viral Seneca
FT Valley virus protease 3C"
FT /evidence="ECO:0000269|PubMed:28566380"
FT SITE 291
FT /note="Cleavage by EMCV protease 3C"
FT /evidence="ECO:0000269|PubMed:26363073"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 129
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 208
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 213
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 341
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 357
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19369195"
FT VAR_SEQ 111..119
FT /note="RRQEVSSPR -> DIASAESSI (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_043702"
FT VAR_SEQ 111..117
FT /note="RRQEVSS -> DIASAES (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004442"
FT VAR_SEQ 118..425
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004443"
FT VAR_SEQ 120..425
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_043703"
FT VARIANT 292
FT /note="G -> R (in dbSNP:rs10183668)"
FT /id="VAR_051409"
FT VARIANT 358
FT /note="P -> L (in dbSNP:rs2229759)"
FT /id="VAR_051410"
FT VARIANT 394
FT /note="R -> Q (in dbSNP:rs3769969)"
FT /id="VAR_051411"
FT MUTAGEN 182
FT /note="Q->A: Abolishes interaction with TRAF2 and TRAF3."
FT /evidence="ECO:0000269|PubMed:12005438"
FT MUTAGEN 184
FT /note="T->A: Abolishes interaction with TRAF2 and TRAF3."
FT /evidence="ECO:0000269|PubMed:12005438"
FT MUTAGEN 185
FT /note="D->A: Abolishes interaction with TRAF2; greatly
FT diminishes interaction with TRAF3."
FT /evidence="ECO:0000269|PubMed:12005438"
FT MUTAGEN 188
FT /note="D->A: Diminishes interaction with TRAF2 and TRAF3."
FT /evidence="ECO:0000269|PubMed:12005438"
FT MUTAGEN 194
FT /note="F->A: Diminishes interaction with TRAF2 and TRAF3."
FT /evidence="ECO:0000269|PubMed:12005438"
FT MUTAGEN 197
FT /note="Q->A: No effect on cleavage by Seneca Valley virus
FT protease 3C."
FT /evidence="ECO:0000269|PubMed:28566380"
FT MUTAGEN 247
FT /note="H->A: No effect on cleavage by Seneca Valley virus
FT protease 3C."
FT /evidence="ECO:0000269|PubMed:28566380"
FT MUTAGEN 251
FT /note="E->A: No effect on cleavage by Seneca Valley virus
FT protease 3C."
FT /evidence="ECO:0000269|PubMed:28566380"
FT MUTAGEN 262
FT /note="E->A: No effect on cleavage by Seneca Valley virus
FT protease 3C."
FT /evidence="ECO:0000269|PubMed:28566380"
FT MUTAGEN 266
FT /note="Q->A: No effect on cleavage by Seneca Valley virus
FT protease 3C."
FT /evidence="ECO:0000269|PubMed:28566380"
FT MUTAGEN 267
FT /note="E->A: No effect on cleavage by Seneca Valley virus
FT protease 3C."
FT /evidence="ECO:0000269|PubMed:28566380"
FT MUTAGEN 272
FT /note="E->A: Complete loss of cleavage by Seneca Valley
FT virus protease 3C."
FT /evidence="ECO:0000269|PubMed:28566380"
FT MUTAGEN 291
FT /note="Q->A: Complete loss of cleavage by Seneca Valley
FT virus protease 3C."
FT /evidence="ECO:0000269|PubMed:28566380"
FT CONFLICT 83
FT /note="E -> D (in Ref. 1; AAC50681)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="N -> T (in Ref. 1; AAC50681)"
FT /evidence="ECO:0000305"
FT CONFLICT 92
FT /note="D -> A (in Ref. 1; AAC50681)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="F -> S (in Ref. 1; AAC50681)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="K -> T (in Ref. 1; AAC50681)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="F -> L (in Ref. 1; AAC50681)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="L -> P (in Ref. 2; AAC50770)"
FT /evidence="ECO:0000305"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:1L0A"
SQ SEQUENCE 425 AA; 47816 MW; 718D30CF03EB27FF CRC64;
MDKNIGEQLN KAYEAFRQAC MDRDSAVKEL QQKTENYEQR IREQQEQLSL QQTIIDKLKS
QLLLVNSTQD NNYGCVPLLE DSETRKNNLT LDQPQDKVIS GIAREKLPKV RRQEVSSPRK
ETSARSLGSP LLHERGNIEK TFWDLKEEFH KICMLAKAQK DHLSKLNIPD TATETQCSVP
IQCTDKTDKQ EALFKPQAKD DINRGAPSIT SVTPRGLCRD EEDTSFESLS KFNVKFPPMD
NDSTFLHSTP ERPGILSPAT SEAVCQEKFN MEFRDNPGNF VKTEETLFEI QGIDPIASAI
QNLKTTDKTK PSNLVNTCIR TTLDRAACLP PGDHNALYVN SFPLLDPSDA PFPSLDSPGK
AIRGPQQPIW KPFPNQDSDS VVLSGTDSEL HIPRVCEFCQ AVFPPSITSR GDFLRHLNSH
FNGET
//
