true2002-03-272024-03-27234TADBP_HUMANCloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs.Ou S.-H.I.Wu F.Harrich D.Garcia-Martinez L.F.Gaynor R.B.doi:10.1128/jvi.69.6.3584-3596.19951995J. Virol.693584-3596NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)CHARACTERIZATIONCervix carcinomaTDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein.Strong M.J.Volkening K.Hammond R.Yang W.Strong W.Leystra-Lantz C.Shoesmith C.doi:10.1016/j.mcn.2007.03.0072007Mol. Cell. Neurosci.35320-327NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)FUNCTIONSUBCELLULAR LOCATIONUBIQUITINATIONComplete sequencing and characterization of 21,243 full-length human cDNAs.Ota T.Suzuki Y.Nishikawa T.Otsuki T.Sugiyama T.Irie R.Wakamatsu A.Hayashi K.Sato H.Nagai K.Kimura K.Makita H.Sekine M.Obayashi M.Nishi T.Shibahara T.Tanaka T.Ishii S.Yamamoto J.Saito K.Kawai Y.Isono Y.Nakamura Y.Nagahari K.Murakami K.Yasuda T.Iwayanagi T.Wagatsuma M.Shiratori A.Sudo H.Hosoiri T.Kaku Y.Kodaira H.Kondo H.Sugawara M.Takahashi M.Kanda K.Yokoi T.Furuya T.Kikkawa E.Omura Y.Abe K.Kamihara K.Katsuta N.Sato K.Tanikawa M.Yamazaki M.Ninomiya K.Ishibashi T.Yamashita H.Murakawa K.Fujimori K.Tanai H.Kimata M.Watanabe M.Hiraoka S.Chiba Y.Ishida S.Ono Y.Takiguchi S.Watanabe S.Yosida M.Hotuta T.Kusano J.Kanehori K.Takahashi-Fujii A.Hara H.Tanase T.-O.Nomura Y.Togiya S.Komai F.Hara R.Takeuchi K.Arita M.Imose N.Musashino K.Yuuki H.Oshima A.Sasaki N.Aotsuka S.Yoshikawa Y.Matsunawa H.Ichihara T.Shiohata N.Sano S.Moriya S.Momiyama H.Satoh N.Takami S.Terashima Y.Suzuki O.Nakagawa S.Senoh A.Mizoguchi H.Goto Y.Shimizu F.Wakebe H.Hishigaki H.Watanabe T.Sugiyama A.Takemoto M.Kawakami B.Yamazaki M.'Watanabe K.Kumagai A.Itakura S.Fukuzumi Y.Fujimori Y.Komiyama M.Tashiro H.Tanigami A.Fujiwara T.Ono T.Yamada K.Fujii Y.Ozaki K.Hirao M.Ohmori Y.Kawabata A.Hikiji T.Kobatake N.Inagaki H.Ikema Y.Okamoto S.Okitani R.Kawakami T.Noguchi S.Itoh T.Shigeta K.Senba T.Matsumura K.Nakajima Y.Mizuno T.Morinaga M.Sasaki M.Togashi T.Oyama M.Hata H.Watanabe M.'Komatsu T.Mizushima-Sugano J.Satoh T.Shirai Y.Takahashi Y.Nakagawa K.Okumura K.Nagase T.Nomura N.Kikuchi H.Masuho Y.Yamashita R.Nakai K.Yada T.Nakamura Y.'Ohara O.Isogai T.Sugano S.doi:10.1038/ng12852004Nat. Genet.3640-45NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)BrainSubstantia nigraCloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201).Ebert L.Schick M.Neubert P.Schatten R.Henze S.Korn B.2004-06EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)Suzuki Y.Sugano S.Totoki Y.Toyoda A.Takeda T.Sakaki Y.Tanaka A.Yokoyama S.2005-04EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)LiverThe full-ORF clone resource of the German cDNA consortium.Bechtel S.Rosenfelder H.Duda A.Schmidt C.P.Ernst U.Wellenreuther R.Mehrle A.Schuster C.Bahr A.Bloecker H.Heubner D.Hoerlein A.Michel G.Wedler H.Koehrer K.Ottenwaelder B.Poustka A.Wiemann S.Schupp I.doi:10.1186/1471-2164-8-3992007BMC Genomics8399NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)The DNA sequence and biological annotation of human chromosome 1.Gregory S.G.Barlow K.F.McLay K.E.Kaul R.Swarbreck D.Dunham A.Scott C.E.Howe K.L.Woodfine K.Spencer C.C.A.Jones M.C.Gillson C.Searle S.Zhou Y.Kokocinski F.McDonald L.Evans R.Phillips K.Atkinson A.Cooper R.Jones C.Hall R.E.Andrews T.D.Lloyd C.Ainscough R.Almeida J.P.Ambrose K.D.Anderson F.Andrew R.W.Ashwell R.I.S.Aubin K.Babbage A.K.Bagguley C.L.Bailey J.Beasley H.Bethel G.Bird C.P.Bray-Allen S.Brown J.Y.Brown A.J.Buckley D.Burton J.Bye J.Carder C.Chapman J.C.Clark S.Y.Clarke G.Clee C.Cobley V.Collier R.E.Corby N.Coville G.J.Davies J.Deadman R.Dunn M.Earthrowl M.Ellington A.G.Errington H.Frankish A.Frankland J.French L.Garner P.Garnett J.Gay L.Ghori M.R.J.Gibson R.Gilby L.M.Gillett W.Glithero R.J.Grafham D.V.Griffiths C.Griffiths-Jones S.Grocock R.Hammond S.Harrison E.S.I.Hart E.Haugen E.Heath P.D.Holmes S.Holt K.Howden P.J.Hunt A.R.Hunt S.E.Hunter G.Isherwood J.James R.Johnson C.Johnson D.Joy A.Kay M.Kershaw J.K.Kibukawa M.Kimberley A.M.King A.Knights A.J.Lad H.Laird G.Lawlor S.Leongamornlert D.A.Lloyd D.M.Loveland J.Lovell J.Lush M.J.Lyne R.Martin S.Mashreghi-Mohammadi M.Matthews L.Matthews N.S.W.McLaren S.Milne S.Mistry S.Moore M.J.F.Nickerson T.O'Dell C.N.Oliver K.Palmeiri A.Palmer S.A.Parker A.Patel D.Pearce A.V.Peck A.I.Pelan S.Phelps K.Phillimore B.J.Plumb R.Rajan J.Raymond C.Rouse G.Saenphimmachak C.Sehra H.K.Sheridan E.Shownkeen R.Sims S.Skuce C.D.Smith M.Steward C.Subramanian S.Sycamore N.Tracey A.Tromans A.Van Helmond Z.Wall M.Wallis J.M.White S.Whitehead S.L.Wilkinson J.E.Willey D.L.Williams H.Wilming L.Wray P.W.Wu Z.Coulson A.Vaudin M.Sulston J.E.Durbin R.M.Hubbard T.Wooster R.Dunham I.Carter N.P.McVean G.Ross M.T.Harrow J.Olson M.V.Beck S.Rogers J.Bentley D.R.doi:10.1038/nature047272006Nature441315-321NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]Mural R.J.Istrail S.Sutton G.G.Florea L.Halpern A.L.Mobarry C.M.Lippert R.Walenz B.Shatkay H.Dew I.Miller J.R.Flanigan M.J.Edwards N.J.Bolanos R.Fasulo D.Halldorsson B.V.Hannenhalli S.Turner R.Yooseph S.Lu F.Nusskern D.R.Shue B.C.Zheng X.H.Zhong F.Delcher A.L.Huson D.H.Kravitz S.A.Mouchard L.Reinert K.Remington K.A.Clark A.G.Waterman M.S.Eichler E.E.Adams M.D.Hunkapiller M.W.Myers E.W.Venter J.C.2005-07EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).The MGC Project Teamdoi:10.1101/gr.25965042004Genome Res.142121-2127NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)LymphTestisLubec G.Afjehi-Sadat L.2007-03UniProtKBPROTEIN SEQUENCE OF 122-136 AND 276-293IDENTIFICATION BY MASS SPECTROMETRYCajal-Retzius cellUbiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.Neumann M.Sampathu D.M.Kwong L.K.Truax A.C.Micsenyi M.C.Chou T.T.Bruce J.Schuck T.Grossman M.Clark C.M.McCluskey L.F.Miller B.L.Masliah E.Mackenzie I.R.Feldman H.Feiden W.Kretzschmar H.A.Trojanowski J.Q.Lee V.M.-Y.doi:10.1126/science.11341082006Science314130-133PROTEIN SEQUENCE OF 252-263; 276-293 AND 409-414SUBCELLULAR LOCATIONPHOSPHORYLATIONUBIQUITINATIONNuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping.Buratti E.Doerk T.Zuccato E.Pagani F.Romano M.Baralle F.E.doi:10.1093/emboj/20.7.17742001EMBO J.201774-1784FUNCTIONCharacterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9.Buratti E.Baralle F.E.doi:10.1074/jbc.m1042362002001J. Biol. Chem.27636337-36343RNA-BINDINGMUTAGENESISStructural determinants of the cellular localization and shuttling of TDP-43.Ayala Y.M.Zago P.D'Ambrogio A.Xu Y.F.Petrucelli L.Buratti E.Baralle F.E.doi:10.1242/jcs.0389502008J. Cell Sci.1213778-3785SUBCELLULAR LOCATIONMOTIFFunctional mapping of the interaction between TDP-43 and hnRNP A2 in vivo.D'Ambrogio A.Buratti E.Stuani C.Guarnaccia C.Romano M.Ayala Y.M.Baralle F.E.doi:10.1093/nar/gkp3422009Nucleic Acids Res.374116-4126INTERACTION WITH HNRNPA2B1Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.Mayya V.Lundgren D.H.Hwang S.-I.Rezaul K.Wu L.Eng J.K.Rodionov V.Han D.K.doi:10.1126/scisignal.20000072009Sci. Signal.2RA46PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Leukemic T-cellTDP-43 is recruited to stress granules in conditions of oxidative insult.Colombrita C.Zennaro E.Fallini C.Weber M.Sommacal A.Buratti E.Silani V.Ratti A.doi:10.1111/j.1471-4159.2009.06383.x2009J. Neurochem.1111051-1061SUBCELLULAR LOCATIONFUNCTIONTDP-43 dimerizes in human cells in culture.Shiina Y.Arima K.Tabunoki H.Satoh J.doi:10.1007/s10571-009-9489-92010Cell. Mol. Neurobiol.30641-652SUBUNITAtaxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS.Elden A.C.Kim H.J.Hart M.P.Chen-Plotkin A.S.Johnson B.S.Fang X.Armakola M.Geser F.Greene R.Lu M.M.Padmanabhan A.Clay-Falcone D.McCluskey L.Elman L.Juhr D.Gruber P.J.Rub U.Auburger G.Trojanowski J.Q.Lee V.M.Van Deerlin V.M.Bonini N.M.Gitler A.D.doi:10.1038/nature093202010Nature4661069-1075INTERACTION WITH ATXN2CHARACTERIZATION OF VARIANT ALS10 LYS-331Initial characterization of the human central proteome.Burkard T.R.Planyavsky M.Kaupe I.Breitwieser F.P.Buerckstuemmer T.Bennett K.L.Superti-Furga G.Colinge J.doi:10.1186/1752-0509-5-172011BMC Syst. Biol.517IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Characterizing the RNA targets and position-dependent splicing regulation by TDP-43.Tollervey J.R.Curk T.Rogelj B.Briese M.Cereda M.Kayikci M.Koenig J.Hortobagyi T.Nishimura A.L.Zupunski V.Patani R.Chandran S.Rot G.Zupan B.Shaw C.E.Ule J.doi:10.1038/nn.27782011Nat. Neurosci.14452-458FUNCTIONCharacterizing TDP-43 interaction with its RNA targets.Bhardwaj A.Myers M.P.Buratti E.Baralle F.E.doi:10.1093/nar/gkt1892013Nucleic Acids Res.415062-5074FUNCTIONRNA-BINDINGTDP-43 associates with stalled ribosomes and contributes to cell survival during cellular stress.Higashi S.Kabuta T.Nagai Y.Tsuchiya Y.Akiyama H.Wada K.doi:10.1111/jnc.121942013J. Neurochem.126288-300FUNCTIONSUBCELLULAR LOCATIONPHOSPHORYLATIONUbiquilin-2 (UBQLN2) binds with high affinity to the C-terminal region of TDP-43 and modulates TDP-43 levels in H4 cells: characterization of inhibition by nucleic acids and 4-aminoquinolines.Cassel J.A.Reitz A.B.doi:10.1016/j.bbapap.2013.03.0202013Biochim. Biophys. Acta1834964-971INTERACTION WITH UBQLN2Toward a comprehensive characterization of a human cancer cell phosphoproteome.Zhou H.Di Palma S.Preisinger C.Peng M.Polat A.N.Heck A.J.Mohammed S.doi:10.1021/pr300630k2013J. Proteome Res.12260-271PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183 AND SER-292IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]ErythroleukemiaAn enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.Bian Y.Song C.Cheng K.Dong M.Wang F.Huang J.Sun D.Wang L.Ye M.Zou H.doi:10.1016/j.jprot.2013.11.0142014J. Proteomics96253-262PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.Guo A.Gu H.Zhou J.Mulhern D.Wang Y.Lee K.A.Yang V.Aguiar M.Kornhauser J.Jia X.Ren J.Beausoleil S.A.Silva J.C.Vemulapalli V.Bedford M.T.Comb M.J.doi:10.1074/mcp.o113.0278702014Mol. Cell. Proteomics13372-387METHYLATION [LARGE SCALE ANALYSIS] AT ARG-293IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Colon carcinomaMutations in the matrin 3 gene cause familial amyotrophic lateral sclerosis.Johnson J.O.Pioro E.P.Boehringer A.Chia R.Feit H.Renton A.E.Pliner H.A.Abramzon Y.Marangi G.Winborn B.J.Gibbs J.R.Nalls M.A.Morgan S.Shoai M.Hardy J.Pittman A.Orrell R.W.Malaspina A.Sidle K.C.Fratta P.Harms M.B.Baloh R.H.Pestronk A.Weihl C.C.Rogaeva E.Zinman L.Drory V.E.Borghero G.Mora G.Calvo A.Rothstein J.D.Drepper C.Sendtner M.Singleton A.B.Taylor J.P.Cookson M.R.Restagno G.Sabatelli M.Bowser R.Chio A.Traynor B.J.doi:10.1038/nn.36882014Nat. Neurosci.17664-666INTERACTION WITH MATR3Uncovering global SUMOylation signaling networks in a site-specific manner.Hendriks I.A.D'Souza R.C.Yang B.Verlaan-de Vries M.Mann M.Vertegaal A.C.doi:10.1038/nsmb.28902014Nat. Struct. Mol. Biol.21927-936SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-181IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]SUMO-2 orchestrates chromatin modifiers in response to DNA damage.Hendriks I.A.Treffers L.W.Verlaan-de Vries M.Olsen J.V.Vertegaal A.C.doi:10.1016/j.celrep.2015.02.0332015Cell Rep.101778-1791SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-102 AND LYS-181IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]USP7 and TDP-43: pleiotropic regulation of cryptochrome protein stability paces the oscillation of the mammalian circadian clock.Hirano A.Nakagawa T.Yoshitane H.Oyama M.Kozuka-Hata H.Lanjakornsiripan D.Fukada Y.doi:10.1371/journal.pone.01542632016PLoS ONE11E0154263FUNCTIONINTERACTION WITH CRY2Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.Hendriks I.A.Lyon D.Young C.Jensen L.J.Vertegaal A.C.Nielsen M.L.doi:10.1038/nsmb.33662017Nat. Struct. Mol. Biol.24325-336SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-79; LYS-84; LYS-95; LYS-181 AND LYS-263IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]TDP-43 stabilises the processing intermediates of mitochondrial transcripts.Izumikawa K.Nobe Y.Yoshikawa H.Ishikawa H.Miura Y.Nakayama H.Nonaka T.Hasegawa M.Egawa N.Inoue H.Nishikawa K.Yamano K.Simpson R.J.Taoka M.Yamauchi Y.Isobe T.Takahashi N.doi:10.1038/s41598-017-06953-y2017Sci. Rep.77709FUNCTIONSUBCELLULAR LOCATIONTDP-43 accelerates deadenylation of target mRNAs by recruiting Caf1 deadenylase.Fukushima M.Hosoda N.Chifu K.Hoshino S.I.doi:10.1002/1873-3468.133102019FEBS Lett.593277-287FUNCTIONINTERACTION WITH CNOT7TDP-43 and RNA form amyloid-like myo-granules in regenerating muscle.Vogler T.O.Wheeler J.R.Nguyen E.D.Hughes M.P.Britson K.A.Lester E.Rao B.Betta N.D.Whitney O.N.Ewachiw T.E.Gomes E.Shorter J.Lloyd T.E.Eisenberg D.S.Taylor J.P.Johnson A.M.Olwin B.B.Parker R.doi:10.1038/s41586-018-0665-22018Nature563508-513FUNCTIONSUBCELLULAR LOCATIONSolution structure of the RNA binding domains of TAR DNA-binding protein-43.RIKEN structural genomics initiative (RSGI)2005-11PDBSTRUCTURE BY NMR OF 96-267Solution structure of RRM domain in tar DNA-binding protein-43.RIKEN structural genomics initiative (RSGI)2009-02PDBSTRUCTURE BY NMR OF 193-267Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43.Lukavsky P.J.Daujotyte D.Tollervey J.R.Ule J.Stuani C.Buratti E.Baralle F.E.Damberger F.F.Allain F.H.doi:10.1038/nsmb.26982013Nat. Struct. Mol. Biol.201443-1449STRUCTURE BY NMR OF 102-269RNA-BINDINGFUNCTIONThe crystal structure of TDP-43 RRM1-DNA complex reveals the specific recognition for UG- and TG-rich nucleic acids.Kuo P.H.Chiang C.H.Wang Y.T.Doudeva L.G.Yuan H.S.doi:10.1093/nar/gkt14072014Nucleic Acids Res.424712-4722X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 103-179FUNCTIONSUBUNITFunctional and dynamic polymerization of the ALS-linked protein TDP-43 antagonizes its pathologic aggregation.Afroz T.Hock E.M.Ernst P.Foglieni C.Jambeau M.Gilhespy L.A.B.Laferriere F.Maniecka Z.Plueckthun A.Mittl P.Paganetti P.Allain F.H.T.Polymenidou M.doi:10.1038/s41467-017-00062-02017Nat. Commun.845X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 2-80SUBUNITSUBCELLULAR LOCATIONA single N-terminal phosphomimic disrupts TDP-43 polymerization, phase separation, and RNA splicing.Wang A.Conicella A.E.Schmidt H.B.Martin E.W.Rhoads S.N.Reeb A.N.Nourse A.Ramirez Montero D.Ryan V.H.Rohatgi R.Shewmaker F.Naik M.T.Mittag T.Ayala Y.M.Fawzi N.L.doi:10.15252/embj.2017974522018EMBO J.37STRUCTURE BY NMR OF 1-80MUTAGENESIS OF SER-48SUBUNITFUNCTIONSUBCELLULAR LOCATIONAtomic-level evidence for packing and positional amyloid polymorphism by segment from TDP-43 RRM2.Guenther E.L.Ge P.Trinh H.Sawaya M.R.Cascio D.Boyer D.R.Gonen T.Zhou Z.H.Eisenberg D.S.doi:10.1038/s41594-018-0045-52018Nat. Struct. Mol. Biol.25311-319STRUCTURE BY ELECTRON MICROSCOPY (1.40 ANGSTROMS) OF 247-257TDP-43 A315T mutation in familial motor neuron disease.Gitcho M.A.Baloh R.H.Chakraverty S.Mayo K.Norton J.B.Levitch D.Hatanpaa K.J.White C.L. IIIBigio E.H.Caselli R.Baker M.Al-Lozi M.T.Morris J.C.Pestronk A.Rademakers R.Goate A.M.Cairns N.J.doi:10.1002/ana.213442008Ann. Neurol.63535-538VARIANT ALS10 THR-315TDP-43 mutation in familial amyotrophic lateral sclerosis.Yokoseki A.Shiga A.Tan C.F.Tagawa A.Kaneko H.Koyama A.Eguchi H.Tsujino A.Ikeuchi T.Kakita A.Okamoto K.Nishizawa M.Takahashi H.Onodera O.doi:10.1002/ana.213922008Ann. Neurol.63538-542VARIANT ALS10 ARG-343TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis.Van Deerlin V.M.Leverenz J.B.Bekris L.M.Bird T.D.Yuan W.Elman L.B.Clay D.Wood E.M.Chen-Plotkin A.S.Martinez-Lage M.Steinbart E.McCluskey L.Grossman M.Neumann M.Wu I.-L.Yang W.-S.Kalb R.Galasko D.R.Montine T.J.Trojanowski J.Q.Lee V.M.-Y.Schellenberg G.D.Yu C.-E.doi:10.1016/s1474-4422(08)70071-12008Lancet Neurol.7409-416VARIANTS ALS10 ALA-290 AND SER-298TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis.Kabashi E.Valdmanis P.N.Dion P.Spiegelman D.McConkey B.J.Vande Velde C.Bouchard J.-P.Lacomblez L.Pochigaeva K.Salachas F.Pradat P.-F.Camu W.Meininger V.Dupre N.Rouleau G.A.doi:10.1038/ng.1322008Nat. Genet.40572-574VARIANTS ALS10 GLY-169; SER-287; THR-315; CYS-348; SER-361; THR-382; ASP-390 AND SER-390VARIANT VAL-90TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis.Sreedharan J.Blair I.P.Tripathi V.B.Hu X.Vance C.Rogelj B.Ackerley S.Durnall J.C.Williams K.L.Buratti E.Baralle F.de Belleroche J.Mitchell J.D.Leigh P.N.Al-Chalabi A.Miller C.C.Nicholson G.Shaw C.E.doi:10.1126/science.11545842008Science3191668-1672VARIANTS ALS10 ALA-294; LYS-331 AND VAL-337VARIANT VAL-90CHARACTERIZATION OF VARIANTS ALS10 LYS-331 AND VAL-337TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration.Benajiba L.Le Ber I.Camuzat A.Lacoste M.Thomas-Anterion C.Couratier P.Legallic S.Salachas F.Hannequin D.Decousus M.Lacomblez L.Guedj E.Golfier V.Camu W.Dubois B.Campion D.Meininger V.Brice A.French clinical and genetic research network on frontotemporal lobar degeneration/frontotemporal lobar degeneration with motoneuron diseasedoi:10.1002/ana.216122009Ann. Neurol.65470-473INVOLVEMENT OF VARIANT ALS10 SER-295 IN FRONTOTEMPORAL LOBAR DEGENERATION WITH MOTOR NEURON DISEASEHigh frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis.Corrado L.Ratti A.Gellera C.Buratti E.Castellotti B.Carlomagno Y.Ticozzi N.Mazzini L.Testa L.Taroni F.Baralle F.E.Silani V.D'Alfonso S.doi:10.1002/humu.209502009Hum. Mutat.30688-694VARIANTS ALS10 SER-267; SER-287; VAL-294; SER-295; ARG-295; ASN-332; ASP-335; VAL-337; PRO-379; CYS-379; THR-382 AND LEU-393Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease.Borroni B.Bonvicini C.Alberici A.Buratti E.Agosti C.Archetti S.Papetti A.Stuani C.Di Luca M.Gennarelli M.Padovani A.doi:10.1002/humu.211002009Hum. Mutat.30E974-E983INVOLVEMENT OF VARIANT ALS10 SER-267 IN FRONTOTEMPORAL DEMENTIAGenetic variants in the promoter of TARDBP in sporadic amyotrophic lateral sclerosis.Luquin N.Yu B.Saunderson R.B.Trent R.J.Pamphlett R.doi:10.1016/j.nmd.2009.07.0052009Neuromuscul. Disord.19696-700VARIANT ALS10 ALA-294Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis.Kirby J.Goodall E.F.Smith W.Highley J.R.Masanzu R.Hartley J.A.Hibberd R.Hollinger H.C.Wharton S.B.Morrison K.E.Ince P.G.McDermott C.J.Shaw P.J.doi:10.1007/s10048-009-0218-92010Neurogenetics11217-225VARIANTS ALS10 SER-287; VAL-321; VAL-337 AND VAL-348VARIANT VAL-90CHARACTERIZATION OF VARIANTS ALS10 SER-287; VAL-321 AND VAL-337FUNCTIONLarge proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene.Chio A.Borghero G.Pugliatti M.Ticca A.Calvo A.Moglia C.Mutani R.Brunetti M.Ossola I.Marrosu M.G.Murru M.R.Floris G.Cannas A.Parish L.D.Cossu P.Abramzon Y.Johnson J.O.Nalls M.A.Arepalli S.Chong S.Hernandez D.G.Traynor B.J.Restagno G.doi:10.1001/archneurol.2010.3522011Arch. Neurol.68594-598VARIANT ALS10 THR-382High frequency of the TARDBP p.Ala382Thr mutation in Sardinian patients with amyotrophic lateral sclerosis.Orru S.Manolakos E.Orru N.Kokotas H.Mascia V.Carcassi C.Petersen M.B.doi:10.1111/j.1399-0004.2011.01668.x2012Clin. Genet.81172-178VARIANT ALS10 THR-382Novel TARDBP mutations in Nordic ALS patients.Chiang H.H.Andersen P.M.Tysnes O.B.Gredal O.Christensen P.B.Graff C.doi:10.1038/jhg.2012.242012J. Hum. Genet.57316-319VARIANT VAL-90VARIANTS ALS10 ARG-357; THR-361 AND PRO-379Peptidylprolyl isomerase A governs TARDBP function and assembly in heterogeneous nuclear ribonucleoprotein complexes.Lauranzano E.Pozzi S.Pasetto L.Stucchi R.Massignan T.Paolella K.Mombrini M.Nardo G.Lunetta C.Corbo M.Mora G.Bendotti C.Bonetto V.doi:10.1093/brain/awv0052015Brain138974-991CHARACTERIZATION OF VARIANTS ALS10 VAL-348; THR-315 AND SER-361FUNCTIONSUBCELLULAR LOCATIONINTERACTION WITH PPIAMUTAGENESIS OF 103-THR--SER-183TDP-43 triggers mitochondrial DNA release via mPTP to activate cGAS/STING in ALS.Yu C.H.Davidson S.Harapas C.R.Hilton J.B.Mlodzianoski M.J.Laohamonthonkul P.Louis C.Low R.R.J.Moecking J.De Nardo D.Balka K.R.Calleja D.J.Moghaddas F.Ni E.McLean C.A.Samson A.L.Tyebji S.Tonkin C.J.Bye C.R.Turner B.J.Pepin G.Gantier M.P.Rogers K.L.McArthur K.Crouch P.J.Masters S.L.doi:10.1016/j.cell.2020.09.0202020Cell183636-649CHARACTERIZATION OF VARIANTS ALS10 THR-315 AND LYS-331SUBCELLULAR LOCATIONSequence problems.Sequence problems.A=193-267A=96-185A=307-349A=311-360A=311-360A=311-360A=1-77A=102-2692.75A=103-1793.00A/B/C/D=101-1912.65A/B=101-1912.10A/B=2-80A=1-1021.40A/B=248-2531.40A=247-2573.800/1/2/3/4/5/6/7/8=247-2571.10A=312-3171.00A=312-3171.00A=370-3751.25A/B=396-4021.00A=312-3171.80A=300-306A=1-77A/B=1-800.75A=312-3171.50A/B=333-3433.80A/B/C/D/E/F/G/H/I/J=311-3603.30A/B/C/D/E/F/G/H/I/J=311-3603.80A/B/C/D/E/F/G/H/I/J=311-3603.30A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=286-3312.55A/C/E/G/I=1-803.20A/B/C/D/E=267-4142.20A=79-1022.60A/B/C/D=1-4143.70A/B/C/D/E=279-360A=309-3502.39A/B/C/D/U=1-4142.50A/B/C/D/U=1-4142.68A/B/C/D/U=1-4145402693 sites, 1 O-linked glycan (3 sites)22 sequenced antibodies1088 antibodies from 47 providershumanTARDBPLow tissue specificitygenephenotypeAmyotrophic lateral sclerosisFrontotemporal dementia with motor neuron diseaseEukaryota724 hits in 1132 CRISPR screenshumanTchemProteinExpressed in secondary oocyte and 207 other cell types or tissuesbaseline and differentialNTD_TDP-43RRM1_TDP43RRM2_TDP43Nucleotide-bd_a/b_plait_sfRBD_domain_sfRRM_domTDP-43_CTDP43_NRNA-BINDING (RRM/RBD/RNP MOTIFS) FAMILY PROTEINTAR DNA-BINDING PROTEIN 43RRM_1TDP-43_CTDP43_NRRMRNA-binding domain, RBDRRMHSTAR DNA-binding protein 43TDP-43TARDBPTDP43RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Regulates also mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:23398327, PubMed:19765185). Participates also in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563).Homodimer (PubMed:20043239, PubMed:24464995). Homooligomer (via its N-terminal domain) (PubMed:28663553, PubMed:29438978). Interacts with BRDT (By similarity). Binds specifically to pyrimidine-rich motifs of TAR DNA and to single stranded TG repeated sequences. Binds to RNA, specifically to UG repeated sequences with a minimum of six contiguous repeats. Interacts with ATXN2; the interaction is RNA-dependent (PubMed:20740007). Interacts with MATR3 (PubMed:24686783). Interacts with UBQLN2 (PubMed:23541532). Interacts with HNRNPA2B1 (PubMed:19429692). Interacts with ZNF106 (By similarity). Interacts with CNOT7/CAF1 (PubMed:30520513). Interacts with CRY2 (PubMed:27123980). Interacts with PPIA/CYPA; the interaction is dependent on RNA-binding activity of TARDBP and PPIase activity of PPIA/CYPA and acetylation of PPIA/CYPA at 'Lys-125' favors the interaction (PubMed:25678563).Continuously travels in and out of the nucleus (PubMed:18957508). Localizes to stress granules in response to oxidative stress (PubMed:19765185). A small subset localizes in mitochondria (PubMed:28794432).Ubiquitously expressed. In particular, expression is high in pancreas, placenta, lung, genital tract and spleen.Consists of an N-terminal domain (NTD) and two tandem RNA recognition motifs, RRM1 and RRM2, followed by a C-terminal glycine-rich region.Contains a nuclear localization sequence and is mostly nuclear; however, its nuclear export sequence permits it to transport mRNAs to the cytoplasm and even to synapses as part of neuronal granules.Hyperphosphorylated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Phosphorylated upon cellular stress.Ubiquitinated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU.Cleaved to generate C-terminal fragments in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU.The disease is caused by variants affecting the gene represented in this entry. Neurodegeneration is caused by activation of the cGAS-STING pathway: defects in TARDBP trigger mitochondrial DNA release into the cytosol via the permeability transition pore (PubMed:33031745). Released mitochondrial DNA is then detected by CGAS, leading to activation of the cGAS-STING pathway, triggering type-I interferon production and autoinflammation (PubMed:33031745).Probable cloning artifact.Probable cloning artifact.TAR DNA-binding protein 43447401414RRM 1104200RRM 2191262Interaction with UBQLN2216Disordered261303Disordered341373Nuclear localization signal8298Nuclear export signal239250Phosphoserine183Phosphoserine292Omega-N-methylarginine293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)79Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)84Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)95Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)102Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)181Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)263In isoform 2.MPQMLAGEIWCMLSTIQK18In isoform 2.19134V90In ALS10.G169In ALS10; also in a patient with frontotemporal dementia.S267In ALS10; loss of ability to negatively regulate the expression of CDK6.S287In ALS10.A290In ALS10.A294In ALS10; a patient with bulbar signs and dementia.VIn ALS10.R295In ALS10; also in patients with frontotemporal lobar degeneration with motor neuron disease.SIn ALS10.S298In ALS10; triggers mitochondrial DNA release into the cytosol, which is then detected by CGAS, leading to activation of the cGAS-STING pathway and autoinflammation; slight reduction in interaction with PPIA/CYPA.T315In ALS10; loss of ability to negatively regulate the expression of CDK6.V321In ALS10; triggers mitochondrial DNA release into the cytosol, which is then detected by CGAS, leading to activation of the cGAS-STING pathway and autoinflammation; impedes the development of normal limb and tail buds and increases the number of apoptotic nuclei when expressed in chick embryos; does not affect the interaction with ATXN2.K331In ALS10.N332In ALS10.D335In ALS10; impedes the development of normal limb and tail buds and increases the number of apoptotic nuclei when expressed in chick embryos; loss of ability to negatively regulate the expression of CDK6.V337In ALS10.R343In ALS10.C348In ALS10; loss of interaction with PPIA/CYPA.VIn ALS10.R357In ALS10; significant reduction in interaction with PPIA/CYPA.S361In ALS10.TIn ALS10.C379In ALS10.PIn ALS10.T382In ALS10.D390In ALS10.SIn ALS10.L393Complete loss of self-oligomerization.E48Loss of RNA-binding and reduced interaction with PPIA/CYPA.103Completely abolishes RNA binding.106175Completely abolishes RNA binding.DIDLGD111Completely abolishes RNA binding.Highly reduces binding to RNA and DNA.LGL147149Alters but does not abolish RNA binding.193257GV2784101622242527283233374044465053555760626567697172768789110117124125127130137139141144154155162166168171176197202204210212214219221231233237242243245247253258265273275283285288296300302305306316334342347350353356367370378384389395405412false3false3false3false6false6false6false3false6false3false3false3false3false6false6false3false6false3false6false6false6false6false3false6false6false6false3false6false3false3false3false3false3false6false6false2false3false6false6false3false6false3false6false6false3false3false6false6false6false3false6false7false6false6false6false6false6false6false6false3false3false8false6false6false7false6false6false3false6false3false6false3false7false3false6false3false6false3false3false3false6false6false3false6false6false3false6false2false6false6false6false6false6false3false3false3false3false3false6false3false6false6false6false6false3false6false3false6false6false6false6false3false6false6false6false6false6false3false6false3false3false6false3false6false6false4false3false6false8false6false6false6false3false3false6false3false3false6false10false6false3false3false6false3false6false3false3false3false6false3false3false3false3false3false3false3false3false6false3false3false3false3false6false6false3false6false6false6false3false3false6false6false3false3false6false6false31false6false6false6false6false6false4false3false3false3false3false3false3false6false3false3false3false3false3false6false3false3false3false3false6false3false6false3false7false6false3false3false4false6false6false6false6true2TARDBPABTB1ADARANKRD13DANXA8AP2B1APPAPPARL16ASB13ASB3ASB9ASB9ASIC4ATF3ATG7ATP6V1B1ATXN2BAG6BAHD1BEX5BIRC5BTBD1C6orf141C8orf48CBLBCBLCCBX2CCINCDC16CDC16CDC23CELF1CEP70CFAP100CHD2CLPPCRLF3CSNK1DDCAF7DCAF8DDI2DDX17DDX3XDDX5DEAF1DNAJA3DPF1DPP9EEDEIF3FELAVL1ENKUREPHB2ESRP1EXOC5FAM117BFAM98CFAM9AFBXL5FBXO4FUSGABPB1GMPPAGNB2GPSM3GTPBP3HDAC6HES4HNRNPCHNRNPCHNRNPDLHNRNPH1HNRNPKHNRNPKHNRNPRHNRNPUHNRNPUL1HNRNPUL1HNRPUL1ID2IFI35IGF2BP2IGF2BP3ILF3ILF3IQSEC1IRAK2JADE3KBTBD4KCTD15KCTD17KLF15KLHL17KLHL20KLHL22KLHL26KLHL32KLHL36KPNA4KRTAP9-2L3MBTL3LDHAL6BLGALS9CLNX1LNX2LONRF2LSM8MAGEC3MAPK11MATR3MED19METTL27MGARPMIER1MKL1MKRN2MKRN3MLC1MNAT1MOCS3MPNDMTF2MYCNME4NSFL1CNUP43NVLOTUB1OTUD7BOTX1PACS1PARP11PATZ1PBX4PCMTD2PDZRN4PP9974PPP1R15APPP1R21PRKNPRPF8PRPS1PSMB4PSMB8PSMD2PTBP1RAD18RBBP4RBCK1RBM10RBM46RBMXRELARMND5ARMND5BRNF10RNF112RNF138RNF14RNF166RNF183RYBPSF3B3SIAH1SKIC8SLC44A5SMARCD1SMURF1SOCS6SPAG8SPATA22SPSB1STAMBPSYMPKSYNCRIPTASOR2TBX22TERF2THAP3TNFRSF14TOB1TRIM23TRIM45TRIM65TRIM69TRIM74TRIM8TRIM9UBA7UBE2V1UBOX5UBQLNLUSP13USP2USP48VHLVPS37AVPS37AVSX2WDR12WDR83WWP2XRN2YBX1ZBTB24ZBTB25ZNF366ZNF581ZSCAN11996-11-01144740d21783f4e4f170aa5d52741bc444bf071MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM2MPQMLAGEIWCMLSTIQKVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMtruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue