ID FUS_HUMAN Reviewed; 526 AA. AC P35637; Q9H4A8; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 02-OCT-2024, entry version 245. DE RecName: Full=RNA-binding protein FUS; DE AltName: Full=75 kDa DNA-pairing protein; DE AltName: Full=Oncogene FUS; DE AltName: Full=Oncogene TLS; DE AltName: Full=POMp75; DE AltName: Full=Translocated in liposarcoma protein; GN Name=FUS; Synonyms=TLS; 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=8510758; DOI=10.1038/363640a0; RA Crozat A., Aman P., Mandahl N., Ron D.; RT "Fusion of CHOP to a novel RNA-binding protein in human myxoid RT liposarcoma."; RL Nature 363:640-644(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND CHROMOSOMAL TRANSLOCATION RP WITH DDIT3. RX PubMed=7503811; DOI=10.1038/ng0693-175; RA Rabbitts T.H., Forster A., Larson R., Nathan P.; RT "Fusion of the dominant negative transcription regulator CHOP with a novel RT gene FUS by translocation t(12;16) in malignant liposarcoma."; RL Nat. Genet. 4:175-180(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS LONG AND SHORT). RX PubMed=9795213; DOI=10.1016/s0378-1119(98)00463-6; RA Morohoshi F., Ootsuka Y., Arai K., Ichikawa H., Mitani S., Munakata N., RA Ohki M.; RT "Genomic structure of the human RBP56/hTAFII68 and FUS/TLS genes."; RL Gene 221:191-198(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC TISSUE=Lung, and Lymph; 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 85-310, CHROMOSOMAL TRANSLOCATION WITH ATF1, RP AND INVOLVEMENT IN AFH. RX PubMed=11063792; DOI=10.1016/s0165-4608(00)00237-5; RA Waters B.L., Panagopoulos I., Allen E.F.; RT "Genetic characterization of angiomatoid fibrous histiocytoma identifies RT fusion of the FUS and ATF-1 genes induced by a chromosomal translocation RT involving bands 12q13 and 16p11."; RL Cancer Genet. Cytogenet. 121:109-116(2000). RN [7] RP PROTEIN SEQUENCE OF 235-244; 307-312; 335-345 AND 349-357, FUNCTION, AND RP DNA-BINDING. RX PubMed=10567410; DOI=10.1074/jbc.274.48.34337; RA Baechtold H., Kuroda M., Sok J., Ron D., Lopez B.S., Akhmedov A.T.; RT "Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein RT TLS/FUS and is able to promote D-loop formation."; RL J. Biol. Chem. 274:34337-34342(1999). RN [8] RP PROTEIN SEQUENCE OF 265-276; 317-331 AND 335-357, AND IDENTIFICATION. RX PubMed=10442642; DOI=10.1038/sj.onc.1203048; RA Bertrand P., Akhmedov A.T., Delacote F., Durrbach A., Lopez B.S.; RT "Human POMp75 is identified as the pro-oncoprotein TLF/FUS: both POMp75 and RT POMp100 DNA homologous pairing activities are associated to cell RT proliferation."; RL Oncogene 18:4515-4521(1999). RN [9] RP PROTEIN SEQUENCE OF 349-357, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Fetal brain cortex; RA Lubec G., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [10] RP CHROMOSOMAL TRANSLOCATION WITH ERG. RX PubMed=8187069; RA Ichikawa H., Shimizu K., Hayashi Y., Ohki M.; RT "An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid RT leukemia with t(16;21) chromosomal translocation."; RL Cancer Res. 54:2865-2868(1994). RN [11] RP INTERACTION WITH SF1. RX PubMed=9660765; DOI=10.1074/jbc.273.29.18086; RA Zhang D., Paley A.J., Childs G.; RT "The transcriptional repressor ZFM1 interacts with and modulates the RT ability of EWS to activate transcription."; RL J. Biol. Chem. 273:18086-18091(1998). RN [12] RP INTERACTION WITH SFRS13A. RX PubMed=9774382; DOI=10.1074/jbc.273.43.27761; RA Yang L., Embree L.J., Tsai S., Hickstein D.D.; RT "Oncoprotein TLS interacts with serine-arginine proteins involved in RNA RT splicing."; RL J. Biol. Chem. 273:27761-27764(1998). RN [13] RP METHYLATION AT ARG-242; ARG-244; ARG-248; ARG-251; ARG-259; ARG-377; RP ARG-383; ARG-386; ARG-388; ARG-394; ARG-407; ARG-473; ARG-476; ARG-481; RP ARG-485; ARG-487; ARG-491; ARG-495; ARG-498 AND ARG-503, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=12964758; DOI=10.1021/ac026283q; RA Rappsilber J., Friesen W.J., Paushkin S., Dreyfuss G., Mann M.; RT "Detection of arginine dimethylated peptides by parallel precursor ion RT scanning mass spectrometry in positive ion mode."; RL Anal. Chem. 75:3107-3114(2003). RN [14] RP INTERACTION WITH SARNP. RX PubMed=17196963; DOI=10.1016/j.yexcr.2006.11.014; RA Sugiura T., Sakurai K., Nagano Y.; RT "Intracellular characterization of DDX39, a novel growth-associated RNA RT helicase."; RL Exp. Cell Res. 313:782-790(2007). RN [15] RP INTERACTION WITH TDRD3. RX PubMed=18632687; DOI=10.1093/hmg/ddn203; RA Goulet I., Boisvenue S., Mokas S., Mazroui R., Cote J.; RT "TDRD3, a novel Tudor domain-containing protein, localizes to cytoplasmic RT stress granules."; RL Hum. Mol. Genet. 17:3055-3074(2008). RN [16] RP PHOSPHORYLATION AT SER-42. RX PubMed=18620545; DOI=10.1042/bj20081135; RA Gardiner M., Toth R., Vandermoere F., Morrice N.A., Rouse J.; RT "Identification and characterization of FUS/TLS as a new target of ATM."; RL Biochem. J. 415:297-307(2008). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277 AND THR-286, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-221, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [20] RP IDENTIFICATION BY MASS 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-340, 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 [22] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=24204307; DOI=10.1371/journal.pgen.1003895; RA Zhou Y., Liu S., Liu G., Oztuerk A., Hicks G.G.; RT "ALS-associated FUS mutations result in compromised FUS alternative RT splicing and autoregulation."; RL PLoS Genet. 9:E1003895-E1003895(2013). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND RNA-BINDING. RX PubMed=25453086; DOI=10.1073/pnas.1414004111; RA Yang L., Gal J., Chen J., Zhu H.; RT "Self-assembled FUS binds active chromatin and regulates gene RT transcription."; RL Proc. Natl. Acad. Sci. U.S.A. 111:17809-17814(2014). RN [24] 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 [25] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-216; ARG-218 AND ARG-503, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [27] RP INTERACTION WITH LRSAM1. RX PubMed=27615052; DOI=10.1002/ana.24776; RA Hu B., Arpag S., Zuchner S., Li J.; RT "A novel missense mutation of CMT2P alters transcription machinery."; RL Ann. Neurol. 80:834-845(2016). RN [28] RP FUNCTION, AND INTERACTION WITH SNRNP70 AND POLR2A. RX PubMed=26124092; DOI=10.1073/pnas.1506282112; RA Yu Y., Reed R.; RT "FUS functions in coupling transcription to splicing by mediating an RT interaction between RNAP II and U1 snRNP."; RL Proc. Natl. Acad. Sci. U.S.A. 112:8608-8613(2015). RN [29] RP FUNCTION, AND INTERACTION WITH SAFB AND MATR3. RX PubMed=27731383; DOI=10.1038/srep35195; RA Yamaguchi A., Takanashi K.; RT "FUS interacts with nuclear matrix-associated protein SAFB1 as well as RT Matrin3 to regulate splicing and ligand-mediated transcription."; RL Sci. Rep. 6:35195-35195(2016). RN [30] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-334, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [31] RP PHOSPHORYLATION AT SER-26 AND SER-30, AND SUBCELLULAR LOCATION. RX PubMed=29897835; DOI=10.1091/mbc.e17-12-0735; RA Rhoads S.N., Monahan Z.T., Yee D.S., Leung A.Y., Newcombe C.G., RA O'Meally R.N., Cole R.N., Shewmaker F.P.; RT "The prionlike domain of FUS is multiphosphorylated following DNA damage RT without altering nuclear localization."; RL Mol. Biol. Cell 29:1786-1797(2018). RN [32] RP INTERACTION WITH RALY, AND SUBCELLULAR LOCATION. RX PubMed=30354839; DOI=10.1091/mbc.e18-02-0108; RA Gasperini L., Rossi A., Cornella N., Peroni D., Zuccotti P., Potrich V., RA Quattrone A., Macchi P.; RT "The hnRNP raly regulates PRMT1 expression and interacts with the ALS- RT linked protein FUS: implication for reciprocal cellular localization."; RL Mol. Biol. Cell 2018:MBCE18020108-MBCE18020108(2018). RN [33] RP STRUCTURE BY NMR OF 282-370. RG Northeast structural genomics consortium (NESG); RT "Northeast structural genomics consortium target HR6430A."; RL Submitted (MAY-2011) to the PDB data bank. RN [34] RP VARIANT [LARGE SCALE ANALYSIS] GLN-312. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [35] RP VARIANTS ALS6 CYS-244; SER-514; CYS-515; LYS-518; CYS-521; GLY-521; RP HIS-521; GLY-522; SER-524; THR-524 AND LEU-525, VARIANT GLN-517, RP SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT ALS6 GLY-521, AND RP CHARACTERIZATION OF VARIANT GLN-517. RX PubMed=19251627; DOI=10.1126/science.1166066; RA Kwiatkowski T.J. Jr., Bosco D.A., Leclerc A.L., Tamrazian E., RA Vanderburg C.R., Russ C., Davis A., Gilchrist J., Kasarskis E.J., RA Munsat T., Valdmanis P., Rouleau G.A., Hosler B.A., Cortelli P., RA de Jong P.J., Yoshinaga Y., Haines J.L., Pericak-Vance M.A., Yan J., RA Ticozzi N., Siddique T., McKenna-Yasek D., Sapp P.C., Horvitz H.R., RA Landers J.E., Brown R.H. Jr.; RT "Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic RT lateral sclerosis."; RL Science 323:1205-1208(2009). RN [36] RP VARIANTS ALS6 GLY-514; CYS-521 AND HIS-521, SUBCELLULAR LOCATION, AND RP CHARACTERIZATION OF VARIANTS ALS6 CYS-521 AND HIS-521. RX PubMed=19251628; DOI=10.1126/science.1165942; RA Vance C., Rogelj B., Hortobagyi T., De Vos K.J., Nishimura A.L., RA Sreedharan J., Hu X., Smith B., Ruddy D., Wright P., Ganesalingam J., RA Williams K.L., Tripathi V., Al-Saraj S., Al-Chalabi A., Leigh P.N., RA Blair I.P., Nicholson G., de Belleroche J., Gallo J.M., Miller C.C., RA Shaw C.E.; RT "Mutations in FUS, an RNA processing protein, cause familial amyotrophic RT lateral sclerosis type 6."; RL Science 323:1208-1211(2009). RN [37] RP VARIANTS ALS6 SER-191; CYS-216; VAL-225; CYS-230; CYS-234; ASP-507 AND RP CYS-521. RX PubMed=19861302; DOI=10.1136/jmg.2009.071027; RA Corrado L., Del Bo R., Castellotti B., Ratti A., Cereda C., Penco S., RA Soraru G., Carlomagno Y., Ghezzi S., Pensato V., Colombrita C., RA Gagliardi S., Cozzi L., Orsetti V., Mancuso M., Siciliano G., Mazzini L., RA Comi G.P., Gellera C., Ceroni M., D'Alfonso S., Silani V.; RT "Mutations of FUS gene in sporadic amyotrophic lateral sclerosis."; RL J. Med. Genet. 47:190-194(2010). RN [38] RP VARIANT ALS6 HIS-521, AND VARIANT VAL-254. RX PubMed=20124201; DOI=10.1212/wnl.0b013e3181ccc732; RA Van Langenhove T., van der Zee J., Sleegers K., Engelborghs S., RA Vandenberghe R., Gijselinck I., Van den Broeck M., Mattheijssens M., RA Peeters K., De Deyn P.P., Cruts M., Van Broeckhoven C.; RT "Genetic contribution of FUS to frontotemporal lobar degeneration."; RL Neurology 74:366-371(2010). RN [39] RP VARIANTS ETM4 CYS-216 AND LEU-431. RX PubMed=22863194; DOI=10.1016/j.ajhg.2012.07.002; RA Merner N.D., Girard S.L., Catoire H., Bourassa C.V., Belzil V.V., RA Riviere J.B., Hince P., Levert A., Dionne-Laporte A., Spiegelman D., RA Noreau A., Diab S., Szuto A., Fournier H., Raelson J., Belouchi M., RA Panisset M., Cossette P., Dupre N., Bernard G., Chouinard S., Dion P.A., RA Rouleau G.A.; RT "Exome sequencing identifies fus mutations as a cause of essential RT tremor."; RL Am. J. Hum. Genet. 91:313-319(2012). RN [40] RP VARIANTS ALS6 HIS-521 AND TYR-526 EXT. RX PubMed=27604643; DOI=10.1038/srep32478; RA Hou L., Jiao B., Xiao T., Zhou L., Zhou Z., Du J., Yan X., Wang J., RA Tang B., Shen L.; RT "Screening of SOD1, FUS and TARDBP genes in patients with amyotrophic RT lateral sclerosis in central-southern China."; RL Sci. Rep. 6:32478-32478(2016). CC -!- FUNCTION: DNA/RNA-binding protein that plays a role in various cellular CC processes such as transcription regulation, RNA splicing, RNA CC transport, DNA repair and damage response (PubMed:27731383). Binds to CC nascent pre-mRNAs and acts as a molecular mediator between RNA CC polymerase II and U1 small nuclear ribonucleoprotein thereby coupling CC transcription and splicing (PubMed:26124092). Binds also its own pre- CC mRNA and autoregulates its expression; this autoregulation mechanism is CC mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in CC DNA repair mechanisms by promoting D-loop formation and homologous CC recombination during DNA double-strand break repair (PubMed:10567410). CC In neuronal cells, plays crucial roles in dendritic spine formation and CC stability, RNA transport, mRNA stability and synaptic homeostasis (By CC similarity). {ECO:0000250|UniProtKB:P56959, CC ECO:0000269|PubMed:10567410, ECO:0000269|PubMed:24204307, CC ECO:0000269|PubMed:26124092, ECO:0000269|PubMed:27731383}. CC -!- SUBUNIT: Self-oligomerizes (via N-terminal region) (PubMed:25453086). CC Oligomerization is essential for chromatin binding (PubMed:25453086). CC Component of nuclear riboprotein complexes. Interacts with ILF3, TDRD3 CC and SF1 (PubMed:9660765). Interacts through its C-terminus with SFRS13A CC (PubMed:9774382). Interacts with OTUB1 and SARNP. Interacts with LRSAM1 CC (PubMed:27615052). Interacts with SAFB1 in a DNA-dependent manner; this CC interaction tethers FUS to chromatin (PubMed:27731383). Interacts with CC MATR3 (PubMed:27731383). Interacts with SNRNP70 and POLR2A; these CC interactions couple RNA transcription and splicing (PubMed:26124092). CC Interacts (through its RNA-binding domain) with RALY (through its RNA- CC binding domain); both are components of the same RNPs CC (PubMed:30354839). {ECO:0000269|PubMed:17196963, CC ECO:0000269|PubMed:18632687, ECO:0000269|PubMed:25453086, CC ECO:0000269|PubMed:26124092, ECO:0000269|PubMed:27615052, CC ECO:0000269|PubMed:27731383, ECO:0000269|PubMed:30354839, CC ECO:0000269|PubMed:9660765, ECO:0000269|PubMed:9774382}. CC -!- INTERACTION: CC P35637; P46379-2: BAG6; NbExp=3; IntAct=EBI-400434, EBI-10988864; CC P35637; O75815: BCAR3; NbExp=3; IntAct=EBI-400434, EBI-702336; CC P35637; Q13191: CBLB; NbExp=3; IntAct=EBI-400434, EBI-744027; CC P35637; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-400434, EBI-9087876; CC P35637; Q9NRR4: DROSHA; NbExp=2; IntAct=EBI-400434, EBI-528367; CC P35637; O60739: EIF1B; NbExp=3; IntAct=EBI-400434, EBI-1043343; CC P35637; Q09472: EP300; NbExp=4; IntAct=EBI-400434, EBI-447295; CC P35637; Q01844: EWSR1; NbExp=5; IntAct=EBI-400434, EBI-739737; CC P35637; P35637: FUS; NbExp=9; IntAct=EBI-400434, EBI-400434; CC P35637; Q05586: GRIN1; NbExp=3; IntAct=EBI-400434, EBI-998542; CC P35637; P49841-2: GSK3B; NbExp=3; IntAct=EBI-400434, EBI-15870655; CC P35637; Q92993: KAT5; NbExp=2; IntAct=EBI-400434, EBI-399080; CC P35637; O15479: MAGEB2; NbExp=3; IntAct=EBI-400434, EBI-1057615; CC P35637; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-400434, EBI-1058491; CC P35637; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-400434, EBI-10302990; CC P35637; Q15149: PLEC; NbExp=4; IntAct=EBI-400434, EBI-297903; CC P35637; Q99873: PRMT1; NbExp=5; IntAct=EBI-400434, EBI-78738; CC P35637; Q99873-3: PRMT1; NbExp=3; IntAct=EBI-400434, EBI-17165527; CC P35637; Q9UKA9-2: PTBP2; NbExp=3; IntAct=EBI-400434, EBI-12255608; CC P35637; Q9UKM9: RALY; NbExp=6; IntAct=EBI-400434, EBI-714796; CC P35637; P38159: RBMX; NbExp=7; IntAct=EBI-400434, EBI-743526; CC P35637; Q04206-3: RELA; NbExp=3; IntAct=EBI-400434, EBI-10223388; CC P35637; Q9BUL9: RPP25; NbExp=3; IntAct=EBI-400434, EBI-366570; CC P35637; P19793: RXRA; NbExp=3; IntAct=EBI-400434, EBI-78598; CC P35637; Q8N488: RYBP; NbExp=4; IntAct=EBI-400434, EBI-752324; CC P35637; Q15424: SAFB; NbExp=8; IntAct=EBI-400434, EBI-348298; CC P35637; P60896: SEM1; NbExp=3; IntAct=EBI-400434, EBI-79819; CC P35637; Q16637: SMN2; NbExp=2; IntAct=EBI-400434, EBI-395421; CC P35637; Q8NHS9: SPATA22; NbExp=3; IntAct=EBI-400434, EBI-7067260; CC P35637; Q92804: TAF15; NbExp=8; IntAct=EBI-400434, EBI-2255091; CC P35637; Q13148: TARDBP; NbExp=9; IntAct=EBI-400434, EBI-372899; CC P35637; Q92973-2: TNPO1; NbExp=2; IntAct=EBI-400434, EBI-11022821; CC P35637; Q9H3D4: TP63; NbExp=2; IntAct=EBI-400434, EBI-2337775; CC P35637; P18206-2: VCL; NbExp=3; IntAct=EBI-400434, EBI-11027067; CC P35637; P45481: Crebbp; Xeno; NbExp=4; IntAct=EBI-400434, EBI-296306; CC P35637; P97801: Smn1; Xeno; NbExp=5; IntAct=EBI-400434, EBI-309807; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19251627, CC ECO:0000269|PubMed:19251628, ECO:0000269|PubMed:24204307, CC ECO:0000269|PubMed:25453086, ECO:0000269|PubMed:30354839}. CC Note=Displays a punctate pattern inside the nucleus and is excluded CC from nucleoli. {ECO:0000269|PubMed:25453086}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=P35637-1; Sequence=Displayed; CC Name=Short; CC IsoId=P35637-2; Sequence=VSP_005798; CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- PTM: Arg-216 and Arg-218 are dimethylated, probably to asymmetric CC dimethylarginine. CC -!- PTM: Phosphorylated in its N-terminal serine residues upon induced DNA CC damage. ATM and DNA-PK are able to phosphorylate FUS N-terminal region. CC {ECO:0000269|PubMed:18620545, ECO:0000269|PubMed:29897835}. CC -!- DISEASE: Note=A chromosomal aberration involving FUS is found in a CC patient with malignant myxoid liposarcoma. Translocation CC t(12;16)(q13;p11) with DDIT3. {ECO:0000269|PubMed:7503811}. CC -!- DISEASE: Note=A chromosomal aberration involving FUS is a cause of CC acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG. CC {ECO:0000269|PubMed:8187069}. CC -!- DISEASE: Angiomatoid fibrous histiocytoma (AFH) [MIM:612160]: A CC distinct variant of malignant fibrous histiocytoma that typically CC occurs in children and adolescents and is manifest by nodular CC subcutaneous growth. Characteristic microscopic features include CC lobulated sheets of histiocyte-like cells intimately associated with CC areas of hemorrhage and cystic pseudovascular spaces, as well as a CC striking cuffing of inflammatory cells, mimicking a lymph node CC metastasis. {ECO:0000269|PubMed:11063792}. Note=The gene represented in CC this entry is involved in disease pathogenesis. A chromosomal CC aberration involving FUS is found in a patient with angiomatoid fibrous CC histiocytoma. Translocation t(12;16)(q13;p11.2) with ATF1 generates a CC chimeric FUS/ATF1 protein. {ECO:0000269|PubMed:11063792}. CC -!- DISEASE: Amyotrophic lateral sclerosis 6, with or without CC frontotemporal dementia (ALS6) [MIM:608030]: A neurodegenerative CC disorder affecting upper motor neurons in the brain and lower motor CC neurons in the brain stem and spinal cord, resulting in fatal CC paralysis. Sensory abnormalities are absent. The pathologic hallmarks CC of the disease include pallor of the corticospinal tract due to loss of CC motor neurons, presence of ubiquitin-positive inclusions within CC surviving motor neurons, and deposition of pathologic aggregates. The CC etiology of amyotrophic lateral sclerosis is likely to be CC multifactorial, involving both genetic and environmental factors. The CC disease is inherited in 5-10% of the cases. CC {ECO:0000269|PubMed:19251627, ECO:0000269|PubMed:19251628, CC ECO:0000269|PubMed:19861302, ECO:0000269|PubMed:20124201, CC ECO:0000269|PubMed:27604643}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Tremor, hereditary essential 4 (ETM4) [MIM:614782]: A common CC movement disorder mainly characterized by postural tremor of the arms. CC Head, legs, trunk, voice, jaw, and facial muscles may also be involved. CC The condition can be aggravated by emotions, hunger, fatigue and CC temperature extremes, and may cause a functional disability or even CC incapacitation. Inheritance is autosomal dominant. CC {ECO:0000269|PubMed:22863194}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the RRM TET family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44/FUS"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; S62140; AAB27102.1; -; mRNA. DR EMBL; S62138; AAB27103.1; ALT_SEQ; mRNA. DR EMBL; X71427; CAA50558.1; ALT_SEQ; mRNA. DR EMBL; X71428; CAA50559.1; ALT_SEQ; mRNA. DR EMBL; AF071213; AAC35285.1; -; Genomic_DNA. DR EMBL; AF071213; AAC35284.1; -; Genomic_DNA. DR EMBL; AC009088; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000402; AAH00402.1; -; mRNA. DR EMBL; BC002459; AAH02459.1; -; mRNA. DR EMBL; AJ295163; CAC15058.1; ALT_TERM; mRNA. DR CCDS; CCDS10707.1; -. [P35637-1] DR CCDS; CCDS58454.1; -. [P35637-2] DR PIR; S33798; S33798. DR PIR; S33799; S33799. DR RefSeq; NP_001164105.1; NM_001170634.1. [P35637-2] DR RefSeq; NP_004951.1; NM_004960.3. [P35637-1] DR PDB; 2LA6; NMR; -; A=282-370. DR PDB; 2LCW; NMR; -; A=278-385. DR PDB; 4FDD; X-ray; 2.30 A; B=498-526. DR PDB; 4FQ3; X-ray; 3.00 A; B=495-526. DR PDB; 5W3N; NMR; -; A/B/C/D/E/F/G/H/I=2-214. DR PDB; 5XRR; X-ray; 1.50 A; A=54-59. DR PDB; 5XSG; EM; 0.73 A; A=37-42. DR PDB; 5YVG; X-ray; 4.05 A; X/Y=1-526. DR PDB; 5YVH; X-ray; 3.15 A; B=371-526. DR PDB; 5YVI; X-ray; 2.90 A; B=456-526. DR PDB; 6BWZ; X-ray; 1.10 A; A=37-42. DR PDB; 6BXV; X-ray; 1.10 A; A=54-61. DR PDB; 6BZP; EM; 1.10 A; A/B=77-82. DR PDB; 6G99; NMR; -; B=419-454. DR PDB; 6GBM; NMR; -; B=280-377. DR PDB; 6KJ1; EM; 0.65 A; A=37-42. DR PDB; 6KJ2; EM; 0.67 A; A=37-42. DR PDB; 6KJ3; EM; 0.60 A; A=37-42. DR PDB; 6KJ4; EM; 0.65 A; A=37-42. DR PDB; 6SNJ; NMR; -; A=260-390. DR PDB; 6XFM; EM; 2.62 A; 1/2/3/4/5/6/7/8=111-214. DR PDB; 7CYL; X-ray; 2.70 A; B=476-526. DR PDB; 7VQQ; EM; 2.90 A; A/B/C=2-214. DR PDBsum; 2LA6; -. DR PDBsum; 2LCW; -. DR PDBsum; 4FDD; -. DR PDBsum; 4FQ3; -. DR PDBsum; 5W3N; -. DR PDBsum; 5XRR; -. DR PDBsum; 5XSG; -. DR PDBsum; 5YVG; -. DR PDBsum; 5YVH; -. DR PDBsum; 5YVI; -. DR PDBsum; 6BWZ; -. DR PDBsum; 6BXV; -. DR PDBsum; 6BZP; -. DR PDBsum; 6G99; -. DR PDBsum; 6GBM; -. DR PDBsum; 6KJ1; -. DR PDBsum; 6KJ2; -. DR PDBsum; 6KJ3; -. DR PDBsum; 6KJ4; -. DR PDBsum; 6SNJ; -. DR PDBsum; 6XFM; -. DR PDBsum; 7CYL; -. DR PDBsum; 7VQQ; -. DR AlphaFoldDB; P35637; -. DR BMRB; P35637; -. DR EMDB; EMD-0696; -. DR EMDB; EMD-0697; -. DR EMDB; EMD-0698; -. DR EMDB; EMD-0699; -. DR EMDB; EMD-22169; -. DR EMDB; EMD-32092; -. DR SMR; P35637; -. DR BioGRID; 108797; 814. DR CORUM; P35637; -. DR DIP; DIP-29857N; -. DR IntAct; P35637; 424. DR MINT; P35637; -. DR STRING; 9606.ENSP00000254108; -. DR GlyCosmos; P35637; 10 sites, 2 glycans. DR GlyGen; P35637; 12 sites, 3 O-linked glycans (12 sites). DR iPTMnet; P35637; -. DR MetOSite; P35637; -. DR PhosphoSitePlus; P35637; -. DR SwissPalm; P35637; -. DR BioMuta; FUS; -. DR DMDM; 544357; -. DR jPOST; P35637; -. DR MassIVE; P35637; -. DR PaxDb; 9606-ENSP00000254108; -. DR PeptideAtlas; P35637; -. DR ProteomicsDB; 55119; -. [P35637-1] DR ProteomicsDB; 55120; -. [P35637-2] DR Pumba; P35637; -. DR TopDownProteomics; P35637-1; -. [P35637-1] DR TopDownProteomics; P35637-2; -. [P35637-2] DR ABCD; P35637; 1 sequenced antibody. DR Antibodypedia; 1307; 535 antibodies from 38 providers. DR DNASU; 2521; -. DR Ensembl; ENST00000254108.12; ENSP00000254108.8; ENSG00000089280.20. [P35637-1] DR Ensembl; ENST00000380244.8; ENSP00000369594.3; ENSG00000089280.20. [P35637-2] DR GeneID; 2521; -. DR KEGG; hsa:2521; -. DR MANE-Select; ENST00000254108.12; ENSP00000254108.8; NM_004960.4; NP_004951.1. DR UCSC; uc002ebh.4; human. [P35637-1] DR AGR; HGNC:4010; -. DR CTD; 2521; -. DR DisGeNET; 2521; -. DR GeneCards; FUS; -. DR HGNC; HGNC:4010; FUS. DR HPA; ENSG00000089280; Low tissue specificity. DR MalaCards; FUS; -. DR MIM; 137070; gene. DR MIM; 608030; phenotype. DR MIM; 612160; phenotype. DR MIM; 614782; phenotype. DR neXtProt; NX_P35637; -. DR OpenTargets; ENSG00000089280; -. DR Orphanet; 803; Amyotrophic lateral sclerosis. DR Orphanet; 275872; Frontotemporal dementia with motor neuron disease. DR Orphanet; 300605; Juvenile amyotrophic lateral sclerosis. DR Orphanet; 79105; Myxofibrosarcoma. DR Orphanet; 99967; Myxoid/round cell liposarcoma. DR PharmGKB; PA28425; -. DR VEuPathDB; HostDB:ENSG00000089280; -. DR eggNOG; KOG1995; Eukaryota. DR GeneTree; ENSGT00940000157290; -. DR InParanoid; P35637; -. DR OMA; SYSKGPM; -. DR OrthoDB; 162112at2759; -. DR PhylomeDB; P35637; -. DR TreeFam; TF322599; -. DR PathwayCommons; P35637; -. DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway. DR Reactome; R-HSA-72203; Processing of Capped Intron-Containing Pre-mRNA. DR SignaLink; P35637; -. DR SIGNOR; P35637; -. DR BioGRID-ORCS; 2521; 58 hits in 1174 CRISPR screens. DR ChiTaRS; FUS; human. DR EvolutionaryTrace; P35637; -. DR GeneWiki; FUS; -. DR GenomeRNAi; 2521; -. DR Pharos; P35637; Tbio. DR PRO; PR:P35637; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P35637; protein. DR Bgee; ENSG00000089280; Expressed in right testis and 213 other cell types or tissues. DR ExpressionAtlas; P35637; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0043232; C:intracellular non-membrane-bounded organelle; IDA:DisProt. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0140693; F:molecular condensate scaffold activity; IDA:DisProt. DR GO; GO:0003730; F:mRNA 3'-UTR binding; IEA:Ensembl. DR GO; GO:0003723; F:RNA binding; IDA:MGI. DR GO; GO:0003713; F:transcription coactivator activity; IDA:CACAO. DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central. DR GO; GO:1990000; P:amyloid fibril formation; IDA:DisProt. DR GO; GO:0048255; P:mRNA stabilization; IDA:MGI. DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; IDA:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0043484; P:regulation of RNA splicing; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0008380; P:RNA splicing; IDA:UniProtKB. DR CDD; cd12535; RRM_FUS_TAF15; 1. DR DisProt; DP01102; -. DR Gene3D; 3.30.70.330; -; 1. DR Gene3D; 4.10.1060.10; Zinc finger, RanBP2-type; 1. DR IDEAL; IID00451; -. DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf. DR InterPro; IPR035979; RBD_domain_sf. DR InterPro; IPR000504; RRM_dom. DR InterPro; IPR034870; TET_fam. DR InterPro; IPR001876; Znf_RanBP2. DR InterPro; IPR036443; Znf_RanBP2_sf. DR PANTHER; PTHR23238; RNA BINDING PROTEIN; 1. DR PANTHER; PTHR23238:SF5; RNA-BINDING PROTEIN FUS; 1. DR Pfam; PF00076; RRM_1; 1. DR Pfam; PF00641; zf-RanBP; 1. DR SMART; SM00360; RRM; 1. DR SMART; SM00547; ZnF_RBZ; 1. DR SUPFAM; SSF90209; Ran binding protein zinc finger-like; 1. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 1. DR PROSITE; PS50102; RRM; 1. DR PROSITE; PS01358; ZF_RANBP2_1; 1. DR PROSITE; PS50199; ZF_RANBP2_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Amyotrophic lateral sclerosis; KW Chromosomal rearrangement; Direct protein sequencing; Disease variant; KW DNA-binding; Isopeptide bond; Metal-binding; Methylation; KW Neurodegeneration; Nucleus; Phosphoprotein; Proteomics identification; KW Proto-oncogene; Reference proteome; Repeat; RNA-binding; Ubl conjugation; KW Zinc; Zinc-finger. FT CHAIN 1..526 FT /note="RNA-binding protein FUS" FT /id="PRO_0000081591" FT DOMAIN 285..371 FT /note="RRM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT ZN_FING 422..453 FT /note="RanBP2-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322" FT REGION 1..286 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 375..424 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 444..526 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..169 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 176..206 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 469..492 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 509..526 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 175 FT /note="Breakpoint for translocation to form chimeric FT FUS/ATF1 protein" FT SITE 266..267 FT /note="Breakpoint for translocation to form FUS/TLS-CHOP FT oncogene" FT MOD_RES 26 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:29897835" FT MOD_RES 30 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:29897835" FT MOD_RES 42 FT /note="Phosphoserine; by ATM" FT /evidence="ECO:0000269|PubMed:18620545" FT MOD_RES 216 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 216 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 218 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 218 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 221 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 242 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 244 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 248 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 251 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 259 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 277 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 286 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 340 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 377 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 383 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 386 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 388 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 394 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 407 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 407 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:P56959" FT MOD_RES 473 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 476 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 481 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 485 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 487 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 491 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 495 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 498 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 503 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0000269|PubMed:12964758" FT MOD_RES 503 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT CROSSLNK 334 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 64..65 FT /note="TG -> S (in isoform Short)" FT /evidence="ECO:0000303|PubMed:7503811" FT /id="VSP_005798" FT VARIANT 191 FT /note="G -> S (in ALS6; dbSNP:rs148758737)" FT /evidence="ECO:0000269|PubMed:19861302" FT /id="VAR_068918" FT VARIANT 216 FT /note="R -> C (in ALS6 and ETM4; dbSNP:rs267606832)" FT /evidence="ECO:0000269|PubMed:19861302, FT ECO:0000269|PubMed:22863194" FT /id="VAR_068919" FT VARIANT 225 FT /note="G -> V (in ALS6; dbSNP:rs1567472455)" FT /evidence="ECO:0000269|PubMed:19861302" FT /id="VAR_068920" FT VARIANT 230 FT /note="G -> C (in ALS6; dbSNP:rs748374535)" FT /evidence="ECO:0000269|PubMed:19861302" FT /id="VAR_068921" FT VARIANT 234 FT /note="R -> C (in ALS6; dbSNP:rs777819849)" FT /evidence="ECO:0000269|PubMed:19861302" FT /id="VAR_068922" FT VARIANT 244 FT /note="R -> C (in ALS6; dbSNP:rs1165095258)" FT /evidence="ECO:0000269|PubMed:19251627" FT /id="VAR_054837" FT VARIANT 254 FT /note="M -> V (found in a patient with frontotemporal lobar FT degeneration; dbSNP:rs752076094)" FT /evidence="ECO:0000269|PubMed:20124201" FT /id="VAR_065229" FT VARIANT 312 FT /note="K -> Q (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035481" FT VARIANT 431 FT /note="P -> L (in ETM4; dbSNP:rs186547381)" FT /evidence="ECO:0000269|PubMed:22863194" FT /id="VAR_068923" FT VARIANT 507 FT /note="G -> D (in ALS6; dbSNP:rs267606831)" FT /evidence="ECO:0000269|PubMed:19861302" FT /id="VAR_068924" FT VARIANT 514 FT /note="R -> G (in ALS6; dbSNP:rs1555509609)" FT /evidence="ECO:0000269|PubMed:19251628" FT /id="VAR_054838" FT VARIANT 514 FT /note="R -> S (in ALS6)" FT /evidence="ECO:0000269|PubMed:19251627" FT /id="VAR_054839" FT VARIANT 515 FT /note="G -> C (in ALS6; dbSNP:rs369757630)" FT /evidence="ECO:0000269|PubMed:19251627" FT /id="VAR_054840" FT VARIANT 517 FT /note="H -> Q (does not affect protein nuclear FT localization; dbSNP:rs121909667)" FT /evidence="ECO:0000269|PubMed:19251627" FT /id="VAR_054841" FT VARIANT 518 FT /note="R -> K (in ALS6; dbSNP:rs121909669)" FT /evidence="ECO:0000269|PubMed:19251627" FT /id="VAR_054842" FT VARIANT 521 FT /note="R -> C (in ALS6; results in aberrant trafficking and FT cytoplasmic retention of the protein; dbSNP:rs121909668)" FT /evidence="ECO:0000269|PubMed:19251627, FT ECO:0000269|PubMed:19251628, ECO:0000269|PubMed:19861302" FT /id="VAR_054843" FT VARIANT 521 FT /note="R -> G (in ALS6; results in aberrant trafficking and FT cytoplasmic retention of the protein; dbSNP:rs121909668)" FT /evidence="ECO:0000269|PubMed:19251627" FT /id="VAR_054844" FT VARIANT 521 FT /note="R -> H (in ALS6; results in aberrant trafficking and FT cytoplasmic retention of the protein; dbSNP:rs121909671)" FT /evidence="ECO:0000269|PubMed:19251627, FT ECO:0000269|PubMed:19251628, ECO:0000269|PubMed:20124201, FT ECO:0000269|PubMed:27604643" FT /id="VAR_054845" FT VARIANT 522 FT /note="R -> G (in ALS6; dbSNP:rs1555509693)" FT /evidence="ECO:0000269|PubMed:19251627" FT /id="VAR_054846" FT VARIANT 524 FT /note="R -> S (in ALS6; dbSNP:rs886041389)" FT /evidence="ECO:0000269|PubMed:19251627" FT /id="VAR_054847" FT VARIANT 524 FT /note="R -> T (in ALS6; dbSNP:rs544088874)" FT /evidence="ECO:0000269|PubMed:19251627" FT /id="VAR_054848" FT VARIANT 525 FT /note="P -> L (in ALS6; dbSNP:rs886041390)" FT /evidence="ECO:0000269|PubMed:19251627" FT /id="VAR_054849" FT VARIANT 526 FT /note="Y -> YY (in ALS6; uncertain significance)" FT /evidence="ECO:0000269|PubMed:27604643" FT /id="VAR_077328" FT CONFLICT 338 FT /note="T -> N (in Ref. 7; AA sequence)" FT /evidence="ECO:0000305" FT TURN 40..43 FT /evidence="ECO:0007829|PDB:7VQQ" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:5W3N" FT STRAND 55..58 FT /evidence="ECO:0007829|PDB:7VQQ" FT STRAND 59..64 FT /evidence="ECO:0007829|PDB:5W3N" FT STRAND 68..70 FT /evidence="ECO:0007829|PDB:7VQQ" FT STRAND 73..75 FT /evidence="ECO:0007829|PDB:5W3N" FT STRAND 93..96 FT /evidence="ECO:0007829|PDB:7VQQ" FT TURN 98..101 FT /evidence="ECO:0007829|PDB:7VQQ" FT STRAND 113..124 FT /evidence="ECO:0007829|PDB:6XFM" FT STRAND 129..132 FT /evidence="ECO:0007829|PDB:6XFM" FT STRAND 139..149 FT /evidence="ECO:0007829|PDB:6XFM" FT HELIX 267..269 FT /evidence="ECO:0007829|PDB:6SNJ" FT STRAND 270..272 FT /evidence="ECO:0007829|PDB:6SNJ" FT HELIX 273..275 FT /evidence="ECO:0007829|PDB:6SNJ" FT STRAND 285..290 FT /evidence="ECO:0007829|PDB:2LA6" FT HELIX 298..305 FT /evidence="ECO:0007829|PDB:2LA6" FT TURN 306..308 FT /evidence="ECO:0007829|PDB:2LA6" FT TURN 315..318 FT /evidence="ECO:0007829|PDB:2LA6" FT STRAND 319..326 FT /evidence="ECO:0007829|PDB:2LA6" FT TURN 328..330 FT /evidence="ECO:0007829|PDB:2LA6" FT STRAND 332..343 FT /evidence="ECO:0007829|PDB:2LA6" FT HELIX 344..354 FT /evidence="ECO:0007829|PDB:2LA6" FT STRAND 358..363 FT /evidence="ECO:0007829|PDB:2LA6" FT STRAND 365..368 FT /evidence="ECO:0007829|PDB:2LA6" FT HELIX 372..375 FT /evidence="ECO:0007829|PDB:6GBM" FT STRAND 379..381 FT /evidence="ECO:0007829|PDB:2LCW" FT TURN 431..433 FT /evidence="ECO:0007829|PDB:6G99" FT TURN 445..447 FT /evidence="ECO:0007829|PDB:6G99" FT STRAND 450..452 FT /evidence="ECO:0007829|PDB:6G99" FT HELIX 514..521 FT /evidence="ECO:0007829|PDB:4FDD" SQ SEQUENCE 526 AA; 53426 MW; 88C8E263B7905549 CRC64; MASNDYTQQA TQSYGAYPTQ PGQGYSQQSS QPYGQQSYSG YSQSTDTSGY GQSSYSSYGQ SQNTGYGTQS TPQGYGSTGG YGSSQSSQSS YGQQSSYPGY GQQPAPSSTS GSYGSSSQSS SYGQPQSGSY SQQPSYGGQQ QSYGQQQSYN PPQGYGQQNQ YNSSSGGGGG GGGGGNYGQD QSSMSSGGGS GGGYGNQDQS GGGGSGGYGQ QDRGGRGRGG SGGGGGGGGG GYNRSSGGYE PRGRGGGRGG RGGMGGSDRG GFNKFGGPRD QGSRHDSEQD NSDNNTIFVQ GLGENVTIES VADYFKQIGI IKTNKKTGQP MINLYTDRET GKLKGEATVS FDDPPSAKAA IDWFDGKEFS GNPIKVSFAT RRADFNRGGG NGRGGRGRGG PMGRGGYGGG GSGGGGRGGF PSGGGGGGGQ QRAGDWKCPN PTCENMNFSW RNECNQCKAP KPDGPGGGPG GSHMGGNYGD DRRGGRGGYD RGGYRGRGGD RGGFRGGRGG GDRGGFGPGK MDSRGEHRQD RRERPY //