FUS_HUMAN
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 03-AUG-2022, entry version 233.
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=5; IntAct=EBI-400434, EBI-714796;
CC P35637; P38159: RBMX; NbExp=5; 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=7; IntAct=EBI-400434, EBI-348298;
CC P35637; P60896: SEM1; NbExp=3; IntAct=EBI-400434, EBI-79819;
CC P35637; Q8NHS9: SPATA22; NbExp=3; IntAct=EBI-400434, EBI-7067260;
CC P35637; Q92804: TAF15; NbExp=7; IntAct=EBI-400434, EBI-2255091;
CC P35637; Q13148: TARDBP; NbExp=8; 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 also may 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="http://atlasgeneticsoncology.org/Genes/FUSID44.html";
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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 SMR; P35637; -.
DR BioGRID; 108797; 711.
DR CORUM; P35637; -.
DR DIP; DIP-29857N; -.
DR IntAct; P35637; 317.
DR MINT; P35637; -.
DR STRING; 9606.ENSP00000254108; -.
DR GlyGen; P35637; 10 sites, 2 O-linked glycans (10 sites).
DR iPTMnet; P35637; -.
DR MetOSite; P35637; -.
DR PhosphoSitePlus; P35637; -.
DR SwissPalm; P35637; -.
DR BioMuta; FUS; -.
DR DMDM; 544357; -.
DR EPD; P35637; -.
DR jPOST; P35637; -.
DR MassIVE; P35637; -.
DR MaxQB; P35637; -.
DR PaxDb; P35637; -.
DR PeptideAtlas; P35637; -.
DR PRIDE; P35637; -.
DR ProteomicsDB; 55119; -. [P35637-1]
DR ProteomicsDB; 55120; -. [P35637-2]
DR TopDownProteomics; P35637-1; -. [P35637-1]
DR TopDownProteomics; P35637-2; -. [P35637-2]
DR ABCD; P35637; 1 sequenced antibody.
DR Antibodypedia; 1307; 479 antibodies from 38 providers.
DR DNASU; 2521; -.
DR Ensembl; ENST00000254108.12; ENSP00000254108.8; ENSG00000089280.19. [P35637-1]
DR Ensembl; ENST00000380244.7; ENSP00000369594.3; ENSG00000089280.19. [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 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 Orphanet; 862; NON RARE IN EUROPE: Hereditary essential tremor.
DR PharmGKB; PA28425; -.
DR VEuPathDB; HostDB:ENSG00000089280; -.
DR eggNOG; KOG1995; Eukaryota.
DR GeneTree; ENSGT00940000157290; -.
DR InParanoid; P35637; -.
DR OMA; DSYNKGP; -.
DR PhylomeDB; P35637; -.
DR TreeFam; TF322599; -.
DR PathwayCommons; P35637; -.
DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway.
DR SignaLink; P35637; -.
DR SIGNOR; P35637; -.
DR BioGRID-ORCS; 2521; 53 hits in 1095 CRISPR screens.
DR ChiTaRS; FUS; human.
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 211 other tissues.
DR ExpressionAtlas; P35637; baseline and differential.
DR Genevisible; P35637; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
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: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: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: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:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IDA:UniProtKB.
DR DisProt; DP01102; -.
DR Gene3D; 3.30.70.330; -; 1.
DR IDEAL; IID00451; -.
DR InterPro; IPR034459; FUS.
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; PTHR23238; 1.
DR PANTHER; PTHR23238:SF5; PTHR23238:SF5; 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; SSF54928; SSF54928; 1.
DR SUPFAM; SSF90209; SSF90209; 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; Proto-oncogene;
KW Reference proteome; Repeat; RNA-binding; Ubl conjugation; Zinc;
KW 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; unknown pathological
FT 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
