ID EWS_HUMAN Reviewed; 656 AA. AC Q01844; B0QYK1; Q5THL0; Q92635; Q96FE8; Q96MN4; Q96MX4; Q9BWA2; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 27-MAR-2024, entry version 245. DE RecName: Full=RNA-binding protein EWS; DE AltName: Full=EWS oncogene; DE AltName: Full=Ewing sarcoma breakpoint region 1 protein; GN Name=EWSR1; Synonyms=EWS; 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 EWS), INVOLVEMENT IN EWS, AND RP CHROMOSOMAL TRANSLOCATION WITH FLI. RC TISSUE=Fetal brain; RX PubMed=1522903; DOI=10.1038/359162a0; RA Delattre O., Zucman J., Plougastel B., Desmaze C., Melot T., Peter M., RA Kovar H., Joubert I., de Jong P., Rouleau G., Aurias A., Thomas G.; RT "Gene fusion with an ETS DNA-binding domain caused by chromosome RT translocation in human tumours."; RL Nature 359:162-165(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8307570; DOI=10.1016/s0888-7543(05)80363-5; RA Plougastel B., Zucman J., Peter M., Thomas G., Delattre O.; RT "Genomic structure of the EWS gene and its relationship to EWSR1, a site of RT tumor-associated chromosome translocation."; RL Genomics 18:609-615(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Zucman-Rossi J., Legoix P., Thomas G.; RT "Genomic sequence of the human EWS gene with the 5' flanking region."; RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS EWS; 3 AND 4). RC TISSUE=Lymph, Muscle, Placenta, and Skin; 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 [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-345. RX PubMed=8975699; DOI=10.1006/geno.1996.0625; RA Zucman-Rossi J., Legoix P., Thomas G.; RT "Identification of new members of the Gas2 and Ras families in the 22q12 RT chromosome region."; RL Genomics 38:247-254(1996). RN [10] RP PROTEIN SEQUENCE OF 128-158; 233-247; 268-324; 334-364; 393-439; 447-518 RP AND 551-641, METHYLATION AT ARG-300; ARG-302; ARG-304; ARG-309; ARG-314; RP ARG-317; ARG-321; ARG-455; ARG-464; ARG-471; ARG-490; ARG-494; ARG-500; RP ARG-503; ARG-506; ARG-563; ARG-565; ARG-572; ARG-575; ARG-581; ARG-589; RP ARG-592; ARG-596; ARG-600; ARG-603; ARG-607; ARG-615; ARG-633 AND ARG-636, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11278906; DOI=10.1074/jbc.m011446200; RA Belyanskaya L.L., Gehrig P.M., Gehring H.; RT "Exposure on cell surface and extensive arginine methylation of Ewing RT sarcoma (EWS) protein."; RL J. Biol. Chem. 276:18681-18687(2001). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 241-268. RC TISSUE=Placenta; RX PubMed=7542907; DOI=10.1002/gcc.2870130209; RA Bhagirath T., Abe S., Nojima T., Yoshida M.C.; RT "Molecular analysis of a t(11;22) translocation junction in a case of RT Ewing's sarcoma."; RL Genes Chromosomes Cancer 13:126-132(1995). RN [12] RP PROTEIN SEQUENCE OF 269-292; 393-404; 411-439; 491-500 AND 615-632, RP METHYLATION AT ARG-494 AND ARG-615, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Colon carcinoma, and Ovarian carcinoma; RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Zebisch A., RA Kolch W.; RL Submitted (DEC-2008) to UniProtKB. RN [13] RP PARTIAL PROTEIN SEQUENCE, AND PHOSPHORYLATION AT SER-266. RX PubMed=9341188; DOI=10.1074/jbc.272.43.27369; RA Deloulme J.C., Prichard L., Delattre O., Storm D.R.; RT "The prooncoprotein EWS binds calmodulin and is phosphorylated by protein RT kinase C through an IQ domain."; RL J. Biol. Chem. 272:27369-27377(1997). RN [14] RP CHROMOSOMAL TRANSLOCATION WITH ATF1. RX PubMed=8401579; DOI=10.1038/ng0893-341; RA Zucman J., Delattre O., Desmaze C., Epstein A.L., Stenman G., Speleman F., RA Fletchers C.D., Aurias A., Thomas G.; RT "EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant RT melanoma of soft parts."; RL Nat. Genet. 4:341-345(1993). RN [15] RP ALTERNATIVE SPLICING, AND RNA-BINDING. RX PubMed=8084618; RA Ohno T., Ouchida M., Lee L., Gatalica Z., Rao V.N., Reddy E.S.P.; RT "The EWS gene, involved in Ewing family of tumors, malignant melanoma of RT soft parts and desmoplastic small round cell tumors, codes for an RNA RT binding protein with novel regulatory domains."; RL Oncogene 9:3087-3097(1994). RN [16] RP CHROMOSOMAL TRANSLOCATION WITH NR4A3. RX PubMed=7539287; DOI=10.1002/gcc.2870120412; RA Gill S., McManus A.P., Crew A.J., Benjamin H., Sheer D., Gusterson B.A., RA Pinkerton C.R., Patel K., Cooper C.S., Shipley J.M.; RT "Fusion of the EWS gene to a DNA segment from 9q22-31 in a human myxoid RT chondrosarcoma."; RL Genes Chromosomes Cancer 12:307-310(1995). RN [17] RP CHROMOSOMAL TRANSLOCATION WITH ETV1. RX PubMed=7700648; RA Jeon I.-S., Davis J.N., Braun B.S., Sublett J.E., Roussel M.F., Denny C.T., RA Shapiro D.N.; RT "A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the RT ETS gene ETV1."; RL Oncogene 10:1229-1234(1995). RN [18] RP CHROMOSOMAL TRANSLOCATION WITH WT1. RX PubMed=7862627; DOI=10.1073/pnas.92.4.1028; RA Gerald W.L., Rosai J., Ladanyi M.; RT "Characterization of the genomic breakpoint and chimeric transcripts in the RT EWS-WT1 gene fusion of desmoplastic small round cell tumor."; RL Proc. Natl. Acad. Sci. U.S.A. 92:1028-1032(1995). RN [19] RP INVOLVEMENT IN EWS, AND CHROMOSOMAL TRANSLOCATION WITH FEV. RX PubMed=9121764; DOI=10.1038/sj.onc.1200933; RA Peter M., Couturier J., Pacquement H., Michon J., Thomas G., Magdelenat H., RA Delattre O.; RT "A new member of the ETS family fused to EWS in Ewing tumors."; RL Oncogene 14:1159-1164(1997). RN [20] 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 [21] RP CHARACTERIZATION. RX PubMed=10767297; DOI=10.1074/jbc.m002961200; RA Li K.K.C., Lee K.A.W.; RT "Transcriptional activation by the Ewing's sarcoma (EWS) oncogene can be RT cis-repressed by the EWS RNA-binding domain."; RL J. Biol. Chem. 275:23053-23058(2000). RN [22] RP CHROMOSOMAL TRANSLOCATION WITH PATZ1. RX PubMed=10949935; DOI=10.1038/sj.onc.1203762; RA Mastrangelo T., Modena P., Tornielli S., Bullrich F., Testi A., RA Mezzelani A., Radice P., Azzarelli A., Pilotti S., Croce C., Pierotti M., RA Sozzi G.; RT "A novel zinc finger gene is fused to EWS in small round cell tumor."; RL Oncogene 19:3799-3804(2000). RN [23] RP CHROMOSOMAL TRANSLOCATION WITH ERG, CHROMOSOMAL TRANSLOCATION WITH FLI1, RP AND INVOLVEMENT IN EWS. RX PubMed=15044653; DOI=10.1056/nejmc032965; RA Bielack S.S., Paulussen M., Koehler G.; RT "A patient with two Ewing's sarcomas with distinct EWS fusion RT transcripts."; RL N. Engl. J. Med. 350:1364-1365(2004). RN [24] RP CHARACTERIZATION OF THE EWSR1-FEV FUSION PROTEIN. RX PubMed=17172842; DOI=10.4161/cc.5.23.3505; RA Braunreiter C.L., Hancock J.D., Coffin C.M., Boucher K.M., Lessnick S.L.; RT "Expression of EWS-ETS fusions in NIH3T3 cells reveals significant RT differences to Ewing's sarcoma."; RL Cell Cycle 5:2753-2759(2006). RN [25] RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF RP ARG-648; ARG-651; ARG-652; ASP-653; ARG-654; PRO-655 AND TYR-656. RX PubMed=16965792; DOI=10.1016/j.jmb.2006.08.018; RA Zakaryan R.P., Gehring H.; RT "Identification and characterization of the nuclear localization/retention RT signal in the EWS proto-oncoprotein."; RL J. Mol. Biol. 363:27-38(2006). RN [26] 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 [27] RP METHYLATION AT ARG-490; ARG-572; ARG-596; ARG-603 AND ARG-607. RX PubMed=18320585; DOI=10.1002/prot.22004; RA Pahlich S., Zakaryan R.P., Gehring H.; RT "Identification of proteins interacting with protein arginine RT methyltransferase 8: the Ewing sarcoma (EWS) protein binds independent of RT its methylation state."; RL Proteins 72:1125-1137(2008). RN [28] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [29] 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 [30] 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 [31] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-471; ARG-486 AND ARG-615, 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 [32] RP STRUCTURE BY NMR OF 353-453. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the RNA recognition motif of Ewing sarcoma (EWS) RT protein."; RL Submitted (NOV-2005) to the PDB data bank. RN [33] RP CHROMOSOMAL TRANSLOCATION WITH ATF1, AND INVOLVEMENT IN AFH. RX PubMed=15884099; DOI=10.1002/gcc.20201; RA Hallor K.H., Mertens F., Jin Y., Meis-Kindblom J.M., Kindblom L.-G., RA Behrendtz M., Kalen A., Mandahl N., Panagopoulos I.; RT "Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M RT transcript in angiomatoid fibrous histiocytoma."; RL Genes Chromosomes Cancer 44:97-102(2005). RN [34] RP CHROMOSOMAL TRANSLOCATION WITH CREB1, AND INVOLVEMENT IN AFH. RX PubMed=17724745; DOI=10.1002/gcc.20491; RA Antonescu C.R., Dal Cin P., Nafa K., Teot L.A., Surti U., Fletcher C.D., RA Ladanyi M.; RT "EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous RT histiocytoma."; RL Genes Chromosomes Cancer 46:1051-1060(2007). CC -!- FUNCTION: Might normally function as a transcriptional repressor. EWS- CC fusion-proteins (EFPS) may play a role in the tumorigenic process. They CC may disturb gene expression by mimicking, or interfering with the CC normal function of CTD-POLII within the transcription initiation CC complex. They may also contribute to an aberrant activation of the CC fusion protein target genes. CC -!- SUBUNIT: Binds POLR2C, SF1, calmodulin and RNA. Interacts with CC PTK2B/FAK2 and TDRD3. Binds calmodulin in the presence, but not in the CC absence, of calcium ion. Forms a complex with REC8, PRDM9, SYCP3 and CC SYCP1; complex formation is dependent of phosphorylated form of REC8 CC and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the CC chromosomal axis through REC8 (By similarity). CC {ECO:0000250|UniProtKB:Q61545, ECO:0000269|PubMed:18632687, CC ECO:0000269|PubMed:9660765}. CC -!- INTERACTION: CC Q01844; Q8N5M1: ATPAF2; NbExp=7; IntAct=EBI-739737, EBI-1166928; CC Q01844; P54252: ATXN3; NbExp=4; IntAct=EBI-739737, EBI-946046; CC Q01844; Q09472: EP300; NbExp=2; IntAct=EBI-739737, EBI-447295; CC Q01844; Q01844: EWSR1; NbExp=3; IntAct=EBI-739737, EBI-739737; CC Q01844; P35637: FUS; NbExp=5; IntAct=EBI-739737, EBI-400434; CC Q01844; Q92993: KAT5; NbExp=2; IntAct=EBI-739737, EBI-399080; CC Q01844; Q8NDC0: MAPK1IP1L; NbExp=5; IntAct=EBI-739737, EBI-741424; CC Q01844; Q9UBV8: PEF1; NbExp=3; IntAct=EBI-739737, EBI-724639; CC Q01844; O15162: PLSCR1; NbExp=4; IntAct=EBI-739737, EBI-740019; CC Q01844; Q99873: PRMT1; NbExp=2; IntAct=EBI-739737, EBI-78738; CC Q01844; Q9NZ81: PRR13; NbExp=3; IntAct=EBI-739737, EBI-740924; CC Q01844; Q9NS23-2: RASSF1; NbExp=3; IntAct=EBI-739737, EBI-438698; CC Q01844; O95486: SEC24A; NbExp=3; IntAct=EBI-739737, EBI-749911; CC Q01844; O94855: SEC24D; NbExp=3; IntAct=EBI-739737, EBI-748817; CC Q01844; Q13485: SMAD4; NbExp=3; IntAct=EBI-739737, EBI-347263; CC Q01844; Q9BWW4: SSBP3; NbExp=3; IntAct=EBI-739737, EBI-2902395; CC Q01844; Q92734: TFG; NbExp=3; IntAct=EBI-739737, EBI-357061; CC Q01844; Q13077: TRAF1; NbExp=3; IntAct=EBI-739737, EBI-359224; CC Q01844; Q12933: TRAF2; NbExp=3; IntAct=EBI-739737, EBI-355744; CC Q01844; P49910: ZNF165; NbExp=2; IntAct=EBI-739737, EBI-741694; CC Q01844-3; P54252: ATXN3; NbExp=9; IntAct=EBI-25973273, EBI-946046; CC Q01844-4; P54252: ATXN3; NbExp=3; IntAct=EBI-25896785, EBI-946046; CC Q01844-4; P42858: HTT; NbExp=3; IntAct=EBI-25896785, EBI-466029; CC Q01844-4; O76024: WFS1; NbExp=3; IntAct=EBI-25896785, EBI-720609; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16965792}. Cytoplasm CC {ECO:0000269|PubMed:16965792}. Cell membrane CC {ECO:0000269|PubMed:16965792}. Note=Relocates from cytoplasm to CC ribosomes upon PTK2B/FAK2 activation. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=EWS; CC IsoId=Q01844-1; Sequence=Displayed; CC Name=EWS-B; CC IsoId=Q01844-2; Sequence=VSP_005793; CC Name=3; CC IsoId=Q01844-3; Sequence=VSP_043453; CC Name=4; CC IsoId=Q01844-4; Sequence=VSP_043452, VSP_043454; CC Name=5; CC IsoId=Q01844-5; Sequence=VSP_043451, VSP_043453; CC Name=6; CC IsoId=Q01844-6; Sequence=VSP_045412; CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- DOMAIN: EWS activation domain (EAD) functions as a potent activation CC domain in EFPS. EWSR1 binds POLR2C but not POLR2E or POLR2G, whereas CC the isolated EAD binds POLR2E and POLR2G but not POLR2C. Cis-linked CC RNA-binding domain (RBD) can strongly and specifically repress trans- CC activation by the EAD. CC -!- PTM: Phosphorylated; calmodulin-binding inhibits phosphorylation of CC Ser-266. {ECO:0000269|PubMed:9341188}. CC -!- PTM: Highly methylated on arginine residues. Methylation is mediated by CC PRMT1 and, at lower level by PRMT8. {ECO:0000269|PubMed:11278906, CC ECO:0000269|PubMed:18320585, ECO:0000269|Ref.12}. CC -!- DISEASE: Ewing sarcoma (ES) [MIM:612219]: A highly malignant, CC metastatic, primitive small round cell tumor of bone and soft tissue CC that affects children and adolescents. It belongs to the Ewing sarcoma CC family of tumors, a group of morphologically heterogeneous neoplasms CC that share the same cytogenetic features. They are considered neural CC tumors derived from cells of the neural crest. Ewing sarcoma represents CC the less differentiated form of the tumors. CC {ECO:0000269|PubMed:15044653, ECO:0000269|PubMed:1522903, CC ECO:0000269|PubMed:7700648, ECO:0000269|PubMed:9121764}. Note=The CC protein represented in this entry is involved in disease pathogenesis. CC Chromosomal aberrations involving EWSR1 are found in patients with CC Ewing sarcoma. Translocation t(11;22)(q24;q12) with FLI1 CC (PubMed:1522903, PubMed:15044653). Translocation t(7;22)(p22;q12) with CC ETV1 (PubMed:7700648). Translocation t(21;22)(q22;q21) with ERG CC (PubMed:15044653). Translocation t(2;21;22)(q23;q22;q12) that forms a CC EWSR1-FEV fusion protein with potential oncogenic activity CC (PubMed:9121764). {ECO:0000269|PubMed:15044653, CC ECO:0000269|PubMed:1522903, ECO:0000269|PubMed:7700648, CC ECO:0000269|PubMed:9121764}. CC -!- DISEASE: Note=A chromosomal aberration involving EWSR1 has been found CC in extraskeletal myxoid chondrosarcoma. Translocation CC t(9;22)(q22-31;q11-12) with NR4A3. {ECO:0000269|PubMed:7539287}. CC -!- DISEASE: Note=A chromosomal aberration involving EWSR1 is associated CC with desmoplastic small round cell tumor (DSRCT). Translocation CC t(11;22)(p13;q12) with WT1. {ECO:0000269|PubMed:7862627}. CC -!- DISEASE: Note=A chromosomal aberration involving EWSR1 is associated CC with malignant melanoma of soft parts (MMSP). Translocation CC t(12;22)(q13;q12) with ATF1. Malignant melanoma of soft parts, also CC known as soft tissue clear cell sarcoma, is a rare tumor developing in CC tendons and aponeuroses. {ECO:0000269|PubMed:8401579}. CC -!- DISEASE: Note=A chromosomal aberration involving EWSR1 is associated CC with small round cell sarcoma. Translocation t(11;22)(p36.1;q12) with CC PATZ1. {ECO:0000269|PubMed:10949935}. 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:15884099, ECO:0000269|PubMed:17724745}. CC Note=The gene represented in this entry is involved in disease CC pathogenesis. Chromosomal aberrations involving EWSR1 are found in CC patients with angiomatoid fibrous histiocytoma. Translocation CC t(12;22)(q13;q12) with ATF1 generates a chimeric EWSR1/ATF1 protein CC (PubMed:15884099). Translocation t(2;22)(q33;q12) with CREB1 generates CC a EWSR1/CREB1 fusion gene that is most common genetic abnormality in CC this tumor type (PubMed:17724745). {ECO:0000269|PubMed:15884099, CC ECO:0000269|PubMed:17724745}. CC -!- DISEASE: Note=EFPS arise due to chromosomal translocations in which CC EWSR1 is fused to a variety of cellular transcription factors. EFPS are CC very potent transcriptional activators dependent on the EAD and a C- CC terminal DNA-binding domain contributed by the fusion partner. The CC spectrum of malignancies associated with EFPS are thought to arise via CC EFP-induced transcriptional deregulation, with the tumor phenotype CC specified by the EWSR1 fusion partner and cell type. Transcriptional CC repression of the transforming growth factor beta type II receptor (TGF CC beta RII) is an important target of the EWS-FLI1, EWS-ERG, or EWS-ETV1 CC oncogene. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the RRM TET family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA70044.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/85/EWSR1"; 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; X66899; CAA47350.1; -; mRNA. DR EMBL; X72990; CAA51489.1; -; Genomic_DNA. DR EMBL; X72991; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X72992; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X72993; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X72994; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X72995; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X72996; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X72997; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X72998; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X72999; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X73000; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X73001; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X73002; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X73003; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; X73004; CAA51489.1; JOINED; Genomic_DNA. DR EMBL; Y07848; CAA69177.1; -; Genomic_DNA. DR EMBL; CR456490; CAG30376.1; -; mRNA. DR EMBL; AK056309; BAB71145.1; -; mRNA. DR EMBL; AK056681; BAB71252.1; -; mRNA. DR EMBL; AL031186; CAI18001.1; -; Genomic_DNA. DR EMBL; AC000026; CAI18001.1; JOINED; Genomic_DNA. DR EMBL; AC002059; CAI18001.1; JOINED; Genomic_DNA. DR EMBL; AL031186; CAQ10937.1; -; Genomic_DNA. DR EMBL; AC000026; CAQ10937.1; JOINED; Genomic_DNA. DR EMBL; AC002059; CAQ10937.1; JOINED; Genomic_DNA. DR EMBL; AL031186; CAQ10938.1; -; Genomic_DNA. DR EMBL; AC000026; CAQ10938.1; JOINED; Genomic_DNA. DR EMBL; AC002059; CAQ10938.1; JOINED; Genomic_DNA. DR EMBL; AL031186; CAQ10940.1; -; Genomic_DNA. DR EMBL; AC000026; CAQ10940.1; JOINED; Genomic_DNA. DR EMBL; AC002059; CAQ10940.1; JOINED; Genomic_DNA. DR EMBL; CH471095; EAW59780.1; -; Genomic_DNA. DR EMBL; CH471095; EAW59781.1; -; Genomic_DNA. DR EMBL; CH471095; EAW59785.1; -; Genomic_DNA. DR EMBL; CH471095; EAW59786.1; -; Genomic_DNA. DR EMBL; CH471095; EAW59787.1; -; Genomic_DNA. DR EMBL; BC000527; AAH00527.1; -; mRNA. DR EMBL; BC004817; AAH04817.1; -; mRNA. DR EMBL; BC011048; AAH11048.1; -; mRNA. DR EMBL; BC072442; AAH72442.1; -; mRNA. DR EMBL; Y08806; CAA70044.1; ALT_INIT; Genomic_DNA. DR EMBL; AB016435; BAA31990.1; -; Genomic_DNA. DR CCDS; CCDS13851.1; -. [Q01844-1] DR CCDS; CCDS13852.2; -. [Q01844-5] DR CCDS; CCDS54512.1; -. [Q01844-4] DR CCDS; CCDS54513.1; -. [Q01844-3] DR CCDS; CCDS54514.1; -. [Q01844-6] DR PIR; A49358; A49358. DR RefSeq; NP_001156757.1; NM_001163285.1. [Q01844-3] DR RefSeq; NP_001156758.1; NM_001163286.1. [Q01844-6] DR RefSeq; NP_001156759.1; NM_001163287.1. [Q01844-4] DR RefSeq; NP_005234.1; NM_005243.3. [Q01844-1] DR RefSeq; NP_053733.2; NM_013986.3. [Q01844-5] DR PDB; 2CPE; NMR; -; A=353-453. DR PDBsum; 2CPE; -. DR AlphaFoldDB; Q01844; -. DR BMRB; Q01844; -. DR SMR; Q01844; -. DR BioGRID; 108431; 829. DR CORUM; Q01844; -. DR DIP; DIP-34449N; -. DR IntAct; Q01844; 214. DR MINT; Q01844; -. DR STRING; 9606.ENSP00000400142; -. DR BindingDB; Q01844; -. DR ChEMBL; CHEMBL3351202; -. DR GlyCosmos; Q01844; 46 sites, 2 glycans. DR GlyGen; Q01844; 50 sites, 2 O-linked glycans (50 sites). DR iPTMnet; Q01844; -. DR MetOSite; Q01844; -. DR PhosphoSitePlus; Q01844; -. DR SwissPalm; Q01844; -. DR BioMuta; EWSR1; -. DR DMDM; 544261; -. DR EPD; Q01844; -. DR jPOST; Q01844; -. DR MassIVE; Q01844; -. DR MaxQB; Q01844; -. DR PaxDb; 9606-ENSP00000400142; -. DR PeptideAtlas; Q01844; -. DR ProteomicsDB; 2658; -. DR ProteomicsDB; 58004; -. [Q01844-1] DR ProteomicsDB; 58005; -. [Q01844-2] DR ProteomicsDB; 58006; -. [Q01844-3] DR ProteomicsDB; 58007; -. [Q01844-4] DR ProteomicsDB; 58008; -. [Q01844-5] DR Pumba; Q01844; -. DR Antibodypedia; 3786; 661 antibodies from 41 providers. DR DNASU; 2130; -. DR Ensembl; ENST00000332035.10; ENSP00000331699.6; ENSG00000182944.18. [Q01844-6] DR Ensembl; ENST00000333395.11; ENSP00000327456.6; ENSG00000182944.18. [Q01844-4] DR Ensembl; ENST00000397938.7; ENSP00000381031.2; ENSG00000182944.18. [Q01844-1] DR Ensembl; ENST00000406548.5; ENSP00000385726.1; ENSG00000182944.18. [Q01844-3] DR Ensembl; ENST00000414183.6; ENSP00000400142.2; ENSG00000182944.18. [Q01844-5] DR GeneID; 2130; -. DR KEGG; hsa:2130; -. DR MANE-Select; ENST00000397938.7; ENSP00000381031.2; NM_005243.4; NP_005234.1. DR UCSC; uc003aes.5; human. [Q01844-1] DR AGR; HGNC:3508; -. DR CTD; 2130; -. DR DisGeNET; 2130; -. DR GeneCards; EWSR1; -. DR HGNC; HGNC:3508; EWSR1. DR HPA; ENSG00000182944; Low tissue specificity. DR MalaCards; EWSR1; -. DR MIM; 133450; gene. DR MIM; 612160; phenotype. DR MIM; 612219; phenotype. DR neXtProt; NX_Q01844; -. DR OpenTargets; ENSG00000182944; -. DR Orphanet; 83469; Desmoplastic small round cell tumor. DR Orphanet; 370334; Extraskeletal Ewing sarcoma. DR Orphanet; 209916; Extraskeletal myxoid chondrosarcoma. DR Orphanet; 97338; Melanoma of soft tissue. DR Orphanet; 319; Skeletal Ewing sarcoma. DR PharmGKB; PA27921; -. DR VEuPathDB; HostDB:ENSG00000182944; -. DR eggNOG; KOG1995; Eukaryota. DR GeneTree; ENSGT00940000154191; -. DR HOGENOM; CLU_025609_1_1_1; -. DR InParanoid; Q01844; -. DR OMA; QSTAHGY; -. DR OrthoDB; 162112at2759; -. DR PhylomeDB; Q01844; -. DR TreeFam; TF322599; -. DR PathwayCommons; Q01844; -. DR SignaLink; Q01844; -. DR SIGNOR; Q01844; -. DR BioGRID-ORCS; 2130; 702 hits in 1193 CRISPR screens. DR ChiTaRS; EWSR1; human. DR EvolutionaryTrace; Q01844; -. DR GeneWiki; Ewing_sarcoma_breakpoint_region_1; -. DR GenomeRNAi; 2130; -. DR Pharos; Q01844; Tbio. DR PRO; PR:Q01844; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q01844; Protein. DR Bgee; ENSG00000182944; Expressed in right uterine tube and 207 other cell types or tissues. DR ExpressionAtlas; Q01844; baseline and differential. DR GO; GO:0015030; C:Cajal body; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005516; F:calmodulin 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:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IEA:InterPro. DR CDD; cd12533; RRM_EWS; 1. DR DisProt; DP00632; -. DR Gene3D; 3.30.70.330; -; 1. DR Gene3D; 4.10.1060.10; Zinc finger, RanBP2-type; 1. DR InterPro; IPR034869; EWS_RRM. 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:SF3; RNA-BINDING PROTEIN EWS; 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. DR Genevisible; Q01844; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Calmodulin-binding; KW Cell membrane; Chromosomal rearrangement; Cytoplasm; KW Direct protein sequencing; Membrane; Metal-binding; Methylation; Nucleus; KW Phosphoprotein; Proto-oncogene; Reference proteome; Repeat; Repressor; KW RNA-binding; Transcription; Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1..656 FT /note="RNA-binding protein EWS" FT /id="PRO_0000081586" FT REPEAT 8..16 FT /note="1" FT REPEAT 17..27 FT /note="2" FT REPEAT 28..34 FT /note="3" FT REPEAT 35..42 FT /note="4" FT REPEAT 43..50 FT /note="5" FT REPEAT 51..59 FT /note="6" FT REPEAT 60..68 FT /note="7" FT REPEAT 69..75 FT /note="8" FT REPEAT 76..84 FT /note="9" FT REPEAT 85..91 FT /note="10" FT REPEAT 92..110 FT /note="11" FT REPEAT 111..116 FT /note="12" FT REPEAT 117..125 FT /note="13" FT REPEAT 126..156 FT /note="14" FT REPEAT 157..163 FT /note="15" FT REPEAT 164..170 FT /note="16" FT REPEAT 171..177 FT /note="17" FT REPEAT 178..188 FT /note="18" FT REPEAT 189..193 FT /note="19" FT REPEAT 194..201 FT /note="20" FT REPEAT 202..206 FT /note="21" FT REPEAT 207..212 FT /note="22" FT REPEAT 213..218 FT /note="23" FT REPEAT 219..224 FT /note="24" FT REPEAT 225..230 FT /note="25" FT REPEAT 231..238 FT /note="26" FT REPEAT 239..245 FT /note="27" FT REPEAT 246..252 FT /note="28" FT REPEAT 253..259 FT /note="29" FT DOMAIN 256..285 FT /note="IQ" FT REPEAT 260..276 FT /note="30" FT REPEAT 277..285 FT /note="31" FT DOMAIN 361..447 FT /note="RRM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT ZN_FING 518..549 FT /note="RanBP2-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322" FT REGION 1..285 FT /note="EAD (Gln/Pro/Thr-rich)" FT REGION 8..285 FT /note="31 X approximate tandem repeats" FT REGION 123..360 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 448..525 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 547..656 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 639..656 FT /note="Nuclear localization signal" FT /evidence="ECO:0000269|PubMed:16965792" FT COMPBIAS 133..178 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 180..194 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 195..293 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 462..476 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 548..562 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 637..656 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 265 FT /note="Breakpoint for translocation to form chimeric FT EWSR1/ATF1 protein" FT SITE 348..349 FT /note="Breakpoint for insertion to form EWSR1-FEV fusion FT protein" FT MOD_RES 266 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000250" FT MOD_RES 300 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 302 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 304 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 309 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 314 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 317 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 321 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 439 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q61545" FT MOD_RES 455 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 464 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 471 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 471 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000269|PubMed:11278906, FT ECO:0007744|PubMed:24129315" FT MOD_RES 486 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 490 FT /note="Asymmetric dimethylarginine; by PRMT8" FT /evidence="ECO:0000269|PubMed:11278906, FT ECO:0000269|PubMed:18320585" FT MOD_RES 494 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906, ECO:0000269|Ref.12" FT MOD_RES 500 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 503 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 506 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 506 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q61545" FT MOD_RES 563 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 565 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 572 FT /note="Asymmetric dimethylarginine; alternate; by PRMT8" FT /evidence="ECO:0000269|PubMed:11278906, FT ECO:0000269|PubMed:18320585" FT MOD_RES 572 FT /note="Omega-N-methylarginine; alternate; by PRMT8" FT /evidence="ECO:0000269|PubMed:11278906, FT ECO:0000269|PubMed:18320585" FT MOD_RES 575 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 581 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 589 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 592 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 596 FT /note="Asymmetric dimethylarginine; alternate; by PRMT8" FT /evidence="ECO:0000269|PubMed:11278906, FT ECO:0000269|PubMed:18320585" FT MOD_RES 596 FT /note="Omega-N-methylarginine; alternate; by PRMT8" FT /evidence="ECO:0000269|PubMed:11278906, FT ECO:0000269|PubMed:18320585" FT MOD_RES 600 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 603 FT /note="Asymmetric dimethylarginine; by PRMT8" FT /evidence="ECO:0000269|PubMed:11278906, FT ECO:0000269|PubMed:18320585" FT MOD_RES 607 FT /note="Asymmetric dimethylarginine; alternate; by PRMT8" FT /evidence="ECO:0000269|PubMed:11278906, FT ECO:0000269|PubMed:18320585" FT MOD_RES 607 FT /note="Omega-N-methylarginine; alternate; by PRMT8" FT /evidence="ECO:0000269|PubMed:11278906, FT ECO:0000269|PubMed:18320585" FT MOD_RES 615 FT /note="Asymmetric dimethylarginine; alternate" FT /evidence="ECO:0000269|PubMed:11278906, ECO:0000269|Ref.12" FT MOD_RES 615 FT /note="Omega-N-methylarginine; alternate" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 633 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT MOD_RES 636 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:11278906" FT VAR_SEQ 74 FT /note="P -> PTVEGTS (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043451" FT VAR_SEQ 136..191 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045412" FT VAR_SEQ 266..338 FT /note="Missing (in isoform EWS-B)" FT /evidence="ECO:0000305" FT /id="VSP_005793" FT VAR_SEQ 326..354 FT /note="SAGERGGFNKPGGPMDEGPDLDLGPPVDP -> LQSESLVYTSILKKYPYSV FT LSRQHNEKWD (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_043452" FT VAR_SEQ 326 FT /note="Missing (in isoform 3 and isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15461802, ECO:0000303|PubMed:15489334" FT /id="VSP_043453" FT VAR_SEQ 355..656 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_043454" FT MUTAGEN 648 FT /note="R->A: Cytoplasmic localization." FT /evidence="ECO:0000269|PubMed:16965792" FT MUTAGEN 648 FT /note="R->K: No effect on nuclear targeting." FT /evidence="ECO:0000269|PubMed:16965792" FT MUTAGEN 651 FT /note="R->A: No effect on nuclear targeting." FT /evidence="ECO:0000269|PubMed:16965792" FT MUTAGEN 652 FT /note="R->A: Cytoplasmic localization." FT /evidence="ECO:0000269|PubMed:16965792" FT MUTAGEN 652 FT /note="R->K: No effect on nuclear targeting." FT /evidence="ECO:0000269|PubMed:16965792" FT MUTAGEN 653 FT /note="D->A: No effect on nuclear targeting." FT /evidence="ECO:0000269|PubMed:16965792" FT MUTAGEN 654 FT /note="R->A: No effect on nuclear targeting." FT /evidence="ECO:0000269|PubMed:16965792" FT MUTAGEN 655 FT /note="P->A: Cytoplasmic localization." FT /evidence="ECO:0000269|PubMed:16965792" FT MUTAGEN 656 FT /note="Y->A: Cytoplasmic localization." FT /evidence="ECO:0000269|PubMed:16965792" FT CONFLICT 224 FT /note="S -> G (in Ref. 5; BAB71252)" FT /evidence="ECO:0000305" FT STRAND 362..366 FT /evidence="ECO:0007829|PDB:2CPE" FT HELIX 374..381 FT /evidence="ECO:0007829|PDB:2CPE" FT TURN 382..384 FT /evidence="ECO:0007829|PDB:2CPE" FT STRAND 391..393 FT /evidence="ECO:0007829|PDB:2CPE" FT STRAND 396..399 FT /evidence="ECO:0007829|PDB:2CPE" FT TURN 404..406 FT /evidence="ECO:0007829|PDB:2CPE" FT STRAND 411..419 FT /evidence="ECO:0007829|PDB:2CPE" FT HELIX 420..430 FT /evidence="ECO:0007829|PDB:2CPE" FT STRAND 441..443 FT /evidence="ECO:0007829|PDB:2CPE" SQ SEQUENCE 656 AA; 68478 MW; 0DA02CEE146720BB CRC64; MASTDYSTYS QAAAQQGYSA YTAQPTQGYA QTTQAYGQQS YGTYGQPTDV SYTQAQTTAT YGQTAYATSY GQPPTGYTTP TAPQAYSQPV QGYGTGAYDT TTATVTTTQA SYAAQSAYGT QPAYPAYGQQ PAATAPTRPQ DGNKPTETSQ PQSSTGGYNQ PSLGYGQSNY SYPQVPGSYP MQPVTAPPSY PPTSYSSTQP TSYDQSSYSQ QNTYGQPSSY GQQSSYGQQS SYGQQPPTSY PPQTGSYSQA PSQYSQQSSS YGQQSSFRQD HPSSMGVYGQ ESGGFSGPGE NRSMSGPDNR GRGRGGFDRG GMSRGGRGGG RGGMGSAGER GGFNKPGGPM DEGPDLDLGP PVDPDEDSDN SAIYVQGLND SVTLDDLADF FKQCGVVKMN KRTGQPMIHI YLDKETGKPK GDATVSYEDP PTAKAAVEWF DGKDFQGSKL KVSLARKKPP MNSMRGGLPP REGRGMPPPL RGGPGGPGGP GGPMGRMGGR GGDRGGFPPR GPRGSRGNPS GGGNVQHRAG DWQCPNPGCG NQNFAWRTEC NQCKAPKPEG FLPPPFPPPG GDRGRGGPGG MRGGRGGLMD RGGPGGMFRG GRGGDRGGFR GGRGMDRGGF GGGRRGGPGG PPGPLMEQMG GRRGGRGGPG KMDKGEHRQE RRDRPY //