{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q01844","secondaryAccessions":["B0QYK1","Q5THL0","Q92635","Q96FE8","Q96MN4","Q96MX4","Q9BWA2"],"uniProtkbId":"EWS_HUMAN","entryAudit":{"firstPublicDate":"1994-06-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1994-06-01","entryVersion":255,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"RNA-binding protein EWS"}},"alternativeNames":[{"fullName":{"value":"EWS oncogene"}},{"fullName":{"value":"Ewing sarcoma breakpoint region 1 protein"}}]},"genes":[{"geneName":{"value":"EWSR1"},"synonyms":[{"value":"EWS"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10767297"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21256132"}],"value":"Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). Might normally function as a transcriptional repressor (PubMed:10767297). EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61545"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18632687"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9660765"}],"value":"Binds POLR2C, SF1, calmodulin and RNA. Interacts with PTK2B/FAK2 and TDRD3. Binds calmodulin in the presence, but not in the absence, of calcium ion. Forms a complex with REC8, PRDM9, SYCP3 and SYCP1; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 (By 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EWSR1 binds POLR2C but not POLR2E or POLR2G, whereas the isolated EAD binds POLR2E and POLR2G but not POLR2C. Cis-linked RNA-binding domain (RBD) can strongly and specifically repress trans-activation by the EAD"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9341188"}],"value":"Phosphorylated; calmodulin-binding inhibits phosphorylation of Ser-266"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11278906"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18320585"},{"evidenceCode":"ECO:0000269","source":"Reference","id":"Ref.12"}],"value":"Highly methylated on arginine residues. 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Ewing sarcoma represents the less differentiated form of the tumors.","diseaseCrossReference":{"database":"MIM","id":"612219"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15044653"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1522903"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7700648"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9121764"}]},"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15044653"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1522903"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7700648"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9121764"}],"value":"The protein represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving EWSR1 are found in patients with Ewing sarcoma. Translocation t(11;22)(q24;q12) with FLI1 (PubMed:15044653, PubMed:1522903). Translocation t(7;22)(p22;q12) with ETV1 (PubMed:7700648). Translocation t(21;22)(q22;q21) with ERG (PubMed:15044653). Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with potential oncogenic activity (PubMed:9121764)"}]}},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7539287"}],"value":"A chromosomal aberration involving EWSR1 has been found in extraskeletal myxoid chondrosarcoma. Translocation t(9;22)(q22-31;q11-12) with NR4A3"}]}},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7862627"}],"value":"A chromosomal aberration involving EWSR1 is associated with desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with WT1"}]}},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8401579"}],"value":"A chromosomal aberration involving EWSR1 is associated with malignant melanoma of soft parts (MMSP). 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Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type (PubMed:17724745)"}]}},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"EFPS arise due to chromosomal translocations in which EWSR1 is fused to a variety of cellular transcription factors. EFPS are very potent transcriptional activators dependent on the EAD and a C-terminal DNA-binding domain contributed by the fusion partner. The spectrum of malignancies associated with EFPS are thought to arise via EFP-induced transcriptional deregulation, with the tumor phenotype specified by the EWSR1 fusion partner and cell type. 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