RNA-binding protein EWS

RNA-binding protein EWS is a protein that in humans is encoded by the EWSR1 gene on human chromosome 22, specifically 22q12.2. It is one of 3 proteins in the FET protein family.

EWSR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CPE
Identifiers
Aliases	EWSR1, EWS, bK984G1.4, EWS-FLI1, Ewing sarcoma breakpoint region 1, EWS RNA binding protein 1
External IDs	OMIM: 133450; MGI: 99960; HomoloGene: 136069; GeneCards: EWSR1; OMA:EWSR1 - orthologs
Gene location (Human) Chr. Chromosome 22 (human) Band 22q12.2 Start 29,268,009 bp End 29,300,525 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 A1 Start 5,069,689 bp End 5,099,266 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube left testis right testis right hemisphere of cerebellum right lobe of thyroid gland right adrenal cortex left adrenal cortex ganglionic eminence body of uterus left lobe of thyroid gland Top expressed in yolk sac neural layer of retina ventricular zone genital tubercle tail of embryo superior frontal gyrus primary visual cortex spermatocyte spermatid lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function metal ion binding protein binding calmodulin binding identical protein binding nucleic acid binding RNA binding Cellular component cytoplasm plasma membrane nucleolus membrane nucleus Biological process regulation of transcription, DNA-templated transcription, DNA-templated Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2130 14030 Ensembl ENSG00000182944 ENSMUSG00000009079 UniProt Q01844 Q61545 RefSeq (mRNA) NM_001163285 NM_001163286 NM_001163287 NM_005243 NM_013986 NM_001283061 NM_001283062 NM_001283063 NM_007968 RefSeq (protein) NP_001156757 NP_001156758 NP_001156759 NP_005234 NP_053733 NP_001269990 NP_001269991 NP_001269992 NP_031994 NP_001349541 NP_001349542 NP_001349543 NP_001349544 NP_001349545 NP_001349546 NP_001349547 NP_001349549 Location (UCSC) Chr 22: 29.27 – 29.3 Mb Chr 11: 5.07 – 5.1 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Clinical significance

The q22.2 region of chromosome 22 encodes the N-terminal transactivation domain of the EWS protein and that region may become joined to one of several other chromosomes which encode various transcription factors; see EWS/FLI and OMIM-133450. The expression of a chimeric protein with the EWS transactivation domain fused to the DNA binding region of a transcription factor generates a powerful oncogenic protein causing Ewing sarcoma and other members of the Ewing family of tumors. These translocations can occur due to chromoplexy, a burst of complex chromosomal rearrangements seen in cancer cells. The normal EWS gene encodes an RNA binding protein closely related to FUS (gene) and TAF15, all of which have been associated to amyotrophic lateral sclerosis.

Interactions

The EWS protein has been shown to interact with:

• ATF1,
• BARD1,
• ERG,
• POU4F1,
• PTK2B
• SF1,
• SNRPC, and
• ZNF165.

Further reading

• Ohno T, Rao VN, Reddy ES (December 1993). "EWS/Fli-1 chimeric protein is a transcriptional activator". Cancer Res. 53 (24): 5859–63. PMID 7503813.
• Ouchida M, Ohno T, Fujimura Y, Rao VN, Reddy ES (September 1995). "Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts". Oncogene. 11 (6): 1049–54. PMID 7566963.
• Ban J, Siligan C, Kreppel M, Aryee D, Kovar H (2006). "Ews-Fli1 in Ewing's Sarcoma: Real Targets and Collateral Damage". New trends in cancer for the 21st century. Advances in Experimental Medicine and Biology. Vol. 587. pp. 41–52. doi:10.1007/978-1-4020-5133-3_4. ISBN 978-1-4020-4966-8. PMID 17163154.
• Meister HP (1976). "[Morphological findings of chronic constipation in childhood]". Monatsschrift für Kinderheilkunde. 124 (5): 354–6. PMID 934118.
• Guthrie GM, Verstraete A, Deines MM, Stern RM (1975). "Symptoms of stress in four societies". The Journal of Social Psychology. 95 (Second half): 165–72. doi:10.1080/00224545.1975.9918699. PMID 1127890.
• Bhagirath T, Abe S, Nojima T, Yoshida MC (1995). "Molecular analysis of a t(11;22) translocation junction in a case of Ewing's sarcoma". Genes Chromosomes Cancer. 13 (2): 126–32. doi:10.1002/gcc.2870130209. PMID 7542907. S2CID 36929552.
• Ohno T, Ouchida M, Lee L, Gatalica Z, Rao VN, Reddy ES (1994). "The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains". Oncogene. 9 (10): 3087–97. PMID 8084618.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Plougastel B, Zucman J, Peter M, Thomas G, Delattre O (1994). "Genomic structure of the EWS gene and its relationship to EWSR1, a site of tumor-associated chromosome translocation". Genomics. 18 (3): 609–15. doi:10.1016/S0888-7543(05)80363-5. PMID 8307570.
• Zucman J, Delattre O, Desmaze C, Epstein AL, Stenman G, Speleman F, Fletchers CD, Aurias A, Thomas G (1993). "EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts". Nat. Genet. 4 (4): 341–5. doi:10.1038/ng0893-341. PMID 8401579. S2CID 10944105.
• Brodie SG, Stocker SJ, Wardlaw JC, Duncan MH, McConnell TS, Feddersen RM, Williams TM (1996). "EWS and WT-1 gene fusion in desmoplastic small round cell tumor of the abdomen". Hum. Pathol. 26 (12): 1370–4. doi:10.1016/0046-8177(95)90303-8. PMID 8522311.
• Fujimura Y, Ohno T, Siddique H, Lee L, Rao VN, Reddy ES (1996). "The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator". Oncogene. 12 (1): 159–67. PMID 8552387.
• Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS (1996). "Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma". Oncogene. 12 (2): 229–35. PMID 8570200.
• Magnaghi-Jaulin L, Masutani H, Robin P, Lipinski M, Harel-Bellan A (1996). "SRE elements are binding sites for the fusion protein EWS-FLI-1". Nucleic Acids Res. 24 (6): 1052–8. doi:10.1093/nar/24.6.1052. PMC 145748. PMID 8604338.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Aman P, Panagopoulos I, Lassen C, Fioretos T, Mencinger M, Toresson H, Höglund M, Forster A, Rabbitts TH, Ron D, Mandahl N, Mitelman F (1997). "Expression patterns of the human sarcoma-associated genes FUS and EWS and the genomic structure of FUS". Genomics. 37 (1): 1–8. doi:10.1006/geno.1996.0513. PMID 8921363.
• Morohoshi F, Arai K, Takahashi EI, Tanigami A, Ohki M (1997). "Cloning and mapping of a human RBP56 gene encoding a putative RNA binding protein similar to FUS/TLS and EWS proteins". Genomics. 38 (1): 51–7. doi:10.1006/geno.1996.0591. PMID 8954779.
• Zucman-Rossi J, Legoix P, Thomas G (1997). "Identification of new members of the Gas2 and Ras families in the 22q12 chromosome region". Genomics. 38 (3): 247–54. doi:10.1006/geno.1996.0625. PMID 8975699.
• Guinamard R, Fougereau M, Seckinger P (1997). "The SH3 domain of Bruton's tyrosine kinase interacts with Vav, Sam68 and EWS". Scand. J. Immunol. 45 (6): 587–95. doi:10.1046/j.1365-3083.1997.d01-447.x. PMID 9201297. S2CID 23303841.
• Deloulme JC, Prichard L, Delattre O, Storm DR (1997). "The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain". J. Biol. Chem. 272 (43): 27369–77. doi:10.1074/jbc.272.43.27369. PMID 9341188.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.

External links

• Ewing sarcoma breakpoint region 1 on the Atlas of Genetics and Oncology