The Ewing Sarcoma breakpoint region 1 gene EWSR1, was discovered as the name suggests as it is located at the breakpoint on human chromosome 22 which may becomes fused to segments of other chromosomes following chromoplexy, a burst of complex chromosomal rearrangement seen in cancer cells. The genetic rearrangement produces a set of aberrant genes consisting of the 5′ of the EWSR1 gene fused to gene segments of several different transcriptional regulator proteins. The normal EWSR1 gene encodes a protein, EWS RNA binding protein 1, containing an N-terminal transactivation domain followed by a single RRM domain and a single Zinc Finger domain of the ZnF RBZ type. Chromoplexy results in the production of aberrant genes encoding the N-terminal EWS transactivation domain fused to DNA binding segments of various transcription factors, resulting in strong activation of transcription. EWS is an abundant, ubiquitous and multifunctional protein involved in regulating gene expression, cell division, RNA processing and transport. EWS is localized primarily in the nucleus of cells, but has also been found in the cytoplasm, and associated with the plasma membrane in a fashion regulated by the protein kinase PYK2.
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