RNA-binding protein EWS; EWS oncogene; Ewing sarcoma breakpoint region 1 protein (EWSR1, EWS)

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Function

might normally function as a repressor
they may disturb gene expression by mimicking, or interfering with the normal function of CTD-POL2 within the transcription initiation complex
they may also contribute to an aberrant activation of the fusion protein target genes
phosphorylated
calmodulin-binding inhibits phosphorylation of Ser-266
highly methyalted on Arg
methylation is mediated by PRMT1 &, at lower level by PRMT8
binds POLR2C, SF1, calmodulin & RNA
interacts with focal adhesion kinase 2 (PTK2B/FAK2) & TDRD3
binds calmodulin in the presence, but not in the absence, of Ca+2

EWS activation domain (EAD) functions as a potent activation domain in EFPS; EWSR1 binds POLR2C but not POLR2E or POLR2G, whereas the isolated EAD binds POLR2E & POLR2G but not POLR2C
cis-linked RNA-binding domain (RBD) can strongly & specifically repress trans-activation by the EAD
belongs to the RRM TET family
contains 1 IQ domain
contains 1 RanBP2-type Zn+2 finger
contains 1 RRM domain (RNA recognition motif)

named isoforms=2; EWS, EWS-B

EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process
chromosomal translocations involving EWSR1 are a cause of Ewing sarcoma [MIM:612219]
- translocation t(11;22)(q24;q12) with FLI1
- translocation t(7;22)(p22;q12) with ETV1
- translocation t(21;22)(q22;q12) with ERG
- translocation t(9;22)(q22-31;q11-12) with NR4A3
- translocation t(2;21;22)(q23;q22;q12) forms a EWSR1-FEV fusion protein with potential oncogenic activity
chromosomal translocation t(11;22)(p13;q12) involving EWSR1 with WT1 is associated with desmoplastic small round cell tumor (DSRCT)
chromosomal translocation t(12;22)(q13;q12) involving EWSR1 with ATF-1 is associated with malignant melanoma of soft parts (MMSP)
chromosomal translocation t(11;22)(p36.1;q12) involving EWSR1 with PATZ1 is associated with small round cell sarcoma
chromosomal translocations involving EWSR1 are associated with angiomatoid fibrous histiocytoma (AFH) [MIM:612160]
- translocation t(12;22)(q13;q12) with ATF1 generates a chimeric EWSR1/ATF1 protein
- translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type