Search
RNA-binding protein EWS; EWS oncogene; Ewing sarcoma breakpoint region 1 protein (EWSR1, EWS)
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
Structure:
- 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)
Compartment:
- nucleus, cytoplasm, cell membrane
- relocates from cytoplasm to ribosomes upon PTK2B/FAK2 activation
Alternative splicing: named isoforms=2; EWS, EWS-B
Expression: ubiquitous
Pathology:
- EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process
- chromosomal translocations involving EWSR1 are a cause of Ewing sarcoma [MIM:612219]
a) translocation t(11;22)(q24;q12) with FLI1
b) translocation t(7;22)(p22;q12) with ETV1
c) translocation t(21;22)(q22;q12) with ERG
d) translocation t(9;22)(q22-31;q11-12) with NR4A3
e) 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]
a) translocation t(12;22)(q13;q12) with ATF1 generates a chimeric EWSR1/ATF1 protein
b) translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type
Related
EWS gene
General
nuclear protein
phosphoprotein
RNA-binding protein
zinc finger protein
Properties
SIZE: MW = 68 kD
entity length = 656 aa
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: EAD (Gln/Pro/Thr-rich). {8-255} (31)
IQ motif {256-285}
MOTIF: breakpoint {265}
Ser phosphorylation site {S266}
FOR-PHOSPHORYLATION-BY: protein kinase C
proline-rich region
SITE: 300-340
MOTIF: proline residue (SEVERAL)
breakpoint {348-349}
RNP motif
NAME: RNP motif
SITE: 361-447
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
NAME: ribonucleoprotein-1 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
ribonucleoprotein-2 motif
FOR-BINDING-OF: ribonucleic acid
MOTIF: ribonucleoprotein-1 motif
ribonucleoprotein-2 motif
proline-rich region
SITE: 454-513
MOTIF: proline residue (SEVERAL)
Zinc finger
NAME: Zinc finger
SITE: 518-549
EFFECTOR-BOUND: Zn+2
proline-rich region
SITE: 559-640
MOTIF: proline residue (SEVERAL)
Database Correlations
OMIM correlations
UniProt Q01844
PFAM correlations
Entrez Gene 2130
Kegg hsa:2130
References
- UniProt :accession Q01844
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/EWSR1ID85.html