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FLASH GENE

Symbol

EWSR1

contributors: mct - updated : 14-12-2018

HGNC name	Ewing sarcoma breakpoint region 1
HGNC id	3508

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DSRCT desmoplastic small round cell tumor EWS Ewing sarcoma
Location	22q12.2      Physical location : 29.663.997 - 29.696.514
Synonym name	RNA binding protein,involved in Ewing sarcoma (EWSR1)
	Ewings sarcoma EWS-Fli1 (type 1) oncogene
	bK984G1.4 (Ewing sarcoma breakpoint region 1 protein)
Synonym symbol(s)	EWS, bK984G1.4

DNA

TYPE	functioning gene
STRUCTURE	32.52 kb     18 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	EWSR1 promoter functions in a bidirectional manner, thereby regulating also RHBDD3, and identifies specific regions that strongly influence promoter activity

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - IGLV@ - D2S10 - BCR - IGLC1 - IGLC2 - D22S209 - CRYB@ - YESP - D22S17 ,D22S208 - D22S46 - D22S1 - (D22S260 - D22S262 ) - D22S33 - D22S41 - D22S213 - D22S193 - D22S42 - XBP1 - D22S56 ,D22S212 - EWSR1 - NEFH - LIF - (D22S32 - D22S38 ),(D22S261 - D22S15 ) - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001163285 17 splicing 2676 NP_001156757 - 655 - 2006 16965792 NM_001163286 16 splicing 2511 NP_001156758 - 600 - 2006 16965792 NM_001163287 9 splicing 1591 NP_001156759 - 354 - 2006 16965792 NM_005243 17 - 2679 NP_005234 - 656 - 2006 16965792 NM_013986 18 - 2694 NP_053733 - 661 - 2006 16965792

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune spleen       highly   thymus       highly   tonsils       highly Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal SER, TYR, GLU, GLY rich domain
	a RNA binding domain and C2-C2 finger motif in the central region
	C terminal RGG region
	one IQ, one RRM domain
	one RANBP2-type zinc finger domain

HOMOLOGY

Homologene

FAMILY

TET (TLS/EWS/TAF15) family of RNA- and DNA-binding proteins

CATEGORY

RNA associated

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
text	with CCNL1 and TFIP11 frequently co-localize to speckled nuclear domains

basic FUNCTION	contributing to an aberrant activation of the fusion protein target genes and to tumorigenic process
	with CCNL1 and TFIP11, participate in a common cellular activity related to RNA splicing events
	indispensable for stem cell quiescence
	is likely to play a significant role in maintaining the functional capacity of stem cells
	is essential for early brown fat lineage determination
	promiscuous' gene that can fuse with many different partner genes, but sometimes this results in phenotypically identical tumours

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	suppression of FOXO1 function by EWS-FLI1 fusion protein may contribute to cellular transformation in Ewing's family tumors
	negatively regulates AKT1S1 expression by binding the 3prime untranslated region in AKT1S1 mRNA)
	ETV1 and EWSR1 transactivate FGF10 directly and cooperatively in response to apical ectodermal ridge (AER)-FGFs
	FEZF1 is transcriptionally regulated by EWSR1-FLI1 in Ewing sarcoma cells and is involved in the regulation of neural-specific genes, which could explain the neural-like phenotype observed in several Ewing sarcoma tumors and cell lines

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

EWS , DSRCT

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion translocation     t(7;22)(p22;q12) ; see ETV1 tumoral fusion translocation     t(21;22)(q22;q12) ; see ERG tumoral fusion translocation     t(12;22)(q13;q12) with malignant melanomas of soft tissues (MMST) ; see ATF1 tumoral fusion translocation     t(11;22)(p13;q12) with desmoplastic small round cell tumor ; see DSRCT tumoral fusion translocation     t(9;22) (q22-q31;q12) with extraskeletal myxoid chondrosarcoma (EMC) ; see TEC tumoral fusion translocation     t(17;22) (q12;q12) with undifferentiated sarcoma in infancy ; see E1AF tumoral fusion       with DDIT3 in t(12;22), in myxoid liposarcoma tumoral fusion       with CREB1 in t(2;22)(q33;q12) in angiomatoid fibrous histiocytoma tumoral fusion       with PBX1 in (1;22)(q23;q12) in myoepithelioma tumoral fusion       with FLI1, t(11;22)(q24;q12) in Ewing sarcoma, cancer-specific molecule that binds to RHA essential for the function of EWS-FLI1 tumoral fusion       wirh POU5F1 in t(6;22)(p21;q12) associated with bone and soft-tissue tumours resulting in a chimaeric molecule fusing the NTD (N-terminal domain) of the EWSR1 to the CTD (C-terminal domain) of POU5F1 embryonic gene tumoral fusion       t(19;22)(q13;q12) leading to the novel fusion gene EWSR1-ZNF444 in soft tissue myoepithelial carcinoma tumoral     --over   in liposarcoma tumoral fusion       with ATF1 is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland tumoral fusion       with CREB3L1, in small cell osteosarcoma tumoral fusion       with YY1 genes in mesothelioma with t(14;22)(q32;q12) tumoral fusion       EWSR1-VGLL1 gene fusion in a soft tissue malignant myoepithelial tumor

Susceptibility

to amyotrophic lateral sclerosis (ALS)

Variant & Polymorphism other	three missense variants in EWSR1 in ALS patients, which were absent in a large number of healthy control individuals (pMID: 22454397)

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   small molecules that disable EWS-FLI1 function with minimal toxicity, in particular sparing hematopoetic stem cells, could potentially provide a valuable adjuvant therapy for patients with Ewing sarcoma family tumors

ANIMAL & CELL MODELS