EWSR1 (Ewing sarcoma region 1)

Identity

Hugo	EWSR1
Location	22q12

DNA/RNA

Description	spans over 40 kb; open reading frame: 2.0 kb (from 44 to 2014); 17 exons
Transcription	2.4 kb mRNA; centromere to telomere direction; differential splicing

Protein

Description	656 amino acids; serine-tyrosine tandem repeats (N-term to amino acid 285 in a region rich in glutamine, threonine and proline; 3 glycine, arginine, proline rich regions in C-term, with a RNA-binding signal in 410-417.
Expression	wide
Function	RNA binding
Homology	with FUS

Implicated in

Entity	1- Ewing tumours with: t(11;22)(q24;q12) --> FLI1 - EWSR1
Disease	Ewing tumours: including Ewing's Sarcoma and peripheral primitive neuroectodermal tumour.
Cytogenetics	t(11;22)(q24;q12) is found in 85% of cases of Ewing tumours.
Hybrid/Mutated Gene	5' EWS - 3' FLI1; breakpoints clustered over a 2-3 kb genomic region and over a 30-40 kb genomic region.
Abnormal Protein	oncogenic protein on the der(22) chromosome generated by fusion of the N terminal domain of EWS protein with DNA binding domain of human FLI1 protein.
Oncogenesis	EWS -FLI1 is a dominant oncogene transformed cells by subverting normal transcriptional controls/FLI1 member of ETS family.
Entity	Ewing tumours with t(21;22)(q21;q12) --> ERG - EWSR1
Disease	Ewing tumours (Ewing's Sarcoma and peripheral primitive neuroectodermal tumour).
Hybrid/Mutated Gene	5' EWS - 3' ERG; the orientation of the ERG gene might by from telomere to centromere, opposite to that demonstrated for EWS.
Abnormal Protein	oncogenic protein on the der(22) chromosome generated by fusion of the N terminal domain of EWS protein with DNA binding domain of human ERG protein.
Entity	Ewing tumours with t(7;22)(p22;q12) --> ETV1 - EWSR1
Disease	Ewing tumours (Ewing's Sarcoma and peripheral primitive neuroectodermal tumour).
Hybrid/Mutated Gene	5' EWS - 3' ETV1
Entity	Ewing tumours with t(17;22)(q12;q12) --> E1AF - EWSR1
Disease	Ewing tumours (Ewing's Sarcoma and peripheral primitive neuroectodermal tumour).
Hybrid/Mutated Gene	5' EWS - 3' E1AF
Entity	2- t(11;22)(p13;q12) / Intra abdominal desmoplastic small round cell sarcoma (IADSRCT) --> WT1 - EWSR1
Hybrid/Mutated Gene	5' EWS - 3' WT1; breakpoints: between EWS exons 7 and 8 and between WT1 exons 7 and 8
Abnormal Protein	transcription activator.
Entity	3- t(12;22)(q13;q12) / malignant melanoma of soft parts--> ATF1 - EWSR1
Hybrid/Mutated Gene	5' EWS - 3' ATF-1
Abnormal Protein	N terminal domain of EWS fused to the bZIP domain of ATF1
Entity	4- t(9;22)(q22;q12) / Myxoid Chondrosarcoma--> TEC - EWSR1
Hybrid/Mutated Gene	5' EWS - 3' TEC (or CHN); the EWS/CHN gene fusion was not detected in any of the remaining cases suggesting genetic heterogeneite within extraskeletal myxoid chondrosarcomas with t(9;17)(q22;q11)

Breakpoints

Note	clustered over a 2.3 kb genomic region.

External links

	Nomenclature
Hugo	EWSR1
GDB	EWSR1
Entrez_Gene	EWSR1  2130  Ewing sarcoma breakpoint region 1
	Cards
Atlas	EWSR1ID85
GeneCards	EWSR1
Ensembl	EWSR1 [Search_View]   ENSG00000182944 [Gene_View]
Genatlas	EWSR1
GeneLynx	EWSR1
eGenome	EWSR1
euGene	2130
	Genomic and cartography
GoldenPath	EWSR1  -  22q12   chr22:27994017-28026515 +  22q12.2   [Description]    (hg18-Mar_2006)
Ensembl	EWSR1 - 22q12.2 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	EWSR1
	Gene and transcription
Genbank	AF327066 [ ENTREZ ]
Genbank	AF524261 [ ENTREZ ]
Genbank	AI564543 [ ENTREZ ]
Genbank	AK026270 [ ENTREZ ]
Genbank	AK056309 [ ENTREZ ]
RefSeq	NM_005243 [ SRS ]    NM_005243 [ ENTREZ ]
RefSeq	NM_013986 [ SRS ]    NM_013986 [ ENTREZ ]
RefSeq	AC_000065 [ SRS ]    AC_000065 [ ENTREZ ]
RefSeq	NC_000022 [ SRS ]    NC_000022 [ ENTREZ ]
RefSeq	NT_011520 [ SRS ]    NT_011520 [ ENTREZ ]
RefSeq	NW_927628 [ SRS ]    NW_927628 [ ENTREZ ]
AceView	EWSR1 AceView - NCBI
Unigene	Hs.374477 [ SRS ]    Hs.374477 [ NCBI ]     HS374477 [ spliceNest ]
Fast-db	3572 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q01844 [ SRS]    Q01844 [ EXPASY ]     Q01844 [ INTERPRO ]
Prosite	PS50096 IQ [ SRS ]    PS50096 IQ [ Expasy ]
Prosite	PS50102 RRM [ SRS ]    PS50102 RRM [ Expasy ]
Prosite	PS01358 ZF_RANBP2_1 [ SRS ]    PS01358 ZF_RANBP2_1 [ Expasy ]
Prosite	PS50199 ZF_RANBP2_2 [ SRS ]    PS50199 ZF_RANBP2_2 [ Expasy ]
Interpro	IPR012677 a_b_plait_nuc_bd [ SRS ]    IPR012677 a_b_plait_nuc_bd [ EBI ]
Interpro	IPR000637 AT_hook_DNA_bd [ SRS ]    IPR000637 AT_hook_DNA_bd [ EBI ]
Interpro	IPR000048 IQ_CaM_bd_region [ SRS ]    IPR000048 IQ_CaM_bd_region [ EBI ]
Interpro	IPR000504 RRM_RNP1 [ SRS ]    IPR000504 RRM_RNP1 [ EBI ]
Interpro	IPR001876 Znf_RanBP2 [ SRS ]    IPR001876 Znf_RanBP2 [ EBI ]
CluSTr	Q01844
Pfam	PF00076 RRM_1 [ SRS ]    PF00076 RRM_1 [ Sanger ]    pfam00076 [ NCBI-CDD ]
Pfam	PF00641 zf-RanBP [ SRS ]    PF00641 zf-RanBP [ Sanger ]    pfam00641 [ NCBI-CDD ]
Smart	SM00360 RRM [EMBL]
Smart	SM00547 ZnF_RBZ [EMBL]
Blocks	Q01844
PDB	2CPE [ SRS ]    2CPE [ PdbSum ],   2CPE [ IMB ]   2CPE [ RSDB ]
HPRD	00592
	Protein Interaction databases
DIP	Q01844
IntAct	Q01844
	Polymorphism : SNP, mutations, diseases
OMIM	133450    [ map ]
GENECLINICS	133450
SNP	EWSR1 [dbSNP-NCBI]
SNP	NM_005243 [SNP-NCI]
SNP	NM_013986 [SNP-NCI]
SNP	EWSR1 [GeneSNPs - Utah]  EWSR1] [HGBASE - SRS]
HAPMAP	EWSR1 [HAPMAP]
COSMIC	EWSR1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	EWSR1
	General knowledge
Family Browser	EWSR1 [UCSC Family Browser]
SOURCE	NM_005243
SOURCE	NM_013986
SMD	Hs.374477
SAGE	Hs.374477
GO	nucleotide binding [Amigo]  nucleotide binding
GO	nucleic acid binding [Amigo]  nucleic acid binding
GO	transcription factor activity [Amigo]  transcription factor activity
GO	RNA binding [Amigo]  RNA binding
GO	calmodulin binding [Amigo]  calmodulin binding
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	zinc ion binding [Amigo]  zinc ion binding
GO	cell surface [Amigo]  cell surface
GO	sequence-specific DNA binding [Amigo]  sequence-specific DNA binding
GO	metal ion binding [Amigo]  metal ion binding
PubGene	EWSR1
TreeFam	EWSR1
CTD	2130 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probe	EWSR1 Related clones (RZPD - Berlin)
	PubMed
PubMed	65 Pubmed reference(s) in LocusLink

Bibliography

Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours.

Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G

Nature. 1992 ; 359 (6391) : 162-165.

PMID 1522903

EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts.

Zucman J, Delattre O, Desmaze C, Epstein AL, Stenman G, Speleman F, Fletchers CD, Aurias A, Thomas G

Nature genetics. 1993 ; 4 (4) : 341-345.

PMID 8401579

DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma.

Bailly RA, Bosselut R, Zucman J, Cormier F, Delattre O, Roussel M, Thomas G, Ghysdael J

Molecular and cellular biology. 1994 ; 14 (5) : 3230-3241.

PMID 8164678

Genetic alterations in the chromosome 22q12 region associated with development of neuroectodermal tumors.

Thomas G, Delattre O, Zucman J, Merel P, Desmaze C, Melot T, Sanson M, Hoang-Xuan K, Plougastel B, Dejong P

Cold Spring Harbor symposia on quantitative biology. 1994 ; 59 : 555-564.

PMID 7587112

Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor.

Gerald WL, Rosai J, Ladanyi M

Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (4) : 1028-1032.

PMID 7862627

A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1.

Jeon IS, Davis JN, Braun BS, Sublett JE, Roussel MF, Denny CT, Shapiro DN

Oncogene. 1995 ; 10 (6) : 1229-1234.

PMID 7700648

Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation.

Labelle Y, Zucman J, Stenman G, Kindblom LG, Knight J, Turc-Carel C, Dockhorn-Dworniczak B, Mandahl N, Desmaze C, Peter M

Human molecular genetics. 1995 ; 4 (12) : 2219-2226.

PMID 8634690

Fusion of the EWS1 and WT1 genes as a result of the t(11;22)(p13;q12) translocation in desmoplastic small round cell tumors.

Benjamin LE, Fredericks WJ, Barr FG, Rauscher FJ 3rd

Medical and pediatric oncology. 1996 ; 27 (5) : 434-439.

PMID 8827070

An EWS/ERG fusion with a truncated N-terminal domain of EWS in a Ewing's tumor.

Peter M, Mugneret F, Aurias A, Thomas G, Magdelenat H, Delattre O

International journal of cancer. Journal international du cancer. 1996 ; 67 (3) : 339-342.

PMID 8707406

A novel chimera gene between EWS and E1A-F, encoding the adenovirus E1A enhancer-binding protein, in extraosseous Ewing's sarcoma.

Urano F, Umezawa A, Hong W, Kikuchi H, Hata J

Biochemical and biophysical research communications. 1996 ; 219 (2) : 608-612.

PMID 8605035

Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma.

Brody RI, Ueda T, Hamelin A, Jhanwar SC, Bridge JA, Healey JH, Huvos AG, Gerald WL, Ladanyi M

The American journal of pathology. 1997 ; 150 (3) : 1049-1058.

PMID 9060841

Multiple chromosomal mechanisms generate an EWS/FLI1 or an EWS/ERG fusion gene in Ewing tumors.

Desmaze C, Brizard F, Turc-Carel C, Melot T, Delattre O, Thomas G, Aurias A

Cancer genetics and cytogenetics. 1997 ; 97 (1) : 12-19.

PMID 9242212

Multiple chromosomal mechanisms generate an EWS/FLI1 or an EWS/ERG fusion gene in Ewing tumors.

Desmaze C, Brizard F, Turc-Carel C, Melot T, Delattre O, Thomas G, Aurias A

Cancer genetics and cytogenetics. 1997 ; 97 (1) : 12-19.

PMID 9242212

Multiple chromosomal mechanisms generate an EWS/FLI1 or an EWS/ERG fusion gene in Ewing tumors.

Desmaze C, Brizard F, Turc-Carel C, Melot T, Delattre O, Thomas G, Aurias A

Cancer genetics and cytogenetics. 1997 ; 97 (1) : 12-19.

PMID 9242212

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Last year publications	automatic search in PubMed

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Contributor(s)

Written	04-1998	Francine Mugneret
		Laboratoire de Cytogénétique, CHU Le Bocage, BP 77908, 21079 DIJON Cédex, France

Citation

This paper should be referenced as such :

Mugneret F . EWSR1 (Ewing sarcoma region 1). Atlas Genet Cytogenet Oncol Haematol. April 1998 . URL : http://AtlasGeneticsOncology.org/Genes/EWSR1ID85.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:23:28 2008