RNA-binding protein EWS

EWSR1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2CPE
Identifiers
Aliases	EWSR1, EWS, bK984G1.4, EWS-FLI1, Ewing sarcoma breakpoint region 1, EWS RNA binding protein 1
External IDs	OMIM: 133450; MGI: 99960; HomoloGene: 136069; GeneCards: EWSR1; OMA:EWSR1 - orthologs
Gene location (Human)
Chr.	Chromosome 22 (human)
End	29,300,525 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	5,099,266 bp
RNA expression pattern
	Top expressed in
	right uterine tube; ; left testis; ; right testis; ; right hemisphere of cerebellum; ; right lobe of thyroid gland; ; right adrenal cortex; ; left adrenal cortex; ; ganglionic eminence; ; body of uterus; ; left lobe of thyroid gland;
	Top expressed in
	yolk sac; ; neural layer of retina; ; ventricular zone; ; genital tubercle; ; tail of embryo; ; superior frontal gyrus; ; primary visual cortex; ; spermatocyte; ; spermatid; ; lip;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	metal ion binding; protein binding; calmodulin binding; identical protein binding; nucleic acid binding; RNA binding;
Cellular component	cytoplasm; plasma membrane; nucleolus; membrane; nucleus;
Biological process	regulation of transcription, DNA-templated; transcription, DNA-templated;
	Sources:Amigo / QuickGO
Orthologs
	2130
	14030
	ENSG00000182944
	ENSMUSG00000009079
	Q01844
	Q61545
	NM_001163285; NM_001163286; NM_001163287; NM_005243; NM_013986
	NM_001283061; NM_001283062; NM_001283063; NM_007968
	NP_001156757; NP_001156758; NP_001156759; NP_005234; NP_053733
NP_001269990; NP_001269991; NP_001269992; NP_031994; NP_001349541;
	NP_001349542; NP_001349543; NP_001349544; NP_001349545; NP_001349546; NP_001349547; NP_001349549
	Wikidata
View/Edit Human	View/Edit Mouse

RNA-binding protein EWS is a protein that in humans is encoded by the EWSR1 gene on human chromosome 22, specifically 22q12.2.^[5]^[6] It is one of 3 proteins in the FET protein family.^[7]

Clinical significance

The q22.2 region of chromosome 22 encodes the N-terminal transactivation domain of the EWS protein and that region may become joined to one of several other chromosomes which encode various transcription factors; see EWS/FLI and OMIM-133450.^[8] The expression of a chimeric protein with the EWS transactivation domain fused to the DNA binding region of a transcription factor generates a powerful oncogenic protein causing Ewing sarcoma and other members of the Ewing family of tumors. These translocations can occur due to chromoplexy, a burst of complex chromosomal rearrangements seen in cancer cells. ^[9] The normal EWS gene encodes an RNA binding protein closely related to FUS (gene) and TAF15, all of which have been associated to amyotrophic lateral sclerosis.^[10]

Interactions

The EWS protein has been shown to interact with:

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000182944 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000009079 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G (October 1992). "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours". Nature. 359 (6391): 162–5. Bibcode:1992Natur.359..162D. doi:10.1038/359162a0. PMID 1522903. S2CID 4331584.
^ "Entrez Gene: EWSR1 Ewing sarcoma breakpoint region 1".
^ Flucke U, van Noesel MM, Siozopoulou V, Creytens D, Tops BB, van Gorp JM, Hiemcke-Jiwa LS (June 2021). "EWSR1-The Most Common Rearranged Gene in Soft Tissue Lesions, Which Also Occurs in Different Bone Lesions: An Updated Review". Diagnostics (Basel, Switzerland). 11 (6): 1093. doi:10.3390/diagnostics11061093. PMC 8232650. PMID 34203801.
^ "EWS family fusion genes - OMIM".
^ Anderson ND, de Borja R, Young MD, Fuligni F, Rosic A, Roberts ND, Hajjar S, Layeghifard M, Novokmet A, Kowalski PE, Anaka M (August 2018). "Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors". Science. 361 (6405): eaam8419. doi:10.1126/science.aam8419. PMC 6176908. PMID 30166462.
^ Couthouis J, Hart MP, Erion R, King OD, Diaz Z, Nakaya T, Ibrahim F, Kim HJ, Mojsilovic-Petrovic J, Panossian S, Kim CE, Frackelton EC, Solski JA, Williams KL, Clay-Falcone D, Elman L, McCluskey L, Greene R, Hakonarson H, Kalb RG, Lee VM, Trojanowski JQ, Nicholson GA, Blair IP, Bonini NM, Van Deerlin VM, Mourelatos Z, Shorter J, Gitler AD (2012). "Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis". Hum. Mol. Genet. 21 (13): 2899–911. doi:10.1093/hmg/dds116. PMC 3373238. PMID 22454397.
^ Fujimura Y, Ohno T, Siddique H, Lee L, Rao VN, Reddy ES (January 1996). "The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator". Oncogene. 12 (1): 159–67. PMID 8552387.
^ Spahn L, Petermann R, Siligan C, Schmid JA, Aryee DN, Kovar H (August 2002). "Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to a common tumor suppressor pathway". Cancer Res. 62 (16): 4583–7. PMID 12183411.
^ Ohno T, Ouchida M, Lee L, Gatalica Z, Rao VN, Reddy ES (Oct 1994). "The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains". Oncogene. 9 (10): 3087–97. PMID 8084618.
^ Thomas GR, Latchman DS (2002). "The pro-oncoprotein EWS (Ewing's Sarcoma protein) interacts with the Brn-3a POU transcription factor and inhibits its ability to activate transcription". Cancer Biol. Ther. 1 (4): 428–32. doi:10.4161/cbt.1.4.23. PMID 12432261.
^ Felsch JS, Lane WS, Peralta EG (May 1999). "Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS". Curr. Biol. 9 (9): 485–8. Bibcode:1999CBio....9..485F. doi:10.1016/s0960-9822(99)80214-0. PMID 10322114.
^ Zhang D, Paley AJ, Childs G (July 1998). "The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription". J. Biol. Chem. 273 (29): 18086–91. doi:10.1074/jbc.273.29.18086. PMID 9660765.
^ Knoop LL, Baker SJ (August 2000). "The splicing factor U1C represses EWS/FLI-mediated transactivation". J. Biol. Chem. 275 (32): 24865–71. doi:10.1074/jbc.M001661200. PMID 10827180.
^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

External links

Ewing sarcoma breakpoint region 1 on the Atlas of Genetics and Oncology

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000182944 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000009079 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1522903-5] Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G (October 1992). "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours". Nature. 359 (6391): 162–5. Bibcode:1992Natur.359..162D. doi:10.1038/359162a0. PMID 1522903. S2CID 4331584.

[entrez-6] "Entrez Gene: EWSR1 Ewing sarcoma breakpoint region 1".

[pmid34203801-7] Flucke U, van Noesel MM, Siozopoulou V, Creytens D, Tops BB, van Gorp JM, Hiemcke-Jiwa LS (June 2021). "EWSR1-The Most Common Rearranged Gene in Soft Tissue Lesions, Which Also Occurs in Different Bone Lesions: An Updated Review". Diagnostics (Basel, Switzerland). 11 (6): 1093. doi:10.3390/diagnostics11061093. PMC 8232650. PMID 34203801.

[8] "EWS family fusion genes - OMIM".

[pmid30166462-9] Anderson ND, de Borja R, Young MD, Fuligni F, Rosic A, Roberts ND, Hajjar S, Layeghifard M, Novokmet A, Kowalski PE, Anaka M (August 2018). "Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors". Science. 361 (6405): eaam8419. doi:10.1126/science.aam8419. PMC 6176908. PMID 30166462.

[pmid22454397-10] Couthouis J, Hart MP, Erion R, King OD, Diaz Z, Nakaya T, Ibrahim F, Kim HJ, Mojsilovic-Petrovic J, Panossian S, Kim CE, Frackelton EC, Solski JA, Williams KL, Clay-Falcone D, Elman L, McCluskey L, Greene R, Hakonarson H, Kalb RG, Lee VM, Trojanowski JQ, Nicholson GA, Blair IP, Bonini NM, Van Deerlin VM, Mourelatos Z, Shorter J, Gitler AD (2012). "Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis". Hum. Mol. Genet. 21 (13): 2899–911. doi:10.1093/hmg/dds116. PMC 3373238. PMID 22454397.

[pmid8552387-11] Fujimura Y, Ohno T, Siddique H, Lee L, Rao VN, Reddy ES (January 1996). "The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator". Oncogene. 12 (1): 159–67. PMID 8552387.

[pmid12183411-12] Spahn L, Petermann R, Siligan C, Schmid JA, Aryee DN, Kovar H (August 2002). "Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to a common tumor suppressor pathway". Cancer Res. 62 (16): 4583–7. PMID 12183411.

[pmid8084618-13] Ohno T, Ouchida M, Lee L, Gatalica Z, Rao VN, Reddy ES (Oct 1994). "The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains". Oncogene. 9 (10): 3087–97. PMID 8084618.

[pmid12432261-14] Thomas GR, Latchman DS (2002). "The pro-oncoprotein EWS (Ewing's Sarcoma protein) interacts with the Brn-3a POU transcription factor and inhibits its ability to activate transcription". Cancer Biol. Ther. 1 (4): 428–32. doi:10.4161/cbt.1.4.23. PMID 12432261.

[pmid10322114-15] Felsch JS, Lane WS, Peralta EG (May 1999). "Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS". Curr. Biol. 9 (9): 485–8. Bibcode:1999CBio....9..485F. doi:10.1016/s0960-9822(99)80214-0. PMID 10322114.

[pmid9660765-16] Zhang D, Paley AJ, Childs G (July 1998). "The transcriptional repressor ZFM1 interacts with and modulates the ability of EWS to activate transcription". J. Biol. Chem. 273 (29): 18086–91. doi:10.1074/jbc.273.29.18086. PMID 9660765.

[pmid10827180-17] Knoop LL, Baker SJ (August 2000). "The splicing factor U1C represses EWS/FLI-mediated transactivation". J. Biol. Chem. 275 (32): 24865–71. doi:10.1074/jbc.M001661200. PMID 10827180.

[pmid16189514-18] Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

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Clinical significance

Interactions

References

Further reading

External links