RNA-binding protein EWS

Last updated
EWSR1
Protein EWSR1 PDB 2cpe.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases EWSR1 , EWS, bK984G1.4, EWS-FLI1, Ewing sarcoma breakpoint region 1, EWS RNA binding protein 1
External IDs OMIM: 133450 HomoloGene: 136069 GeneCards: EWSR1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001163285
NM_001163286
NM_001163287
NM_005243
NM_013986

Contents

n/a

RefSeq (protein)

NP_001156757
NP_001156758
NP_001156759
NP_005234
NP_053733

n/a

Location (UCSC) Chr 22: 29.27 – 29.3 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

RNA-binding protein EWS is a protein that in humans is encoded by the EWSR1 gene on human chromosome 22, specifically 22q12.2. [3] [4] It is one of 3 proteins in the FET protein family. [5]

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. [6] 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. [7] 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. [8]

Interactions

The EWS protein has been shown to interact with:

Related Research Articles

<span class="mw-page-title-main">Oncogene</span> Gene that has the potential to cause cancer

An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

<span class="mw-page-title-main">Desmoplastic small-round-cell tumor</span> Aggressive and rare cancer

Desmoplastic small-round-cell tumor (DSRCT) is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones. It is characterized by the EWS-WT1 fusion protein.

<span class="mw-page-title-main">PAX3</span> Paired box gene 3

The PAX3 gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse Pax3 are present in a subfamily along with the highly homologous human PAX7 and mouse Pax7 genes. The human PAX3 gene is located in the 2q36.1 chromosomal region, and contains 10 exons within a 100 kb region.

<span class="mw-page-title-main">Ewing sarcoma</span> Type of cancer

Ewing sarcoma is a type of pediatric cancer that forms in bone or soft tissue. Symptoms may include swelling and pain at the site of the tumor, fever, and a bone fracture. The most common areas where it begins are the legs, pelvis, and chest wall. In about 25% of cases, the cancer has already spread to other parts of the body at the time of diagnosis. Complications may include a pleural effusion or paraplegia.

<span class="mw-page-title-main">FLI1</span> Protein-coding gene in the species Homo sapiens

Friend leukemia integration 1 transcription factor (FLI1), also known as transcription factor ERGB, is a protein that in humans is encoded by the FLI1 gene, which is a proto-oncogene.

<span class="mw-page-title-main">ATF1</span> Protein-coding gene in humans

Cyclic AMP-dependent transcription factor ATF-1 is a protein that in humans is encoded by the ATF1 gene.

<span class="mw-page-title-main">ETV4</span> Protein-coding gene in the species Homo sapiens

ETS translocation variant 4 (ETV4), also known as polyoma enhancer activator 3 (PEA3), is a member of the PEA3 subfamily of Ets transcription factors.

<span class="mw-page-title-main">DEK (gene)</span> Protein-coding gene in the species Homo sapiens

The human DEKgene encodes the DEK protein.

<i>ERG</i> (gene) Protein-coding gene in the species Homo sapiens

ERG is an oncogene. ERG is a member of the ETS family of transcription factors. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis.

<span class="mw-page-title-main">RNA-binding protein FUS</span> Human protein and coding gene

RNA-binding protein FUS/TLS, also known as heterogeneous nuclear ribonucleoprotein P2 is a protein that in humans is encoded by the FUS gene.

<span class="mw-page-title-main">SSX2</span> Mammalian protein found in Homo sapiens

Protein SSX2 is a protein that in humans is encoded by the SSX2 gene.

<span class="mw-page-title-main">TAF15</span> Protein-coding gene in the species Homo sapiens

TATA-binding protein-associated factor 2N is a protein that in humans is encoded by the TAF15 gene.

<span class="mw-page-title-main">USP6</span> Protein-coding gene in the species Homo sapiens

Ubiquitin carboxyl-terminal hydrolase 6 (USB6), also termed TRE17 and Tre-2, is a deubiquitinating enzyme that in humans is encoded by the hominid USP6 gene located at band 13.2 on the short arm of chromosome 17. Deubiquitinating enzymes (DUBs) are enzymes that act within cells to remove ubiquitins from various functionally important proteins. Ubiquitin enzymes add ubiquitin to these proteins and thereby regulate their cellular location, alter their activity, and/or promote their degradation. By deubiquitinating these proteins, DUBs counter the effects of the ubiquinating enzymes and contribute to regulating the actions of the targeted proteins. In normal adult tissues, USP6 is highly expressed in testicle tissue, modestly expressed in ovarian tissue, and absent or minimally expressed in other tissues. It is also highly expressed in fetal brain tissue. The specific functions of USP6 are poorly defined primarily because its presence is restricted to primates: there are no available animal models to determine the effects of its deletion, although some studies suggest that UPSP6 contributes to normal brain development. In all events, USP6 has gained wide interest because of its abnormally increased expression by the neoplastic cells in various tumors derived from mesenchymal tissue.

<span class="mw-page-title-main">ETS transcription factor family</span> Protein family

In the field of molecular biology, the ETSfamily is one of the largest families of transcription factors and is unique to animals. There are 29 genes in humans, 28 in the mouse, 10 in Caenorhabditis elegans and 9 in Drosophila. The founding member of this family was identified as a gene transduced by the leukemia virus, E26. The members of the family have been implicated in the development of different tissues as well as cancer progression.

<span class="mw-page-title-main">Myxoid liposarcoma</span> Medical condition

A myxoid liposarcoma is a malignant adipose tissue neoplasm of myxoid appearance histologically.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare low-grade malignant mesenchymal neoplasm of the soft tissues, that differs from other sarcomas by unique histology and characteristic chromosomal translocations. There is an uncertain differentiation and neuroendocrine differentiation is even possible.

<span class="mw-page-title-main">Low-grade fibromyxoid sarcoma</span> Medical condition

Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of low-grade sarcoma first described by H. L. Evans in 1987. LGFMS are soft tissue tumors of the mesenchyme-derived connective tissues; on microscopic examination, they are found to be composed of spindle-shaped cells that resemble fibroblasts. These fibroblastic, spindle-shaped cells are neoplastic cells that in most cases of LGFMS express fusion genes, i.e. genes composed of parts of two different genes that form as a result of mutations. The World Health Organization (2020) classified LGFMS as a specific type of tumor in the category of malignant fibroblastic and myofibroblastic tumors.

EWS/FLI1 is an oncogenic protein that is pathognomonic for Ewing sarcoma. It is found in approximately 90% of all Ewing sarcoma tumors with the remaining 10% of fusions substituting one fusion partner with a closely related family member.

Sclerosing epithelioid fibrosarcoma (SEF) is a very rare malignant tumor of soft tissues that on microscopic examination consists of small round or ovoid neoplastic epithelioid fibroblast-like cells, i.e. cells that have features resembling both epithelioid cells and fibroblasts. In 2020, the World Health Organization classified SEF as a distinct tumor type in the category of malignant fibroblastic and myofibroblastic tumors. However, current studies have reported that low-grade fibromyxoid sarcoma (LGFMS) has many clinically and pathologically important features characteristic of SEF; these studies suggest that LGSFMS may be an early form of, and over time progress to become, a SEF. Since the World Health Organization has classified LGFMS as one of the malignant fibroblastic and myofibroblastic tumors that is distinctly different than SEF, SEF and LGFMS are here regarded as different tumor forms.

The FET protein family consists of three similarly structured and functioning proteins. They and the genes in the FET gene family which encode them are: 1) the EWSR1 protein encoded by the EWSR1 gene located at band 12.2 of the long arm of chromosome 22; 2) the FUS protein encoded by the FUS gene located at band 16 on the short arm of chromosome 16; and 3) the TAF15 protein encoded by the TAF15 gene located at band 12 on the long arm of chromosome 7 The FET in this protein family's name derives from the first letters of FUS, EWSR1, and TAF15.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000182944 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  4. "Entrez Gene: EWSR1 Ewing sarcoma breakpoint region 1".
  5. 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.
  6. "EWS family fusion genes - OMIM".
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
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Further reading