Mouse EWSR1 Monoclonal Antibody | anti-EWSR1 antibody

EWSR1 Antibody

Cat. Num. AAA415276

• Gene Names: EWSR1; EWS; bK984G1.4
• Applications: Immunofluorescence, Western Blot
• Purity: Affinity purified
• Synonyms: EWSR1; Monoclonal Antibody; EWSR1 Antibody; anti-EWSR1 antibody

• Host: Mouse
• Clonality: Monoclonal
• Isotype: IgG2b
• Purity/Purification: Affinity purified
• Form/Format: Liquid
• Concentration: 100ug/100ul (varies by lot)
• Sequence Length: 655

• Applicable Applications for anti-EWSR1 antibody: Immunofluorescence (IF), Western Blot (WB)
• Application Notes: The antibody solution can be used at dilutions of 1:500 for immunofluorescence. For western blots try at 1:1000.
• Immunogen: Ewing sarcoma breakpoint region 1 is a protein belonging to the family of RNA binding proteins which contain a single RRM domain. It also has a single Zinc Finger domain of the ZnF_RBZ subtype found in Ran binding proteins. Ran is a small G protein related to p21-Ras which regulates the import and export of proteins to the nucleus. EWSR1 appears to be a multifunctional protein that is involved in various cellular processes, including gene expression, cell signaling, and RNA processing and transport. In particular, EWSR1 is required for cell survival in the central nervous system (1). The EWSR1 gene was identified based on its location at the chromosome 22 breakpoint of the t(11;22)(q24;q12) translocation that characterizes Ewing sarcoma and related neuroectodermal tumors. This results in the production of an aberrant fusion protein containing the N-terminus of a protein encoded by the Friend leukemia virus integration 1 (FLI1) protein and the C-terminal of the EWS protein. The chromosomal region harboring the EWS gene appears to be particularly prone to translocations, and such translocations can result in the production of several other aberrant fusion proteins, in each case with C-terminus of EWS fused with an another protein (2, see also the OMIM link). EWSR1 is ubiquitely expressed and is localized primarily in the nucleus of cell (3). It has also been found in the cytoplasm, and associated with the plasma membrane in a fashion regulated by the protein kinase Pyk2 (4). Expression of EWS in the various subcellular compartments is affected by the methylation state of its RNA-binding domain (5). Localization of EWS in different subcellular compartments reflects a dynamic distribution during cell cycle. EWS associates with and stablizes microtubules, leading to cell cycle arrest (6). EWSR1, TAF15 and FUS/TLS are closely related proteins which are believed to have evolved by gene multiplication, and all have been implication in the etiology of some forms of Amyotrophic Lateral Sclerosis (ALS, a.k.a. Lou Gehrig's Disease) (7). Monoclonal antibody MCA-5H7 was raised against full length recombinant human EWS expressed in and purified from E. coli. The HGNC name for EWS is EWSR1.
• Storage Buffer: PBS, pH 7.4 with 0.02% sodium azide.
• Preparation and Storage: Store at -20 degree C/1 year

Western Blot (WB)

Testing Data #2

References

1: Azuma M, Embree LJ, Sabaawy H, Hickstein DD. Ewing sarcoma protein ewsr1 maintains mitotic integrity and proneural cell survival in the zebrafish embryo. PLoS One. 2:e979 (2007).2: Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 359:162-5 (1992).3. Andersson MK, Ståhlberg A, Arvidsson Y, Olofsson A, Semb H, Stenman G, Nilsson O, Aman P. The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC Cell Biol. 11:9:37 (2008).4: Felsch JS, Lane WS, Peralta EG. Tyrosine kinase Pyk2 mediates G-protein-coupled receptor regulation of the Ewing sarcoma RNA-binding protein EWS. Curr Biol. 9:485-8 (1999).5: Belyanskaya LL, Delattre O, Gehring H.Expression and subcellular localization of Ewing sarcoma (EWS) protein is affected by the methylation process. Exp Cell Res. Aug 15;288(2):374-81 (2003). Exp Cell Res. 288:374-81 (2003).6: Leemann-Zakaryan RP, Pahlich S, Sedda MJ, Quero L, Grossenbacher D, Gehring H. Dynamic subcellular localization of the Ewing sarcoma proto-oncoprotein and its association with and stabilization of microtubules. J Mol Biol. 386:1-13 (2009).7. Da Cruz S, Cleveland DW. Understanding the role of TDP-43 and FUS/TLS in ALS and beyond. Curr Opin Neurobiol. [Epub ahead of print] (2011).

NCBI and Uniprot Product Information

• NCBI GI #: 47678511
• NCBI GeneID: 2130
• UniProt Accession #: Q96FE8; Q5THL0; Q92635; Q96MN4; Q96MX4; Q9BWA2; B0QYK1; Q01844
• Molecular Weight: 68,478 Da
• NCBI Official Full Name: EWSR1
• NCBI Official Synonym Full Names: EWS RNA-binding protein 1
• NCBI Official Symbol: EWSR1
• NCBI Official Synonym Symbols: EWS; bK984G1.4
• NCBI Protein Information: RNA-binding protein EWS; Ewing sarcoma breakpoint region 1; Ewings sarcoma EWS-Fli1 (type 1) oncogene
• UniProt Protein Name: RNA-binding protein EWS
• Protein Family: RNA-binding protein
• UniProt Gene Name: EWSR1
• UniProt Synonym Gene Names: EWS
• UniProt Entry Name: EWS_HUMAN

NCBI Description

This gene encodes a multifunctional protein that is involved in various cellular processes, including gene expression, cell signaling, and RNA processing and transport. The protein includes an N-terminal transcriptional activation domain and a C-terminal RNA-binding domain. Chromosomal translocations between this gene and various genes encoding transcription factors result in the production of chimeric proteins that are involved in tumorigenesis. These chimeric proteins usually consist of the N-terminal transcriptional activation domain of this protein fused to the C-terminal DNA-binding domain of the transcription factor protein. Mutations in this gene, specifically a t(11;22)(q24;q12) translocation, are known to cause Ewing sarcoma as well as neuroectodermal and various other tumors. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1 and 14. [provided by RefSeq, Jul 2009]

Uniprot Description

Function: Might normally function as a transcriptionnal repressor. EWS-fusion-proteins (EFPS) may play a role in the tumorigenic process. They may disturb gene expression by mimicking, or interfering with the normal function of CTD-POLII within the transcription initiation complex. They may also contribute to an aberrant activation of the fusion protein target genes.

Subunit structure: Binds POLR2C, SF1, calmodulin and RNA. Interacts with PTK2B/FAK2 and TDRD3. Binds calmodulin in the presence, but not in the absence, of calcium ion. Ref.16 Ref.20

Subcellular location: Nucleus. Cytoplasm. Cell membrane. Note: Relocates from cytoplasm to ribosomes upon PTK2B/FAK2 activation. Ref.19

Tissue specificity: Ubiquitous.

Domain: 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 and POLR2G but not POLR2C. Cis-linked RNA-binding domain (RBD) can strongly and specifically repress trans-activation by the EAD.

Post-translational modification: Phosphorylated; calmodulin-binding inhibits phosphorylation of Ser-266. Ref.13Highly methylated on arginine residues. Methylation is mediated by PRMT1 and, at lower level by PRMT8. Ref.10 Ref.12 Ref.21

Involvement in disease: Ewing sarcoma (ES) [MIM:612219]: A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors.Note: The disease is caused by mutations affecting the gene represented in this entry. Chromosomal aberrations involving EWSR1 are found in patients with Ewing sarcoma. Translocation t(11;22)(q24;q12) with FLI1; translocation t(7;22)(p22;q12) with ETV1; translocation t(21;22)(q22;q12) with ERG; translocation t(9;22)(q22-31;q11-12) with NR4A3. Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with potential oncogenic activity.A chromosomal aberration involving EWSR1 is associated with desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with WT1.A chromosomal aberration involving EWSR1 is associated with malignant melanoma of soft parts (MMSP). Translocation t(12;22)(q13;q12) with ATF-1. Malignant melanoma of soft parts, also known as soft tissue clear cell sarcoma, is a rare tumor developing in tendons and aponeuroses.A chromosomal aberration involving EWSR1 is associated with small round cell sarcoma. Translocation t(11;22)(p36.1;q12) with PATZ1.Angiomatoid fibrous histiocytoma (AFH) [MIM:612160]: A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis.Note: The disease may be caused by mutations affecting the gene represented in this entry. Chromosomal aberrations involving EWSR1 are found in patients with angiomatoid fibrous histiocytoma. Translocation t(12;22)(q13;q12) with ATF1 generates a chimeric EWSR1/ATF1 protein. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type.EFPS arise due to chromosomal translocations in which EWSR1 is fused to a variety of cellular transcription factors. EFPS are very potent transcriptional activators dependent on the EAD and a C-terminal DNA-binding domain contributed by the fusion partner. The spectrum of malignancies associated with EFPS are thought to arise via EFP-induced transcriptional deregulation, with the tumor phenotype specified by the EWSR1 fusion partner and cell type. Transcriptional repression of the transforming growth factor beta type II receptor (TGF beta RII) is an important target of the EWS-FLI1, EWS-ERG, or EWS-ETV1 oncogene.

Sequence similarities: Belongs to the RRM TET family.Contains 1 IQ domain.Contains 1 RanBP2-type zinc finger.Contains 1 RRM (RNA recognition motif) domain.

Sequence caution: The sequence CAA70044.1 differs from that shown. Reason: Erroneous initiation.