AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation Science
RNA-Binding Protein EWSRNA-Binding ProteinsRNAMolecular Sequence DataProtein BindingBinding SitesRibonucleoproteinsHeterogeneous-Nuclear RibonucleoproteinsRNA, MessengerAmino Acid SequencePoly(A)-Binding ProteinsBase SequenceRNA, ViralHu Paraneoplastic Encephalomyelitis AntigensRNA SplicingRNA StabilityRNA, Small InterferingRNA, Double-StrandedRNA EditingProto-Oncogene Protein c-fli-1Nuclear Factor 90 ProteinsRNA Processing, Post-Transcriptional3' Untranslated RegionsHeterogeneous-Nuclear Ribonucleoprotein Group A-BRNA, BacterialProtein Structure, TertiaryRNA InterferenceNucleic Acid ConformationSarcoma, EwingCarrier ProteinsRNA, RibosomalRNA PrecursorsRNA-Binding Protein FUSSequence Homology, Amino AcidHeLa CellsNuclear Factor 45 ProteinDNA-Binding ProteinsProtein BiosynthesisNuclear ProteinsMutationRNA HelicasesCell LineTranscription FactorsRNA, FungalHeterogeneous-Nuclear Ribonucleoprotein DPolypyrimidine Tract-Binding ProteinCell NucleusModels, MolecularAlternative SplicingTranscription, GeneticRNA, ProtozoanRNA, ChloroplastRNA, PlantRecombinant Fusion ProteinsmRNA Cleavage and Polyadenylation FactorsPolyadenylationCloning, MolecularGene Expression RegulationEscherichia coliDNA-Directed RNA PolymerasesRNA, Small NuclearAmino Acid MotifsConserved SequenceRecombinant ProteinsCytoplasmHost Factor 1 Protein
EWSR1PolymeraseCalmodulinHelicaseEwingOncogenicKinaseFLI1GeneInhibitsInteractsRepressorTranslocationsCytoplasmInteractionMotifVitroReceptorGenesTRANSCRIPTSRecognitionEndosomalRegulationRegulatoryMetabolismFamilyMalignantIQGAP1ActivationAffinityDomainHomoMoleculeActivityUnlikeErythrocyteSiteExpressionDomainsComplexValidateSitesAlternativeEssential
EWSR13
  • RNA-binding protein EWS is a protein that in humans is encoded by the EWSR1 gene on human chromosome 22, specifically 22q12.2. (wikipedia.org)
  • The protein produced from the EWSR1/FLI1 fusion gene, called EWS/FLI, has functions of the protein products of both genes. (medlineplus.gov)
  • The EWS protein, produced from the EWSR1 gene, also regulates transcription. (medlineplus.gov)
Polymerase3
  • EWS binds RNA, calmodulin, and the RNA polymerase II 33 kD polypeptide (RPB3), but not RPB5 or RPB7. (medindex.am)
  • Mechanistically, SEs recruited bromodomain containing 4 (BRD4) at the site of ZBTB16 , which then bound to RNA polymerase II-associated protein 2 (RPAP2) that transported RNA polymerase II (POL II) into the nucleus. (nature.com)
  • Within SEC two elongation factors, positive transcription elongation factor b (P-TEFb) and elongation factor for RNA polymerase II 2 (ELL2) are key components. (biomedcentral.com)
Calmodulin5
  • Short calmodulin-binding motif containing conserved Ile and Gln residues. (embl.de)
  • Calmodulin-binding motif. (embl.de)
  • The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain. (embl.de)
  • Here we report that EWS, a nuclear RNA-binding prooncoprotein, contains an IQ domain, is phosphorylated by protein kinase C, and interacts with calmodulin. (embl.de)
  • Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. (embl.de)
Helicase3
  • Oncogenesis of EWS-FLI1 needs proteins partnering with RNA Helicase A (RHA), which is essential to improve the change of EWS-FLI1 [12]. (acancerjourney.info)
  • DHX9 is an RNA/DNA helicase that is involved in multiple cellular processes, including transcription and maintaining genome stability. (gla.ac.uk)
  • Furthermore, PDE4D7 was found to bind within DHX9's helicase core domain, suggesting that it may play a role in regulating its activity. (gla.ac.uk)
Ewing3
  • 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. (wikipedia.org)
  • The most common combination- EWS exon 7 fused to FLI1 exon 6 (type 1 translocation)-occurs in approximately 50-64% of tumors of Ewing sarcomas. (medscape.com)
  • Bailly RA, Bosselut R, Zucman J, Cormier F, Delattre O, Roussel M, Thomas G, Ghysdael J. DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma. (medlineplus.gov)
Oncogenic1
  • Oncogenic fusion proteins, such as for example EWS-FLI1, are great therapeutic targets because they are just located inside the tumor. (acancerjourney.info)
Kinase2
  • Acts as a 'third messenger' substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. (embl.de)
  • The 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) are known to play a role in disease progression as they mediate downstream signalling pathways that can promote cell growth and disease progression. (gla.ac.uk)
FLI111
  • In any individual patient, t(11;22) fuses one of many observed combinations of exons from EWS and FLI1 to form the fusion message. (medscape.com)
  • EWS-FLI1 is normally predicted to become an intrinsically disordered proteins (IDP), which really is a proteins lacking stable supplementary or tertiary buildings under physiological circumstances [5]. (acancerjourney.info)
  • EWS-FLI1 needs disorder for maximal transactivation of transcription [10] as well as the disordered character from the transcription aspect facilitates the protein-protein complexes that result in oncogenesis [11]. (acancerjourney.info)
  • The purification of recombinant EWS-FLI1 [13] allowed for the testing of a collection of little molecules with surface area plasmon resonance to recognize compounds with immediate binding [14]. (acancerjourney.info)
  • The tiny molecule lead substance and its own derivative, YK-4-279, bind to EWS-FLI1 and so are GS-7340 manufacture in a position to disrupt the EWS-FLI1/RHA connections. (acancerjourney.info)
  • Treatment with YK-4-279 particularly inhibits EWS-FLI1 function both and rearrangements. (acancerjourney.info)
  • Which means enantiomeric improvement of racemic substance to (S)-YK-4-279 is definitely relatively particular for ESFT cells in comparison with tumor cell lines missing EWS-FLI1. (acancerjourney.info)
  • Using a CRISPR Cas9-guided immunoprecipitation assay, we identify a circular RNA in the FLI1 promoter chromatin complex, consisting of FLI1 exons 4-2-3, referred to as FECR1.Overexpression of FECR1 enhances invasiveness of MDA-MB231 breast cancer cells. (biomedcentral.com)
  • FECR1 binds to the FLI1 promoter in cis and recruits TET1, a demethylase that is actively involved in DNA demethylation. (biomedcentral.com)
  • Thus, FLI1 drives tumor metastasis not only through the canonical oncoprotein pathway, but also by using epigenetic mechanisms mediated by its exonic circular RNA. (biomedcentral.com)
  • Using this CasIP assay, we identified FECR1, a FLI1 exonic circular RNA that binds to the FLI1 promoter and epigenetically activates FLI1 in breast cancer cells. (biomedcentral.com)
Gene6
  • 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. (wikipedia.org)
  • During osteogenesis, histones on osteogenic identity genes are acetylated, and OB-gain SEs appear, enabling the binding of BRD4 to the osteogenic identity gene ZBTB16. (nature.com)
  • The fusion proteins produced from the less common gene translocations have the same function as the EWS/FLI protein. (medlineplus.gov)
  • The protein encoded by this gene represents the beta subunit and is a type I membrane protein. (cancer-genetics.org)
  • What does this gene/protein do? (cancer-genetics.org)
  • What pathways are this gene/protein implicaed in? (cancer-genetics.org)
Inhibits2
  • Interestingly, PKC phosphorylation of EWS inhibits its binding to RNA homopolymers, and conversely, RNA binding to EWS interferes with PKC phosphorylation. (embl.de)
  • PKC phosphorylation of these proteins also inhibits their binding to RNA in vitro. (embl.de)
Interacts1
  • EWS interacts with FAK2 and relocates from cytoplasm to ribosomes upon FAK2 activation. (medindex.am)
Repressor1
  • Ubiquitous nuclear and cytoplasmic RNA Binding Protein EWS belongs to the TET family of RNP proteins, contains an RNA recognition motif and a RANBP2-type zinc finger, and may function as a repressor. (medindex.am)
Translocations1
  • Alternative translocations include EWS-ERG t(21;22), EWS-ETV t(7;22), and EWS-FEV t(2;22), all of which involve the ETS family protein. (medscape.com)
Cytoplasm1
  • RPAP2 transports RNA Pol II from the cytoplasm to the nucleus and guides Pol II to target ZBTB16 via recognition of the navigator BRD4 on SEs. (nature.com)
Interaction3
  • Many investigations have focused on defining the region of interaction between CaM and its cellular targets and the action of CaM on target protein function. (embl.de)
  • Three recognition motifs for CaM interaction are discussed in the context of experimental investigations of a variety of CaM target proteins. (embl.de)
  • By using peptide array technology, I was able to map where this interaction took place and define docking sites on both protein partners. (gla.ac.uk)
Motif1
  • A modified version of the IQ motif as a consensus for Ca2+-independent binding and two related motifs for Ca2+-dependent binding, termed 18-14 and 1-5-10 based on the position of conserved hydrophobic residues, are proposed. (embl.de)
Vitro1
Receptor2
  • Unlike other dynamin family proteins, however, Drp1 does not have a lipid-interacting pleckstrin homology domain [ 7 ], and thus the anchorage of Drp1 to the mitochondrial membrane is mediated by its receptor binding. (en-journal.org)
  • The interleukin 2 receptor, which is involved in T cell-mediated immune responses, is present in 3 forms with respect to ability to bind interleukin 2. (cancer-genetics.org)
Genes4
  • Without SEs located on osteogenic genes, BRD4 is not able to bind to osteogenic identity genes due to its closed structure before osteogenesis. (nature.com)
  • which is the first step in the production of proteins from genes. (medlineplus.gov)
  • The FLI protein controls the growth and development of some cell types by regulating the transcription of certain genes. (medlineplus.gov)
  • It is thought that the EWS/FLI protein turns the transcription of a variety of genes on and off abnormally. (medlineplus.gov)
TRANSCRIPTS1
  • For this step to be efficiently executed, the viral Trans-Activator of Transcription, Tat, acts as a master regulator of transcription elongation by tethering SEC to the HIV trans-activator response (TAR) stem-loop RNA on the viral short transcripts, and synergistically enhancing RNAPII pause-release and elongation. (biomedcentral.com)
Recognition1
  • Although considerable sequence diversity is observed among the different binding regions, these three classes of recognition motifs exist for many of the known CaM binding proteins. (embl.de)
Endosomal2
  • VPS26 endosomal protein sorting fac. (gsea-msigdb.org)
  • Several studies have identified oxidative stress, glutamate excitotoxicity, apoptosis, neurofilament dysfunction, protein misfolding and aggregation, impairment of RNA processing, disrupted axonal transport, endosomal trafficking dysfunction, inflammation, and mitochondrial impairment as the molecular pathways which lead to the disease and indicate ALS pathogenesis. (encyclopedia.pub)
Regulation2
  • The EWS/FLI protein has the DNA-binding function of the FLI protein as well as the transcription regulation function of the EWS protein. (medlineplus.gov)
  • These data suggest that FECR1 circular RNA acts as an upstream regulator to control breast cancer tumor growth by coordinating the regulation of DNA methylating and demethylating enzymes. (biomedcentral.com)
Regulatory2
  • These data suggest that PKC may regulate interactions of EWS and other RNA-binding proteins with their RNA targets and that IQ domains may provide a regulatory link between Ca2+ signal transduction pathways and RNA processing. (embl.de)
  • Several regulatory proteins such as dynamin-related protein 1 (Drp1) are required to maintain mitochondrial morphology via a balance between continuous fusion and fission. (en-journal.org)
Metabolism1
  • RNA metabolism and protein metabolism have been indicated as commonly proposed ALS pathogenic mechanisms [ 11 ] . (encyclopedia.pub)
Family1
  • It is one of 3 proteins in the FET protein family. (wikipedia.org)
Malignant1
  • Fused in sarcoma (FUS) is a DNA/RNA binding protein that is dysfunctional in various malignant tumors. (biomedcentral.com)
IQGAP11
  • Ras GTPase-activating-like protein IQGAP1. (embl.de)
Activation1
  • EWS contains a transcription activation domain, but the RNA-binding domain can repress trans-activation by the activation domain. (medindex.am)
Affinity1
  • Because CaM can bind with high affinity to a relatively small alpha-helical region of many proteins, success in clearly defining the essential elements of CaM binding motifs seems feasible and should provide a means of identifying CaM binding proteins. (embl.de)
Domain4
  • Taxonomic distribution of proteins containing IQ domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with IQ domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing IQ domain in the selected taxonomic class. (embl.de)
  • DNA binding domain [3]. (acancerjourney.info)
Homo1
  • Mfn1/2 is located on the outer membrane of mitochondria (OMM), and binding and homo- or hetero-dimerization of mitofusins promote fusion of two neighboring OMM. (en-journal.org)
Molecule2
  • Our results indicate that only 1 enantiomer of our little molecule can specifically focus on a protein-protein connections. (acancerjourney.info)
  • This work is normally significant because of its id of an individual enantiomer impact upon a proteins connections suggesting that little molecule concentrating on of intrinsically disordered protein can be particular. (acancerjourney.info)
Activity1
  • The RNA-binding activity is localized to a C-terminal RGG box. (medindex.am)
Unlike1
  • Unlike concentrating on an enzyme on the ATP binding site, advancement of a healing target for the transcription aspect requires very particular disruption of the DNA-protein or protein-protein connections [4]. (acancerjourney.info)
Erythrocyte1
Site1
  • DHX9 was found to bind within the newly identified FLY multi docking site within the upstream conserved region-1 (UCR1) of PDE4D7. (gla.ac.uk)
Expression2
  • Pearson's or Spearman's correlation test was used to determine the association between these two proteins expression. (biomedcentral.com)
  • Scope includes mutations and abnormal protein expression. (cancer-genetics.org)
Domains1
  • There are 165951 IQ domains in 60575 proteins in SMART's nrdb database. (embl.de)
Complex2
  • adaptor related protein complex 1 s. (gsea-msigdb.org)
  • After the binding of the RPAP2-Pol II complex to BRD4 on SEs, RPAP2 dephosphorylates Ser5 at the Pol II CTD to terminate the transcriptional pause, and BRD4 phosphorylates Ser2 at the Pol II CTD to initiate transcriptional elongation, which synergistically drives efficient transcription of ZBTB16, ensuring proper osteogenesis. (nature.com)
Validate1
  • His research utilizes the tools of synthetic chemistry, protein biochemistry, and cancer biology to discover and validate new strategies for the inhibition of anti-cancer targets. (stanford.edu)
Sites1
  • IDPs frequently have a great prospect of binding to little molecules because of higher induced-fit sampling properties and also have the prospect of multiple binding sites to little substances [6]. (acancerjourney.info)
Alternative1
  • The use of alternative promoters results in multiple transcript variants encoding the same protein. (cancer-genetics.org)
Essential1
  • FECR1 also binds to and downregulates in trans DNMT1, a methyltransferase that is essential for the maintenance of DNA methylation. (biomedcentral.com)