LOCUS       NM_005243               2400 bp    mRNA    linear   PRI 29-OCT-2024
DEFINITION  Homo sapiens EWS RNA binding protein 1 (EWSR1), transcript variant
            2, mRNA.
ACCESSION   NM_005243
VERSION     NM_005243.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2400)
  AUTHORS   Lee,J.C., Koo,S.C., Furtado,L.V., Breuer,A., Eldomery,M.K.,
            Bag,A.K., Stow,P., Rose,G., Larkin,T., Sances,R.,
            Kleinschmidt-DeMasters,B.K., Bodmer,J.L., Willard,N., Gokden,M.,
            Dahiya,S., Roberts,K., Bertrand,K.C., Moreira,D.C., Robinson,G.W.,
            Mo,J.Q., Ellison,D.W. and Orr,B.A.
  TITLE     Concurrent ependymal and ganglionic differentiation in a subset of
            supratentorial neuroepithelial tumors with EWSR1-PLAGL1
            rearrangement
  JOURNAL   Acta Neuropathol Commun 12 (1), 143 (2024)
   PUBMED   39228008
  REMARK    GeneRIF: Concurrent ependymal and ganglionic differentiation in a
            subset of supratentorial neuroepithelial tumors with EWSR1-PLAGL1
            rearrangement.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2400)
  AUTHORS   Boulay,G., Broye,L.C., Dong,R., Iyer,S., Sanalkumar,R., Xing,Y.H.,
            Buisson,R., Rengarajan,S., Naigles,B., Duc,B., Volorio,A.,
            Awad,M.E., Renella,R., Chebib,I., Nielsen,G.P., Choy,E., Cote,G.M.,
            Zou,L., Letovanec,I., Stamenkovic,I., Rivera,M.N. and Riggi,N.
  TITLE     EWS-WT1 fusion isoforms establish oncogenic programs and
            therapeutic vulnerabilities in desmoplastic small round cell tumors
  JOURNAL   Nat Commun 15 (1), 7460 (2024)
   PUBMED   39198430
  REMARK    GeneRIF: EWS-WT1 fusion isoforms establish oncogenic programs and
            therapeutic vulnerabilities in desmoplastic small round cell
            tumors.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2400)
  AUTHORS   Folpe,A.L., Tetzlaff,M.T., Billings,S.D., Torres-Mora,J.,
            Borowsky,A.D., Santiago,T.C., Ameline,B. and Baumhoer,D.
  TITLE     Superficial Neurocristic EWSR1::FLI1 Fusion Tumor: A Distinctive,
            Clinically Indolent, S100 Protein/SOX10-Positive Neoplasm
  JOURNAL   Mod Pathol 37 (8), 100537 (2024)
   PUBMED   38866368
  REMARK    GeneRIF: Superficial Neurocristic EWSR1::FLI1 Fusion Tumor: A
            Distinctive, Clinically Indolent, S100 Protein/SOX10-Positive
            Neoplasm.
REFERENCE   4  (bases 1 to 2400)
  AUTHORS   Bielamowicz,K.J., Littrell,M.B., Albert,G.W., Parker,L.S.,
            Jayappa,S., Aldape,K. and Gokden,M.
  TITLE     Central nervous system embryonal tumors with EWSR1-PLAGL1
            rearrangements reclassified as INI-1 deficient tumors at relapse
  JOURNAL   J Neurooncol 168 (2), 367-373 (2024)
   PUBMED   38639853
  REMARK    GeneRIF: Central nervous system embryonal tumors with EWSR1-PLAGL1
            rearrangements reclassified as INI-1 deficient tumors at relapse.
REFERENCE   5  (bases 1 to 2400)
  AUTHORS   Zakaryan,R.P. and Gehring,H.
  TITLE     Identification and characterization of the nuclear
            localization/retention signal in the EWS proto-oncoprotein
  JOURNAL   J Mol Biol 363 (1), 27-38 (2006)
   PUBMED   16965792
  REMARK    GeneRIF: Regions in the N-terminal transcriptional activation
            domain guide the subnuclear partition of EWS protein and contain
            another but different nuclear localization/retention signal that
            allows nucleocytoplasmic shuttling of the N-terminal domain.
REFERENCE   6  (bases 1 to 2400)
  AUTHORS   Bhagirath,T., Abe,S., Nojima,T. and Yoshida,M.C.
  TITLE     Molecular analysis of a t(11;22) translocation junction in a case
            of Ewing's sarcoma
  JOURNAL   Genes Chromosomes Cancer 13 (2), 126-132 (1995)
   PUBMED   7542907
REFERENCE   7  (bases 1 to 2400)
  AUTHORS   Ohno,T., Ouchida,M., Lee,L., Gatalica,Z., Rao,V.N. and Reddy,E.S.
  TITLE     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
  JOURNAL   Oncogene 9 (10), 3087-3097 (1994)
   PUBMED   8084618
REFERENCE   8  (bases 1 to 2400)
  AUTHORS   Plougastel,B., Zucman,J., Peter,M., Thomas,G. and Delattre,O.
  TITLE     Genomic structure of the EWS gene and its relationship to EWSR1, a
            site of tumor-associated chromosome translocation
  JOURNAL   Genomics 18 (3), 609-615 (1993)
   PUBMED   8307570
REFERENCE   9  (bases 1 to 2400)
  AUTHORS   Zucman,J., Delattre,O., Desmaze,C., Epstein,A.L., Stenman,G.,
            Speleman,F., Fletchers,C.D., Aurias,A. and Thomas,G.
  TITLE     EWS and ATF-1 gene fusion induced by t(12;22) translocation in
            malignant melanoma of soft parts
  JOURNAL   Nat Genet 4 (4), 341-345 (1993)
   PUBMED   8401579
REFERENCE   10 (bases 1 to 2400)
  AUTHORS   Delattre,O., Zucman,J., Plougastel,B., Desmaze,C., Melot,T.,
            Peter,M., Kovar,H., Joubert,I., de Jong,P., Rouleau,G. et al.
  TITLE     Gene fusion with an ETS DNA-binding domain caused by chromosome
            translocation in human tumours
  JOURNAL   Nature 359 (6391), 162-165 (1992)
   PUBMED   1522903
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB443651.1, BC004817.1 and
            AW205707.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_005243.3.
            
            Summary: 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].
            
            Transcript Variant: This variant (2) lacks an alternate in-frame
            exon and uses an alternate in-frame splice site in the coding
            region, compared to variant 1. The resulting isoform (2) is shorter
            than isoform 1.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803615.238893.1,
                                           SRR1803617.109132.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000397938.7/ ENSP00000381031.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-50                DB443651.1         251-300
            51-2215             BC004817.1         1-2165
            2216-2400           AW205707.1         21-205              c
FEATURES             Location/Qualifiers
     source          1..2400
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="22"
                     /map="22q12.2"
     gene            1..2400
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /note="EWS RNA binding protein 1"
                     /db_xref="GeneID:2130"
                     /db_xref="HGNC:HGNC:3508"
                     /db_xref="MIM:133450"
     exon            1..82
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     CDS             70..2040
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /note="isoform 2 is encoded by transcript variant 2;
                     RNA-binding protein EWS; Ewings sarcoma EWS-Fli1 (type 1)
                     oncogene; Ewing sarcoma breakpoint region 1"
                     /codon_start=1
                     /product="RNA-binding protein EWS isoform 2"
                     /protein_id="NP_005234.1"
                     /db_xref="CCDS:CCDS13851.1"
                     /db_xref="GeneID:2130"
                     /db_xref="HGNC:HGNC:3508"
                     /db_xref="MIM:133450"
                     /translation="MASTDYSTYSQAAAQQGYSAYTAQPTQGYAQTTQAYGQQSYGTY
                     GQPTDVSYTQAQTTATYGQTAYATSYGQPPTGYTTPTAPQAYSQPVQGYGTGAYDTTT
                     ATVTTTQASYAAQSAYGTQPAYPAYGQQPAATAPTRPQDGNKPTETSQPQSSTGGYNQ
                     PSLGYGQSNYSYPQVPGSYPMQPVTAPPSYPPTSYSSTQPTSYDQSSYSQQNTYGQPS
                     SYGQQSSYGQQSSYGQQPPTSYPPQTGSYSQAPSQYSQQSSSYGQQSSFRQDHPSSMG
                     VYGQESGGFSGPGENRSMSGPDNRGRGRGGFDRGGMSRGGRGGGRGGMGSAGERGGFN
                     KPGGPMDEGPDLDLGPPVDPDEDSDNSAIYVQGLNDSVTLDDLADFFKQCGVVKMNKR
                     TGQPMIHIYLDKETGKPKGDATVSYEDPPTAKAAVEWFDGKDFQGSKLKVSLARKKPP
                     MNSMRGGLPPREGRGMPPPLRGGPGGPGGPGGPMGRMGGRGGDRGGFPPRGPRGSRGN
                     PSGGGNVQHRAGDWQCPNPGCGNQNFAWRTECNQCKAPKPEGFLPPPFPPPGGDRGRG
                     GPGGMRGGRGGLMDRGGPGGMFRGGRGGDRGGFRGGRGMDRGGFGGGRRGGPGGPPGP
                     LMEQMGGRRGGRGGPGKMDKGEHRQERRDRPY"
     exon            83..119
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            120..171
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            172..295
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            296..482
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            483..650
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            651..862
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            863..1043
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            1044..1081
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            1082..1114
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            1115..1233
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            1234..1363
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            1364..1486
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            1487..1649
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            1650..1747
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            1748..2000
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     exon            2001..2400
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2375..2380
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /note="hexamer: AATAAA"
     polyA_site      2400
                     /gene="EWSR1"
                     /gene_synonym="bK984G1.4; EWS; EWS-FLI1"
                     /note="major polyA site"
ORIGIN      
        1 gcagtgcggc gcctagaggg aaagcgagag ggagacggac gttgagagaa cgaggaggaa
       61 ggagagaaaa tggcgtccac ggattacagt acctatagcc aagctgcagc gcagcagggc
      121 tacagtgctt acaccgccca gcccactcaa ggatatgcac agaccaccca ggcatatggg
      181 caacaaagct atggaaccta tggacagccc actgatgtca gctataccca ggctcagacc
      241 actgcaacct atgggcagac cgcctatgca acttcttatg gacagcctcc cactggttat
      301 actactccaa ctgcccccca ggcatacagc cagcctgtcc aggggtatgg cactggtgct
      361 tatgatacca ccactgctac agtcaccacc acccaggcct cctatgcagc tcagtctgca
      421 tatggcactc agcctgctta tccagcctat gggcagcagc cagcagccac tgcacctaca
      481 agaccgcagg atggaaacaa gcccactgag actagtcaac ctcaatctag cacagggggt
      541 tacaaccagc ccagcctagg atatggacag agtaactaca gttatcccca ggtacctggg
      601 agctacccca tgcagccagt cactgcacct ccatcctacc ctcctaccag ctattcctct
      661 acacagccga ctagttatga tcagagcagt tactctcagc agaacaccta tgggcaaccg
      721 agcagctatg gacagcagag tagctatggt caacaaagca gctatgggca gcagcctccc
      781 actagttacc caccccaaac tggatcctac agccaagctc caagtcaata tagccaacag
      841 agcagcagct acgggcagca gagttcattc cgacaggacc accccagtag catgggtgtt
      901 tatgggcagg agtctggagg attttccgga ccaggagaga accggagcat gagtggccct
      961 gataaccggg gcaggggaag agggggattt gatcgtggag gcatgagcag aggtgggcgg
     1021 ggaggaggac gcggtggaat gggcagcgct ggagagcgag gtggcttcaa taagcctggt
     1081 ggacccatgg atgaaggacc agatcttgat ctaggcccac ctgtagatcc agatgaagac
     1141 tctgacaaca gtgcaattta tgtacaagga ttaaatgaca gtgtgactct agatgatctg
     1201 gcagacttct ttaagcagtg tggggttgtt aagatgaaca agagaactgg gcaacccatg
     1261 atccacatct acctggacaa ggaaacagga aagcccaaag gcgatgccac agtgtcctat
     1321 gaagacccac ccactgccaa ggctgccgtg gaatggtttg atgggaaaga ttttcaaggg
     1381 agcaaactta aagtctccct tgctcggaag aagcctccaa tgaacagtat gcggggtggt
     1441 ctgccacccc gtgagggcag aggcatgcca ccaccactcc gtggaggtcc aggaggccca
     1501 ggaggtcctg ggggacccat gggtcgcatg ggaggccgtg gaggagatag aggaggcttc
     1561 cctccaagag gaccccgggg ttcccgaggg aacccctctg gaggaggaaa cgtccagcac
     1621 cgagctggag actggcagtg tcccaatccg ggttgtggaa accagaactt cgcctggaga
     1681 acagagtgca accagtgtaa ggccccaaag cctgaaggct tcctcccgcc accctttccg
     1741 cccccgggtg gtgatcgtgg cagaggtggc cctggtggca tgcggggagg aagaggtggc
     1801 ctcatggatc gtggtggtcc cggtggaatg ttcagaggtg gccgtggtgg agacagaggt
     1861 ggcttccgtg gtggccgggg catggaccga ggtggctttg gtggaggaag acgaggtggc
     1921 cctggggggc cccctggacc tttgatggaa cagatgggag gaagaagagg aggacgtgga
     1981 ggacctggaa aaatggataa aggcgagcac cgtcaggagc gcagagatcg gccctactag
     2041 atgcagagac cccgcagagc tgcattgact accagattta ttttttaaac cagaaaatgt
     2101 tttaaattta taattccata tttataatgt tggccacaac attatgatta ttccttgtct
     2161 gtactttagt atttttcacc atttgtgaag aaacattaaa acaagttaaa tggtagtgtg
     2221 cggagttttt ttttcttcct tcttttaaaa atggttgttt aagactttaa caatgggaac
     2281 cccttgtgag catgctcagt atcattgtgg agaaccaaga gggcctctta actgtaacaa
     2341 tgttcatggt tgtgatgttt tttttttttt tttaaataaa attccaaatg tttataaaga
//
