LOCUS       NM_005069               4461 bp    mRNA    linear   PRI 20-SEP-2024
DEFINITION  Homo sapiens SIM bHLH transcription factor 2 (SIM2), transcript
            variant SIM2, mRNA.
ACCESSION   NM_005069
VERSION     NM_005069.6
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 4461)
  AUTHORS   Viard,J., Loe-Mie,Y., Daudin,R., Khelfaoui,M., Plancon,C.,
            Boland,A., Tejedor,F., Huganir,R.L., Kim,E., Kinoshita,M., Liu,G.,
            Haucke,V., Moncion,T., Yu,E., Hindie,V., Blehaut,H., Mircher,C.,
            Herault,Y., Deleuze,J.F., Rain,J.C., Simonneau,M. and
            Lepagnol-Bestel,A.M.
  TITLE     Chr21 protein-protein interactions: enrichment in proteins involved
            in intellectual disability, autism, and late-onset Alzheimer's
            disease
  JOURNAL   Life Sci Alliance 5 (12), e202101205 (2022)
   PUBMED   35914814
  REMARK    Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4461)
  AUTHORS   Button,E.L., Rossi,J.J., McDougal,D.P., Bruning,J.B., Peet,D.J.,
            Bersten,D.C., Rosenfeld,J.A. and Whitelaw,M.L.
  TITLE     Characterization of functionally deficient SIM2 variants found in
            patients with neurological phenotypes
  JOURNAL   Biochem J 479 (13), 1441-1454 (2022)
   PUBMED   35730699
  REMARK    GeneRIF: Characterization of functionally deficient SIM2 variants
            found in patients with neurological phenotypes.
REFERENCE   3  (bases 1 to 4461)
  AUTHORS   Qin,B., Dong,M., Wang,Z., Wan,J., Xie,Y., Jiao,Y. and Yan,D.
  TITLE     Long non-coding RNA CASC15 facilitates esophageal squamous cell
            carcinoma tumorigenesis via decreasing SIM2 stability via
            FTO-mediated demethylation
  JOURNAL   Oncol Rep 45 (3), 1059-1071 (2021)
   PUBMED   33650646
  REMARK    GeneRIF: Long noncoding RNA CASC15 facilitates esophageal squamous
            cell carcinoma tumorigenesis via decreasing SIM2 stability via
            FTOmediated demethylation.
REFERENCE   4  (bases 1 to 4461)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   5  (bases 1 to 4461)
  AUTHORS   Dahmane,N., Ghezala,G.A., Gosset,P., Chamoun,Z.,
            Dufresne-Zacharia,M.C., Lopes,C., Rabatel,N.,
            Gassanova-Maugenre,S., Chettouh,Z., Abramowski,V., Fayet,E.,
            Yaspo,M.L., Korn,B., Blouin,J.L., Lehrach,H., Poutska,A.,
            Antonarakis,S.E., Sinet,P.M., Creau,N. and Delabar,J.M.
  TITLE     Transcriptional map of the 2.5-Mb CBR-ERG region of chromosome 21
            involved in Down syndrome
  JOURNAL   Genomics 48 (1), 12-23 (1998)
   PUBMED   9503011
REFERENCE   6  (bases 1 to 4461)
  AUTHORS   Chrast,R., Scott,H.S., Chen,H., Kudoh,J., Rossier,C., Minoshima,S.,
            Wang,Y., Shimizu,N. and Antonarakis,S.E.
  TITLE     Cloning of two human homologs of the Drosophila single-minded gene
            SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome
            chromosomal region
  JOURNAL   Genome Res 7 (6), 615-624 (1997)
   PUBMED   9199934
REFERENCE   7  (bases 1 to 4461)
  AUTHORS   Yamaki,A., Noda,S., Kudoh,J., Shindoh,N., Maeda,H., Minoshima,S.,
            Kawasaki,K., Shimizu,Y. and Shimizu,N.
  TITLE     The mammalian single-minded (SIM) gene: mouse cDNA structure and
            diencephalic expression indicate a candidate gene for Down syndrome
  JOURNAL   Genomics 35 (1), 136-143 (1996)
   PUBMED   8661114
REFERENCE   8  (bases 1 to 4461)
  AUTHORS   Muenke,M., Bone,L.J., Mitchell,H.F., Hart,I., Walton,K.,
            Hall-Johnson,K., Ippel,E.F., Dietz-Band,J., Kvaloy,K., Fan,C.M. et
            al.
  TITLE     Physical mapping of the holoprosencephaly critical region in
            21q22.3, exclusion of SIM2 as a candidate gene for
            holoprosencephaly, and mapping of SIM2 to a region of chromosome 21
            important for Down syndrome
  JOURNAL   Am J Hum Genet 57 (5), 1074-1079 (1995)
   PUBMED   7485157
REFERENCE   9  (bases 1 to 4461)
  AUTHORS   Dahmane,N., Charron,G., Lopes,C., Yaspo,M.L., Maunoury,C.,
            Decorte,L., Sinet,P.M., Bloch,B. and Delabar,J.M.
  TITLE     Down syndrome-critical region contains a gene homologous to
            Drosophila sim expressed during rat and human central nervous
            system development
  JOURNAL   Proc Natl Acad Sci U S A 92 (20), 9191-9195 (1995)
   PUBMED   7568099
REFERENCE   10 (bases 1 to 4461)
  AUTHORS   Chen,H., Chrast,R., Rossier,C., Gos,A., Antonarakis,S.E., Kudoh,J.,
            Yamaki,A., Shindoh,N., Maeda,H., Minoshima,S. et al.
  TITLE     Single-minded and Down syndrome?
  JOURNAL   Nat Genet 10 (1), 9-10 (1995)
   PUBMED   7647800
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP000697.1, BM848475.1,
            BC052313.1, U80456.2 and BC110444.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_005069.5.
            
            Summary: This gene represents a homolog of the Drosophila
            single-minded (sim) gene, which encodes a transcription factor that
            is a master regulator of neurogenesis. The encoded protein is
            ubiquitinated by RING-IBR-RING-type E3 ubiquitin ligases, including
            the parkin RBR E3 ubiquitin protein ligase. This gene maps within
            the so-called Down syndrome chromosomal region, and is thus thought
            to contribute to some specific Down syndrome phenotypes.
            Alternative splicing of this gene results in multiple transcript
            variants. [provided by RefSeq, Sep 2014].
            
            Transcript Variant: This variant (SIM2) represents the longer
            transcript and encodes the longer isoform (long).
            
            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 :: U80456.2, DRR138523.336567.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2144335, SAMEA2145774
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000290399.11/ ENSP00000290399.6
            RefSeq Select criteria :: based on conservation, longest protein
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-6                 AP000697.1         72537-72542
            7-18                BM848475.1         1-12
            19-250              BC052313.1         1-232
            251-251             AP000697.1         72787-72787
            252-576             BC052313.1         234-558
            577-1393            U80456.2           1-817
            1394-2208           BC110444.2         788-1602
            2209-4461           U80456.2           1633-3885
FEATURES             Location/Qualifiers
     source          1..4461
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="21"
                     /map="21q22.13"
     gene            1..4461
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /note="SIM bHLH transcription factor 2"
                     /db_xref="GeneID:6493"
                     /db_xref="HGNC:HGNC:10883"
                     /db_xref="MIM:600892"
     exon            1..807
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     CDS             633..2636
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /note="long isoform is encoded by transcript variant SIM2;
                     transcription factor SIM2; class E basic helix-loop-helix
                     protein 15; single-minded family bHLH transcription factor
                     2"
                     /codon_start=1
                     /product="single-minded homolog 2 long isoform"
                     /protein_id="NP_005060.1"
                     /db_xref="CCDS:CCDS13646.1"
                     /db_xref="GeneID:6493"
                     /db_xref="HGNC:HGNC:10883"
                     /db_xref="MIM:600892"
                     /translation="MKEKSKNAAKTRREKENGEFYELAKLLPLPSAITSQLDKASIIR
                     LTTSYLKMRAVFPEGLGDAWGQPSRAGPLDGVAKELGSHLLQTLDGFVFVVASDGKIM
                     YISETASVHLGLSQVELTGNSIYEYIHPSDHDEMTAVLTAHQPLHHHLLQEYEIERSF
                     FLRMKCVLAKRNAGLTCSGYKVIHCSGYLKIRQYMLDMSLYDSCYQIVGLVAVGQSLP
                     PSAITEIKLYSNMFMFRASLDLKLIFLDSRVTEVTGYEPQDLIEKTLYHHVHGCDVFH
                     LRYAHHLLLVKGQVTTKYYRLLSKRGGWVWVQSYATVVHNSRSSRPHCIVSVNYVLTE
                     IEYKELQLSLEQVSTAKSQDSWRTALSTSQETRKLVKPKNTKMKTKLRTNPYPPQQYS
                     SFQMDKLECGQLGNWRASPPASAAAPPELQPHSESSDLLYTPSYSLPFSYHYGHFPLD
                     SHVFSSKKPMLPAKFGQPQGSPCEVARFFLSTLPASGECQWHYANPLVPSSSSPAKNP
                     PEPPANTARHSLVPSYEAPAAAVRRFGEDTAPPSFPSCGHYREEPALGPAKAARQAAR
                     DGARLALARAAPECCAPPTPEAPGAPAQLPFVLLNYHRVLARRGPLGGAAPAASGLAC
                     APGGPEAATGALRLRHPSPAATSPPGAPLPHYLGASVIITNGR"
     exon            808..890
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     exon            891..980
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     exon            981..1089
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     exon            1090..1175
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     exon            1176..1375
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     exon            1376..1482
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     exon            1483..1630
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     exon            1631..1799
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     exon            1800..2208
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     exon            2209..4461
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3132..3137
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /note="hexamer: AATACA"
     polyA_site      3161
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /note="major polyA site"
     regulatory      3511..3516
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /note="hexamer: AATAAA"
     polyA_site      3534
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
     regulatory      4319..4324
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
                     /note="hexamer: AATAAA"
     polyA_site      4339
                     /gene="SIM2"
                     /gene_synonym="bHLHe15; HMC13F06; HMC29C01; SIM"
ORIGIN      
        1 ataaacaaac gcggctcggc cgcacgtgga cagcggaggt gctgcgccta gccacacatc
       61 gcgggctccg gcgctgcgtc tccaggcaca gggagccgcc aggaagggca ggagagcgcg
      121 cccgggccag ggcccggccc cagccgcctg cgactcgctc ccctccgctg ggctcccgct
      181 ccatggctcc gcggccaccg ccgcccctgt cgccctccgg tccggagggg ccttgccgca
      241 gccggttcga gcactcgacg aaggagtaag cagcgcctcc gcctccgcgc cggccgcccc
      301 caccccccag gaaggccgag gcaggagagg caggagggag gaaacaggag cgagcaggaa
      361 cggggctccg gttgctgcag gacggtccag cccggaggag gctgcgctcc gggcagcggc
      421 gggcggcgcc gccgggttgc tcggagctca ggcccggcgg ctgcggggag gcgtctcgga
      481 accccgggag gccccccgca cctgcccgcg gcccactccg cggactcacc tggctcccgg
      541 ctcccccttc cccatccccg ccgccgcagc ccgagcgggg ctccgcgggc ctggagcacg
      601 gccgggtcta atatgcccgg agccgaggcg cgatgaagga gaagtccaag aatgcggcca
      661 agaccaggag ggagaaggaa aatggcgagt tttacgagct tgccaagctg ctcccgctgc
      721 cgtcggccat cacttcgcag ctggacaaag cgtccatcat ccgcctcacc acgagctacc
      781 tgaagatgcg cgccgtcttc cccgaaggtt taggagacgc gtggggacag ccgagccgcg
      841 ccgggcccct ggacggcgtc gccaaggagc tgggatcgca cttgctgcag actttggatg
      901 gatttgtttt tgtggtagca tctgatggca aaatcatgta tatatccgag accgcttctg
      961 tccatttagg cttatcccag gtggagctca cgggcaacag tatttatgaa tacatccatc
     1021 cttctgacca cgatgagatg accgctgtcc tcacggccca ccagccgctg caccaccacc
     1081 tgctccaaga gtatgagata gagaggtcgt tctttcttcg aatgaaatgt gtcttggcga
     1141 aaaggaacgc gggcctgacc tgcagcggat acaaggtcat ccactgcagt ggctacttga
     1201 agatcaggca gtatatgctg gacatgtccc tgtacgactc ctgctaccag attgtggggc
     1261 tggtggccgt gggccagtcg ctgccaccca gtgccatcac cgagatcaag ctgtacagta
     1321 acatgttcat gttcagggcc agccttgacc tgaagctgat attcctggat tccagggtga
     1381 ccgaggtgac ggggtacgag ccgcaggacc tgatcgagaa gaccctatac catcacgtgc
     1441 acggctgcga cgtgttccac ctccgctacg cacaccacct cctgttggtg aagggccagg
     1501 tcaccaccaa gtactaccgg ctgctgtcca agcggggcgg ctgggtgtgg gtgcagagct
     1561 acgccaccgt ggtgcacaac agccgctcgt cccggcccca ctgcatcgtg agtgtcaatt
     1621 atgtactcac ggagattgaa tacaaggaac ttcagctgtc cctggagcag gtgtccactg
     1681 ccaagtccca ggactcctgg aggaccgcct tgtctacctc acaagaaact aggaaattag
     1741 tgaaacccaa aaataccaag atgaagacaa agctgagaac aaacccttac cccccacagc
     1801 aatacagctc gttccaaatg gacaaactgg aatgcggcca gctcggaaac tggagagcca
     1861 gtccccctgc aagcgctgct gctcctccag aactgcagcc ccactcagaa agcagtgacc
     1921 ttctgtacac gccatcctac agcctgccct tctcctacca ttacggacac ttccctctgg
     1981 actctcacgt cttcagcagc aaaaagccaa tgttgccggc caagttcggg cagccccaag
     2041 gatccccttg tgaggtggca cgctttttcc tgagcacact gccagccagc ggtgaatgcc
     2101 agtggcatta tgccaacccc ctagtgccta gcagctcgtc tccagctaaa aatcctccag
     2161 agccaccggc gaacactgct aggcacagcc tggtgccaag ctacgaagcg cccgccgccg
     2221 ccgtgcgcag gttcggcgag gacaccgcgc ccccgagctt cccgagctgc ggccactacc
     2281 gcgaggagcc cgcgctgggc ccggccaaag ccgcccgcca ggccgcccgg gacggggcgc
     2341 ggctggcgct ggcccgcgcg gcacccgagt gctgcgcgcc cccgaccccc gaggccccgg
     2401 gcgcgccggc gcagctgccc ttcgtgctgc tcaactacca ccgcgtgctg gcccggcgcg
     2461 gaccgctggg gggcgccgca cccgccgcct ccggcctggc ctgcgctccc ggcggccccg
     2521 aggcggcgac cggcgcgctg cggctccggc acccgagccc cgccgccacc tccccgcccg
     2581 gcgcgcccct gccgcactac ctgggcgcct cggtcatcat caccaacggg aggtgacccg
     2641 ctggccgccc gcgccaggag cctggacccg gcctcccggg gctgcggcgc caccgagccc
     2701 ggcaaatgcg cacgacctac attaatttat gcagagacag ctgtttgaat tggaccccgc
     2761 cgccgacttg cggatttcca ccgcggaggc cccgcgcgcc ggtgccgagg gccgaggagc
     2821 gcccgggtcc gggcaggtga ccgcccgcct ctgtcctgcg agggccggtg cgacccagtt
     2881 gctgggggct tggtttcctc accttgaaat cgggcttcac gcgtcttgcc ttgtccccaa
     2941 cgttccacaa cagtcccgct gggggattga agcggtttca ctccgcaaat atcctccact
     3001 ttcaggaggg aaaacccacc ctaccacagt ccgctcttcc aagtggacgg cagacctggg
     3061 aggggacgcc tgtgtcacga gcccttttag atgcttaggt gaaggcagaa gtgatgattg
     3121 taagtcccat gaatacacaa ctccactgtc tttaaaagtc attcaagagt ctcattattt
     3181 ttgtttttat ttaacccttt cttcaataca aaaagccaac aaaccaagac taagggggtg
     3241 accatgcaat tccattttgt gtctgtgaac ataggtgtgc ttcccaaata cattaacaag
     3301 ctcttacttc cccctaaccc ctatgaactc ttgataacac caagagtagc accttcagaa
     3361 tatattgaat aggcattaaa tgcaaaaata tatatgtagc cagacagttt atgagaatga
     3421 ccctgtcaag cttcattatt acgtggcaaa atccctctgg cccacacaga tctgtaattc
     3481 actaggctcg tgtttgctac aaatagtgct aataaagtta aattgcacgt gcaatacgga
     3541 acactgtcaa tggactgcac cttgtgaagg aaaaacatgc ttaagggggt gtaatgaaaa
     3601 tgatgtagac attttaagca ttttctacac agcgagaaaa cttcgtaaga acatgttacg
     3661 tgtgcaacag gtaaacagaa atcctttcat aaagcaccag cagtgtttaa aaaatgagct
     3721 tccattaatt tttacttttt atgggttttg cttaaagatc tcaacatgga aaaatcctgt
     3781 catggctctg aactgcacaa tgcattgaac cgccgtcctt caattttctt cacactatca
     3841 acactgcagc attttgctgc tttatcaaaa tggtttattt taggaaactt tttccacctt
     3901 tctgaatgga aagaggtttt cacaaatgtt ttaaactcat cgttctaaaa tcaagtgcac
     3961 ctacaccaac tgctctcaaa atgtgaactg actttttttt tttttttttt gccaaccctg
     4021 tgtcacttag tgaggacctg acacaatccc tacagggtgt ctgtcagtgg gcctcatggt
     4081 aagagtcaca atttgcaaat ttaggaccgt gggtcatgca gcgaaggggc tggatggtag
     4141 gaagggatgt gcccgcctct ccacgcactc agctatacct cattcacagc tccttgtgag
     4201 tgtgtgcaca ggaaataagc cgagggtatt atttttttat gttcatgagt cttgtaatta
     4261 aaccgtgatt cttgaaaggt gtaggtttga ttactaggag ataccaccga catttttcaa
     4321 taaagtactg caaaatgctt ttgtgtctac cttgttatta acttttgggg ctgtatttag
     4381 taaaaataaa tcaaggctat cggagcagtt caataacaaa ggttactgtt gagaaaaaag
     4441 accctatcat agatttacaa g
//
