LOCUS       NM_013964              11983 bp    mRNA    linear   PRI 24-OCT-2024
DEFINITION  Homo sapiens neuregulin 1 (NRG1), transcript variant HRG-alpha,
            mRNA.
ACCESSION   NM_013964
VERSION     NM_013964.5
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 11983)
  AUTHORS   Li,X., Zhang,H., Li,W., Tuo,H., He,B. and Jiang,H.
  TITLE     The role and mechanism of NRG1/ErbB4 in inducing the
            differentiation of induced pluripotent stem cells into
            cardiomyocytes
  JOURNAL   BMC Cardiovasc Disord 24 (1), 559 (2024)
   PUBMED   39407109
  REMARK    GeneRIF: The role and mechanism of NRG1/ErbB4 in inducing the
            differentiation of induced pluripotent stem cells into
            cardiomyocytes.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 11983)
  AUTHORS   Zhang,W., Dao,J.J., Li,Q., Liu,C., Qiao,C.M., Cui,C., Shen,Y.Q. and
            Zhao,W.J.
  TITLE     Neuregulin 1 mitigated prolactin deficiency through enhancing TRPM8
            signaling under the influence of melatonin in senescent pituitary
            lactotrophs
  JOURNAL   Int J Biol Macromol 275 (Pt 1), 133659 (2024)
   PUBMED   38969045
  REMARK    GeneRIF: Neuregulin 1 mitigated prolactin deficiency through
            enhancing TRPM8 signaling under the influence of melatonin in
            senescent pituitary lactotrophs.
REFERENCE   3  (bases 1 to 11983)
  AUTHORS   Liu,X., Bates,R., Yin,D.M., Shen,C., Wang,F., Su,N., Kirov,S.A.,
            Luo,Y., Wang,J.Z., Xiong,W.C. and Mei,L.
  TITLE     Specific regulation of NRG1 isoform expression by neuronal activity
  JOURNAL   J Neurosci 31 (23), 8491-8501 (2011)
   PUBMED   21653853
  REMARK    GeneRIF: each of the six types of NRG1 has a distinct expression
            pattern in the brain at different ages, resulting in a change in
            NRG1 isoform composition. Also, the expression of each NRG1 isoform
            is distinctly regulated by neuronal activity.
REFERENCE   4  (bases 1 to 11983)
  AUTHORS   Shamir,A. and Buonanno,A.
  TITLE     Molecular and cellular characterization of Neuregulin-1 type IV
            isoforms
  JOURNAL   J Neurochem 113 (5), 1163-1176 (2010)
   PUBMED   20218976
  REMARK    GeneRIF: NRG1 type IV expression levels can selectively modify
            signaling of NRG1 released from somato-dendritic compartments, in
            contrast to the type III NRG1 that is also associated with axons
REFERENCE   5  (bases 1 to 11983)
  AUTHORS   Tan,W., Wang,Y., Gold,B., Chen,J., Dean,M., Harrison,P.J.,
            Weinberger,D.R. and Law,A.J.
  TITLE     Molecular cloning of a brain-specific, developmentally regulated
            neuregulin 1 (NRG1) isoform and identification of a functional
            promoter variant associated with schizophrenia
  JOURNAL   J Biol Chem 282 (33), 24343-24351 (2007)
   PUBMED   17565985
  REMARK    GeneRIF: type IV is a unique brain-specific NRG1 that is
            differentially expressed and processed during early development, is
            translated, and its expression regulated by a schizophrenia
            risk-associated functional promoter or single nucleotide
            polymorphism
REFERENCE   6  (bases 1 to 11983)
  AUTHORS   Steinthorsdottir,V., Stefansson,H., Ghosh,S., Birgisdottir,B.,
            Bjornsdottir,S., Fasquel,A.C., Olafsson,O., Stefansson,K. and
            Gulcher,J.R.
  TITLE     Multiple novel transcription initiation sites for NRG1
  JOURNAL   Gene 342 (1), 97-105 (2004)
   PUBMED   15527969
  REMARK    GeneRIF: NRG1, with nine potential promoter, plays a central role
            in neural development and is most likely involved in regulation of
            synaptic plasticity, or how the brain responds or adapts to the
            environment.
REFERENCE   7  (bases 1 to 11983)
  AUTHORS   Wang,J.Y., Miller,S.J. and Falls,D.L.
  TITLE     The N-terminal region of neuregulin isoforms determines the
            accumulation of cell surface and released neuregulin ectodomain
  JOURNAL   J Biol Chem 276 (4), 2841-2851 (2001)
   PUBMED   11042203
REFERENCE   8  (bases 1 to 11983)
  AUTHORS   Marchionni,M.A., Goodearl,A.D., Chen,M.S., Bermingham-McDonogh,O.,
            Kirk,C., Hendricks,M., Danehy,F., Misumi,D., Sudhalter,J.,
            Kobayashi,K. et al.
  TITLE     Glial growth factors are alternatively spliced erbB2 ligands
            expressed in the nervous system
  JOURNAL   Nature 362 (6418), 312-318 (1993)
   PUBMED   8096067
REFERENCE   9  (bases 1 to 11983)
  AUTHORS   Holmes,W.E., Sliwkowski,M.X., Akita,R.W., Henzel,W.J., Lee,J.,
            Park,J.W., Yansura,D., Abadi,N., Raab,H., Lewis,G.D. et al.
  TITLE     Identification of heregulin, a specific activator of p185erbB2
  JOURNAL   Science 256 (5060), 1205-1210 (1992)
   PUBMED   1350381
REFERENCE   10 (bases 1 to 11983)
  AUTHORS   Peles,E., Bacus,S.S., Koski,R.A., Lu,H.S., Wen,D., Ogden,S.G.,
            Levy,R.B. and Yarden,Y.
  TITLE     Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein
            that induces differentiation of mammary tumor cells
  JOURNAL   Cell 69 (1), 205-216 (1992)
   PUBMED   1348215
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK298132.1, AK097005.1,
            BC006492.2, M94165.1, DA805080.1, AC113209.4 and CA429204.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_013964.4.
            
            Summary: The protein encoded by this gene is a membrane
            glycoprotein that mediates cell-cell signaling and plays a critical
            role in the growth and development of multiple organ systems. An
            extraordinary variety of different isoforms are produced from this
            gene through alternative promoter usage and splicing. These
            isoforms are expressed in a tissue-specific manner and differ
            significantly in their structure, and are classified as types I,
            II, III, IV, V and VI. Dysregulation of this gene has been linked
            to diseases such as cancer, schizophrenia, and bipolar disorder
            (BPD). [provided by RefSeq, Apr 2016].
            
            Transcript Variant: This variant (HRG-alpha), which uses the type I
            promoter, lacks two in-frame exons but contains a different
            in-frame exon in the central coding region, compared to variant
            HRG-beta1. The resulting isoform (HRG-alpha, also known as erbB2 or
            gp30/alpha 1) contains an alternate internal segment and is shorter
            than isoform HRG-beta1.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: M94165.1, S68256.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA1968968
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000405005.8/ ENSP00000384620.2
            RefSeq Select criteria :: based on manual assertion, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-150               AK298132.1         102-251
            151-223             AK097005.1         152-224
            224-284             BC006492.2         297-357
            285-2492            M94165.1           1-2208
            2493-2977           DA805080.1         84-568
            2978-5247           AC113209.4         164882-167151       c
            5248-5894           CA429204.1         18-664              c
            5895-11983          AC113209.4         158146-164234       c
FEATURES             Location/Qualifiers
     source          1..11983
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8p12"
     gene            1..11983
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /note="neuregulin 1"
                     /db_xref="GeneID:3084"
                     /db_xref="HGNC:HGNC:7997"
                     /db_xref="MIM:142445"
     exon            1..516
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     CDS             417..2339
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /note="isoform HRG-alpha proprotein is encoded by
                     transcript variant HRG-alpha; heregulin, alpha (45kD,
                     ERBB2 p185-activator); neu differentiation factor; sensory
                     and motor neuron derived factor; pro-NRG1; glial growth
                     factor 2; acetylcholine receptor-inducing activity; NRG1
                     class VII isoform beta 3; NRG1 class VII isoform alpha
                     beta 3; NRG1 class VII isoform beta 2a; NRG1 class VII
                     isoform alpha 2a; NRG1 class VII isoform alpha 2b; NRG1
                     class VII isoform alpha beta 2a"
                     /codon_start=1
                     /product="pro-neuregulin-1, membrane-bound isoform isoform
                     HRG-alpha proprotein"
                     /protein_id="NP_039258.1"
                     /db_xref="CCDS:CCDS6085.1"
                     /db_xref="GeneID:3084"
                     /db_xref="HGNC:HGNC:7997"
                     /db_xref="MIM:142445"
                     /translation="MSERKEGRGKGKGKKKERGSGKKPESAAGSQSPALPPRLKEMKS
                     QESAAGSKLVLRCETSSEYSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKA
                     SLADSGEYMCKVISKLGNDSASANITIVESNEIITGMPASTEGAYVSSESPIRISVST
                     EGANTSSSTSTSTTGTSHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCQPGFTG
                     ARCTENVPMKVQNQEKAEELYQKRVLTITGICIALLVVGIMCVVAYCKTKKQRKKLHD
                     RLRQSLRSERNNMMNIANGPHHPNPPPENVQLVNQYVSKNVISSEHIVEREAETSFST
                     SHYTSTAHHSTTVTQTPSHSWSNGHTESILSESHSVIVMSSVENSRHSSPTGGPRGRL
                     NGTGGPRECNSFLRHARETPDSYRDSPHSERYVSAMTTPARMSPVDFHTPSSPKSPPS
                     EMSPPVSSMTVSMPSMAVSPFMEEERPLLLVTPPRLREKKFDHHPQQFSSFHHNPAHD
                     SNSLPASPLRIVEDEEYETTQEYEPAQEPVKKLANSRRAKRTKPNGHIANRLEVDSNT
                     SSQSSNSESETEDERVGEDTPFLGIQNPLAASLEATPAFRLADSRTNPAGRFSTQEEI
                     QARLSSVIANQDPIAV"
     exon            517..694
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     exon            695..816
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     exon            817..867
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     exon            868..918
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     exon            919..1048
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     exon            1049..1116
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     exon            1117..1219
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     exon            1220..1346
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     exon            1347..1477
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     exon            1478..1684
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     exon            1685..11983
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5873..5878
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /note="hexamer: AATAAA"
     polyA_site      5894
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /note="major polyA site"
     regulatory      11962..11967
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /note="hexamer: AATAAA"
     polyA_site      11983
                     /gene="NRG1"
                     /gene_synonym="ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA;
                     MST131; MSTP131; NDF; NRG1-IT2; SMDF"
                     /note="major polyA site"
ORIGIN      
        1 aaacttgttg gaactccggg ctcgcgcgga ggccaggagc tgagcggcgg cggctgccgg
       61 acgatgggag cgtgagcagg acggtgataa cctctccccg atcgggttgc gagggcgccg
      121 ggcagaggcc aggacgcgag ccgccagcgg tgggacccat cgacgacttc ccggggcgac
      181 aggagcagcc ccgagagcca gggcgagcgc ccgttccagg tggccggacc gcccgccgcg
      241 tccgcgccgc gctccctgca ggcaacggga gacgcccccg cgcagcgcga gcgcctcagc
      301 gcggccgctc gctctccccc tcgagggaca aacttttccc aaacccgatc cgagcccttg
      361 gaccaaactc gcctgcgccg agagccgtcc gcgtagagcg ctccgtctcc ggcgagatgt
      421 ccgagcgcaa agaaggcaga ggcaaaggga agggcaagaa gaaggagcga ggctccggca
      481 agaagccgga gtccgcggcg ggcagccaga gcccagcctt gcctccccga ttgaaagaga
      541 tgaaaagcca ggaatcggct gcaggttcca aactagtcct tcggtgtgaa accagttctg
      601 aatactcctc tctcagattc aagtggttca agaatgggaa tgaattgaat cgaaaaaaca
      661 aaccacaaaa tatcaagata caaaaaaagc cagggaagtc agaacttcgc attaacaaag
      721 catcactggc tgattctgga gagtatatgt gcaaagtgat cagcaaatta ggaaatgaca
      781 gtgcctctgc caatatcacc atcgtggaat caaacgagat catcactggt atgccagcct
      841 caactgaagg agcatatgtg tcttcagagt ctcccattag aatatcagta tccacagaag
      901 gagcaaatac ttcttcatct acatctacat ccaccactgg gacaagccat cttgtaaaat
      961 gtgcggagaa ggagaaaact ttctgtgtga atggagggga gtgcttcatg gtgaaagacc
     1021 tttcaaaccc ctcgagatac ttgtgcaagt gccaacctgg attcactgga gcaagatgta
     1081 ctgagaatgt gcccatgaaa gtccaaaacc aagaaaaggc ggaggagctg taccagaaga
     1141 gagtgctgac cataaccggc atctgcatcg ccctccttgt ggtcggcatc atgtgtgtgg
     1201 tggcctactg caaaaccaag aaacagcgga aaaagctgca tgaccgtctt cggcagagcc
     1261 ttcggtctga acgaaacaat atgatgaaca ttgccaatgg gcctcaccat cctaacccac
     1321 cccccgagaa tgtccagctg gtgaatcaat acgtatctaa aaacgtcatc tccagtgagc
     1381 atattgttga gagagaagca gagacatcct tttccaccag tcactatact tccacagccc
     1441 atcactccac tactgtcacc cagactccta gccacagctg gagcaacgga cacactgaaa
     1501 gcatcctttc cgaaagccac tctgtaatcg tgatgtcatc cgtagaaaac agtaggcaca
     1561 gcagcccaac tgggggccca agaggacgtc ttaatggcac aggaggccct cgtgaatgta
     1621 acagcttcct caggcatgcc agagaaaccc ctgattccta ccgagactct cctcatagtg
     1681 aaaggtatgt gtcagccatg accaccccgg ctcgtatgtc acctgtagat ttccacacgc
     1741 caagctcccc caaatcgccc ccttcggaaa tgtctccacc cgtgtccagc atgacggtgt
     1801 ccatgccttc catggcggtc agccccttca tggaagaaga gagacctcta cttctcgtga
     1861 caccaccaag gctgcgggag aagaagtttg accatcaccc tcagcagttc agctccttcc
     1921 accacaaccc cgcgcatgac agtaacagcc tccctgctag ccccttgagg atagtggagg
     1981 atgaggagta tgaaacgacc caagagtacg agccagccca agagcctgtt aagaaactcg
     2041 ccaatagccg gcgggccaaa agaaccaagc ccaatggcca cattgctaac agattggaag
     2101 tggacagcaa cacaagctcc cagagcagta actcagagag tgaaacagaa gatgaaagag
     2161 taggtgaaga tacgcctttc ctgggcatac agaaccccct ggcagccagt cttgaggcaa
     2221 cacctgcctt ccgcctggct gacagcagga ctaacccagc aggccgcttc tcgacacagg
     2281 aagaaatcca ggccaggctg tctagtgtaa ttgctaacca agaccctatt gctgtataaa
     2341 acctaaataa acacatagat tcacctgtaa aactttattt tatataataa agtattccac
     2401 cttaaattaa acaatttatt ttattttagc agttctgcaa atagaaaaca ggaaaaaaac
     2461 ttttataaat taaatatatg tatgtaaaaa tgtgttatgt gccatatgta gcaatttttt
     2521 acagtatttc aaaacgagaa agatatcaat ggtgccttta tgttatgtta tgtcgagagc
     2581 aagttttgta cagttacagt gattgctttt ccacagtatt tctgcaaaac ctctcataga
     2641 ttcagttttt gctggcttct tgtgcattgc attatgatgt tgactggatg tatgatttgc
     2701 aagacttgca actgtccctc tgtttgcttg tagtagcacc cgatcagtat gtcttgtaat
     2761 ggcacatcca tccagatatg cctctcttgt gtatgaagtt ttctttgctt tcagaatatg
     2821 aaatgagttg tgtctactct gccagccaaa ggtttgcctc attgggctct gagataatag
     2881 tagatccaac agcatgctac tattaaatac agcaagaaac tgcattaagt aatgttaaat
     2941 attaggaaga aagtaatact gtgatttaaa aaaaactata ttattaatca gaagacagct
     3001 tgctcttact aaaaggagct ctcatttact ttatttgatt ttatttttct tgacaaaaag
     3061 caacagtttt agggatagct tagaaaatgg gttctggctt gctatcaggg taaatctaac
     3121 accttacaag aggactgagt gtcactttct ctctggggga atgatccagc agcttatcta
     3181 gttgacaatc aaaacacggc tgataaaggt gcaatcattt ctgacatgta tttttcactg
     3241 attttgaagc tagtgattgg ttgtgtcttc ttggctcaaa aagaagcata ttacggcaca
     3301 aaaagcccag cccagacagc acatgcagca ttttgtctga aatacttcta gagtcaaacg
     3361 tgcctgctgt acatagcgat gacttgtcat catagggaag tatttccatc gtagagtgtt
     3421 cagaaggagt gactgtatag gtggagagaa gcttagtgac tccgttgaaa ttttaaaatg
     3481 tggatgacca cccctttctc ccccttattt ttcttttatc tttccatgtt gccttgatca
     3541 ggtcataact atgcatgaac attttttatc aggaatggcc gatgtgtatg tgatttgtaa
     3601 tcacaagtaa tgattcatca ggaaatgtca atcctgttgg aaagattgca cctttacttg
     3661 cagaagtgac ccccacctgt gtcctgacct ctccatttac aggctctctc acccatttcc
     3721 cccacctcct ttaatttttg ctttactgtc ataaagtagg actaagattg gtctaagcat
     3781 tgcatgttct tttgtgatgg taaatccaaa ggaaggccta taagtattaa catttgaaat
     3841 aactgctaat tcaggaaaat ggaagaaaaa aaattatttg aaacacagaa cccatttcat
     3901 ggcctgcctg atatctgtga aatcagggct ggagctttac ttaggattca catggcctcc
     3961 taggaaccat gggacaaatg ggaaacaggt tatcggggga ttcatgaagt cagtgagagt
     4021 aattgcttct tttttgcggg tgaactgaat gtatttcttc accaaatctt gatgttaaca
     4081 attaaaaaga agaaatgaca tgcaagtagg tcttagcaga aaaatgcagg ctgggcatga
     4141 gtcatgttgt taccctccca catgctccta caatccacag agatgcctgt ctgcaggttc
     4201 ttgaagttat tgttagtatt tggtatctca aatttttcgt cactgttcac atgccacttt
     4261 ctctgtgcac agtggtatcc tcatttgctt tttaacctac actgaggagt ctttgtcagg
     4321 ttgcactgat tttccaattc tgcagtaatg agtaagctca cggcatgggg aagaagacag
     4381 tcagtccaat gaagttctct aaattatttt aacattgcct ttgaaggcct tgactcatcc
     4441 ttagctattt caatgaagaa attcctacca tgaatttaaa accctaaaaa ttctgtttca
     4501 aattctttgg gcattggggt actcagatat cccattgtgg aagaatttta agaataaata
     4561 gaagtttctg ttgagaacca tgagcaacat gtttcttaca atgagaattg ctatgcattt
     4621 taaaattgca aatatatatg aaaattgaag acaagaggaa attgtatttc taacttgatt
     4681 ctgatcactc acagaggtgg catattatta tagttgggac atcctttgca cccttcataa
     4741 aaaaggccag ctgactgctc agcatcacct gccaaggcca ctagatttgt gtttacaggg
     4801 gtatctctgt gatgcttgtc acatcactct tgaccacctc tgttaataaa ttccgacagt
     4861 gcagtggcga tcggagtgtg aacttatgtt cccagcatat ggaaagctat cttaggtttt
     4921 aaggtagtag aaattgccca ggagtttgac agcaactttg tttcccgggt ctaaaatcgt
     4981 atcccactga ggtgtatgca gtggagcata atacatgcaa atacatgcaa aactcctttt
     5041 gtttcaccta agattcactt tctatcttac tttcccttcc tgcctagtgt gacttttgcc
     5101 cccaagagtg cctggacagc attctagttt ctacaaaatg gtcctctgtg taggtgaatg
     5161 tgtcccaaac ctgctatcac tttcttgttt cagtgtgact gtcttgttag aggtgaagtt
     5221 tatccagggt aacttgctca ctaactattc ctttttatgg cctggggtta aagggcgcat
     5281 ggctcacact ggtgaaaata aggaaggcct ggtcttatct tgtattaata atactggctg
     5341 cattccacca gccagagatt tctatctgcg aagacctatg aaacactgaa gagaaatgta
     5401 ggcagaagga aatggccaca tatcacaagt tctattatat attcttttgt aaatacatat
     5461 tgtatattac ttggatgttt tcttatatca tttactgtct ttttgagtta atgtcagttt
     5521 ttactctctc aacttactat gtaacattgt aaataacata atgtccttta ttatttatat
     5581 ttaagcatct aacatataga gttgttttca tataagttta agataaatgt caaaaatata
     5641 tgttcttttg tttttctttg ctttaaaatt atgtatcttt tccttttctt ttttttaaga
     5701 ataatttatt gttcaggaga aagaatgtat atgtaactga aactatctga agaatgcaca
     5761 ttgaaggccg tgaggtactg ataaactaaa gaatttatta ttcaaaatac taagcaataa
     5821 gtaattgtga tttatttaaa gttttgtcca ttttccatga aagacatact gcaataaaaa
     5881 tgctactctg tggagacctg ggagtgttgc tcagcagact acagcttcag tctgttagac
     5941 cagcaccttt catctcattc ccatagttat gctaatttag gattgtgttc catggacccc
     6001 atgatcacct tgtctatacg ttgcttcttg tctgtccatt gcttttgcca caccacctgt
     6061 tctcaaatca tctcctccct accaatgctg tttatcactt tcttccttgt tgaagaggcc
     6121 acacaaccag acagtactat gcttcctttt tcctccatac acaataacag agagagaata
     6181 ttctagggca tgactgcctg gatcctggct gttgctatct tttgtagtgg cagtaagaaa
     6241 ctccttcaga ctaatgaaaa tgtcaacgtg ccattcaatc acgaaaggta acgaaaaatg
     6301 ctctcatggt tcaaatagtc caatggccca tagtggccta aaaggcagcc agttgacacc
     6361 tggccatgct aagcttcctt ataccatccg ctaatgactt tccattgggc ccacaattta
     6421 cggattcata attttaaaag aggagaaggc caagttaggt tcattcccct tattctgtca
     6481 ataaaacaaa tcaaactcat gtctatctaa ctgctcaggg aggagccttt gcatgagaaa
     6541 attctcatat tctaagactg agtcatagaa atgagggtat tacttttctt actgcaatta
     6601 acctaaacaa aagccatatt ttaacaaata gatatttgca tggtaccctt catatattcc
     6661 aagcatttca ctcattattc caggtaggtt aagagcttct gaagtgtatg aagtaaaggt
     6721 cagcaatcct ttggggtgaa cagtggcctc ctttggagtt tgggggtaac ctgagacttc
     6781 ccaccaatgt ccacctccat ctgtgtacct aattcctatt acctagttat ggctcctcta
     6841 ggatcatttc caaacactct ggatgtccag gaaatttaaa ttgtagcttt tgactgagct
     6901 agtttttcct atttatatta ataaattttc aaaaatgctt gaaatcttca catttgcaac
     6961 aactttagtt ttcatgcaca tacaaacaca gagagacaaa aattccaaac agacactctc
     7021 caaaagccac cacactcttt cacttgctct atagtcattt agccaaccag ccatgcagag
     7081 aatatttaaa acttaaagat tgagacatta ttctcagttt ttgctgaggc tttgtaacga
     7141 aattgaacac tataagcagc tattgtagta attttggtta aaattgtttg cctgggatat
     7201 agtatttgag gcagaagcac gtgtgtgaag gaggtgaggt ggtttggaaa gagtgaagac
     7261 tcgcagccag attgaatgtc tggataatta ctataattct cccttcttgg ttgaaaccat
     7321 gttctctctt gatttttaaa cccaggctgc ctctggaaac aagcaaacct gagtctttct
     7381 aacctgagtc ttcccaatca ttagatttct tttctgtcct aacgatgaat gataaaagga
     7441 cttgatgttc acaatttggg gttataaggc aggtctgaaa tctggagact caagatgctg
     7501 gaaggagtgg aaagtttcga tgactttata tgaatcactt tgcactctat gtttggcttg
     7561 tcctctttga aactgattta ctaaaataaa tgtaagggaa ctattactcc aaaagattaa
     7621 cttggcagga aataccaata ctttcagttt atgaaagaca aaactgtctt gttgctacag
     7681 gaagctgcaa tgttcctaac ctttaaggtt ggtgttgaat agggtggtca tgccctcccc
     7741 tgcaggtatc tttaggctcc tgttgacctc ctggtactat aactgttcgt cttctctggg
     7801 tagctattga ttttgaactt taacatgctt caaaacttta ttcatcaggg aaataggaaa
     7861 agagttttgt tacctggagg aaatctattg tgatctacct gagcttttta aaaacagacc
     7921 aggagaagga aaccagtaat ttttaaagaa gagacagaga atgggataat agtttcaccc
     7981 aggatctctt tctaaccctt tcccttcaaa tgaacttatt ggaacagaat tggaaagaag
     8041 aaaggacatc tctgcccacc ccacaggatg ccaaaaaggc taaagaatta cctctgtaga
     8101 tttaaacatc tttaatggct tatgtataga tttgctaata cagagagaaa tgaactatta
     8161 aataaaaatc acattttata atatttttat ggcttaaaac atcctttatc tcctttttgt
     8221 tctctctaca tgatatggta agtgatgagg aaaatttagg ctcaggaagg ttaaaatctt
     8281 tcttggagtt acacatctaa gagagctgca gagctgacac ttgtacccag gttttctgac
     8341 tgcaaatcca gtttctttct attgcgttct tcccctttcc ctgcctcaag cagaaacagg
     8401 ttttttattt tcaaccttta tgtatacagt atgttatgtt acatctacag ctaagtttct
     8461 ttttagaaga atgtgagccc ttctagcttt ggtttagagt gattctagaa gccaatttcc
     8521 ttggcttagt gattctatgc acctttccta aacttagctt tctaaggaaa tgaagtgtac
     8581 gagtgagaat gaattcacaa tttcgacatg taggtagcat cctaaagtga aaagaggagg
     8641 aaatttgtgg tcaaagcact ctccccacca cttagaaact tactgactgt gggcagcttc
     8701 ctcctccaag tttccttcct gatttacaag accgtggtgt ggtcaggatt aaacttgaat
     8761 acatgtaagg aagcctgaaa gtgtctaaca catagcgagt attcaaatgc caccttctat
     8821 ttgatccttc ccctccagtt ccttaagttt tggaatctag gtttctcagt tccaaatgga
     8881 ttgacatttg catatcccca ttgcacaatg gatcaaataa actttatgtt atcatttctc
     8941 caacatagtg ccagtaagca aatccttttt aataacaaca gtatgttgag aaacatatca
     9001 ccaaataata tttaactttg tagctttgat aagttcttta ggttttggtt ttggttttgt
     9061 tttctgagac agggtcttga tctgtcaccc agactggagt gcaatggttc aattttagct
     9121 cactgcaacc tgtaactcct gagctcaagt gatcctccca cctcagcctc tcaagtagct
     9181 gggactacag gtgtgctcca ccatgcccag cgattttttt tttttttttt tttttttttt
     9241 ttggtaggga caaggtctcg ctatgttgcc caggctggtc ttcaattcct ggccttaagt
     9301 gatcctcctg cctcggcctc ccaaagtgct ggaattacag gcatgagcca ccacccataa
     9361 ctttatgttt gtttttttga tgcagtataa gttcagcttg cttcttatgc agccatacca
     9421 tttcatgtta actctgattt ttagcagctt attacattag tgttttatta ttaatataat
     9481 tttacagaaa tttactaaac catgactctg tagagtttta ataatactac ctccaaacat
     9541 cattgcaaac atctagaaga atgaacaaaa atgatcttag atcgacagta tatctgtttg
     9601 tcttagtttc tacacaggat gttcagacat attccatttc tttaaaaaaa aaatatatat
     9661 atatatatat atatataggc ctggcacggt ggctcatgac tgtaatccca gcactttggg
     9721 aggcttaggc aggcaaatca cctgaggtca ggagtttgag actggcctga ccaacatggt
     9781 gaaacctcgt ctctattaaa attacaaaaa ttagccgggc gtggtggcac atgcctgtaa
     9841 tcccagctac tcgggaggct gaggcaggag aatcacttga acctgggagg cagaggttgc
     9901 agtgagttga gatcacgcca ttgcactcca gccttggtga caagagtgaa actccgtctc
     9961 aaaaaaaaaa aaaatatgta tatatatata tatatatata tatatatata tatatatata
    10021 tatataaaat cccaccaaaa gtctgcagag tgaccaaatt agacggctct ggtttcagat
    10081 taaattctaa atgtgagaaa ccacatagct cccatgatcc atccaataat tcctcacgtc
    10141 ctcttcactc tttactccat gcataaaaca gaattttttt ttctcatcct gggtatgaag
    10201 caattaataa tttacggatt tagcctattt ggattcaatc ccttcaaact ccatactaca
    10261 tccaaggtgg aagtgactta aactctgata tcaatcatca ggcttgtaat ataggctttg
    10321 ttaatggcag gagagtctaa taaaactttc tgttccttat ccttcattta aatgaaaaac
    10381 tttttattga aaacaatcat aactctagct catcataaat ataattcatg aggacatttt
    10441 attattttta tattaaagaa ataatattat agatgtaaac tttgcacctt tctaattatt
    10501 atcatgagtt aagctaatac ttgtcttctg gtccctagat gatgattctt ttttgcctta
    10561 ctggaggagc ccttgtcttg aagtgagttg cttcaacagc agaggacttc tagtttctcc
    10621 cagttgagcc taaagtgaac ttttcatctt cttcagagga aggggcttcc ttgatttgta
    10681 cttttgtggc tcctcagata acacagacaa ttttatcttg gatcccaggt tctcttcacc
    10741 attaagaata agaaagagag aaaatgctgt gcatgacagc cacctactcc aaactaccca
    10801 accccctgta accaggtacc ttccaacaac gagatgattc tgccctcact caagagtctc
    10861 ccccacaaag attccattct ccctttactt tttatttttt atttttttgc aaaacaaagg
    10921 cctcctttag tacctcctta gtttataacc cttatcttcc cagctcttcc cttcactgat
    10981 acctctgatt tcaaaagttc tgaagtcgga agaccacaca atttcagact gtgaacagaa
    11041 attcagtcag aaattattgg agttagaaag aatttagaga aattgtattg aactagaaag
    11101 tcctctttga ttagtggtgg ccctttagaa agttctaggg cagagtccca tggtgtttca
    11161 tcttttccat gatttgcttg accaaaaact tttctttcac aacatgaaaa tatgctaatc
    11221 caccacacat tttggattct gctctgtttg cctgaggtgt tagatctcta gccaggactg
    11281 tgaagggaag gaacttgaat ccttcctatt gagctattaa tgcagagtca gtgagatgaa
    11341 gggttccact cggggtcaaa atcatgtcag ttaccaagca aaggagcaag taaggggaaa
    11401 catctcctca tctggttagt ggagccacat ttcacccact gatcaagcca gacctgagca
    11461 atagtctaga tttctccctc cacatctaat tggtgacaat ggtgattgta ccactgacag
    11521 gtcacacaag tccacaccct ccttcacagc ctcactgctt cggctcttgt ttatgctctt
    11581 atcagcatct gtcactagga tccatttgtc tcctgactca tctacttcct ttcactcccc
    11641 tgggccatcc ttcacatcat gctagaagac tgtgtctaac ttgcagaact tattgtgtca
    11701 atctcctggt tacggcccct ccatggctcc ccacctgaca taggaggccc ttcacaatct
    11761 ggcttctgtc actcataact tgtctccagc cttcattctt cagtctgatt ttatggtttt
    11821 ctagttcccc aatacaccac accagtgttt atgaaaccct agtcattggc ctacgaactt
    11881 tatgattatt gacatattca tgtaccacct gtattatttt ttgcatagtg tttattttta
    11941 attgactaca tttttaacta caataaagta atttcaacta aaa
//
