LOCUS       NM_001100858            5667 bp    mRNA    linear   ROD 31-MAR-2024
DEFINITION  Rattus norvegicus DNA topoisomerase II beta (Top2b), mRNA.
ACCESSION   NM_001100858 XM_001067768 XM_341386
VERSION     NM_001100858.2
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Rattus norvegicus (Norway rat)
  ORGANISM  Rattus norvegicus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Rattus.
REFERENCE   1  (bases 1 to 5667)
  AUTHORS   Hu,H.L., Shiflett,L.A., Kobayashi,M., Chao,M.V., Wilson,A.C.,
            Mohr,I. and Huang,T.T.
  TITLE     TOP2beta-Dependent Nuclear DNA Damage Shapes Extracellular Growth
            Factor Responses via Dynamic AKT Phosphorylation to Control Virus
            Latency
  JOURNAL   Mol Cell 74 (3), 466-480 (2019)
   PUBMED   30930055
  REMARK    GeneRIF: Suppression of host DNA-repair pathways that remove
            TOP2bcc trigger HSV-1 reactivation. Moreover, perturbation of AKT
            phosphorylation dynamics by downregulating the PHLPP1 phosphatase
            led to AKT mis-localization and disruption of DSB-induced HSV-1
            reactivation.
REFERENCE   2  (bases 1 to 5667)
  AUTHORS   Rochette,L., Guenancia,C., Gudjoncik,A., Hachet,O., Zeller,M.,
            Cottin,Y. and Vergely,C.
  TITLE     Anthracyclines/trastuzumab: new aspects of cardiotoxicity and
            molecular mechanisms
  JOURNAL   Trends Pharmacol Sci 36 (6), 326-348 (2015)
   PUBMED   25895646
  REMARK    Review article
REFERENCE   3  (bases 1 to 5667)
  AUTHORS   Onoda,A., Hosoya,O., Sano,K., Kiyama,K., Kimura,H., Kawano,S.,
            Furuta,R., Miyaji,M., Tsutsui,K. and Tsutsui,K.M.
  TITLE     Nuclear dynamics of topoisomerase IIbeta reflects its catalytic
            activity that is regulated by binding of RNA to the C-terminal
            domain
  JOURNAL   Nucleic Acids Res 42 (14), 9005-9020 (2014)
   PUBMED   25034690
REFERENCE   4  (bases 1 to 5667)
  AUTHORS   Yang,F., Teves,S.S., Kemp,C.J. and Henikoff,S.
  TITLE     Doxorubicin, DNA torsion, and chromatin dynamics
  JOURNAL   Biochim Biophys Acta 1845 (1), 84-89 (2014)
   PUBMED   24361676
  REMARK    Review article
REFERENCE   5  (bases 1 to 5667)
  AUTHORS   Vavrova,A., Jansova,H., Mackova,E., Machacek,M., Haskova,P.,
            Tichotova,L., Sterba,M. and Simunek,T.
  TITLE     Catalytic inhibitors of topoisomerase II differently modulate the
            toxicity of anthracyclines in cardiac and cancer cells
  JOURNAL   PLoS One 8 (10), e76676 (2013)
   PUBMED   24116135
  REMARK    GeneRIF: Data indicate that dexrazoxane may protect cardiomyocytes
            via its catalytic topoisomerase II (TOP2) inhibitory activity.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 5667)
  AUTHORS   Yang,X., Li,W., Prescott,E.D., Burden,S.J. and Wang,J.C.
  TITLE     DNA topoisomerase IIbeta and neural development
  JOURNAL   Science 287 (5450), 131-134 (2000)
   PUBMED   10615047
REFERENCE   7  (bases 1 to 5667)
  AUTHORS   Bjergbaek,L., Jensen,S., Westergaard,O. and Andersen,A.H.
  TITLE     Using a biochemical approach to identify the primary dimerization
            regions in human DNA topoisomerase IIalpha
  JOURNAL   J Biol Chem 274 (37), 26529-26536 (1999)
   PUBMED   10473615
REFERENCE   8  (bases 1 to 5667)
  AUTHORS   Adachi,N., Miyaike,M., Kato,S., Kanamaru,R., Koyama,H. and
            Kikuchi,A.
  TITLE     Cellular distribution of mammalian DNA topoisomerase II is
            determined by its catalytically dispensable C-terminal domain
  JOURNAL   Nucleic Acids Res 25 (15), 3135-3142 (1997)
   PUBMED   9224616
REFERENCE   9  (bases 1 to 5667)
  AUTHORS   Meyer,K.N., Kjeldsen,E., Straub,T., Knudsen,B.R., Hickson,I.D.,
            Kikuchi,A., Kreipe,H. and Boege,F.
  TITLE     Cell cycle-coupled relocation of types I and II topoisomerases and
            modulation of catalytic enzyme activities
  JOURNAL   J Cell Biol 136 (4), 775-788 (1997)
   PUBMED   9049244
REFERENCE   10 (bases 1 to 5667)
  AUTHORS   Tsutsui,K., Tsutsui,K., Okada,S., Watanabe,M., Shohmori,T., Seki,S.
            and Inoue,Y.
  TITLE     Molecular cloning of partial cDNAs for rat DNA topoisomerase II
            isoforms and their differential expression in brain development
  JOURNAL   J Biol Chem 268 (25), 19076-19083 (1993)
   PUBMED   8395528
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            JAXUCZ010000015.1.
            
            On Sep 14, 2022 this sequence version replaced NM_001100858.1.
            
            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 :: AB262979.1, SRR26643296.33985.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA5760383,
                                           SAMEA5760386 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-549               JAXUCZ010000015.1  11541916-11542464   c
            550-705             JAXUCZ010000015.1  11525493-11525648   c
            706-796             JAXUCZ010000015.1  11524183-11524273   c
            797-860             JAXUCZ010000015.1  11522858-11522921   c
            861-1006            JAXUCZ010000015.1  11520359-11520504   c
            1007-1104           JAXUCZ010000015.1  11519256-11519353   c
            1105-1317           JAXUCZ010000015.1  11518469-11518681   c
            1318-1491           JAXUCZ010000015.1  11515132-11515305   c
            1492-1593           JAXUCZ010000015.1  11512854-11512955   c
            1594-1731           JAXUCZ010000015.1  11512634-11512771   c
            1732-1870           JAXUCZ010000015.1  11510803-11510941   c
            1871-2028           JAXUCZ010000015.1  11509959-11510116   c
            2029-2154           JAXUCZ010000015.1  11509693-11509818   c
            2155-2265           JAXUCZ010000015.1  11508640-11508750   c
            2266-2371           JAXUCZ010000015.1  11508439-11508544   c
            2372-2481           JAXUCZ010000015.1  11507425-11507534   c
            2482-2574           JAXUCZ010000015.1  11506959-11507051   c
            2575-2689           JAXUCZ010000015.1  11506758-11506872   c
            2690-2811           JAXUCZ010000015.1  11505181-11505302   c
            2812-2960           JAXUCZ010000015.1  11504827-11504975   c
            2961-3192           JAXUCZ010000015.1  11504125-11504356   c
            3193-3327           JAXUCZ010000015.1  11502227-11502361   c
            3328-3528           JAXUCZ010000015.1  11501136-11501336   c
            3529-3724           JAXUCZ010000015.1  11500503-11500698   c
            3725-3816           JAXUCZ010000015.1  11500268-11500359   c
            3817-3972           JAXUCZ010000015.1  11497536-11497691   c
            3973-4056           JAXUCZ010000015.1  11497269-11497352   c
            4057-4251           JAXUCZ010000015.1  11494194-11494388   c
            4252-4396           JAXUCZ010000015.1  11492130-11492274   c
            4397-4558           JAXUCZ010000015.1  11491766-11491927   c
            4559-4760           JAXUCZ010000015.1  11490058-11490259   c
            4761-4840           JAXUCZ010000015.1  11489103-11489182   c
            4841-4951           JAXUCZ010000015.1  11487277-11487387   c
            4952-5083           JAXUCZ010000015.1  11484127-11484258   c
            5084-5178           JAXUCZ010000015.1  11483340-11483434   c
            5179-5667           JAXUCZ010000015.1  11482089-11482577   c
FEATURES             Location/Qualifiers
     source          1..5667
                     /organism="Rattus norvegicus"
                     /mol_type="mRNA"
                     /strain="BN"
                     /db_xref="taxon:10116"
                     /chromosome="15"
                     /map="15p16"
     gene            1..5667
                     /gene="Top2b"
                     /note="DNA topoisomerase II beta"
                     /db_xref="GeneID:361100"
                     /db_xref="RGD:1586156"
     exon            1..549
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     CDS             502..5346
                     /gene="Top2b"
                     /EC_number="5.6.2.3"
                     /note="topoisomerase II beta; topoisomerase (DNA) II beta"
                     /codon_start=1
                     /product="DNA topoisomerase 2-beta"
                     /protein_id="NP_001094328.2"
                     /db_xref="GeneID:361100"
                     /db_xref="RGD:1586156"
                     /translation="MAKSSLAGVDGALTWVNNAAKKEELETANKNDSSKKLSVERVYQ
                     KKTQLEHILLRPDTYIGSVEPLTQLMWVYDEDVGMNCREVTFVPGLYKIFDEILVNAA
                     DNKQRDKNMTCIKVSIDPESNIISIWNNGKGIPVVEHKVEKVYVPALIFGQLLTSSNY
                     DDDEKKVTGGRNGYGAKLCNIFSTKFTVETACKEYKHSFKQTWMNNMMKTSEAKIKHF
                     DGEDYTCITFQPDLAKFKMEKLDKDIVALMTRRAYDLAGSCKGVKVMFNGKKLPVNGF
                     RSYVDLYVKDKLDETGVALKVIHELANERWDVCLTLSEKGFQQISFVNSIATTKGGRH
                     VDYVVDQVVGKLIEVVKKKNKAGVSVKPFQVKNHIWVFINCLIENPTFDSQTKENMTL
                     QPKSFGSKCQLSEKFFKAASNCGIVESILNWVKFKAQTQLNKKCSSVKYSKIKGIPKL
                     DDANDAGGKHSLECTLILTEGDSAKSLAVSGLGVIGRDRYGVFPLRGKILNVREASHK
                     QIMENAEINNIIKIVGLQYKKSYDDAESLKTLRYGKIMIMTDQDQDGSHIKGLLINFI
                     HHNWPSLLKHGFLEEFITPIVKASKNKQELSFYSIPEFDEWKKHIENQKAWKIKYYKG
                     LGTSTAKEAKEYFADMERHRILFRYAGPEDDAAITLAFSKKKIDDRKEWLTNFMEDRR
                     QRRLHGLPEQFLYGTATKHLTYNDFINKELILFSNSDNERSIPSLVDGFKPGQRKVLF
                     TCFKRNDKREVKVAQLAGSVAEMSAYHHGEQALMMTIVNLAQNFVGSNNINLLQPIGQ
                     FGTRLHGGKDAASPRYIFTMLSSLARLLFPAVDDNLLKFLYDDNQRVEPEWYIPIIPM
                     VLINGAEGIGTGWACKLPNYDAREIVNNVRRMLEGLDPHPMLPNYKNFKGTIQELGQN
                     QYAVSGEIFVVDRNTVEITELPVRTWTQVYKEQVLEPMLNGTDKTPALISDYKEYHTD
                     TTVKFVVKMTEEKLAQAEAAGLHKVFKLQTTLTCNSMVLFDHMGCLKKYETVQDILKE
                     FFDLRLSYYGLRKEWLVGMLGAESTKLNNQARFILEKIQGKITIENRSKKDLIQMLVQ
                     RGYESDPVKAWKEAQEKAAEEEDAQNPHDDSSSDSGTPSGPDFNYILNMSLWSLTKEK
                     VEELIKQRDTKGREVNDLKRKSPSDLWKEDLAAFVEELDKVEAQEREDILAGMSGKAV
                     KGKVGKAKVKKLQLEETMPSPYGRRIVPEITAMKADASRKLLKKKKGDPDTTVVKVEF
                     DEEFSGTPAEGTGEETLTPSAPVNKGPKPKREKKEPGTRVRKTPASTGKPNTKKVKKR
                     NPWSDDESKSESDLEEAEPVVIPRDSLLRRAAAERPKYTFDFSEEEEDDADDDDDNND
                     LEELKVKASPITNDGEDEFVPSDGIDKDEYAFSPGKSKATPEKSSHDKKSQDFGNLFS
                     FPSYSQKSEDDSAKFDSNEEDTTSVFAPSFGLKQTDKVPSQTVAAKKGKAPSDAAAPK
                     AKRAPRQRKVVEPANSDSDSELGNIPKKTAAPKGKGRGAKKRKASGSENEGDYNPGRK
                     PSKTASKKPKKTSFDQDSDVDIFPSDFTSEPPALPRTGRARKEVKYFAESDEEEDVDF
                     AMFN"
     exon            550..705
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            706..796
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            797..860
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            861..1006
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            1007..1104
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            1105..1317
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            1318..1491
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            1492..1593
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            1594..1731
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            1732..1870
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            1871..2028
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            2029..2154
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            2155..2265
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            2266..2371
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            2372..2481
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            2482..2574
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            2575..2689
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            2690..2811
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            2812..2960
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            2961..3192
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            3193..3327
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            3328..3528
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            3529..3724
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            3725..3816
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            3817..3972
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            3973..4056
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            4057..4251
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            4252..4396
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            4397..4558
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            4559..4760
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            4761..4840
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            4841..4951
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            4952..5083
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            5084..5178
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
     exon            5179..5667
                     /gene="Top2b"
                     /inference="alignment:Splign:2.1.0"
ORIGIN      
        1 gtgtgtgcgg tgttatgccg gactaaaggg aggccaccac agcggctgtt tattgtccct
       61 ctcggccagt gctcctaagg acccggtcag acaccgcttg agcggcttta aggcagtggc
      121 ggcctttgag gcggcggcga ccgcgtcgag gactctgcgg attcggttgc gtgaggagaa
      181 gcagtgactc cttcgtgtca gggctctgac tcgcgtctcc tagccggccc gcgccggccc
      241 gcgccgaccc tcgcccctca ttcgcgatcc cgatcgcctg cgtgagcccc ggaagaccgc
      301 gtctcactgc tagcccttcc tcgccctcgg ccgcgctcta ggcccgggcg ccgcgctcga
      361 gtttgagggc ggcgggcggc gcggcctcct cagcggctcg ggcccgcgat ggggcgcggc
      421 taggagtgcg gcgcgcagcg gtcagtgcga gccgcgtccc cggtgcgcga gcagcccctg
      481 gcctgcacgg gaggcgctgc catggccaag tccagcctcg cgggcgttga cggggcgctg
      541 acctgggtga acaatgctgc aaaaaaggaa gagttggaga cagcgaacaa aaatgattct
      601 tccaagaagt tgtctgttga gagagtgtac cagaagaaga cccaactgga gcatattctc
      661 cttcgtcctg atacatacat tggatcagtg gaaccactga cacagttaat gtgggtgtat
      721 gacgaagatg taggcatgaa ctgcagagag gttacctttg ttccgggctt atacaagatc
      781 tttgatgaaa ttttggtcaa tgctgctgac aacaagcaga gggataagaa catgacctgt
      841 attaaggttt ctattgatcc tgaatctaat attataagca tttggaataa tggaaaaggc
      901 attccagtag tagaacacaa agtagagaaa gtttatgttc ctgctttaat ttttggacag
      961 cttttaacat cgagtaatta tgatgatgat gagaaaaaag ttacaggagg ccgtaatggt
     1021 tatggtgcaa aactttgtaa tatttttagt acaaagttta cagtagaaac ggcttgcaaa
     1081 gaatacaaac atagttttaa gcagacatgg atgaataata tgatgaagac ttctgaagcc
     1141 aaaatcaaac attttgatgg ggaagattat acatgcataa cattccagcc agatctagcc
     1201 aagtttaaga tggaaaaact tgacaaggac attgtggccc tcatgaccag aagggcatac
     1261 gatttagctg gttcctgcaa aggcgtcaag gtcatgttca atggcaagaa gttgcctgta
     1321 aatggatttc gcagctatgt agacctttat gtgaaagaca aattggatga aactggggtc
     1381 gctctcaaag ttattcatga acttgcaaat gaaagatggg atgtttgtct aaccttgagt
     1441 gaaaaaggtt tccagcagat cagctttgtg aatagtattg caactacaaa aggtggacgg
     1501 cacgtggatt acgtagtaga tcaagttgtt ggtaaactga ttgaagtagt taagaaaaag
     1561 aacaaagctg gtgtatcagt gaagccattt caagttaaaa accacatatg ggtttttatt
     1621 aattgtctta ttgaaaatcc aacctttgat tctcaaacta aggaaaacat gactctgcag
     1681 cccaagagct ttgggtctaa atgccagctg tcagaaaagt tctttaaagc ggcctctaat
     1741 tgtggcattg tagaaagcat attgaactgg gtgaaattta aggctcagac tcagctgaat
     1801 aagaagtgct cctcagtaaa gtacagcaaa atcaaaggca ttcccaaact ggatgatgcc
     1861 aatgatgctg gtggcaaaca ttccctggag tgtacattaa tattaacaga gggggactct
     1921 gccaaatctc tagctgtctc tggattaggt gtgattggga gagacagata tggagtcttc
     1981 cctctcaggg gtaaaattct caatgtacga gaagcgtctc ataaacagat tatggaaaat
     2041 gcagaaataa acaatattat taaaatagtt ggtttgcaat acaagaaaag ttatgatgat
     2101 gcagaatctc tgaaaacttt acgttatggg aagattatga ttatgactga tcaggatcaa
     2161 gatggttctc acattaaagg cctgctaatc aattttattc atcacaattg gccatcactt
     2221 ttgaagcatg gctttcttga agaattcatt actcccattg taaaggcgag caaaaataag
     2281 caggaacttt ccttttatag tattcctgaa tttgatgagt ggaaaaaaca tatagaaaac
     2341 cagaaagcct ggaaaataaa gtactacaaa ggattgggta ccagtacagc taaggaagcc
     2401 aaggaatatt ttgctgatat ggaaaggcat cgcattttgt ttagatatgc tggccctgag
     2461 gatgatgctg ccattacctt ggcatttagt aagaagaaga ttgatgacag aaaagaatgg
     2521 ttaaccaact ttatggagga tcggagacag cggaggttac atggcctacc agagcaattt
     2581 ttatatggta cagcaactaa gcatttgaca tacaatgatt tcatcaacaa ggaattgatt
     2641 ctcttctcaa actcggacaa tgagagatct ataccctctc ttgtggatgg cttcaagcca
     2701 ggtcaacgaa aagttttgtt tacctgtttc aagaggaatg ataaacgtga agttaaagtc
     2761 gcacagctgg ctggatctgt tgctgaaatg tctgcttatc atcatggaga acaagcgttg
     2821 atgatgacta ttgtgaattt ggctcagaat tttgtgggca gcaacaacat taacttgctt
     2881 cagcccattg gtcagtttgg aactcggctt cacggtggca aagatgctgc aagcccccgt
     2941 tatatcttca caatgttaag ctctctggca agactacttt ttccagctgt ggatgataac
     3001 ttgcttaagt tcctttatga tgataatcag cgtgtagagc cggagtggta tatccccata
     3061 atccccatgg ttttgattaa tggtgctgag ggtattggga ctggatgggc ttgtaaattg
     3121 cccaactatg atgccagaga aattgtgaac aatgtcaggc ggatgctaga aggtttggat
     3181 cctcacccca tgcttccaaa ctataagaac ttcaaaggca ccatccagga gcttggtcag
     3241 aaccagtatg ctgttagtgg tgagatattt gtggtggaca gaaacacagt agagattaca
     3301 gaacttccag ttagaacctg gacacaggta tacaaggagc aggtcctaga acctatgctt
     3361 aatggaacag ataaaacacc agcactgatt tctgattaca aagaatatca cactgataca
     3421 actgtgaaat ttgtggtgaa gatgacagaa gagaagctcg cccaagcgga agctgccggc
     3481 ctgcataaag tttttaaact ccaaaccact cttacttgca attccatggt actctttgat
     3541 catatgggat gtctgaagaa gtatgaaact gtgcaagaca ttttgaaaga attctttgat
     3601 ttacggttaa gttattatgg tttacggaag gagtggcttg taggaatgtt gggagcagaa
     3661 tccacaaagc ttaacaatca agcccgtttc attttagaga agatacaagg gaaaatcacg
     3721 atagagaata ggtcaaagaa agatttgatt caaatgttag tccagagagg ttatgaatct
     3781 gacccagtga aagcctggaa agaagcacaa gaaaaggctg cggaagagga agatgcacaa
     3841 aacccacatg atgacagttc ctctgactca ggaactcctt caggccctga ttttaattat
     3901 attttaaata tgtctctatg gtctcttact aaagaaaaag ttgaagaact cattaaacag
     3961 agagatacaa aaggacgaga ggttaatgat ctcaaaagga aatctccctc agatctttgg
     4021 aaagaagatt tagcagcatt tgttgaagaa ttggataaag tggaagcaca agaacgagaa
     4081 gacattctgg cagggatgtc tgggaaagca gtgaaaggca aagtcggcaa agctaaagta
     4141 aagaagctcc agctggagga gacgatgccc tcgccttacg ggagaagaat cgttcctgag
     4201 attactgcca tgaaggcaga cgccagcaga aaactgctga agaagaagaa gggtgatcct
     4261 gatactacag ttgtgaaagt agaatttgat gaagaattta gtggaacacc agcagaaggt
     4321 acaggagaag agacattgac accatctgct cctgtaaata aaggccccaa acccaaaagg
     4381 gagaaaaagg agcctggtac cagggttaga aaaacacctg catcaactgg caaacctaat
     4441 acaaagaaag tgaagaagcg gaatccttgg tcagatgatg agtccaaatc agagagtgac
     4501 ttggaagaag cagagcctgt ggttatccca agagattctt tgcttaggag agcagctgct
     4561 gaaagaccta agtacacttt tgatttctca gaagaggagg aggatgatgc tgatgatgat
     4621 gacgacaata atgatttaga agaattgaaa gttaaagcat ctcccataac aaatgatggg
     4681 gaggatgaat ttgttccttc agatggcata gataaagatg agtatgcctt ttctccaggc
     4741 aaatccaaag ctacaccaga aaaatcttca catgacaaaa aaagtcagga ttttggaaat
     4801 cttttttcat ttccttcata ttctcagaag tcagaagatg attcagctaa atttgacagt
     4861 aatgaagaag acaccacatc tgtttttgca ccatcatttg gtctgaagca aacagataaa
     4921 gttccaagtc aaacagtcgc tgctaaaaag ggtaaagcac cttcagatgc agcagcccct
     4981 aaggccaaga gagcccctag acagaggaag gtagtagagc ctgcaaactc cgactcggat
     5041 tctgaactcg gcaacattcc aaagaagacg gccgcaccga aaggtaaagg ccgaggggca
     5101 aagaaaagga aagcatcagg ctcagaaaat gaaggtgatt ataaccctgg caggaaacca
     5161 tctaaaacag ccagcaagaa accgaagaaa acgtcttttg atcaggattc agatgtagac
     5221 atcttccctt cagacttcac ttctgaacca cctgctctcc cacggactgg tcgggctagg
     5281 aaagaagtaa aatattttgc agagtctgat gaagaagaag acgttgattt tgcaatgttt
     5341 aattaagtgc ccaaggagca cgaacatttt tcaaaaatat cttgtgttgt cctttgtctt
     5401 ttctgtctca gaattttgta catctggctt attttaatgt gatgatgtaa ttgatggttt
     5461 tttattattg tggtaggcct tttaacattt tgttcttaca catacagttt tatgctcttt
     5521 tttactcatt gaaatgtcat gtgttgtctg attggcttgt agaattgtta tagattaacg
     5581 tgcattagca cagattttaa ttgtcatgat tgcagactac agacctgctt tttgaaatga
     5641 aatttaaaca ttaaaaatgg aactgtg
//
