LOCUS       NM_001067               5695 bp    mRNA    linear   PRI 11-JUN-2024
DEFINITION  Homo sapiens DNA topoisomerase II alpha (TOP2A), mRNA.
ACCESSION   NM_001067
VERSION     NM_001067.4
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 5695)
  AUTHORS   Zhang,K., Zheng,X., Sun,Y., Feng,X., Wu,X., Liu,W., Gao,C., Yan,Y.,
            Tian,W. and Wang,Y.
  TITLE     TOP2A modulates signaling via the AKT/mTOR pathway to promote
            ovarian cancer cell proliferation
  JOURNAL   Cancer Biol Ther 25 (1), 2325126 (2024)
   PUBMED   38445610
  REMARK    GeneRIF: TOP2A modulates signaling via the AKT/mTOR pathway to
            promote ovarian cancer cell proliferation.
REFERENCE   2  (bases 1 to 5695)
  AUTHORS   Wu,J., Li,W., Zhang,X., Shi,F., Jia,Q., Wang,Y., Shi,Y., Wu,S. and
            Wang,X.
  TITLE     Expression and potential molecular mechanism of TOP2A in metastasis
            of non-small cell lung cancer
  JOURNAL   Sci Rep 14 (1), 12228 (2024)
   PUBMED   38806610
  REMARK    GeneRIF: Expression and potential molecular mechanism of TOP2A in
            metastasis of non-small cell lung cancer.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 5695)
  AUTHORS   Ye,J.H., Yu,J., Huang,M.Y. and Mo,Y.M.
  TITLE     The correlation study between TOP2A gene expression in circulating
            tumor cells and chemotherapeutic drug resistance of patients with
            breast cancer
  JOURNAL   Breast Cancer 31 (3), 417-425 (2024)
   PUBMED   38561479
  REMARK    GeneRIF: The correlation study between TOP2A gene expression in
            circulating tumor cells and chemotherapeutic drug resistance of
            patients with breast cancer.
REFERENCE   4  (bases 1 to 5695)
  AUTHORS   Petsalaki,E. and Zachos,G.
  TITLE     Activating the abscission checkpoint: Top2alpha senses chromatin
            bridges in cytokinesis: Top2alpha binds to DNA knots on chromatin
            bridges to activate the abscission checkpoint in human cells
  JOURNAL   Bioessays 46 (5), e2400011 (2024)
   PUBMED   38403725
  REMARK    GeneRIF: Activating the abscission checkpoint: Top2alpha senses
            chromatin bridges in cytokinesis: Top2alpha binds to DNA knots on
            chromatin bridges to activate the abscission checkpoint in human
            cells.
            Review article
REFERENCE   5  (bases 1 to 5695)
  AUTHORS   Keith,W.N., Tan,K.B. and Brown,R.
  TITLE     Amplification of the topoisomerase II alpha gene in a non-small
            cell lung cancer cell line and characterisation of polymorphisms at
            the human topoisomerase II alpha and beta loci in normal tissue
  JOURNAL   Genes Chromosomes Cancer 4 (2), 169-175 (1992)
   PUBMED   1373318
REFERENCE   6  (bases 1 to 5695)
  AUTHORS   Tan,K.B., Dorman,T.E., Falls,K.M., Chung,T.D., Mirabelli,C.K.,
            Crooke,S.T. and Mao,J.
  TITLE     Topoisomerase II alpha and topoisomerase II beta genes:
            characterization and mapping to human chromosomes 17 and 3,
            respectively
  JOURNAL   Cancer Res 52 (1), 231-234 (1992)
   PUBMED   1309226
REFERENCE   7  (bases 1 to 5695)
  AUTHORS   Bugg,B.Y., Danks,M.K., Beck,W.T. and Suttle,D.P.
  TITLE     Expression of a mutant DNA topoisomerase II in CCRF-CEM human
            leukemic cells selected for resistance to teniposide
  JOURNAL   Proc Natl Acad Sci U S A 88 (17), 7654-7658 (1991)
   PUBMED   1652758
REFERENCE   8  (bases 1 to 5695)
  AUTHORS   Chung,T.D., Drake,F.H., Tan,K.B., Per,S.R., Crooke,S.T. and
            Mirabelli,C.K.
  TITLE     Characterization and immunological identification of cDNA clones
            encoding two human DNA topoisomerase II isozymes
  JOURNAL   Proc Natl Acad Sci U S A 86 (23), 9431-9435 (1989)
   PUBMED   2556712
REFERENCE   9  (bases 1 to 5695)
  AUTHORS   Tsai-Pflugfelder,M., Liu,L.F., Liu,A.A., Tewey,K.M., Whang-Peng,J.,
            Knutsen,T., Huebner,K., Croce,C.M. and Wang,J.C.
  TITLE     Cloning and sequencing of cDNA encoding human DNA topoisomerase II
            and localization of the gene to chromosome region 17q21-22
  JOURNAL   Proc Natl Acad Sci U S A 85 (19), 7177-7181 (1988)
   PUBMED   2845399
REFERENCE   10 (bases 1 to 5695)
  AUTHORS   Singh,S.P., Mohamed,R., Salmond,C. and Lavin,M.F.
  TITLE     Reduced DNA topoisomerase II activity in ataxia-telangiectasia
            cells
  JOURNAL   Nucleic Acids Res 16 (9), 3919-3929 (1988)
   PUBMED   2836804
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB069825.1, BC140791.1 and
            AC080112.15.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_001067.3.
            
            Summary: This gene encodes a DNA topoisomerase, an enzyme that
            controls and alters the topologic states of DNA during
            transcription. This nuclear enzyme is involved in processes such as
            chromosome condensation, chromatid separation, and the relief of
            torsional stress that occurs during DNA transcription and
            replication. It catalyzes the transient breaking and rejoining of
            two strands of duplex DNA which allows the strands to pass through
            one another, thus altering the topology of DNA. Two forms of this
            enzyme exist as likely products of a gene duplication event. The
            gene encoding this form, alpha, is localized to chromosome 17 and
            the beta gene is localized to chromosome 3. The gene encoding this
            enzyme functions as the target for several anticancer agents and a
            variety of mutations in this gene have been associated with the
            development of drug resistance. Reduced activity of this enzyme may
            also play a role in ataxia-telangiectasia. [provided by RefSeq, Jul
            2010].
            
            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 :: BC140791.1, J04088.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000423485.6/ ENSP00000411532.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-76                DB069825.1         55-130
            77-4701             BC140791.1         1-4625
            4702-5695           AC080112.15        34180-35173
FEATURES             Location/Qualifiers
     source          1..5695
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17q21.2"
     gene            1..5695
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /note="DNA topoisomerase II alpha"
                     /db_xref="GeneID:7153"
                     /db_xref="HGNC:HGNC:11989"
                     /db_xref="MIM:126430"
     exon            1..126
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     CDS             106..4701
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /EC_number="5.6.2.2"
                     /note="DNA gyrase; DNA topoisomerase (ATP-hydrolyzing);
                     DNA topoisomerase II, 170 kD; DNA topoisomerase II, alpha
                     isozyme; topoisomerase (DNA) II alpha 170kDa"
                     /codon_start=1
                     /product="DNA topoisomerase 2-alpha"
                     /protein_id="NP_001058.2"
                     /db_xref="CCDS:CCDS45672.1"
                     /db_xref="GeneID:7153"
                     /db_xref="HGNC:HGNC:11989"
                     /db_xref="MIM:126430"
                     /translation="MEVSPLQPVNENMQVNKIKKNEDAKKRLSVERIYQKKTQLEHIL
                     LRPDTYIGSVELVTQQMWVYDEDVGINYREVTFVPGLYKIFDEILVNAADNKQRDPKM
                     SCIRVTIDPENNLISIWNNGKGIPVVEHKVEKMYVPALIFGQLLTSSNYDDDEKKVTG
                     GRNGYGAKLCNIFSTKFTVETASREYKKMFKQTWMDNMGRAGEMELKPFNGEDYTCIT
                     FQPDLSKFKMQSLDKDIVALMVRRAYDIAGSTKDVKVFLNGNKLPVKGFRSYVDMYLK
                     DKLDETGNSLKVIHEQVNHRWEVCLTMSEKGFQQISFVNSIATSKGGRHVDYVADQIV
                     TKLVDVVKKKNKGGVAVKAHQVKNHMWIFVNALIENPTFDSQTKENMTLQPKSFGSTC
                     QLSEKFIKAAIGCGIVESILNWVKFKAQVQLNKKCSAVKHNRIKGIPKLDDANDAGGR
                     NSTECTLILTEGDSAKTLAVSGLGVVGRDKYGVFPLRGKILNVREASHKQIMENAEIN
                     NIIKIVGLQYKKNYEDEDSLKTLRYGKIMIMTDQDQDGSHIKGLLINFIHHNWPSLLR
                     HRFLEEFITPIVKVSKNKQEMAFYSLPEFEEWKSSTPNHKKWKVKYYKGLGTSTSKEA
                     KEYFADMKRHRIQFKYSGPEDDAAISLAFSKKQIDDRKEWLTNFMEDRRQRKLLGLPE
                     DYLYGQTTTYLTYNDFINKELILFSNSDNERSIPSMVDGLKPGQRKVLFTCFKRNDKR
                     EVKVAQLAGSVAEMSSYHHGEMSLMMTIINLAQNFVGSNNLNLLQPIGQFGTRLHGGK
                     DSASPRYIFTMLSSLARLLFPPKDDHTLKFLYDDNQRVEPEWYIPIIPMVLINGAEGI
                     GTGWSCKIPNFDVREIVNNIRRLMDGEEPLPMLPSYKNFKGTIEELAPNQYVISGEVA
                     ILNSTTIEISELPVRTWTQTYKEQVLEPMLNGTEKTPPLITDYREYHTDTTVKFVVKM
                     TEEKLAEAERVGLHKVFKLQTSLTCNSMVLFDHVGCLKKYDTVLDILRDFFELRLKYY
                     GLRKEWLLGMLGAESAKLNNQARFILEKIDGKIIIENKPKKELIKVLIQRGYDSDPVK
                     AWKEAQQKVPDEEENEESDNEKETEKSDSVTDSGPTFNYLLDMPLWYLTKEKKDELCR
                     LRNEKEQELDTLKRKSPSDLWKEDLATFIEELEAVEAKEKQDEQVGLPGKGGKAKGKK
                     TQMAEVLPSPRGQRVIPRITIEMKAEAEKKNKKKIKNENTEGSPQEDGVELEGLKQRL
                     EKKQKREPGTKTKKQTTLAFKPIKKGKKRNPWSDSESDRSSDESNFDVPPRETEPRRA
                     ATKTKFTMDLDSDEDFSDFDEKTDDEDFVPSDASPPKTKTSPKLSNKELKPQKSVVSD
                     LEADDVKGSVPLSSSPPATHFPDETEITNPVPKKNVTVKKTAAKSQSSTSTTGAKKRA
                     APKGTKRDPALNSGVSQKPDPAKTKNRRKRKPSTSDDSDSNFEKIVSKAVTSKKSKGE
                     SDDFHMDFDSAVAPRAKSVRAKKPIKYLEESDEDDLF"
     exon            127..282
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            283..373
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            374..437
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            438..583
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            584..681
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            682..894
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            895..1068
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            1069..1170
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            1171..1308
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            1309..1447
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            1448..1605
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            1606..1731
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            1732..1842
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            1843..1948
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            1949..2058
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            2059..2151
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            2152..2266
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            2267..2388
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            2389..2537
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            2538..2769
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            2770..2904
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            2905..3105
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            3106..3301
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            3302..3393
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            3394..3558
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            3559..3642
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            3643..3825
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            3826..3916
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            3917..4069
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            4070..4193
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            4194..4237
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            4238..4372
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            4373..4572
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     exon            4573..5695
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5672..5677
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /note="hexamer: AATAAA"
     polyA_site      5695
                     /gene="TOP2A"
                     /gene_synonym="TOP2; TOP2alpha; TOPIIA; TP2A"
                     /note="major polyA site"
ORIGIN      
        1 aaccgacgcg cgtctgtgga gaagcggctt ggtcgggggt ggtctcgtgg ggtcctgcct
       61 gtttagtcgc tttcagggtt cttgagcccc ttcacgaccg tcaccatgga agtgtcacca
      121 ttgcagcctg taaatgaaaa tatgcaagtc aacaaaataa agaaaaatga agatgctaag
      181 aaaagactgt ctgttgaaag aatctatcaa aagaaaacac aattggaaca tattttgctc
      241 cgcccagaca cctacattgg ttctgtggaa ttagtgaccc agcaaatgtg ggtttacgat
      301 gaagatgttg gcattaacta tagggaagtc acttttgttc ctggtttgta caaaatcttt
      361 gatgagattc tagttaatgc tgcggacaac aaacaaaggg acccaaaaat gtcttgtatt
      421 agagtcacaa ttgatccgga aaacaattta attagtatat ggaataatgg aaaaggtatt
      481 cctgttgttg aacacaaagt tgaaaagatg tatgtcccag ctctcatatt tggacagctc
      541 ctaacttcta gtaactatga tgatgatgaa aagaaagtga caggtggtcg aaatggctat
      601 ggagccaaat tgtgtaacat attcagtacc aaatttactg tggaaacagc cagtagagaa
      661 tacaagaaaa tgttcaaaca gacatggatg gataatatgg gaagagctgg tgagatggaa
      721 ctcaagccct tcaatggaga agattataca tgtatcacct ttcagcctga tttgtctaag
      781 tttaaaatgc aaagcctgga caaagatatt gttgcactaa tggtcagaag agcatatgat
      841 attgctggat ccaccaaaga tgtcaaagtc tttcttaatg gaaataaact gccagtaaaa
      901 ggatttcgta gttatgtgga catgtatttg aaggacaagt tggatgaaac tggtaactcc
      961 ttgaaagtaa tacatgaaca agtaaaccac aggtgggaag tgtgtttaac tatgagtgaa
     1021 aaaggctttc agcaaattag ctttgtcaac agcattgcta catccaaggg tggcagacat
     1081 gttgattatg tagctgatca gattgtgact aaacttgttg atgttgtgaa gaagaagaac
     1141 aagggtggtg ttgcagtaaa agcacatcag gtgaaaaatc acatgtggat ttttgtaaat
     1201 gccttaattg aaaacccaac ctttgactct cagacaaaag aaaacatgac tttacaaccc
     1261 aagagctttg gatcaacatg ccaattgagt gaaaaattta tcaaagctgc cattggctgt
     1321 ggtattgtag aaagcatact aaactgggtg aagtttaagg cccaagtcca gttaaacaag
     1381 aagtgttcag ctgtaaaaca taatagaatc aagggaattc ccaaactcga tgatgccaat
     1441 gatgcagggg gccgaaactc cactgagtgt acgcttatcc tgactgaggg agattcagcc
     1501 aaaactttgg ctgtttcagg ccttggtgtg gttgggagag acaaatatgg ggttttccct
     1561 cttagaggaa aaatactcaa tgttcgagaa gcttctcata agcagatcat ggaaaatgct
     1621 gagattaaca atatcatcaa gattgtgggt cttcagtaca agaaaaacta tgaagatgaa
     1681 gattcattga agacgcttcg ttatgggaag ataatgatta tgacagatca ggaccaagat
     1741 ggttcccaca tcaaaggctt gctgattaat tttatccatc acaactggcc ctctcttctg
     1801 cgacatcgtt ttctggagga atttatcact cccattgtaa aggtatctaa aaacaagcaa
     1861 gaaatggcat tttacagcct tcctgaattt gaagagtgga agagttctac tccaaatcat
     1921 aaaaaatgga aagtcaaata ttacaaaggt ttgggcacca gcacatcaaa ggaagctaaa
     1981 gaatactttg cagatatgaa aagacatcgt atccagttca aatattctgg tcctgaagat
     2041 gatgctgcta tcagcctggc ctttagcaaa aaacagatag atgatcgaaa ggaatggtta
     2101 actaatttca tggaggatag aagacaacga aagttacttg ggcttcctga ggattacttg
     2161 tatggacaaa ctaccacata tctgacatat aatgacttca tcaacaagga acttatcttg
     2221 ttctcaaatt ctgataacga gagatctatc ccttctatgg tggatggttt gaaaccaggt
     2281 cagagaaagg ttttgtttac ttgcttcaaa cggaatgaca agcgagaagt aaaggttgcc
     2341 caattagctg gatcagtggc tgaaatgtct tcttatcatc atggtgagat gtcactaatg
     2401 atgaccatta tcaatttggc tcagaatttt gtgggtagca ataatctaaa cctcttgcag
     2461 cccattggtc agtttggtac caggctacat ggtggcaagg attctgctag tccacgatac
     2521 atctttacaa tgctcagctc tttggctcga ttgttatttc caccaaaaga tgatcacacg
     2581 ttgaagtttt tatatgatga caaccagcgt gttgagcctg aatggtacat tcctattatt
     2641 cccatggtgc tgataaatgg tgctgaagga atcggtactg ggtggtcctg caaaatcccc
     2701 aactttgatg tgcgtgaaat tgtaaataac atcaggcgtt tgatggatgg agaagaacct
     2761 ttgccaatgc ttccaagtta caagaacttc aagggtacta ttgaagaact ggctccaaat
     2821 caatatgtga ttagtggtga agtagctatt cttaattcta caaccattga aatctcagag
     2881 cttcccgtca gaacatggac ccagacatac aaagaacaag ttctagaacc catgttgaat
     2941 ggcaccgaga agacacctcc tctcataaca gactataggg aataccatac agataccact
     3001 gtgaaatttg ttgtgaagat gactgaagaa aaactggcag aggcagagag agttggacta
     3061 cacaaagtct tcaaactcca aactagtctc acatgcaact ctatggtgct ttttgaccac
     3121 gtaggctgtt taaagaaata tgacacggtg ttggatattc taagagactt ttttgaactc
     3181 agacttaaat attatggatt aagaaaagaa tggctcctag gaatgcttgg tgctgaatct
     3241 gctaaactga ataatcaggc tcgctttatc ttagagaaaa tagatggcaa aataatcatt
     3301 gaaaataagc ctaagaaaga attaattaaa gttctgattc agaggggata tgattcggat
     3361 cctgtgaagg cctggaaaga agcccagcaa aaggttccag atgaagaaga aaatgaagag
     3421 agtgacaacg aaaaggaaac tgaaaagagt gactccgtaa cagattctgg accaaccttc
     3481 aactatcttc ttgatatgcc cctttggtat ttaaccaagg aaaagaaaga tgaactctgc
     3541 aggctaagaa atgaaaaaga acaagagctg gacacattaa aaagaaagag tccatcagat
     3601 ttgtggaaag aagacttggc tacatttatt gaagaattgg aggctgttga agccaaggaa
     3661 aaacaagatg aacaagtcgg acttcctggg aaagggggga aggccaaggg gaaaaaaaca
     3721 caaatggctg aagttttgcc ttctccgcgt ggtcaaagag tcattccacg aataaccata
     3781 gaaatgaaag cagaggcaga aaagaaaaat aaaaagaaaa ttaagaatga aaatactgaa
     3841 ggaagccctc aagaagatgg tgtggaacta gaaggcctaa aacaaagatt agaaaagaaa
     3901 cagaaaagag aaccaggtac aaagacaaag aaacaaacta cattggcatt taagccaatc
     3961 aaaaaaggaa agaagagaaa tccctggtct gattcagaat cagataggag cagtgacgaa
     4021 agtaattttg atgtccctcc acgagaaaca gagccacgga gagcagcaac aaaaacaaaa
     4081 ttcacaatgg atttggattc agatgaagat ttctcagatt ttgatgaaaa aactgatgat
     4141 gaagattttg tcccatcaga tgctagtcca cctaagacca aaacttcccc aaaacttagt
     4201 aacaaagaac tgaaaccaca gaaaagtgtc gtgtcagacc ttgaagctga tgatgttaag
     4261 ggcagtgtac cactgtcttc aagccctcct gctacacatt tcccagatga aactgaaatt
     4321 acaaacccag ttcctaaaaa gaatgtgaca gtgaagaaga cagcagcaaa aagtcagtct
     4381 tccacctcca ctaccggtgc caaaaaaagg gctgccccaa aaggaactaa aagggatcca
     4441 gctttgaatt ctggtgtctc tcaaaagcct gatcctgcca aaaccaagaa tcgccgcaaa
     4501 aggaagccat ccacttctga tgattctgac tctaattttg agaaaattgt ttcgaaagca
     4561 gtcacaagca agaaatccaa gggggagagt gatgacttcc atatggactt tgactcagct
     4621 gtggctcctc gggcaaaatc tgtacgggca aagaaaccta taaagtacct ggaagagtca
     4681 gatgaagatg atctgtttta aaatgtgagg cgattatttt aagtaattat cttaccaagc
     4741 ccaagactgg ttttaaagtt acctgaagct cttaacttcc tcccctctga atttagtttg
     4801 gggaaggtgt ttttagtaca agacatcaaa gtgaagtaaa gcccaagtgt tctttagctt
     4861 tttataatac tgtctaaata gtgaccatct catgggcatt gttttcttct ctgctttgtc
     4921 tgtgttttga gtctgctttc ttttgtcttt aaaacctgat ttttaagttc ttctgaactg
     4981 tagaaatagc tatctgatca cttcagcgta aagcagtgtg tttattaacc atccactaag
     5041 ctaaaactag agcagtttga tttaaaagtg tcactcttcc tccttttcta ctttcagtag
     5101 atatgagata gagcataatt atctgtttta tcttagtttt atacataatt taccatcaga
     5161 tagaacttta tggttctagt acagatactc tactacactc agcctcttat gtgccaagtt
     5221 tttctttaag caatgagaaa ttgctcatgt tcttcatctt ctcaaatcat cagaggccga
     5281 agaaaaacac tttggctgtg tctataactt gacacagtca atagaatgaa gaaaattaga
     5341 gtagttatgt gattatttca gctcttgacc tgtcccctct ggctgcctct gagtctgaat
     5401 ctcccaaaga gagaaaccaa tttctaagag gactggattg cagaagactc ggggacaaca
     5461 tttgatccaa gatcttaaat gttatattga taaccatgct cagcaatgag ctattagatt
     5521 cattttggga aatctccata atttcaattt gtaaactttg ttaagacctg tctacattgt
     5581 tatatgtgtg tgacttgagt aatgttatca acgtttttgt aaatatttac tatgtttttc
     5641 tattagctaa attccaacaa ttttgtactt taataaaatg ttctaaacat tgcaa
//
