LOCUS       NM_014953              10571 bp    mRNA    linear   PRI 04-APR-2024
DEFINITION  Homo sapiens DIS3 homolog, exosome endoribonuclease and 3'-5'
            exoribonuclease (DIS3), transcript variant 1, mRNA.
ACCESSION   NM_014953
VERSION     NM_014953.5
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 10571)
  AUTHORS   Favasuli,V.K., Ronchetti,D., Silvestris,I., Puccio,N., Fabbiano,G.,
            Traini,V., Todoerti,K., Erratico,S., Ciarrocchi,A., Fragliasso,V.,
            Giannandrea,D., Tumiatti,F., Chiaramonte,R., Torrente,Y.,
            Finelli,P., Morelli,E., Munshi,N.C., Bolli,N., Neri,A. and
            Taiana,E.
  TITLE     DIS3 depletion in multiple myeloma causes extensive perturbation in
            cell cycle progression and centrosome amplification
  JOURNAL   Haematologica 109 (1), 231-244 (2024)
   PUBMED   37439377
  REMARK    GeneRIF: DIS3 depletion in multiple myeloma causes extensive
            perturbation in cell cycle progression and centrosome
            amplification.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 10571)
  AUTHORS   Johnstone,E.B., Gorsi,B., Coelho,E., Moore,B., Farr,A.M.,
            Cooper,A.R., Mardis,E.R., Rajkovic,A., Chow,C.Y., Yandell,M. and
            Welt,C.K.
  TITLE     DIS3 Variants are Associated With Primary Ovarian Insufficiency:
            Importance of Transcription/Translation in Oogenesis
  JOURNAL   J Clin Endocrinol Metab 108 (9), 2330-2335 (2023)
   PUBMED   36869713
  REMARK    GeneRIF: DIS3 Variants are Associated With Primary Ovarian
            Insufficiency: Importance of Transcription/Translation in
            Oogenesis.
REFERENCE   3  (bases 1 to 10571)
  AUTHORS   Ohguchi,Y. and Ohguchi,H.
  TITLE     DIS3: The Enigmatic Gene in Multiple Myeloma
  JOURNAL   Int J Mol Sci 24 (4), 4079 (2023)
   PUBMED   36835493
  REMARK    GeneRIF: DIS3: The Enigmatic Gene in Multiple Myeloma.
            Review article
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 10571)
  AUTHORS   Gritti,I., Basso,V., Rinchai,D., Corigliano,F., Pivetti,S.,
            Gaviraghi,M., Rosano,D., Mazza,D., Barozzi,S., Roncador,M.,
            Parmigiani,G., Legube,G., Parazzoli,D., Cittaro,D., Bedognetti,D.,
            Mondino,A., Segalla,S. and Tonon,G.
  TITLE     Loss of ribonuclease DIS3 hampers genome integrity in myeloma by
            disrupting DNA:RNA hybrid metabolism
  JOURNAL   EMBO J 41 (22), e108040 (2022)
   PUBMED   36215697
  REMARK    GeneRIF: Loss of ribonuclease DIS3 hampers genome integrity in
            myeloma by disrupting DNA:RNA hybrid metabolism.
REFERENCE   5  (bases 1 to 10571)
  AUTHORS   Fujiwara,N., Shigemoto,M., Hirayama,M., Fujita,K.I., Seno,S.,
            Matsuda,H., Nagahama,M. and Masuda,S.
  TITLE     MPP6 stimulates both RRP6 and DIS3 to degrade a specified subset of
            MTR4-sensitive substrates in the human nucleus
  JOURNAL   Nucleic Acids Res 50 (15), 8779-8806 (2022)
   PUBMED   35902094
  REMARK    GeneRIF: MPP6 stimulates both RRP6 and DIS3 to degrade a specified
            subset of MTR4-sensitive substrates in the human nucleus.
REFERENCE   6  (bases 1 to 10571)
  AUTHORS   Rozenblum,E., Vahteristo,P., Sandberg,T., Bergthorsson,J.T.,
            Syrjakoski,K., Weaver,D., Haraldsson,K., Johannsdottir,H.K.,
            Vehmanen,P., Nigam,S., Golberger,N., Robbins,C., Pak,E., Dutra,A.,
            Gillander,E., Stephan,D.A., Bailey-Wilson,J., Juo,S.H., Kainu,T.,
            Arason,A., Barkardottir,R.B., Nevanlinna,H., Borg,A. and
            Kallioniemi,O.P.
  TITLE     A genomic map of a 6-Mb region at 13q21-q22 implicated in cancer
            development: identification and characterization of candidate genes
  JOURNAL   Hum Genet 110 (2), 111-121 (2002)
   PUBMED   11935316
REFERENCE   7  (bases 1 to 10571)
  AUTHORS   Raijmakers,R., Noordman,Y.E., van Venrooij,W.J. and Pruijn,G.J.
  TITLE     Protein-protein interactions of hCsl4p with other human exosome
            subunits
  JOURNAL   J Mol Biol 315 (4), 809-818 (2002)
   PUBMED   11812149
REFERENCE   8  (bases 1 to 10571)
  AUTHORS   Chen,C.Y., Gherzi,R., Ong,S.E., Chan,E.L., Raijmakers,R.,
            Pruijn,G.J., Stoecklin,G., Moroni,C., Mann,M. and Karin,M.
  TITLE     AU binding proteins recruit the exosome to degrade ARE-containing
            mRNAs
  JOURNAL   Cell 107 (4), 451-464 (2001)
   PUBMED   11719186
REFERENCE   9  (bases 1 to 10571)
  AUTHORS   Brouwer,R., Allmang,C., Raijmakers,R., van Aarssen,Y.,
            Egberts,W.V., Petfalski,E., van Venrooij,W.J., Tollervey,D. and
            Pruijn,G.J.
  TITLE     Three novel components of the human exosome
  JOURNAL   J Biol Chem 276 (9), 6177-6184 (2001)
   PUBMED   11110791
REFERENCE   10 (bases 1 to 10571)
  AUTHORS   Shiomi,T., Fukushima,K., Suzuki,N., Nakashima,N., Noguchi,E. and
            Nishimoto,T.
  TITLE     Human dis3p, which binds to either GTP- or GDP-Ran, complements
            Saccharomyces cerevisiae dis3
  JOURNAL   J Biochem 123 (5), 883-890 (1998)
   PUBMED   9562621
  REMARK    GeneRIF: Dis3p is identical to Rrp44p, which comprises the exosome
            involved in ribosomal RNA processing. Similar to S. cerevisiae
            Dis3p, human Dis3p enhanced RCC1-stimulated nucleotide release from
            Ran, in a dose-dependent manner, and bound to GTP- or GDP-Ran.
            GeneRIF: S. cerevisiae Dis3p is identical to Rrp44p, which
            comprises the exosome involved in ribosomal RNA processing, S.
            cerevisiae Dis3p was found to be localized in the nucleolus.
            Erratum:[J Biochem (Tokyo) 1998 Jul;124(1):250]
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            BC056143.1, AL832266.1, AL080158.1, AL138695.13 and U79246.1.
            
            On Nov 23, 2018 this sequence version replaced NM_014953.4.
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (a).
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on 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 :: AF330044.1, BC056143.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000377767.9/ ENSP00000366997.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1044              BC056143.1         34-1077
            1045-1834           AL832266.1         1066-1855
            1835-3201           AL080158.1         790-2156
            3202-5936           AL138695.13        45269-48003         c
            5937-7338           U79246.1           410-1811
            7339-10571          AL138695.13        40634-43866         c
FEATURES             Location/Qualifiers
     source          1..10571
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="13"
                     /map="13q21.33"
     gene            1..10571
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /note="DIS3 homolog, exosome endoribonuclease and 3'-5'
                     exoribonuclease"
                     /db_xref="GeneID:22894"
                     /db_xref="HGNC:HGNC:20604"
                     /db_xref="MIM:607533"
     exon            1..296
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     CDS             69..2945
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /note="isoform a is encoded by transcript variant 1;
                     mitotic control protein dis3 homolog; DIS3 exosome
                     endoribonuclease and 3'-5' exoribonuclease; exosome
                     component 11; exosome complex exonuclease RRP44; DIS3
                     mitotic control homolog; ribosomal RNA-processing protein
                     44"
                     /codon_start=1
                     /product="exosome complex exonuclease RRP44 isoform a"
                     /protein_id="NP_055768.3"
                     /db_xref="CCDS:CCDS9447.1"
                     /db_xref="GeneID:22894"
                     /db_xref="HGNC:HGNC:20604"
                     /db_xref="MIM:607533"
                     /translation="MLKSKTFLKKTRAGGVMKIVREHYLRDDIGCGAPGCAACGGAHE
                     GPALEPQPQDPASSVCPQPHYLLPDTNVLLHQIDVLEDPAIRNVIVLQTVLQEVRNRS
                     APVYKRIRDVTNNQEKHFYTFTNEHHRETYVEQEQGENANDRNDRAIRVAAKWYNEHL
                     KKMSADNQLQVIFITNDRRNKEKAIEEGIPAFTCEEYVKSLTANPELIDRLACLSEEG
                     NEIESGKIIFSEHLPLSKLQQGIKSGTYLQGTFRASRENYLEATVWIHGDNEENKEII
                     LQGLKHLNRAVHEDIVAVELLPKSQWVAPSSVVLHDEGQNEEDVEKEEETERMLKTAV
                     SEKMLKPTGRVVGIIKRNWRPYCGMLSKSDIKESRRHLFTPADKRIPRIRIETRQAST
                     LEGRRIIVAIDGWPRNSRYPNGHFVRNLGDVGEKETETEVLLLEHDVPHQPFSQAVLS
                     FLPKMPWSITEKDMKNREDLRHLCICSVDPPGCTDIDDALHCRELENGNLEVGVHIAD
                     VSHFIRPGNALDQESARRGTTVYLCEKRIDMVPELLSSNLCSLKCDVDRLAFSCIWEM
                     NHNAEILKTKFTKSVINSKASLTYAEAQLRIDSANMNDDITTSLRGLNKLAKILKKRR
                     IEKGALTLSSPEVRFHMDSETHDPIDLQTKELRETNSMVEEFMLLANISVAKKIHEEF
                     SEHALLRKHPAPPPSNYEILVKAARSRNLEIKTDTAKSLAESLDQAESPTFPYLNTLL
                     RILATRCMMQAVYFCSGMDNDFHHYGLASPIYTHFTSPIRRYADVIVHRLLAVAIGAD
                     CTYPELTDKHKLADICKNLNFRHKMAQYAQRASVAFHTQLFFKSKGIVSEEAYILFVR
                     KNAIVVLIPKYGLEGTVFFEEKDKPNPQLIYDDEIPSLKIEDTVFHVFDKVKVKIMLD
                     SSNLQHQKIRMSLVEPQIPGISIPTDTSNMDLNGPKKKKMKLGK"
     exon            297..454
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            455..648
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            649..722
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            723..890
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            891..1055
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            1056..1169
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            1170..1307
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            1308..1454
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            1455..1571
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            1572..1673
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            1674..1738
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            1739..1823
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            1824..1951
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            1952..2038
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            2039..2195
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            2196..2410
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            2411..2579
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            2580..2738
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            2739..2861
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     exon            2862..10571
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3668..3673
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /note="hexamer: AATAAA"
     polyA_site      3699
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /note="major polyA site"
     regulatory      3780..3785
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /note="hexamer: AATAAA"
     polyA_site      3786
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /note="major polyA site"
     regulatory      7318..7323
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /note="hexamer: AATAAA"
     polyA_site      7338
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
     regulatory      10550..10555
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
                     /note="hexamer: AATAAA"
     polyA_site      10571
                     /gene="DIS3"
                     /gene_synonym="2810028N01Rik; dis3p; EXOSC11; KIAA1008;
                     RRP44"
ORIGIN      
        1 gtattctaga ttgacgcctt ttgctggaag agcgctgctg gggttaggat tctgcgcggc
       61 gaggcaagat gctcaagtcc aagacgttct taaaaaagac ccgggcgggc ggcgtgatga
      121 agatcgtgcg cgagcactac ctgcgagacg acatcggctg cggtgcgccc gggtgcgcag
      181 cgtgtggagg ggcgcacgag gggccggccc tggagccgca gccccaggac ccggcgagca
      241 gcgtctgccc gcaaccgcac tacttgctgc ccgacactaa tgtgttactg caccagattg
      301 atgttcttga ggaccctgcc atcaggaatg taattgtgct acaaacagtt cttcaagaag
      361 tgagaaatcg cagtgccccc gtatataaac gcatccgaga tgtgactaat aaccaagaga
      421 agcatttcta tactttcact aatgagcacc atagagaaac ctatgtagaa caagaacagg
      481 gagaaaatgc taatgacagg aatgatagag cgattcgagt agcagcaaaa tggtacaatg
      541 aacatttgaa aaaaatgtca gcagacaacc agctgcaagt tatcttcata acaaatgaca
      601 ggagaaacaa agagaaagcc atagaagaag gaataccagc tttcacttgt gaagaatatg
      661 taaagagcct aactgctaac cccgaactca tagatcgtct tgcttgtttg tctgaagaag
      721 ggaatgaaat agaaagtgga aaaataatat tttcagagca tcttccctta agtaagctac
      781 agcaaggcat aaaatctggt acataccttc aaggaacatt tagagctagc agggaaaatt
      841 acttggaagc tacagtatgg attcatggcg acaatgaaga aaataaagag ataatcttac
      901 agggacttaa acatttaaac agagctgttc acgaagatat tgtggctgtg gagcttctcc
      961 ccaagagtca gtgggtagca ccatcttctg tggttttaca tgatgaaggt caaaatgaag
     1021 aagatgtgga gaaagaagaa gagacagaac gaatgcttaa gactgctgta agcgagaaaa
     1081 tgttgaagcc tacaggtaga gttgtaggaa taataaaaag gaattggaga ccatattgtg
     1141 gcatgctttc caagtctgac attaaggagt caagaagaca tctctttaca cctgctgata
     1201 agagaatccc tcgaattcgc atagaaacca gacaggcttc cacattagaa ggacggagaa
     1261 ttattgttgc tattgatggt tggcccagaa attccagata tccaaatgga cactttgtga
     1321 gaaatttagg tgatgttgga gagaaagaga ctgaaacaga agttttgtta cttgaacacg
     1381 atgttcccca tcagcctttt tcacaggctg ttcttagttt tctgccaaag atgccctgga
     1441 gcattactga aaaggacatg aaaaaccgag aagacctgag gcatctgtgt atttgtagtg
     1501 tagacccacc aggatgtact gatatagacg atgctctaca ttgtcgagaa ctcgaaaatg
     1561 gaaatttgga ggttggtgtt catattgctg atgtgagcca ttttattagg ccaggaaatg
     1621 ccttggatca agaatcagcc agaagaggaa caactgtgta tctttgtgaa aagaggattg
     1681 acatggttcc agagttgctt agctctaact tgtgttcctt aaaatgtgac gtggacaggc
     1741 tggcattttc atgtatttgg gaaatgaatc acaatgctga aatcttaaaa acgaagttta
     1801 ccaaaagtgt tattaattca aaggcatctc tgacgtatgc tgaagctcag ttgagaattg
     1861 attcagcaaa catgaatgat gatattacca ctagtctccg tggactgaat aaactagcca
     1921 aaattctgaa gaaaagaagg attgaaaaag gggctttgac tctatcctct cctgaagttc
     1981 gattccacat ggacagtgaa actcacgatc ctatagatct gcagaccaag gaacttaggg
     2041 aaacaaattc catggttgaa gaatttatgt tacttgccaa tatttctgtt gcaaaaaaaa
     2101 ttcatgagga attttctgaa catgctctgc ttcgaaaaca tcctgctcca cctccatcaa
     2161 attatgaaat tcttgttaag gcagccaggt caaggaattt ggaaattaag actgatacag
     2221 ccaagtcttt ggctgagtct ttggatcagg ccgaatctcc tacttttcca tatctaaaca
     2281 ctctgttgag aatattagcc actcgctgta tgatgcaagc tgtgtacttc tgttctggaa
     2341 tggataatga ttttcatcac tatggcttag cgtctccaat atacacacat tttacttcac
     2401 ccattagaag atacgcagat gtcattgttc atcggctttt ggctgtggct attggggctg
     2461 actgtactta tccagagttg acagacaaac acaagcttgc agatatatgt aaaaatctaa
     2521 atttccggca caaaatggct caatatgccc aacgtgcatc agtggctttt catacccagt
     2581 tattcttcaa aagcaaagga atagtaagtg aagaagccta tattttattt gtaagaaaga
     2641 atgccattgt ggtattaatt ccaaagtatg gtttagaagg gacagtcttt tttgaagaaa
     2701 aggacaaacc aaacccacag cttatttatg atgatgagat accctcactt aaaatagaag
     2761 atacagtgtt ccatgtattt gataaagtta aagtgaaaat catgttagac tcatctaatc
     2821 ttcaacatca gaagatccga atgtccctgg tagaaccaca gataccagga ataagcattc
     2881 ctactgatac ttcaaacatg gaccttaatg gaccaaagaa aaagaagatg aagcttggaa
     2941 aatagctata ttcaacaaaa atcttcaaag actggtttct tttttaaaag aaaaaacttg
     3001 aaagaacact tctaagccta agtgtgtgat acagtttgtt acttttaagt acattttaat
     3061 aatttcagac atctgcattt ttattgaaca gttgactgta tctgacccat catactacta
     3121 tacttctggg ttgaacagaa ttatttatgc agaataattc aattgaatat ccatcactta
     3181 aatacagtga caggacagca acttcaggga tctgtaaaga tcatttaaat ggagtgctca
     3241 tctcattgag gagcagatta attttgcgta agtactttga ttatttaata tttgtaagaa
     3301 aaaactttca ttttcctaca gaggaaaata gaacaatttt agaagcaagg aacaatctct
     3361 tttctaagtc ttggaagctg tcagtgttga ggatgtaatc tcctttgcca tctttaattc
     3421 acctaactta cactaggtgt tctcttactg tctttaaaag cttcctgtat tttattagtg
     3481 gtccttgaaa aactgtgaat gtttgggaat tggtagaaag gcaaaaagta ggatattttg
     3541 acctgactgg aaagatggtt gtgtttttat tgccaggtaa taagtgtgat cattgttgaa
     3601 cttcagctcc agtgtctctc cagaataaga cattggcatt caaatgtcta tatcttgtta
     3661 cttacaaaat aaaaaacaga ttaattagtg gcttttaaat tgtagttata tcagtgtata
     3721 tacacgaggg gaactgtata aagacatact aaagggaaca gattaaaata agtattatta
     3781 ataaaatttg gtgtgccaga ctgactactt cccttgctaa tcacagagat tagtaatgat
     3841 taaattaata tcttcaggaa tattttggga tagggttgcc ttaaaacatt ttacttggct
     3901 tattcaattt ctaaagcact tacgttgtgc caggttccac tcaagtaaat tatctctgcc
     3961 ttcaaggagc ttgcagtata gtgagaaaag cctgccaagt aaatcagcag gtatactaaa
     4021 taggtagtca tttaggcact caataaatgt tgactaattt ttccagtttc ctattactga
     4081 ggaaaacctc catacactga ggcagaaact tgtgtcagtt ggaggaaaat agacttgagt
     4141 agtctttggt ccaggtaaaa tgggtcagtg acactgaaac agtagagtag gagtcaaaaa
     4201 accttttctg tgaagtgcta gaacatttta gactttgttg gctatggtct gtattgcaac
     4261 tatagtacac aactctgccg ttgatagtgt gtaaggagcc atatacaata tgtaaacaaa
     4321 tcaacatgac tgtgtttcaa caaggcctga tttgttaagt ttcatatata gtcatatgtc
     4381 acttaatgac agggatatgt tctgagacat gtcacttggc aatttcatca ttgtgtgaaa
     4441 atcatgatgt agttacacaa acctagatgg tataccctat ggtatcctat atgggatagc
     4501 ctattgctcc taacctacaa acctgtatgg catattactg tactgattac tgtaggcggt
     4561 tgtaacacag tgctaagtat ttgtgtatct aaacatatct aaacatagaa aaggtacagt
     4621 aaaaatatat atatagatat atataagata taaaatggta cacctattta ggacatttac
     4681 catgaacaag ttggcaggac tggaagctgg ctctgggtga gtcagtaagt ggttagtgaa
     4741 tgtgaaggcc atgatattac tgtgcactac tgtagacttt tataaacact atatacttag
     4801 gctacataaa gtaatttcac tatgatgtta ccatggctgt gtccccaggc aataggaatt
     4861 tttcagctcc attgtaatct tacgggatca tcatcgtata tttggccatt gttgaccaaa
     4921 agttatgcag cacatcatta taattttgat gtgtcacaaa acattactca tttgatttcc
     4981 cccacccccg ccaaccattt aaaaaagttt gccggctagg tgcggtggct catgcctgta
     5041 atcctagcat tttgggagga cgaggcgggt ggatcactcg atgtcaggag tttgagacca
     5101 gcctggccaa catggtaaaa cgccgtctct actaaaaata caaaaactta gctgggtgta
     5161 acggcggatg cctgtaatcc cagctacttg ggaggctgag gcaggagaat cgcttgaacc
     5221 tgggaggcgg aagttgcagt gagccgagat tgcaccactg cagttcagcc tggatgatga
     5281 gagtgagact ccatcgcaaa aaaaaaaaaa aaaaaagaaa agaaaattag ccaggtgtgg
     5341 tggcaagtgc ctttaatccc acctcaggag gctgaggcag gagaatcgct tgaacctggg
     5401 aggcagaggt tgcagtgagc caagatcgcg ccactgcact ccagcctggg tgacagaaca
     5461 agactgtctc aaaaaaaaaa aaagagaaga aaaactgcct acaggccata gttaacctgc
     5521 aatagagaag aaagggaagt agggcagtgc atgactggcc ttaggttttt tctttccaag
     5581 tttattttct tgtgcttcag ctactagaaa ggtttaattc agggataagt cccaattgag
     5641 tagttcaaga tgatcagaga ctttgctatt ttcccctaag ttctattcca taatctaaaa
     5701 tgttctgttt ctagtgccag ttcttatgct aagcaggtta cgtggaatat atcacttaac
     5761 tcaaaaagcc ctgttaagcc aggactgtta tctccattta acagatgaga aaatggaggt
     5821 ttatggtctg ttctcacact gctacgaaga aataccccaa actgggtaat tattataaag
     5881 gaaagaggtt taatggactc agttccgcat tgctggtgag gcctcaggac acttacacaa
     5941 tcatggcaga aaaaggagaa gcaggcacct ttttcacagg gcggcaggat gaaaatgact
     6001 gccagcagtg gaaatgccag acgcttataa aaccttcaga tctcatgaga ccggctcact
     6061 atcacaggaa cagcatggag gaaaccgccc ccatgatcca gttacctcca cctggtccca
     6121 cccttgacac gtggggattg ctacaattca aggttagatt tgggtgagga cacagagcca
     6181 taccatatca gcccagatca agtagtgaca gagtagggat ttgaatacag gttatagtca
     6241 ctattgtgtt atttcttgac ttttgtacta ttaaaaaact gtagccagtg aggcttctac
     6301 ccttagtacc cagaactcct tttaggtata gcaattgttt ttaggtaaat ttatattgag
     6361 tttaacacct gtgtgattaa agacaacttt ccaatgtagt atctgtagcc atgtccccta
     6421 atggctatta gtgttcatgg ttagtgtgtt gaagatgagc caggtacata acgcggcaca
     6481 ttttctgcag gtcagcagta aggtttcaag gtacagttat ggaggaaaga agaaaatgac
     6541 acattgataa cacaggtctt tattcccttt tgaatgagac agtttttaaa agttgattta
     6601 taaatacaaa aatacattct ccaaagatag tatttccaaa ctgttatata cccatctact
     6661 cccaacatgg atataagttt tttaaaaaaa tagttgtata taacatacat atctgcccca
     6721 gtgttacttc acaggcctat gccctacggg aactccactc tcccagcccc actttttctc
     6781 ttggttctcc cacattctta ttctcccaca tccctaccca cgtttgagct ggaaaggatg
     6841 tccctaccct aggcatgagg tatattttat tctgggcacc acacatttgc cccatagata
     6901 acaatacacg tgatgatgtc actagtacta cctttctagt atttacatac ttaaaagtag
     6961 taactagaac agttatcact ggaactaaga attttcccca cagaggtgaa cagaccaaga
     7021 actaaaattt caggaaacct gtttaatttc ttttgtatct ttgaaaagtt agttttatat
     7081 ctaagatttc ttcacatagg ttataattca tctgtatgtt caagctttta tgtaaaaata
     7141 tatagtgcct tcagttttaa catagtttca catgttctca gaactgctaa attcagtgct
     7201 accagtaagg cttaataagt agttcattga ccctgtaaga taggagcact cagctctgtc
     7261 acaatttgtt gttaaacaca tcactcaatg taagtataaa aatatttatt gataaaaaat
     7321 aaacttataa ttcagcaact tgaagttcca ggagcatttc tgttgttcct atgtcagtaa
     7381 gcccttgatt tttcacatta aggagggaaa gctaagcatg ttacttgaag taattttttc
     7441 ccagtcacca tcatgttgat cctgtgcaca acgatatatg cgaggaactc ttaagcttag
     7501 tctttgattc tgacagaggc attctatgga ctgctgcatt gaaaagggct tgctgttttc
     7561 atccaacacc tctgtgttgt gtggtcttgc tgtgaaaaag aagacaatac cttgttttca
     7621 gtttaagtag gaccactgga ggatgcaatt atcgggactg tttttaaaac ctaaaagcac
     7681 gtttctttag ctgaactctg aagggacagt aaagatacag tattttataa atcaatattc
     7741 tgcatcaaaa agcatcccaa cactttgaga ggccaaggtg ggaggatcgc acgagcccag
     7801 gagtttggga ctagccctgg caacatagtg agaccctgtc tctaccaaaa attttaaaaa
     7861 gctgggtgtg gtggcacatg cctgtagccc tagctactca ggaggctgag gtggtaagac
     7921 tgcttgagtc tgggaggtga aggctacagt gagctgtggt cgtgccacta cactctagcc
     7981 tgggtgacag aatgagacct tgtctcaaaa aaaataaaat aataaaattt aaaaaaatcc
     8041 ttcatttatc tctacttatg tttagataga caactgcatc ctgaaatagg atggattttg
     8101 ttcaggttaa tattagaaga gacctgctct gatactacat acaacagaaa ggcagtttgc
     8161 tcctactaca tacaacagaa aggaaaacta aggtggcctc cctattaaac atttgttgca
     8221 catttgctga tatttatagt attttataag aaactggcat ataacagcag ggcaaggtgg
     8281 ttcacacctg tagttctagc tactcaggag ggtgaggcag gaggattgct tgagcccagc
     8341 agttaaaggc tgtagtgatc tgattctacg actgcactcc agcccgggtg acagagtaag
     8401 accctgtctc aaaaaaaaaa aaaaagaaaa aaaagaaacg gcatacaagg ctgggcatgt
     8461 tggctcatgc ctgtaatcgc gcagcacttt gcgaggctga ggcagaaaga ctgcttgaca
     8521 ccaggagttt gagaccagcc tgggcaacac agcaggccct gtctctacaa aaaaataaaa
     8581 tgcaaaaaaa attggcacat aaaattaaag actgtcctga ctagtgcctg aaattatgat
     8641 gagtttcttc aagtatgaat atataaccac cacctggaag gttcagtaaa tgccctcatc
     8701 aaatacacgc tacctttgca cactttgtag tatgtaagat acttgtgtat tcagagtaac
     8761 caaaatattt aaaggttatt ggatgttaag aaaacaggct taccttttag tgttttaaat
     8821 ttcatatagt ttctcaatag tactattgtc taataatcaa aattatttta tatttctaat
     8881 ctaaacaata ttaagctttc actatatttt ctccgtacct tcatattaaa tgcttgagat
     8941 ttactctcaa cttcacatgt ttgtgcatca ctttctttgc agtaactttc tgccccaact
     9001 gtatccataa tattgcttcc acaattctgc gtattatagc cactatccat ctgacaggag
     9061 aaaaaagaaa aaaatatatt gtgaggaact taaaagtcaa atatttaaat aagtaaacca
     9121 ctataaactc tcattcacta catctgaatg atcctaacat gtaatattga tcatgttgaa
     9181 caaaattcaa aagtaatgca caaatataaa aggtagtcct gcatagtact gattattgta
     9241 gtcattttac aattccttcc aatgaaatat atcttgtaac ttccttaaga atcagtgaac
     9301 agcctactga cacaatgctt tcctgttatt ttgtgatcgt acctagtaga caaaaatgag
     9361 tattacaact aacttcacct tccaacgcat tttccaggct tgtctctaaa tggcttgagg
     9421 catgctgcct ttaaaaaagt ggattatatt atatttacac ctagttgttc acaataatgc
     9481 cacatatata atggctctag atgttagttc agcttttcat gttaataaaa attgtagcat
     9541 cctaagatac actgtttcag tgcaaaagag caaaaaagaa agattctagc gaacttccag
     9601 cttggaaaca tttattgagt gtctaaaaag gccaggcact atctctatat atttaatatt
     9661 tttttctcct ttcaacaacc ctaatacttt actagagaag gaaattaagg cttaaaaagc
     9721 ttaactttca caatgtcatc cagtgatgag gtgatgaaga tgtgagacct aagtccaggt
     9781 tctgttcact gcacaacgct ccatttacct gtataatgct gagcaccaaa gaaagcaatc
     9841 cacaagggaa tcattttgca tttaagccct ccctgcaagt taggatcaga gggaaggaaa
     9901 aagctgactg tcattttgtt tccctcacaa aggtacagac tagcctagaa acggcactct
     9961 ttatcactta ataatcctga aaaaatgttc ccagatttca aggctggata catatctgct
    10021 tactactaga ggtcatgttc caattagaac aaaagccttg tgatgtgtaa catttttggg
    10081 gaaaagcctt gttctgctat cattcaatag ctacttgatc aaaaatataa atgtcagatt
    10141 gctcccagag attctgccaa tagctcttcc ttctaatatt catcactgcc aaatagctgg
    10201 cttataatgc aatactaata tgtaactgga tatatatgga gggaagagtt actcattagt
    10261 acagcaggaa gtaaggcatg cggggagttt gtcccacact atgggaagag caggattgat
    10321 gagagccaag ttgagatggt ggctgacttc actgtctctc atctagactt ctgctaatgt
    10381 caatgcctaa tatgtaccaa ccaggcaaca gataccttgt tatcccccac aggcatcaag
    10441 gcaggcatca atctcacttt atagctaaga aggatgaggg gacaaaaatt aaaaagtcat
    10501 gttctattca ctgctatgta aatcttgcct taagatccca cagcctggaa ataaaagaac
    10561 tctaattcaa a
//
