GenomeNet

Database: RefSeq
Entry: NC_001526
LinkDB: NC_001526
Original site: NC_001526 
LOCUS       NC_001526               7906 bp    DNA     circular VRL 13-AUG-2018
DEFINITION  Human papillomavirus type 16, complete genome.
ACCESSION   NC_001526
VERSION     NC_001526.4
DBLINK      BioProject: PRJNA485481
KEYWORDS    RefSeq.
SOURCE      Human papillomavirus type 16
  ORGANISM  Human papillomavirus type 16
            Viruses; Monodnaviria; Shotokuvirae; Cossaviricota;
            Papovaviricetes; Zurhausenvirales; Papillomaviridae;
            Firstpapillomavirinae; Alphapapillomavirus.
REFERENCE   1  (bases 5380 to 6090)
  AUTHORS   Kirnbauer,R., Taub,J., Greenstone,H., Roden,R., Durst,M.,
            Gissmann,L., Lowy,D.R. and Schiller,J.T.
  TITLE     Efficient self-assembly of human papillomavirus type 16 L1 and
            L1-L2 into virus-like particles
  JOURNAL   J. Virol. 67 (12), 6929-6936 (1993)
   PUBMED   8230414
REFERENCE   2  (bases 3503 to 3503)
  AUTHORS   Baker,C.C.
  TITLE     The Genomes of the Papillomaviruses
  JOURNAL   (in) O'Brien,S.J. (Ed.);
            GENETIC MAPS: LOCUS MAPS OF COMPLEX GENOMES, 6TH EDITION, BOOK 1:
            VIRUSES.;
            Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA
            (1993)
  REMARK    revision: substitution of 't' for 'a' at bp 4365
REFERENCE   3  (bases 3503 to 3503)
  AUTHORS   Xi,S.Z. and Banks,L.M.
  TITLE     Baculovirus expression of the human papillomavirus type 16 capsid
            proteins: detection of L1-L2 protein complexes
  JOURNAL   J. Gen. Virol. 72 (PT 12), 2981-2988 (1991)
   PUBMED   1662690
REFERENCE   4  (sites)
  AUTHORS   Kennedy,I.M., Haddow,J.K. and Clements,J.B.
  TITLE     A negative regulatory element in the human papillomavirus type 16
            genome acts at the level of late mRNA stability
  JOURNAL   J. Virol. 65 (4), 2093-2097 (1991)
   PUBMED   1848319
REFERENCE   5  (bases 6044 to 6090)
  AUTHORS   Parton,A.
  TITLE     Nucleotide sequence of the HPV16 L1 open reading frame
  JOURNAL   Nucleic Acids Res. 18 (12), 3631 (1990)
   PUBMED   2163522
REFERENCE   6  (bases 7001 to 7001)
  AUTHORS   Romanczuk,H., Thierry,F. and Howley,P.M.
  TITLE     Mutational analysis of cis elements involved in E2 modulation of
            human papillomavirus type 16 P97 and type 18 P105 promoters
  JOURNAL   J. Virol. 64 (6), 2849-2859 (1990)
   PUBMED   2159546
REFERENCE   7  (bases 3045 to 3045)
  AUTHORS   Bubb,V., McCance,D.J. and Schlegel,R.
  TITLE     DNA sequence of the HPV-16 E5 ORF and the structural conservation
            of its encoded protein
  JOURNAL   Virology 163 (1), 243-246 (1988)
   PUBMED   2831662
REFERENCE   8  (bases 3045 to 3045)
  AUTHORS   Halbert,C.L. and Galloway,D.A.
  TITLE     Identification of the E5 open reading frame of human papillomavirus
            type 16
  JOURNAL   J. Virol. 62 (3), 1071-1075 (1988)
   PUBMED   2828656
REFERENCE   9  (bases 276 to 277)
  AUTHORS   Baker,C.C., Phelps,W.C., Lindgren,V., Braun,M.J., Gonda,M.A. and
            Howley,P.M.
  TITLE     Structural and transcriptional analysis of human papillomavirus
            type 16 sequences in cervical carcinoma cell lines
  JOURNAL   J. Virol. 61 (4), 962-971 (1987)
   PUBMED   3029430
REFERENCE   10 (bases 276 to 277)
  AUTHORS   Matsukura,T., Kanda,T., Furuno,A., Yoshikawa,H., Kawana,T. and
            Yoshiike,K.
  TITLE     Cloning of monomeric human papillomavirus type 16 DNA integrated
            within cell DNA from a cervical carcinoma
  JOURNAL   J. Virol. 58 (3), 979-982 (1986)
   PUBMED   3009901
REFERENCE   11 (bases 1 to 7906)
  AUTHORS   Seedorf,K., Krammer,G., Durst,M., Suhai,S. and Rowekamp,W.G.
  TITLE     Human papillomavirus type 16 DNA sequence
  JOURNAL   Virology 145 (1), 181-185 (1985)
   PUBMED   2990099
REFERENCE   12 (bases 1 to 7906)
  CONSRTM   NCBI Genome Project
  TITLE     Direct Submission
  JOURNAL   Submitted (01-AUG-2000) National Center for Biotechnology
            Information, NIH, Bethesda, MD 20894, USA
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence is identical to K02718.
            On Jul 28, 2016 this sequence version replaced NC_001526.3.
            The annotation of this sequence was improved with a kind help of
            Robert D. Burk, M.D. (Albert Einstein College of Medicine, Bronx,
            NY).  The sequencing mistakes in the original sequence K02718 were
            corrected based on publication: Sequencing errors in reference HPV
            clones. In: Myers,G., Baker,C., Munger,K., Sverdrup,F., McBride,A.
            and  Bernard,H.-U. (eds), Human Papillomaviruses 1997. Los Alamos
            National Laboratory, Los Alamos, NM, pp. III110-III123.  The sense
            strand of this double-stranded circular genome is shown, with a
            numbering system matching the first ATG of the E1 ORF.
            COMPLETENESS: full length.
FEATURES             Location/Qualifiers
     source          1..7906
                     /organism="Human papillomavirus type 16"
                     /mol_type="genomic DNA"
                     /db_xref="taxon:333760"
     gene            1..2756
                     /gene="E1^E4"
                     /locus_tag="HpV16gp5"
                     /db_xref="GeneID:1489076"
     CDS             join(1..16,2494..2756)
                     /gene="E1^E4"
                     /locus_tag="HpV16gp5"
                     /experiment="EXISTENCE:"
                     /note="Spliced. E1^E4. Contributes to the replication of
                     the viral plasmid genome as a nuclear plasmid in basal
                     cells. It is a multifunctional protein and contributes to
                     different processes in both the early and late stages of
                     the virus life cycle."
                     /codon_start=1
                     /product="cell cycle modulating protein E1^E4"
                     /protein_id="YP_009268708.1"
                     /db_xref="GeneID:1489076"
                     /translation="MADPAAATKYPLLKLLGSTWPTTPPRPIPKPSPWAPKKHRRLSS
                     DQDQSQTPETPATPLSCCTETQWTVLQSSLHLTAHTKDGLTVIVTLHP"
     misc_feature    join(16,2494..2750)
                     /gene="E1^E4"
                     /locus_tag="HpV16gp5"
                     /note="E4 protein; Region: Pap_E4; pfam02711"
                     /db_xref="CDD:308375"
     gene            1..1950
                     /gene="E1"
                     /locus_tag="HpV16gp3"
                     /db_xref="GeneID:1489075"
     CDS             1..1950
                     /gene="E1"
                     /locus_tag="HpV16gp3"
                     /experiment="EXISTENCE:"
                     /note="E1. Inhibits viral DNA replication (ATP-dependent
                     DNA helicase). Replication protein E1 forms a complex with
                     the viral regulatory protein E2. The E1-E2 complex binds
                     to the replication origin which contains binding sites for
                     both proteins"
                     /codon_start=1
                     /product="replication protein E1"
                     /protein_id="NP_041327.2"
                     /db_xref="GeneID:1489075"
                     /translation="MADPAGTNGEEGTGCNGWFYVEAVVEKKTGDAISDDENENDSDT
                     GEDLVDFIVNDNDYLTQAETETAHALFTAQEAKQHRDAVQVLKRKYLGSPLSDISGCV
                     DNNISPRLKAICIEKQSRAAKRRLFESEDSGYGNTEVETQQMLQVEGRHETETPCSQY
                     SGGSGGGCSQYSSGSGGEGVSERHTICQTPLTNILNVLKTSNAKAAMLAKFKELYGVS
                     FSELVRPFKSNKSTCCDWCIAAFGLTPSIADSIKTLLQQYCLYLHIQSLACSWGMVVL
                     LLVRYKCGKNRETIEKLLSKLLCVSPMCMMIEPPKLRSTAAALYWYKTGISNISEVYG
                     DTPEWIQRQTVLQHSFNDCTFELSQMVQWAYDNDIVDDSEIAYKYAQLADTNSNASAF
                     LKSNSQAKIVKDCATMCRHYKRAEKKQMSMSQWIKYRCDRVDDGGDWKQIVMFLRYQG
                     VEFMSFLTALKRFLQGIPKKNCILLYGAANTGKSLFGMSLMKFLQGSVICFVNSKSHF
                     WLQPLADAKIGMLDDATVPCWNYIDDNLRNALDGNLVSMDVKHRPLVQLKCPPLLITS
                     NINAGTDSRWPYLHNRLVVFTFPNEFPFDENGNPVYELNDKNWKSFFSRTWSRLSLHE
                     DEDKENDGDSLPTFKCVSGQNTNTL"
     misc_feature    1..1947
                     /gene="E1"
                     /locus_tag="HpV16gp3"
                     /note="E1; Provisional; Region: PHA02774"
                     /db_xref="CDD:222927"
     misc_difference 275
                     /gene="E1"
                     /locus_tag="HpV16gp3"
                     /note="Inserted G was absent in original clone (Seedorf et
                     al., 1985). Restores E1 ORF.'"
                     /citation=[11]
     gene            1892..2989
                     /gene="E2"
                     /locus_tag="HpV16gp4"
                     /db_xref="GeneID:1489080"
     CDS             1892..2989
                     /gene="E2"
                     /locus_tag="HpV16gp4"
                     /note="E2. Plays a role in the initiation of viral DNA
                     replication. Forms E1-E2 dimer with replication protein
                     E1. The E1-E2 complex binds to the replication origin
                     which contains binding sites for both proteins."
                     /codon_start=1
                     /product="regulatory protein E2"
                     /protein_id="NP_041328.1"
                     /db_xref="GeneID:1489080"
                     /translation="METLCQRLNVCQDKILTHYENDSTDLRDHIDYWKHMRLECAIYY
                     KAREMGFKHINHQVVPTLAVSKNKALQAIELQLTLETIYNSQYSNEKWTLQDVSLEVY
                     LTAPTGCIKKHGYTVEVQFDGDICNTMHYTNWTHIYICEEASVTVVEGQVDYYGLYYV
                     HEGIRTYFVQFKDDAEKYSKNKVWEVHAGGQVILCPTSVFSSNEVSSPEIIRQHLANH
                     PAATHTKAVALGTEETQTTIQRPRSEPDTGNPCHTTKLLHRDSVDSAPILTAFNSSHK
                     GRINCNSNTTPIVHLKGDANTLKCLRYRFKKHCTLYTAVSSTWHWTGHNVKHKSAIVT
                     LTYDSEWQRDQFLSQVKIPKTITVSTGFMSI"
     misc_feature    1892..2476
                     /gene="E2"
                     /locus_tag="HpV16gp4"
                     /note="E2 (early) protein, N terminal; Region: PPV_E2_N;
                     pfam00508"
                     /db_xref="CDD:278909"
     misc_feature    2750..2980
                     /gene="E2"
                     /locus_tag="HpV16gp4"
                     /note="E2 (early) protein, C terminal; Region: PPV_E2_C;
                     pfam00511"
                     /db_xref="CDD:395411"
     misc_difference 2062
                     /gene="E2"
                     /locus_tag="HpV16gp4"
                     /note="replaced G with A"
     gene            2986..3237
                     /gene="E5"
                     /locus_tag="HpV16gp6"
                     /db_xref="GeneID:1489077"
     CDS             2986..3237
                     /gene="E5"
                     /locus_tag="HpV16gp6"
                     /experiment="EXISTENCE:"
                     /note="E5. Oncoprotein. Contributes to cell
                     transformation. Produces polyploid cells by
                     endoreplication."
                     /codon_start=1
                     /product="transforming protein E5"
                     /protein_id="NP_041330.2"
                     /db_xref="GeneID:1489077"
                     /translation="MTNLDTASTTLLACFLLCFCVLLCVCLLIRPLLLSVSTYTSLII
                     LVLLLWITAASAFRCFIVYIIFVYIPLFLIHTHARFLIT"
     misc_feature    3016..3234
                     /gene="E5"
                     /locus_tag="HpV16gp6"
                     /note="Papillomavirus E5; Region: Papilloma_E5; pfam03025"
                     /db_xref="CDD:145918"
     misc_difference 3043
                     /gene="E5"
                     /locus_tag="HpV16gp6"
                     /note="Inserted T was absent in the original sequence.
                     Restores E5 ORF."
                     /citation=[7]
                     /citation=[8]
     regulatory      3351..3356
                     /regulatory_class="polyA_signal_sequence"
                     /note="putative"
     gene            3373..4794
                     /gene="L2"
                     /locus_tag="HpV16gp7"
                     /db_xref="GeneID:1489081"
     CDS             3373..4794
                     /gene="L2"
                     /locus_tag="HpV16gp7"
                     /experiment="EXISTENCE:"
                     /note="L2. Forms an icosahedral capsid. Plays an essential
                     role in virus assembly by recruiting viral components to
                     PML bodies, the proposed sites of virus morphogenesis."
                     /codon_start=1
                     /product="minor capsid protein L2"
                     /protein_id="NP_041331.2"
                     /db_xref="GeneID:1489081"
                     /translation="MRHKRSAKRTKRASATQLYKTCKQAGTCPPDIIPKVEGKTIADQ
                     ILQYGSMGVFFGGLGIGTGSGTGGRTGYIPLGTRPPTATDTLAPVRPPLTVDPVGPSD
                     PSIVSLVEETSFIDAGAPTSVPSIPPDVSGFSITTSTDTTPAILDINNTVTTVTTHNN
                     PTFTDPSVLQPPTPAETGGHFTLSSSTISTHNYEEIPMDTFIVSTNPNTVTSSTPIPG
                     SRPVARLGLYSRTTQQVKVVDPAFVTTPTKLITYDNPAYEGIDVDNTLYFSSNDNSIN
                     IAPDPDFLDIVALHRPALTSRRTGIRYSRIGNKQTLRTRSGKSIGAKVHYYYDLSTID
                     PAEEIELQTITPSTYTTTSHAASPTSINNGLYDIYADDFITDTSTTPVPSVPSTSLSG
                     YIPANTTIPFGGAYNIPLVSGPDIPINITDQAPSLIPIVPGSPQYTIIADAGDFYLHP
                     SYYMLRKRRKRLPYFFSDVSLAA"
     misc_feature    3394..4755
                     /gene="L2"
                     /locus_tag="HpV16gp7"
                     /note="Late Protein L2; Region: Late_protein_L2;
                     pfam00513"
                     /db_xref="CDD:278914"
     regulatory      3427..3433
                     /regulatory_class="TATA_box"
                     /gene="L2"
                     /locus_tag="HpV16gp7"
     misc_difference 3501
                     /gene="L2"
                     /locus_tag="HpV16gp7"
                     /note="A in the original sequence is changed to T."
                     /citation=[2]
                     /citation=[3]
     gene            4775..6292
                     /gene="L1"
                     /locus_tag="HpV16gp8"
                     /db_xref="GeneID:1489082"
     CDS             4775..6292
                     /gene="L1"
                     /locus_tag="HpV16gp8"
                     /experiment="EXISTENCE:"
                     /note="L1. Forms an icosahedral capsid. Binds to heparan
                     sulfate proteoglycans on cell surface of basal layer
                     keratinocytes to provide initial virion attachment"
                     /codon_start=1
                     /product="major capsid protein L1"
                     /protein_id="NP_041332.2"
                     /db_xref="GeneID:1489082"
                     /translation="MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLA
                     VGHPYFPIKKPNNNKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWAC
                     VGVEVGRGQPLGVGISGHPLLNKLDDTENASAYAANAGVDNRECISMDYKQTQLCLIG
                     CKPPIGEHWGKGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKS
                     EVPLDICTSICKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGTVGENVPDDLY
                     IKGSGSTANLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVV
                     DTTRSTNMSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIH
                     SMNSTILEDWNFGLQPPPGGTLEDTYRFVTSQAIACQKHTPPAPKEDPLKKYTFWEVN
                     LKEKFSADLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPTTSSTSTTAKRKKRKL"
     misc_feature    4775..6286
                     /gene="L1"
                     /locus_tag="HpV16gp8"
                     /note="major capsid L1 protein; Provisional; Region:
                     PHA02778"
                     /db_xref="CDD:222928"
     misc_difference 5378
                     /gene="L1"
                     /locus_tag="HpV16gp8"
                     /note="C in original clone replaced wth G"
                     /citation=[1]
     misc_difference 6039..6041
                     /gene="L1"
                     /locus_tag="HpV16gp8"
                     /note="inserted CAT absent from original sequence"
                     /citation=[5]
     misc_difference 6088
                     /gene="L1"
                     /locus_tag="HpV16gp8"
                     /note="GAT in original sequence deleted"
                     /citation=[1]
                     /citation=[5]
     misc_feature    6293..7124
                     /note="Upstream regulatory region (URR). Contains
                     DNA-protein binding motifs. Involved in replication.
                     Synonims: long control region (LCR), noncoding region
                     (NCR)."
                     /function="URR"
     regulatory      6398..6403
                     /regulatory_class="polyA_signal_sequence"
     misc_difference 6570
                     /note="GC in original sequence change to CGG"
     misc_feature    6589..6600
                     /note="E2BS"
                     /function="E2 binding site"
     misc_feature    6996..7007
                     /function="E2 binding site"
     misc_difference 6997
                     /note="A in original sequence was deleted"
                     /citation=[6]
     regulatory      7059..7065
                     /regulatory_class="TATA_box"
     misc_feature    7077..7088
                     /note="E2BS"
                     /function="E2 binding site"
     misc_feature    7092..7103
                     /note="E2BS"
                     /function="E2 binding site"
     regulatory      7107..7113
                     /regulatory_class="TATA_box"
     gene            7125..7601
                     /gene="E6"
                     /locus_tag="HpV16gp1"
                     /db_xref="GeneID:1489078"
     CDS             7125..7601
                     /gene="E6"
                     /locus_tag="HpV16gp1"
                     /experiment="EXISTENCE:"
                     /note="Oncoprotein. It has long been recognized as a
                     potent oncogene and is intimately associated with the
                     events that result in the malignant conversion of virally
                     infected cells."
                     /codon_start=1
                     /product="transforming protein E6"
                     /protein_id="NP_041325.1"
                     /db_xref="GeneID:1489078"
                     /translation="MHQKRTAMFQDPQERPRKLPQLCTELQTTIHDIILECVYCKQQL
                     LRREVYDFAFRDLCIVYRDGNPYAVCDKCLKFYSKISEYRHYCYSLYGTTLEQQYNKP
                     LCDLLIRCINCQKPLCPEEKQRHLDKKQRFHNIRGRWTGRCMSCCRSSRTRRETQL"
     misc_feature    7233..7556
                     /gene="E6"
                     /locus_tag="HpV16gp1"
                     /note="Early Protein (E6); Region: E6; pfam00518"
                     /db_xref="CDD:306907"
     CDS             join(7125..7268,7451..7459)
                     /gene="E6"
                     /locus_tag="HpV16gp1"
                     /experiment="EXISTENCE:"
                     /note="Spliced. E6*. Function is not known yet."
                     /codon_start=1
                     /product="protein E6*"
                     /protein_id="YP_009268707.1"
                     /db_xref="GeneID:1489078"
                     /translation="MHQKRTAMFQDPQERPRKLPQLCTELQTTIHDIILECVYCKQQL
                     LRREVY"
     gene            7604..7900
                     /gene="E7"
                     /locus_tag="HpV16gp2"
                     /db_xref="GeneID:1489079"
     CDS             7604..7900
                     /gene="E7"
                     /locus_tag="HpV16gp2"
                     /experiment="EXISTENCE:"
                     /note="E7. Plays a role in viral genome replication by
                     driving entry of quiescent cells into the cell cycle."
                     /codon_start=1
                     /product="transforming protein E7"
                     /protein_id="NP_041326.1"
                     /db_xref="GeneID:1489079"
                     /translation="MHGDTPTLHEYMLDLQPETTDLYCYEQLNDSSEEEDEIDGPAGQ
                     AEPDRAHYNIVTFCCKCDSTLRLCVQSTHVDIRTLEDLLMGTLGIVCPICSQKP"
     misc_feature    7610..7885
                     /gene="E7"
                     /locus_tag="HpV16gp2"
                     /note="E7 protein, Early protein; Region: E7; pfam00527"
                     /db_xref="CDD:278928"
ORIGIN      
        1 atggctgatc ctgcaggtac caatggggaa gagggtacgg gatgtaatgg atggttttat
       61 gtagaggctg tagtggaaaa aaaaacaggg gatgctatat cagatgacga gaacgaaaat
      121 gacagtgata caggtgaaga tttggtagat tttatagtaa atgataatga ttatttaaca
      181 caggcagaaa cagagacagc acatgcgttg tttactgcac aggaagcaaa acaacataga
      241 gatgcagtac aggttctaaa acgaaagtat ttgggtagtc cacttagtga tattagtgga
      301 tgtgtagaca ataatattag tcctagatta aaagctatat gtatagaaaa acaaagtaga
      361 gctgcaaaaa ggagattatt tgaaagcgaa gacagcgggt atggcaatac tgaagtggaa
      421 actcagcaga tgttacaggt agaagggcgc catgagactg aaacaccatg tagtcagtat
      481 agtggtggaa gtgggggtgg ttgcagtcag tacagtagtg gaagtggggg agagggtgtt
      541 agtgaaagac acactatatg ccaaacacca cttacaaata ttttaaatgt actaaaaact
      601 agtaatgcaa aggcagcaat gttagcaaaa tttaaagagt tatacggggt gagtttttca
      661 gaattagtaa gaccatttaa aagtaataaa tcaacgtgtt gcgattggtg tattgctgca
      721 tttggactta cacccagtat agctgacagt ataaaaacac tattacaaca atattgttta
      781 tatttacaca ttcaaagttt agcatgttca tggggaatgg ttgtgttact attagtaaga
      841 tataaatgtg gaaaaaatag agaaacaatt gaaaaattgc tgtctaaact attatgtgtg
      901 tctccaatgt gtatgatgat agagcctcca aaattgcgta gtacagcagc agcattatat
      961 tggtataaaa caggtatatc aaatattagt gaagtgtatg gagacacgcc agaatggata
     1021 caaagacaaa cagtattaca acatagtttt aatgattgta catttgaatt atcacagatg
     1081 gtacaatggg cctacgataa tgacatagta gacgatagtg aaattgcata taaatatgca
     1141 caattggcag acactaatag taatgcaagt gcctttctaa aaagtaattc acaggcaaaa
     1201 attgtaaagg attgtgcaac aatgtgtaga cattataaac gagcagaaaa aaaacaaatg
     1261 agtatgagtc aatggataaa atatagatgt gatagggtag atgatggagg tgattggaag
     1321 caaattgtta tgtttttaag gtatcaaggt gtagagttta tgtcattttt aactgcatta
     1381 aaaagatttt tgcaaggcat acctaaaaaa aattgcatat tactatatgg tgcagctaac
     1441 acaggtaaat cattatttgg tatgagttta atgaaatttc tgcaagggtc tgtaatatgt
     1501 tttgtaaatt ctaaaagcca tttttggtta caaccattag cagatgccaa aataggtatg
     1561 ttagatgatg ctacagtgcc ctgttggaac tacatagatg acaatttaag aaatgcattg
     1621 gatggaaatt tagtttctat ggatgtaaag catagaccat tggtacaact aaaatgccct
     1681 ccattattaa ttacatctaa cattaatgct ggtacagatt ctaggtggcc ttatttacat
     1741 aatagattgg tggtgtttac atttcctaat gagtttccat ttgacgaaaa cggaaatcca
     1801 gtgtatgagc ttaatgataa gaactggaaa tcctttttct caaggacgtg gtccagatta
     1861 agtttgcacg aggacgagga caaggaaaac gatggagact ctttgccaac gtttaaatgt
     1921 gtgtcaggac aaaatactaa cacattatga aaatgatagt acagacctac gtgaccatat
     1981 agactattgg aaacacatgc gcctagaatg tgctatttat tacaaggcca gagaaatggg
     2041 atttaaacat attaaccacc aggtggtgcc aacactggct gtatcaaaga ataaagcatt
     2101 acaagcaatt gaactgcaac taacgttaga aacaatatat aactcacaat atagtaatga
     2161 aaagtggaca ttacaagacg ttagccttga agtgtattta actgcaccaa caggatgtat
     2221 aaaaaaacat ggatatacag tggaagtgca gtttgatgga gacatatgca atacaatgca
     2281 ttatacaaac tggacacata tatatatttg tgaagaagca tcagtaactg tggtagaggg
     2341 tcaagttgac tattatggtt tatattatgt tcatgaagga atacgaacat attttgtgca
     2401 gtttaaagat gatgcagaaa aatatagtaa aaataaagta tgggaagttc atgcgggtgg
     2461 tcaggtaata ttatgtccta catctgtgtt tagcagcaac gaagtatcct ctcctgaaat
     2521 tattaggcag cacttggcca accaccccgc cgcgacccat accaaagccg tcgccttggg
     2581 caccgaagaa acacagacga ctatccagcg accaagatca gagccagaca ccggaaaccc
     2641 ctgccacacc actaagttgt tgcacagaga ctcagtggac agtgctccaa tcctcactgc
     2701 atttaacagc tcacacaaag gacggattaa ctgtaatagt aacactacac ccatagtaca
     2761 tttaaaaggt gatgctaata ctttaaaatg tttaagatat agatttaaaa agcattgtac
     2821 attgtatact gcagtgtcgt ctacatggca ttggacagga cataatgtaa aacataaaag
     2881 tgcaattgtt acacttacat atgatagtga atggcaacgt gaccaatttt tgtctcaagt
     2941 taaaatacca aaaactatta cagtgtctac tggatttatg tctatatgac aaatcttgat
     3001 actgcatcca caacattact ggcgtgcttt ttgctttgct tttgtgtgct tttgtgtgtc
     3061 tgcctattaa tacgtccgct gcttttgtct gtgtctacat acacatcatt aataatattg
     3121 gtattactat tgtggataac agcagcctct gcgtttaggt gttttattgt atatattata
     3181 tttgtttata taccattatt tttaatacat acacatgcac gctttttaat tacataatgt
     3241 atatgtacat aatgtaattg ttacatataa ttgttgtata ccataactta ctattttttc
     3301 ttttttattt tcatatataa tttttttttt tgtttgtttg tttgtttttt aataaactgt
     3361 tattacttaa caatgcgaca caaacgttct gcaaaacgca caaaacgtgc atcggctacc
     3421 caactttata aaacatgcaa acaggcaggt acatgtccac ctgacattat acctaaggtt
     3481 gaaggcaaaa ctattgctga tcaaatatta caatatggaa gtatgggtgt attttttggt
     3541 gggttaggaa ttggaacagg gtcgggtaca ggcggacgca ctgggtatat tccattggga
     3601 acaaggcctc ccacagctac agatacactt gctcctgtaa gacccccttt aacagtagat
     3661 cctgtgggcc cttctgatcc ttctatagtt tctttagtgg aagaaactag ttttattgat
     3721 gctggtgcac caacatctgt accttccatt cccccagatg tatcaggatt tagtattact
     3781 acttcaactg ataccacacc tgctatatta gatattaata atactgttac tactgttact
     3841 acacataata atcccacttt cactgaccca tctgtattgc agcctccaac acctgcagaa
     3901 actggagggc attttacact ttcatcatcc actattagta cacataatta tgaagaaatt
     3961 cctatggata catttattgt tagcacaaac cctaacacag taactagtag cacacccata
     4021 ccagggtctc gcccagtggc acgcctagga ttatatagtc gcacaacaca acaggttaaa
     4081 gttgtagacc ctgcttttgt aaccactccc actaaactta ttacatatga taatcctgca
     4141 tatgaaggta tagatgtgga taatacatta tatttttcta gtaatgataa tagtattaat
     4201 atagctccag atcctgactt tttggatata gttgctttac ataggccagc attaacctct
     4261 aggcgtactg gcattaggta cagtagaatt ggtaataaac aaacactacg tactcgtagt
     4321 ggaaaatcta taggtgctaa ggtacattat tattatgatt taagtactat tgatcctgca
     4381 gaagaaatag aattacaaac tataacacct tctacatata ctaccacttc acatgcagcc
     4441 tcacctactt ctattaataa tggattatat gatatttatg cagatgactt tattacagat
     4501 acttctacaa ccccggtacc atctgtaccc tctacatctt tatcaggtta tattcctgca
     4561 aatacaacaa ttccttttgg tggtgcatac aatattcctt tagtatcagg tcctgatata
     4621 cccattaata taactgacca agctccttca ttaattccta tagttccagg gtctccacaa
     4681 tatacaatta ttgctgatgc aggtgacttt tatttacatc ctagttatta catgttacga
     4741 aaacgacgta aacgtttacc atattttttt tcagatgtct ctttggctgc ctagtgaggc
     4801 cactgtctac ttgcctcctg tcccagtatc taaggttgta agcacggatg aatatgttgc
     4861 acgcacaaac atatattatc atgcaggaac atccagacta cttgcagttg gacatcccta
     4921 ttttcctatt aaaaaaccta acaataacaa aatattagtt cctaaagtat caggattaca
     4981 atacagggta tttagaatac atttacctga ccccaataag tttggttttc ctgacacctc
     5041 attttataat ccagatacac agcggctggt ttgggcctgt gtaggtgttg aggtaggtcg
     5101 tggtcagcca ttaggtgtgg gcattagtgg ccatccttta ttaaataaat tggatgacac
     5161 agaaaatgct agtgcttatg cagcaaatgc aggtgtggat aatagagaat gtatatctat
     5221 ggattacaaa caaacacaat tgtgtttaat tggttgcaaa ccacctatag gggaacactg
     5281 gggcaaagga tccccatgta ccaatgttgc agtaaatcca ggtgattgtc caccattaga
     5341 gttaataaac acagttattc aggatggtga tatggttgat actggctttg gtgctatgga
     5401 ctttactaca ttacaggcta acaaaagtga agttccactg gatatttgta catctatttg
     5461 caaatatcca gattatatta aaatggtgtc agaaccatat ggcgacagct tattttttta
     5521 tttacgaagg gaacaaatgt ttgttagaca tttatttaat agggctggta ctgttggtga
     5581 aaatgtacca gacgatttat acattaaagg ctctgggtct actgcaaatt tagccagttc
     5641 aaattatttt cctacaccta gtggttctat ggttacctct gatgcccaaa tattcaataa
     5701 accttattgg ttacaacgag cacagggcca caataatggc atttgttggg gtaaccaact
     5761 atttgttact gttgttgata ctacacgcag tacaaatatg tcattatgtg ctgccatatc
     5821 tacttcagaa actacatata aaaatactaa ctttaaggag tacctacgac atggggagga
     5881 atatgattta cagtttattt ttcaactgtg caaaataacc ttaactgcag acgttatgac
     5941 atacatacat tctatgaatt ccactatttt ggaggactgg aattttggtc tacaacctcc
     6001 cccaggaggc acactagaag atacttatag gtttgtaaca tcccaggcaa ttgcttgtca
     6061 aaaacataca cctccagcac ctaaagaaga tccccttaaa aaatacactt tttgggaagt
     6121 aaatttaaag gaaaagtttt ctgcagacct agatcagttt cctttaggac gcaaattttt
     6181 actacaagca ggattgaagg ccaaaccaaa atttacatta ggaaaacgaa aagctacacc
     6241 caccacctca tctacctcta caactgctaa acgcaaaaaa cgtaagctgt aagtattgta
     6301 tgtatgttga attagtgttg tttgttgtgt atatgtttgt atgtgcttgt atgtgcttgt
     6361 aaatattaag ttgtatgtgt gtttgtatgt atggtataat aaacacgtgt gtatgtgttt
     6421 ttaaatgctt gtgtaactat tgtgtcatgc aacataaata aacttattgt ttcaacacct
     6481 actaattgtg ttgtggttat tcattgtata taaactatat ttgctacatc ctgtttttgt
     6541 tttatatata ctatattttg tagcgccagc ggccattttg tagcttcaac cgaattcggt
     6601 tgcatgcttt ttggcacaaa atgtgttttt ttaaatagtt ctatgtcagc aactatggtt
     6661 taaacttgta cgtttcctgc ttgccatgcg tgccaaatcc ctgttttcct gacctgcact
     6721 gcttgccaac cattccattg ttttttacac tgcactatgt gcaactactg aatcactatg
     6781 tacattgtgt catataaaat aaatcactat gcgccaacgc cttacatacc gctgttaggc
     6841 acatattttt ggcttgtttt aactaaccta attgcatatt tggcataagg tttaaacttc
     6901 taaggccaac taaatgtcac cctagttcat acatgaactg tgtaaaggtt agtcatacat
     6961 tgttcatttg taaaactgca catgggtgtg tgcaaaccgt tttgggttac acatttacaa
     7021 gcaacttata taataatact aaactacaat aattcatgta taaaactaag ggcgtaaccg
     7081 aaatcggttg aaccgaaacc ggttagtata aaagcagaca ttttatgcac caaaagagaa
     7141 ctgcaatgtt tcaggaccca caggagcgac ccagaaagtt accacagtta tgcacagagc
     7201 tgcaaacaac tatacatgat ataatattag aatgtgtgta ctgcaagcaa cagttactgc
     7261 gacgtgaggt atatgacttt gcttttcggg atttatgcat agtatataga gatgggaatc
     7321 catatgctgt atgtgataaa tgtttaaagt tttattctaa aattagtgag tatagacatt
     7381 attgttatag tttgtatgga acaacattag aacagcaata caacaaaccg ttgtgtgatt
     7441 tgttaattag gtgtattaac tgtcaaaagc cactgtgtcc tgaagaaaag caaagacatc
     7501 tggacaaaaa gcaaagattc cataatataa ggggtcggtg gaccggtcga tgtatgtctt
     7561 gttgcagatc atcaagaaca cgtagagaaa cccagctgta atcatgcatg gagatacacc
     7621 tacattgcat gaatatatgt tagatttgca accagagaca actgatctct actgttatga
     7681 gcaattaaat gacagctcag aggaggagga tgaaatagat ggtccagctg gacaagcaga
     7741 accggacaga gcccattaca atattgtaac cttttgttgc aagtgtgact ctacgcttcg
     7801 gttgtgcgta caaagcacac acgtagacat tcgtactttg gaagacctgt taatgggcac
     7861 actaggaatt gtgtgcccca tctgttctca gaaaccataa tctacc
//
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