LOCUS HPV16 7905 bp ds-DNA circular VRL 15-APR-1991 DEFINITION Human papillomavirus type 16 (HPV16), complete genome. ACCESSION K02718 KEYWORDS circular; complete genome. SOURCE Papilloma virus type 16 DNA recovered from a human invasive cervical carcinoma. ORGANISM Human papillomavirus type 16 Viridae; ds-DNA nonenveloped viruses; Papovaviridae; Papillomavirus. REFERENCE 1 (bases 1 to 7904) AUTHORS Seedorf,K., Kraemmer,G., Duerst,M., Suhai,S. and Roewekamp,W.G. TITLE Human papillomavirus type 16 DNA sequence JOURNAL Virology 145, 181-185 (1985) STANDARD full staff_review REFERENCE 2 (sites) AUTHORS Kennedy,I.M., Haddow,J.K. and Clements,J.B. TITLE A negative element in the human papillomavirus type 16 genome acts at the level of late mRNA stability JOURNAL J. Virol. 65, 2093-2097 (1991) STANDARD full staff_review REFERENCE 3 (base 4363) AUTHORS Baker,C.C. TITLE The genomes of the papillomaviruses. JOURNAL (in) O'Brien,S.J. (Ed.); Genetic Maps; Locus Maps of Complex Genomes: 1.134, Cold Spring Harbor Laboratory Press, Cold Spring Harbor (1993) STANDARD full staff_review REFERENCE 4 (base 3906) 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, 243-246 (1988) STANDARD full staff_review COMMENT In developing countries, cancer of the cervix is responsible for 24% of all cancers in women. In these areas, it is the most frequent female malignancy. In developed countries, it ranks behind cancers of the breast, lung, uterus, and ovaries and accounts for 7% of all female cancers. HPV-16 is most often found in lesions of the genital mucosa which may have a risk for malignant progression. Estimates indicate that HPV-16 has been recovered from about 50-60% of all invasive cervical cancers. Studies show that the predominance of HPV-16 in high-grade anogenital lesions and invasive cancers is evident also for the vulva, the penis, and the anus. HPV-16 has also been found in approximately 80% of the Bowenoid papulosis lesions (premalignant). In contrast to the extrachromosomal form of the viral genome found in skin carcinomas of EV patients, the viral genome of HPV16 is frequently found integrated into the cellular genome in genital tract cancers. The integration of the genome requires linearization of the genome which most often occurs in the E1/E2 region. This results in the inactivation of the E2 repressor of the E6 and E7 genes. With repression removed, the E6 and E7 genes are able to immortalize keratinocytes. The DNA of HPV-16 has been molecularly cloned from a genomic library of an invasive cervical carcinoma in bateriophage lambda. This sequence has been corrected as stated in [3] and [4]; at nt 4363 a substitution of a T for an A, and at nt 3906 an additional T, respectively. The sense strand is shown, with a numbering system matching the first 60 bp of HPV1a, HPV6b and BPV1. The designation of the early and late reading frames of HPV-16 is based solely upon homology comparison with HPV-6b and BPV-1. Two TATA boxes have been identified upstream from the E6 open reading frame, at bp 17 and 65, and another upstream from the L1 coding region, at bp 4289. A potential CAT box precedes the TATA boxes near the E6 region, at bp 7895. Polyadenylation signals can be found at the end of the early and late gene regions, at bp 4213 and 7260. Open reading frame E4 does not have a translation initiation codon, which is present in most other sequenced papilloma viruses. Also, the open reading frame for a possible E1 gene product, thought to be involved in DNA replication, seems to be interrupted. The author contends that an insertion of one nucleotide somewhere in the region between positions 1101 and 1168 would generate an E1 open reading frame of normal size. FEATURES Location/Qualifiers TATA_signal 17..23 TATA_signal 65..71 CDS 83..559 /note="E6 ORF from 65 to 559" /product="transforming protein" /gene="E6" /note="putative" /codon_start=1 /translation="MHQKRTAMFQDPQERPRKLPQLCTELQTTIHDIILECVYCKQQL LRREVYDFAFRDLCIVYRDGNPYAVCDKCLKFYSKISEYRHYCYSLYGTTLEQQYNKP LCDLLIRCINCQKPLCPEEKQRHLDKKQRFHNIRGRWTGRCMSCCRSSRTRRETQL" CDS 562..858 /note="E7 ORF from 544 to 858" /product="transforming protein" /gene="E7" /note="putative" /codon_start=1 /translation="MHGDTPTLHEYMLDLQPETTDLYCYEQLNDSSEEEDEIDGPAGQ AEPDRAHYNIVTFCCKCDSTLRLCVQSTHVDIRTLEDLLMGTLGIVCPICSQKP" CDS join(865..1140,1140..2813) /note="E1 interrupted ORF from 859 to 2813" /product="replication protein" /gene="E1" /note="putative" /codon_start=1 /translation="MADPAGTNGEEGTGCNGWFYVEAVVEKKTGDAISDDENENDSDT GEDLVDFIVNDNDYLTQAETETAHALFTAQEAKQHRDAVQVLKRKYLVSPLSDISGCV DNNISPRLKAICIEKQSRAAKRRLFESEDSGYGNTEVETQQMLQVEGRHETETPCSQY SGGSGGGCSQYSSGSGGEGVSERHTICQTPLTNILNVLKTSNAKAAMLAKFKELYGVS FSELVRPFKSNKSTCCDWCIAAFGLTPSIADSIKTLLQQYCLYLHIQSLACSWGMVVL LLVRYKCGKNRETIEKLLSKLLCVSPMCMMIEPPKLRSTAAALYWYKTGISNISEVYG DTPEWIQRQTVLQHSFNDCTFELSQMVQWAYDNDIVDDSEIAYKYAQLADTNSNASAF LKSNSQAKIVKDCATMCRHYKRAEKKQMSMSQWIKYRCDRVDDGGDWKQIVMFLRYQG VEFMSFLTALKRFLQGIPKKNCILLYGAANTGKSLFGMSLMKFLQGSVICFVNSKSHF WLQPLADAKIGMLDDATVPCWNYIDDNLRNALDGNLVSMDVKHRPLVQLKCPPLLITS NINAGTDSRWPYLHNRLVVFTFPNEFPFDENGNPVYELNDKNWKSFFSRTWSRLSLHE DEDKENDGDSLPTFKCVSGQNTNTL" CDS 2755..3852 /note="E2 ORF from 2725 to 3852" /product="regulatory protein" /gene="E2" /note="putative" /codon_start=1 /translation="METLCQRLNVCQDKILTHYENDSTDLRDHIDYWKHMRLECAIYY KAREMGFKHINHQVVPTLAVSKNKALQAIELQLTLETIYNSQYSNEKWTLQDVSLEVY LTAPTGCIKKHGYTVEVQFDGDICNTMHYTNWTHIYICEEASVTVVEGQVDYYGLYYV HEGIRTYFVQFKDDAEKYSKNKVWEVHAGGQVILCPTSVFSSNEVSSPEIIRQHLANH PAATHTKAVALGTEETQTTIQRPRSEPDTGNPCHTTKLLHRDSVDSAPILTAFNSSHK GRINCNSNTTPIVHLKGDANTLKCLRYRFKKHCTLYTAVSSTWHWTGHNVKHKSAIVT LTYDSEWQRDQFLSQVKIPKTITVSTGFMSI" CDS <3332..3619 /note="E4 ORF from 3332 to 3619" /gene="E4" /note="putative" /codon_start=1 /translation="YYVLHLCLAATKYPLLKLLGSTWPTTPPRPIPKPSPWAPKKHRR LSSDQDQSQTPETPATPLSCCTETQWTVLQSSLHLTAHTKDGLTVIVTLHP" CDS 3849..4100 /note="E5 ORF from 3804 to 4100" /gene="E5" /note="putative" /codon_start=1 /translation="MTNLDTASTTLLACFLLCFCVLLCVCLLIRPLLLSVSTYTSLII LVLLLWITAASAFRCFIVYIIFVYIPLFLIHTHARFLIT" polyA_signal 4214..4219 /note="putative" CDS 4236..5657 /note="L2 ORF from 4134 to 5657" /product="minor capsid protein" /gene="L2" /note="putative" /codon_start=1 /translation="MRHKRSAKRTKRASATQLYKTCKQAGTCPPDIIPKVEGKTIAEQ ILQYGSMGVFFGGLGIGTGSGTGGRTGYIPLGTRPPTATDTLAPVRPPLTVDPVGPSD PSIVSLVEETSFIDAGAPTSVPSIPPDVSGFSITTSTDTTPAILDINNTVTTVTTHNN PTFTDPSVLQPPTPAETGGHFTLSSSTISTHNYEEIPMDTFIVSTNPNTVTSSTPIPG SRPVARLGLYSRTTQQVKVVDPAFVTTPTKLITYDNPAYEGIDVDNTLYFSSNDNSIN IAPDPDFLDIVALHRPALTSRRTGIRYSRIGNKQTLRTRSGKSIGAKVHYYYDLSTID PAEEIELQTITPSTYTTTSHAASPTSINNGLYDIYADDFITDTSTTPVPSVPSTSLSG YIPANTTIPFGGAYNIPLVSGPDIPINITDQAPSLIPIVPGSPQYTIIADAGDFYLHP SYYMLRKRRKRLPYFFSDVSLAA" TATA_signal 4290..4296 CDS 5560..7155 /note="L1 ORF from 5527 to 7155" /product="major capsid protein" /gene="L1" /note="putative" /codon_start=1 /translation="MQVTFIYILVITCYENDVNVYHIFFQMSLWLPSEATVYLPPVPV SKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNNNKILVPKVSGLQYRVFRIH LPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLGVGISGHPLLNKLDDTENASA YAANAGVDNRECISMDYKQTQLCLIGCKPPIGEHWGKGSPCTNVAVNPGDCPPLELIN TVIQDGDMVHTGFGAMDFTTLQANKSEVPLDICTSICKYPDYIKMVSEPYGDSLFFYL RREQMFVRHLFNRAGTVGENVPDDLYIKGSGSTANLASSNYFPTPSGSMVTSDAQIFN KPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMSLCAAISTSETTYKNTNFKEYLRH GEEYDLQFIFQLCKITLTADVMTYIHSMNSTILEDWNFGLQPPPGGTLEDTYRFVTQA IACQKHTPPAPKEDDPLKKYTFWEVNLKEKFSADLDQFPLGRKFLLQAGLKAKPKFTL GKRKATPTTSSTSTTAKRKKRKL" polyA_signal 7261..7266 source 1..7905 /organism="Human papillomavirus type 16" BASE COUNT 2601 a 1377 c 1509 g 2417 t ORIGIN Unreported. 1 actacaataa ttcatgtata aaactaaggg cgtaaccgaa atcggttgaa ccgaaaccgg 61 ttagtataaa agcagacatt ttatgcacca aaagagaact gcaatgtttc aggacccaca 121 ggagcgaccc agaaagttac cacagttatg cacagagctg caaacaacta tacatgatat 181 aatattagaa tgtgtgtact gcaagcaaca gttactgcga cgtgaggtat atgactttgc 241 ttttcgggat ttatgcatag tatatagaga tgggaatcca tatgctgtat gtgataaatg 301 tttaaagttt tattctaaaa ttagtgagta tagacattat tgttatagtt tgtatggaac 361 aacattagaa cagcaataca acaaaccgtt gtgtgatttg ttaattaggt gtattaactg 421 tcaaaagcca ctgtgtcctg aagaaaagca aagacatctg gacaaaaagc aaagattcca 481 taatataagg ggtcggtgga ccggtcgatg tatgtcttgt tgcagatcat caagaacacg 541 tagagaaacc cagctgtaat catgcatgga gatacaccta cattgcatga atatatgtta 601 gatttgcaac cagagacaac tgatctctac tgttatgagc aattaaatga cagctcagag 661 gaggaggatg aaatagatgg tccagctgga caagcagaac cggacagagc ccattacaat 721 attgtaacct tttgttgcaa gtgtgactct acgcttcggt tgtgcgtaca aagcacacac 781 gtagacattc gtactttgga agacctgtta atgggcacac taggaattgt gtgccccatc 841 tgttctcaga aaccataatc taccatggct gatcctgcag gtaccaatgg ggaagagggt 901 acgggatgta atggatggtt ttatgtagag gctgtagtgg aaaaaaaaac aggggatgct 961 atatcagatg acgagaacga aaatgacagt gatacaggtg aagatttggt agattttata 1021 gtaaatgata atgattattt aacacaggca gaaacagaga cagcacatgc gttgtttact 1081 gcacaggaag caaaacaaca tagagatgca gtacaggttc taaaacgaaa gtatttggta 1141 gtccacttag tgatattagt ggatgtgtag acaataatat tagtcctaga ttaaaagcta 1201 tatgtataga aaaacaaagt agagctgcaa aaaggagatt atttgaaagc gaagacagcg 1261 ggtatggcaa tactgaagtg gaaactcagc agatgttaca ggtagaaggg cgccatgaga 1321 ctgaaacacc atgtagtcag tatagtggtg gaagtggggg tggttgcagt cagtacagta 1381 gtggaagtgg gggagagggt gttagtgaaa gacacactat atgccaaaca ccacttacaa 1441 atattttaaa tgtactaaaa actagtaatg caaaggcagc aatgttagca aaatttaaag 1501 agttatacgg ggtgagtttt tcagaattag taagaccatt taaaagtaat aaatcaacgt 1561 gttgcgattg gtgtattgct gcatttggac ttacacccag tatagctgac agtataaaaa 1621 cactattaca acaatattgt ttatatttac acattcaaag tttagcatgt tcatggggaa 1681 tggttgtgtt actattagta agatataaat gtggaaaaaa tagagaaaca attgaaaaat 1741 tgctgtctaa actattatgt gtgtctccaa tgtgtatgat gatagagcct ccaaaattgc 1801 gtagtacagc agcagcatta tattggtata aaacaggtat atcaaatatt agtgaagtgt 1861 atggagacac gccagaatgg atacaaagac aaacagtatt acaacatagt tttaatgatt 1921 gtacatttga attatcacag atggtacaat gggcctacga taatgacata gtagacgata 1981 gtgaaattgc atataaatat gcacaattgg cagacactaa tagtaatgca agtgcctttc 2041 taaaaagtaa ttcacaggca aaaattgtaa aggattgtgc aacaatgtgt agacattata 2101 aacgagcaga aaaaaaacaa atgagtatga gtcaatggat aaaatataga tgtgataggg 2161 tagatgatgg aggtgattgg aagcaaattg ttatgttttt aaggtatcaa ggtgtagagt 2221 ttatgtcatt tttaactgca ttaaaaagat ttttgcaagg catacctaaa aaaaattgca 2281 tattactata tggtgcagct aacacaggta aatcattatt tggtatgagt ttaatgaaat 2341 ttctgcaagg gtctgtaata tgttttgtaa attctaaaag ccatttttgg ttacaaccat 2401 tagcagatgc caaaataggt atgttagatg atgctacagt gccctgttgg aactacatag 2461 atgacaattt aagaaatgca ttggatggaa atttagtttc tatggatgta aagcatagac 2521 cattggtaca actaaaatgc cctccattat taattacatc taacattaat gctggtacag 2581 attctaggtg gccttattta cataatagat tggtggtgtt tacatttcct aatgagtttc 2641 catttgacga aaacggaaat ccagtgtatg agcttaatga taagaactgg aaatcctttt 2701 tctcaaggac gtggtccaga ttaagtttgc acgaggacga ggacaaggaa aacgatggag 2761 actctttgcc aacgtttaaa tgtgtgtcag gacaaaatac taacacatta tgaaaatgat 2821 agtacagacc tacgtgacca tatagactat tggaaacaca tgcgcctaga atgtgctatt 2881 tattacaagg ccagagaaat gggatttaaa catattaacc accaagtggt gccaacactg 2941 gctgtatcaa agaataaagc attacaagca attgaactgc aactaacgtt agaaacaata 3001 tataactcac aatatagtaa tgaaaagtgg acattacaag acgttagcct tgaagtgtat 3061 ttaactgcac caacaggatg tataaaaaaa catggatata cagtggaagt gcagtttgat 3121 ggagacatat gcaatacaat gcattataca aactggacac atatatatat ttgtgaagaa 3181 gcatcagtaa ctgtggtaga gggtcaagtt gactattatg gtttatatta tgttcatgaa 3241 ggaatacgaa catattttgt gcagtttaaa gatgatgcag aaaaatatag taaaaataaa 3301 gtatgggaag ttcatgcggg tggtcaggta atattatgtc ctacatctgt gtttagcagc 3361 aacgaagtat cctctcctga aattattagg cagcacttgg ccaaccaccc cgccgcgacc 3421 cataccaaag ccgtcgcctt gggcaccgaa gaaacacaga cgactatcca gcgaccaaga 3481 tcagagccag acaccggaaa cccctgccac accactaagt tgttgcacag agactcagtg 3541 gacagtgctc caatcctcac tgcatttaac agctcacaca aaggacggat taactgtaat 3601 agtaacacta cacccatagt acatttaaaa ggtgatgcta atactttaaa atgtttaaga 3661 tatagattta aaaagcattg tacattgtat actgcagtgt cgtctacatg gcattggaca 3721 ggacataatg taaaacataa aagtgcaatt gttacactta catatgatag tgaatggcaa 3781 cgtgaccaat ttttgtctca agttaaaata ccaaaaacta ttacagtgtc tactggattt 3841 atgtctatat gacaaatctt gatactgcat ccacaacatt actggcgtgc tttttgcttt 3901 gcttttgtgt gcttttgtgt gtctgcctat taatacgtcc gctgcttttg tctgtgtcta 3961 catacacatc attaataata ttggtattac tattgtggat aacagcagcc tctgcgttta 4021 ggtgttttat tgtatatatt atatttgttt atataccatt atttttaata catacacatg 4081 cacgcttttt aattacataa tgtatatgta cataatgtaa ttgttacata taattgttgt 4141 ataccataac ttactatttt ttctttttta ttttcatata taattttttt ttttgtttgt 4201 ttgtttgttt tttaataaac tgttattact taacaatgcg acacaaacgt tctgcaaaac 4261 gcacaaaacg tgcatcggct acccaacttt ataaaacatg caaacaggca ggtacatgtc 4321 cacctgacat tatacctaag gttgaaggca aaactattgc tgaacaaata ttacaatatg 4381 gaagtatggg tgtatttttt ggtgggttag gaattggaac agggtcgggt acaggcggac 4441 gcactgggta tattccattg ggaacaaggc ctcccacagc tacagataca cttgctcctg 4501 taagaccccc tttaacagta gatcctgtgg gcccttctga tccttctata gtttctttag 4561 tggaagaaac tagttttatt gatgctggtg caccaacatc tgtaccttcc attcccccag 4621 atgtatcagg atttagtatt actacttcaa ctgataccac acctgctata ttagatatta 4681 ataatactgt tactactgtt actacacata ataatcccac tttcactgac ccatctgtat 4741 tgcagcctcc aacacctgca gaaactggag ggcattttac actttcatca tccactatta 4801 gtacacataa ttatgaagaa attcctatgg atacatttat tgttagcaca aaccctaaca 4861 cagtaactag tagcacaccc ataccagggt ctcgcccagt ggcacgccta ggattatata 4921 gtcgcacaac acaacaggtt aaagttgtag accctgcttt tgtaaccact cccactaaac 4981 ttattacata tgataatcct gcatatgaag gtatagatgt ggataataca ttatattttt 5041 ctagtaatga taatagtatt aatatagctc cagatcctga ctttttggat atagttgctt 5101 tacataggcc agcattaacc tctaggcgta ctggcattag gtacagtaga attggtaata 5161 aacaaacact acgtactcgt agtggaaaat ctataggtgc taaggtacat tattattatg 5221 atttaagtac tattgatcct gcagaagaaa tagaattaca aactataaca ccttctacat 5281 atactaccac ttcacatgca gcctcaccta cttctattaa taatggatta tatgatattt 5341 atgcagatga ctttattaca gatacttcta caaccccggt accatctgta ccctctacat 5401 ctttatcagg ttatattcct gcaaatacaa caattccttt tggtggtgca tacaatattc 5461 ctttagtatc aggtcctgat atacccatta atataactga ccaagctcct tcattaattc 5521 ctatagttcc agggtctcca caatatacaa ttattgctga tgcaggtgac ttttatttac 5581 atcctagtta ttacatgtta cgaaaacgac gtaaacgttt accatatttt ttttcagatg 5641 tctctttggc tgcctagtga ggccactgtc tacttgcctc ctgtcccagt atctaaggtt 5701 gtaagcacgg atgaatatgt tgcacgcaca aacatatatt atcatgcagg aacatccaga 5761 ctacttgcag ttggacatcc ctattttcct attaaaaaac ctaacaataa caaaatatta 5821 gttcctaaag tatcaggatt acaatacagg gtatttagaa tacatttacc tgaccccaat 5881 aagtttggtt ttcctgacac ctcattttat aatccagata cacagcggct ggtttgggcc 5941 tgtgtaggtg ttgaggtagg tcgtggtcag ccattaggtg tgggcattag tggccatcct 6001 ttattaaata aattggatga cacagaaaat gctagtgctt atgcagcaaa tgcaggtgtg 6061 gataatagag aatgtatatc tatggattac aaacaaacac aattgtgttt aattggttgc 6121 aaaccaccta taggggaaca ctggggcaaa ggatccccat gtaccaatgt tgcagtaaat 6181 ccaggtgatt gtccaccatt agagttaata aacacagtta ttcaggatgg tgatatggtt 6241 catactggct ttggtgctat ggactttact acattacagg ctaacaaaag tgaagttcca 6301 ctggatattt gtacatctat ttgcaaatat ccagattata ttaaaatggt gtcagaacca 6361 tatggcgaca gcttattttt ttatttacga agggaacaaa tgtttgttag acatttattt 6421 aatagggctg gtactgttgg tgaaaatgta ccagacgatt tatacattaa aggctctggg 6481 tctactgcaa atttagccag ttcaaattat tttcctacac ctagtggttc tatggttacc 6541 tctgatgccc aaatattcaa taaaccttat tggttacaac gagcacaggg ccacaataat 6601 ggcatttgtt ggggtaacca actatttgtt actgttgttg atactacacg cagtacaaat 6661 atgtcattat gtgctgccat atctacttca gaaactacat ataaaaatac taactttaag 6721 gagtacctac gacatgggga ggaatatgat ttacagttta tttttcaact gtgcaaaata 6781 accttaactg cagacgttat gacatacata cattctatga attccactat tttggaggac 6841 tggaattttg gtctacaacc tcccccagga ggcacactag aagatactta taggtttgta 6901 acccaggcaa ttgcttgtca aaaacataca cctccagcac ctaaagaaga tgatcccctt 6961 aaaaaataca ctttttggga agtaaattta aaggaaaagt tttctgcaga cctagatcag 7021 tttcctttag gacgcaaatt tttactacaa gcaggattga aggccaaacc aaaatttaca 7081 ttaggaaaac gaaaagctac acccaccacc tcatctacct ctacaactgc taaacgcaaa 7141 aaacgtaagc tgtaagtatt gtatgtatgt tgaattagtg ttgtttgttg tgtatatgtt 7201 tgtatgtgct tgtatgtgct tgtaaatatt aagttgtatg tgtgtttgta tgtatggtat 7261 aataaacacg tgtgtatgtg tttttaaatg cttgtgtaac tattgtgtca tgcaacataa 7321 ataaacttat tgtttcaaca cctactaatt gtgttgtggt tattcattgt atataaacta 7381 tatttgctac atcctgtttt tgttttatat atactatatt ttgtagcgcc aggcccattt 7441 tgtagcttca accgaattcg gttgcatgct ttttggcaca aaatgtgttt ttttaaatag 7501 ttctatgtca gcaactatgg tttaaacttg tacgtttcct gcttgccatg cgtgccaaat 7561 ccctgttttc ctgacctgca ctgcttgcca accattccat tgttttttac actgcactat 7621 gtgcaactac tgaatcacta tgtacattgt gtcatataaa ataaatcact atgcgccaac 7681 gccttacata ccgctgttag gcacatattt ttggcttgtt ttaactaacc taattgcata 7741 tttggcataa ggtttaaact tctaaggcca actaaatgtc accctagttc atacatgaac 7801 tgtgtaaagg ttagtcatac attgttcatt tgtaaaactg cacatgggtg tgtgcaaacc 7861 gattttgggt tacacattta caagcaactt atataataat actaa