LOCUS HIVHXB2CG 9719 bp RNA linear VRL 21-OCT-2002 DEFINITION Human immunodeficiency virus type 1 (HXB2), complete genome; HIV1/HTLV-III/LAV reference genome. ACCESSION K03455 M38432 VERSION K03455.1 KEYWORDS TAR protein; acquired immune deficiency syndrome; complete genome; env protein; gag protein; long terminal repeat (LTR); pol protein; polyprotein; proviral gene; reverse transcriptase; transactivator. SOURCE Human immunodeficiency virus 1 (HIV-1) ORGANISM Human immunodeficiency virus 1 Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes; Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus. REFERENCE 1 (sites) AUTHORS van Beveren,C.P., Coffin,J. and Hughes,S. TITLE Appendix B: HTLV-3/LAV genome JOURNAL (in) Weiss,R.L., Teich,N., Varmus,H. and Coffin,J. (Eds.); RNA TUMOR VIRUSES, SECOND EDITION, 2, Vol. 2: 1102-1123; Cold Spring Harbor Laboratory, Cold Spring Harbor (1985) REFERENCE 2 (bases 493 to 674; 9577 to 9718) AUTHORS Ratner,L., Haseltine,W., Patarca,R., Livak,K.J., Starcich,B., Josephs,S.F., Doran,E.R., Rafalski,J.A., Whitehorn,E.A., Baumeister,K., Ivanoff,L., Petteway,S.R. Jr., Pearson,M.L., Lautenberger,J.A., Papas,T.S., Ghrayeb,J., Chang,N.T., Gallo,R.C. and Wong-Staal,F. TITLE Complete nucleotide sequence of the AIDS virus, HTLV-III JOURNAL Nature 313 (6000), 277-284 (1985) PUBMED 2578615 REFERENCE 3 (bases 1 to 653) AUTHORS Starcich,B., Ratner,L., Josephs,S.F., Okamoto,T., Gallo,R.C. and Wong-Staal,F. TITLE Characterization of long terminal repeat sequences of HTLV-III JOURNAL Science 227 (4686), 538-540 (1985) PUBMED 2981438 REFERENCE 4 (sites) AUTHORS Allan,J.S., Coligan,J.E., Barin,F., McLane,M.F., Sodroski,J.G., Rosen,C.A., Haseltine,W.A., Lee,T.H. and Essex,M. TITLE Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III JOURNAL Science 228 (4703), 1091-1094 (1985) PUBMED 2986290 REFERENCE 5 (sites) AUTHORS Rosen,C.A., Sodroski,J.G. and Haseltine,W.A. TITLE The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat JOURNAL Cell 41 (3), 813-823 (1985) PUBMED 2988790 REFERENCE 6 (sites) AUTHORS Arya,S.K., Guo,C., Josephs,S.F. and Wong-Staal,F. TITLE Trans-activator gene of human T-lymphotropic virus type III (HTLV-III) JOURNAL Science 229 (4708), 69-73 (1985) PUBMED 2990040 REFERENCE 7 (sites) AUTHORS Sodroski,J., Patarca,R., Rosen,C., Wong-Staal,F. and Haseltine,W. TITLE Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III JOURNAL Science 229 (4708), 74-77 (1985) PUBMED 2990041 REFERENCE 8 (sites) AUTHORS Rabson,A.B., Daugherty,D.F., Venkatesan,S., Boulukos,K.E., Benn,S.I., Folks,T.M., Feorino,P. and Martin,M.A. TITLE Transcription of novel open reading frames of AIDS retrovirus during infection of lymphocytes JOURNAL Science 229 (4720), 1388-1390 (1985) PUBMED 2994220 REFERENCE 9 (sites) AUTHORS Allan,J.S., Coligan,J.E., Lee,T.H., McLane,M.F., Kanki,P.J., Groopman,J.E. and Essex,M. TITLE A new HTLV-III/LAV encoded antigen detected by antibodies from AIDS patients JOURNAL Science 230 (4727), 810-813 (1985) PUBMED 2997921 REFERENCE 10 (sites) AUTHORS Rosen,C.A., Sodroski,J.G., Goh,W.C., Dayton,A.I., Lippke,J. and Haseltine,W.A. TITLE Post-transcriptional regulation accounts for the trans-activation of the human T-lymphotropic virus type III JOURNAL Nature 319 (6054), 555-559 (1986) PUBMED 3003584 REFERENCE 11 (sites) AUTHORS di Marzo Veronese,F., Copeland,T.D., DeVico,A.L., Rahman,R., Oroszlan,S., Gallo,R.C. and Sarngadharan,M.G. TITLE Characterization of highly immunogenic p66/p51 as the reverse transcriptase of HTLV-III/LAV JOURNAL Science 231 (4743), 1289-1291 (1986) PUBMED 2418504 REFERENCE 12 (sites) AUTHORS Kramer,R.A., Schaber,M.D., Skalka,A.M., Ganguly,K., Wong-Staal,F. and Reddy,E.P. TITLE HTLV-III gag protein is processed in yeast cells by the virus pol-protease JOURNAL Science 231 (4745), 1580-1584 (1986) PUBMED 2420008 REFERENCE 13 (sites) AUTHORS Dayton,A.I., Sodroski,J.G., Rosen,C.A., Goh,W.C. and Haseltine,W.A. TITLE The trans-activator gene of the human T cell lymphotropic virus type III is required for replication JOURNAL Cell 44 (6), 941-947 (1986) PUBMED 2420471 REFERENCE 14 (sites) AUTHORS Lee,T.H., Coligan,J.E., Allan,J.S., McLane,M.F., Groopman,J.E. and Essex,M. TITLE A new HTLV-III/LAV protein encoded by a gene found in cytopathic retroviruses JOURNAL Science 231 (4745), 1546-1549 (1986) PUBMED 3006243 REFERENCE 15 (sites) AUTHORS Sodroski,J., Goh,W.C., Rosen,C., Tartar,A., Portetelle,D., Burny,A. and Haseltine,W. TITLE Replicative and cytopathic potential of HTLV-III/LAV with sor gene deletions JOURNAL Science 231 (4745), 1549-1553 (1986) PUBMED 3006244 REFERENCE 16 (sites) AUTHORS Kan,N.C., Franchini,G., Wong-Staal,F., DuBois,G.C., Robey,W.G., Lautenberger,J.A. and Papas,T.S. TITLE Identification of HTLV-III/LAV sor gene product and detection of antibodies in human sera JOURNAL Science 231 (4745), 1553-1555 (1986) PUBMED 3006245 REFERENCE 17 (sites) AUTHORS Arya,S.K. and Gallo,R.C. TITLE Three novel genes of human T-lymphotropic virus type III: immune reactivity of their products with sera from acquired immune deficiency syndrome patients JOURNAL Proc. Natl. Acad. Sci. U.S.A. 83 (7), 2209-2213 (1986) PUBMED 3008154 REFERENCE 18 (sites) AUTHORS Jones,K.A., Kadonaga,J.T., Luciw,P.A. and Tjian,R. TITLE Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1 JOURNAL Science 232 (4751), 755-759 (1986) PUBMED 3008338 REFERENCE 19 (sites) AUTHORS Sodroski,J., Goh,W.C., Rosen,C., Dayton,A., Terwilliger,E. and Haseltine,W. TITLE A second post-transcriptional trans-activator gene required for HTLV-III replication JOURNAL Nature 321 (6068), 412-417 (1986) PUBMED 3012355 REFERENCE 20 (sites) AUTHORS Starcich,B.R., Hahn,B.H., Shaw,G.M., McNeely,P.D., Modrow,S., Wolf,H., Parks,E.S., Parks,W.P., Josephs,S.F., Gallo,R.C. and Wong-Staal,F. TITLE Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS JOURNAL Cell 45 (5), 637-648 (1986) PUBMED 2423250 REFERENCE 21 (sites) AUTHORS Willey,R.L., Rutledge,R.A., Dias,S., Folks,T., Theodore,T., Buckler,C.E. and Martin,M.A. TITLE Identification of conserved and divergent domains within the envelope gene of the acquired immunodeficiency syndrome retrovirus JOURNAL Proc. Natl. Acad. Sci. U.S.A. 83 (14), 5038-5042 (1986) PUBMED 3014529 REFERENCE 22 (bases 8761 to 9060) AUTHORS Fisher,A.G., Ratner,L., Mitsuya,H., Marselle,L.M., Harper,M.E., Broder,S., Gallo,R.C. and Wong-Staal,F. TITLE Infectious mutants of HTLV-III with changes in the 3' region and markedly reduced cytopathic effects JOURNAL Science 233 (4764), 655-659 (1986) PUBMED 3014663 REFERENCE 23 (sites) AUTHORS Feinberg,M.B., Jarrett,R.F., Aldovini,A., Gallo,R.C. and Wong-Staal,F. TITLE HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA JOURNAL Cell 46 (6), 807-817 (1986) PUBMED 3638988 REFERENCE 24 (sites) AUTHORS Lightfoote,M.M., Coligan,J.E., Folks,T.M., Fauci,A.S., Martin,M.A. and Venkatesan,S. TITLE Structural characterization of reverse transcriptase and endonuclease polypeptides of the acquired immunodeficiency syndrome retrovirus JOURNAL J. Virol. 60 (2), 771-775 (1986) PUBMED 2430111 REFERENCE 25 (sites) AUTHORS Terwilliger,E., Sodroski,J.G., Rosen,C.A. and Haseltine,W.A. TITLE Effects of mutations within the 3' orf open reading frame region of human T-cell lymphotropic virus type III (HTLV-III/LAV) on replication and cytopathogenicity JOURNAL J. Virol. 60 (2), 754-760 (1986) PUBMED 3490583 REFERENCE 26 (sites) AUTHORS Wright,C.M., Felber,B.K., Paskalis,H. and Pavlakis,G.N. TITLE Expression and characterization of the trans-activator of HTLV-III/LAV virus JOURNAL Science 234 (4779), 988-992 (1986) PUBMED 3490693 REFERENCE 27 (sites) AUTHORS Patarca,R., Heath,C., Goldenberg,G.J., Rosen,C.A., Sodroski,J.G., Haseltine,W.A. and Hansen,U.M. TITLE Transcription directed by the HIV long terminal repeat in vitro JOURNAL AIDS Res. Hum. Retroviruses 3 (1), 41-55 (1987) PUBMED 3040054 REFERENCE 28 (bases 1 to 9635) AUTHORS Ratner,L., Fisher,A., Jagodzinski,L.L., Mitsuya,H., Liou,R.S., Gallo,R.C. and Wong-Staal,F. TITLE Complete nucleotide sequences of functional clones of the AIDS virus JOURNAL AIDS Res. Hum. Retroviruses 3 (1), 57-69 (1987) PUBMED 3040055 REFERENCE 29 (sites) AUTHORS Wong-Staal,F., Chanda,P.K. and Ghrayeb,J. TITLE Human immunodeficiency virus: the eighth gene JOURNAL AIDS Res. Hum. Retroviruses 3 (1), 33-39 (1987) PUBMED 3476127 REFERENCE 30 (sites) AUTHORS Modrow,S., Hahn,B.H., Shaw,G.M., Gallo,R.C., Wong-Staal,F. and Wolf,H. TITLE Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions JOURNAL J. Virol. 61 (2), 570-578 (1987) PUBMED 2433466 REFERENCE 31 (sites) AUTHORS Goh,W.C., Sodroski,J.G., Rosen,C.A. and Haseltine,W.A. TITLE Expression of the art gene protein of human T-lymphotropic virus type III (HTLV-III/LAV) in bacteria JOURNAL J. Virol. 61 (2), 633-637 (1987) PUBMED 3543401 REFERENCE 32 (sites) AUTHORS Muesing,M.A., Smith,D.H. and Capon,D.J. TITLE Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein JOURNAL Cell 48 (4), 691-701 (1987) PUBMED 3643816 REFERENCE 33 (sites) AUTHORS Nabel,G. and Baltimore,D. TITLE An inducible transcription factor activates expression of human immunodeficiency virus in T cells JOURNAL Nature 326 (6114), 711-713 (1987) PUBMED 3031512 REMARK Erratum:[Nature 1990 Mar 8;344(6262):178] REFERENCE 34 (sites) AUTHORS Fisher,A.G., Ensoli,B., Ivanoff,L., Chamberlain,M., Petteway,S., Ratner,L., Gallo,R.C. and Wong-Staal,F. TITLE The sor gene of HIV-1 is required for efficient virus transmission in vitro JOURNAL Science 237 (4817), 888-893 (1987) PUBMED 3497453 REFERENCE 35 (bases 6225 to 8795) AUTHORS Reitz,M.S. Jr., Wilson,C., Naugle,C., Gallo,R.C. and Robert-Guroff,M. TITLE Generation of a neutralization-resistant variant of HIV-1 is due to selection for a point mutation in the envelope gene JOURNAL Cell 54 (1), 57-63 (1988) PUBMED 2838179 REFERENCE 36 (bases 790 to 2292) AUTHORS Pal,R., Reitz,M.S. Jr., Tschachler,E., Gallo,R.C., Sarngadharan,M.G. and Veronese,F.D. TITLE Myristoylation of gag proteins of HIV-1 plays an important role in virus assembly JOURNAL AIDS Res. Hum. Retroviruses 6 (6), 721-730 (1990) PUBMED 2194551 REFERENCE 37 (sites) AUTHORS Ido,E., Han,H.P., Kezdy,F.J. and Tang,J. TITLE Kinetic studies of human immunodeficiency virus type 1 protease and its active-site hydrogen bond mutant A28S JOURNAL J. Biol. Chem. 266 (36), 24359-24366 (1991) PUBMED 1761538 COMMENT On Mar 25, 1997 this sequence version replaced gi:327742. [6] sites; tat mRNA and other transcript boundaries. [7] sites; tat mRNA. [8] sites; mRNA splice sites. [9] sites; 27K antigen cds. [5] sites; gp160 and gp120 coding sequences. [1] sites; regulatory sequences in the LTR. [(in) Weiss,R., Teich,N., Varmus,H. and Coffin,J. (Eds.);RNA Tumor Viruses, Secon] review; bases 1 to 9718. [15] sites; trans-activator function and TAR sequence. [19] sites; pol coding sequence. [22] sites; 23K sor gene product. [23] sites; pol NH2-terminal region. [20] sites; sor 23K protein. [21] sites; sor 23K protein. [24] sites; Sp1 binding sites in the promoter region. [17] sites; acceptor and donor splice sites for tat and 27K. [10] sites; deletion mutants in the tat gene. [18] sites; env gene conserved/varable regions; separate entries. [16] sites; trs cds boundaries. [12] sites; trs cds boundaries. [11] sites; env gene conserved/variable regions; separate entries. [26] sites; tar or transactivator target. [13] sites; 3' orf mutations. [14] sites; pol p34 terminus. [31] sites; promoter, TAR, tat-III mutants. [32] sites; envelope protein epitopes. [33] sites; trs/art protein. [34] sites; inducible enhancer element. [27] revises [30]. [29] sites; long terminal repeat. [28] sites; R orf. [35] sites; sor. Sequence for [25] kindly provided in computer-readable form by L.Ratner, 19-AUG-1986. The HXB2 sequence is being used as a reference genome for all the HIV entries because it has been derived from a demonstrably infectious clone. Hence not all of the 'sites' references above were concerned with this isolate. FEATURES Location/Qualifiers source 1..9719 /organism="Human immunodeficiency virus 1" /proviral /mol_type="genomic RNA" /isolate="HXB2" /db_xref="taxon:11676" /note="HTLV-III/LAV" repeat_region 1..634 /note="5' LTR" /rpt_type=long_terminal_repeat repeat_region 454..551 /note="R repeat 5' copy" mRNA 455..9635 /product="HXB2 genomic mRNA" prim_transcript 455..9635 /note="tat, trs, 27K subgenomic mRNA" intron 744..5777 /note="tat, trs, 27K mRNA intron 1" CDS 790..2292 /note="gag polyprotein" /codon_start=1 /protein_id="AAB50258.1" /translation="MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERF AVNPGLLETSEGCRQILGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALD KIEEEQNKSKKKAQQAAADTGHSNQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVE EKAFSPEVIPMFSALSEGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPV HAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRM YSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQEVKNWMTETLLVQNANPDCKTIL KALGPAATLEEMMTACQGVGGPGHKARVLAEAMSQVTNSATIMMQRGNFRNQRKIVKC FNCGKEGHTARNCRAPRKKGCWKCGKEGHQMKDCTERQANFLGKIWPSYKGRPGNFLQ SRPEPTAPPEESFRSGVETTTPPQKQEPIDKELYPLTSLRSLFGNDPSSQ" CDS 2358..5096 /note="pol polyprotein (NH2-terminus uncertain)" /codon_start=1 /protein_id="AAB50259.1" /translation="MSLPGRWKPKMIGGIGGFIKVRQYDQILIEICGHKAIGTVLVGP TPVNIIGRNLLTQIGCTLNFPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEIC TEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPH PAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWK GSPAIFQSSMTKILEPFRKQNPDIVIYQYMDDLYVGSDLEIGQHRTKIEELRQHLLRW GLTTPDKKHQKEPPFLWMGYELHPDKWTVQPIVLPEKDSWTVNDIQKLVGKLNWASQI YPGIKVRQLCKLLRGTKALTEVIPLTEEAELELAENREILKEPVHGVYYDPSKDLIAE IQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAHTNDVKQLTEAVQKITTESIVIWGKT PKFKLPIQKETWETWWTEYWQATWIPEWEFVNTPPLVKLWYQLEKEPIVGAETFYVDG AANRETKLGKAGYVTNRGRQKVVTLTDTTNQKTELQAIYLALQDSGLEVNIVTDSQYA LGIIQAQPDQSESELVNQIIEQLIKKEKVYLAWVPAHKGIGGNEQVDKLVSAGIRKVL FLDGIDKAQDEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSP GIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTIHTD NGSNFTGATVRAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKT AVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDSRN PLWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED" CDS 5041..5619 /note="sor 23K protein" /codon_start=1 /protein_id="AAB50260.1" /translation="MENRWQVMIVWQVDRMRIRTWKSLVKHHMYVSGKARGWFYRHHY ESPHPRISSEVHIPLGDARLVITTYWGLHTGERDWHLGQGVSIEWRKKRYSTQVDPEL ADQLIHLYYFDCFSDSAIRKALLGHIVSPRCEYQAGHNKVGSLQYLALAALITPKKIK PPLPSVTKLTEDRWNKPQKTKGHRGSHTMNGH" CDS 5559..5795 /note="R (ORF) protein" /codon_start=1 /protein_id="AAB50261.1" /translation="MEQAPEDQGPQREPHNEWTLELLEELKNEAVRHFPRIWLHGLGQ HIYETYGDTWAGVEAIIRILQQLLFIHFQNWVST" CDS join(5831..6045,8379..8424) /note="tat protein" /codon_start=1 /protein_id="AAB50256.1" /translation="MEPVDPRLEPWKHPGSQPKTACTNCYCKKCCFHCQVCFITKALG ISYGRKKRRQRRRAHQNSQTHQASLSKQPTSQPRGDPTGPKE" exon 5831..6045 /note="tat protein, first expressed exon" /number=2 CDS join(5970..6045,8379..8653) /note="trs protein" /codon_start=1 /protein_id="AAB50257.1" /translation="MAGRSGDSDEELIRTVRLIKLLYQSNPPPNPEGTRQARRNRRRR WRERQRQIHSISERILGTYLGRSAEPVPLQLPPLERLTLDCNEDCGTSGTQGVGSPQI LVESPTVLESGTKE" exon 5970..6045 /note="trs protein, first expressed exon" /number=2 intron 6046..8378 /note="tat, trs, 27K mRNA intron 2" CDS 6225..8795 /note="envelope polyprotein" /codon_start=1 /protein_id="AAB50262.1" /translation="MRVKEKYQHLWRWGWRWGTMLLGMLMICSATEKLWVTVYYGVPV WKEATTTLFCASDAKAYDTEVHNVWATHACVPTDPNPQEVVLVNVTENFNMWKNDMVE QMHEDIISLWDQSLKPCVKLTPLCVSLKCTDLKNDTNTNSSSGRMIMEKGEIKNCSFN ISTSIRGKVQKEYAFFYKLDIIPIDNDTTSYKLTSCNTSVITQACPKVSFEPIPIHYC APAGFAILKCNNKTFNGTGPCTNVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSVN FTDNAKTIIVQLNTSVEINCTRPNNNTRKRIRIQRGPGRAFVTIGKIGNMRQAHCNIS RAKWNNTLKQIASKLREQFGNNKTIIFKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFN STWFNSTWSTEGSNNTEGSDTITLPCRIKQIINMWQKVGKAMYAPPISGQIRCSSNIT GLLLTRDGGNSNNESEIFRPGGGDMRDNWRSELYKYKVVKIEPLGVAPTKAKRRVVQR EKRAVGIGALFLGFLGAAGSTMGAASMTLTVQARQLLSGIVQQQNNLLRAIEAQQHLL QLTVWGIKQLQARILAVERYLKDQQLLGIWGCSGKLICTTAVPWNASWSNKSLEQIWN HTTWMEWDREINNYTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWFNITNWLWYI KLFIMIVGGLVGLRIVFAVLSIVNRVRQGYSPLSFQTHLPTPRGPDRPEGIEEEGGER DRDRSIRLVNGSLALIWDDLRSLCLFSYHRLRDLLLIVTRIVELLGRRGWEALKYWWN LLQYWSQELKNSAVSLLNATAIAVAEGTDRVIEVVQGACRAIRHIPRRIRQGLERILL " exon 8379..8652 /note="trs protein" /number=3 exon 8379..8424 /note="tat protein" /number=3 CDS 8797..9168 /note="27K protein (premature termination)" /codon_start=1 /protein_id="AAB50263.1" /translation="MGGKWSKSSVIGWPTVRERMRRAEPAADRVGAASRDLEKHGAIT SSNTAATNAACAWLEAQEEEEVGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGLEGLIH SQRRQDILDLWIYHTQGYFPD" repeat_region 9086..9719 /note="3' LTR" /rpt_type=long_terminal_repeat repeat_region 9540..9636 /note="R repeat 3' copy" regulatory 9612..9617 /regulatory_class="polyA_signal_sequence" /note="HXB2 mRNA polyadenyation signal" BASE COUNT 3411 a 1772 c 2373 g 2163 t ORIGIN 1 tggaagggct aattcactcc caacgaagac aagatatcct tgatctgtgg atctaccaca 61 cacaaggcta cttccctgat tagcagaact acacaccagg gccagggatc agatatccac 121 tgacctttgg atggtgctac aagctagtac cagttgagcc agagaagtta gaagaagcca 181 acaaaggaga gaacaccagc ttgttacacc ctgtgagcct gcatggaatg gatgacccgg 241 agagagaagt gttagagtgg aggtttgaca gccgcctagc atttcatcac atggcccgag 301 agctgcatcc ggagtacttc aagaactgct gacatcgagc ttgctacaag ggactttccg 361 ctggggactt tccagggagg cgtggcctgg gcgggactgg ggagtggcga gccctcagat 421 cctgcatata agcagctgct ttttgcctgt actgggtctc tctggttaga ccagatctga 481 gcctgggagc tctctggcta actagggaac ccactgctta agcctcaata aagcttgcct 541 tgagtgcttc aagtagtgtg tgcccgtctg ttgtgtgact ctggtaacta gagatccctc 601 agaccctttt agtcagtgtg gaaaatctct agcagtggcg cccgaacagg gacctgaaag 661 cgaaagggaa accagaggag ctctctcgac gcaggactcg gcttgctgaa gcgcgcacgg 721 caagaggcga ggggcggcga ctggtgagta cgccaaaaat tttgactagc ggaggctaga 781 aggagagaga tgggtgcgag agcgtcagta ttaagcgggg gagaattaga tcgatgggaa 841 aaaattcggt taaggccagg gggaaagaaa aaatataaat taaaacatat agtatgggca 901 agcagggagc tagaacgatt cgcagttaat cctggcctgt tagaaacatc agaaggctgt 961 agacaaatac tgggacagct acaaccatcc cttcagacag gatcagaaga acttagatca 1021 ttatataata cagtagcaac cctctattgt gtgcatcaaa ggatagagat aaaagacacc 1081 aaggaagctt tagacaagat agaggaagag caaaacaaaa gtaagaaaaa agcacagcaa 1141 gcagcagctg acacaggaca cagcaatcag gtcagccaaa attaccctat agtgcagaac 1201 atccaggggc aaatggtaca tcaggccata tcacctagaa ctttaaatgc atgggtaaaa 1261 gtagtagaag agaaggcttt cagcccagaa gtgataccca tgttttcagc attatcagaa 1321 ggagccaccc cacaagattt aaacaccatg ctaaacacag tggggggaca tcaagcagcc 1381 atgcaaatgt taaaagagac catcaatgag gaagctgcag aatgggatag agtgcatcca 1441 gtgcatgcag ggcctattgc accaggccag atgagagaac caaggggaag tgacatagca 1501 ggaactacta gtacccttca ggaacaaata ggatggatga caaataatcc acctatccca 1561 gtaggagaaa tttataaaag atggataatc ctgggattaa ataaaatagt aagaatgtat 1621 agccctacca gcattctgga cataagacaa ggaccaaagg aaccctttag agactatgta 1681 gaccggttct ataaaactct aagagccgag caagcttcac aggaggtaaa aaattggatg 1741 acagaaacct tgttggtcca aaatgcgaac ccagattgta agactatttt aaaagcattg 1801 ggaccagcgg ctacactaga agaaatgatg acagcatgtc agggagtagg aggacccggc 1861 cataaggcaa gagttttggc tgaagcaatg agccaagtaa caaattcagc taccataatg 1921 atgcagagag gcaattttag gaaccaaaga aagattgtta agtgtttcaa ttgtggcaaa 1981 gaagggcaca cagccagaaa ttgcagggcc cctaggaaaa agggctgttg gaaatgtgga 2041 aaggaaggac accaaatgaa agattgtact gagagacagg ctaatttttt agggaagatc 2101 tggccttcct acaagggaag gccagggaat tttcttcaga gcagaccaga gccaacagcc 2161 ccaccagaag agagcttcag gtctggggta gagacaacaa ctccccctca gaagcaggag 2221 ccgatagaca aggaactgta tcctttaact tccctcaggt cactctttgg caacgacccc 2281 tcgtcacaat aaagataggg gggcaactaa aggaagctct attagataca ggagcagatg 2341 atacagtatt agaagaaatg agtttgccag gaagatggaa accaaaaatg atagggggaa 2401 ttggaggttt tatcaaagta agacagtatg atcagatact catagaaatc tgtggacata 2461 aagctatagg tacagtatta gtaggaccta cacctgtcaa cataattgga agaaatctgt 2521 tgactcagat tggttgcact ttaaattttc ccattagccc tattgagact gtaccagtaa 2581 aattaaagcc aggaatggat ggcccaaaag ttaaacaatg gccattgaca gaagaaaaaa 2641 taaaagcatt agtagaaatt tgtacagaga tggaaaagga agggaaaatt tcaaaaattg 2701 ggcctgaaaa tccatacaat actccagtat ttgccataaa gaaaaaagac agtactaaat 2761 ggagaaaatt agtagatttc agagaactta ataagagaac tcaagacttc tgggaagttc 2821 aattaggaat accacatccc gcagggttaa aaaagaaaaa atcagtaaca gtactggatg 2881 tgggtgatgc atatttttca gttcccttag atgaagactt caggaagtat actgcattta 2941 ccatacctag tataaacaat gagacaccag ggattagata tcagtacaat gtgcttccac 3001 agggatggaa aggatcacca gcaatattcc aaagtagcat gacaaaaatc ttagagcctt 3061 ttagaaaaca aaatccagac atagttatct atcaatacat ggatgatttg tatgtaggat 3121 ctgacttaga aatagggcag catagaacaa aaatagagga gctgagacaa catctgttga 3181 ggtggggact taccacacca gacaaaaaac atcagaaaga acctccattc ctttggatgg 3241 gttatgaact ccatcctgat aaatggacag tacagcctat agtgctgcca gaaaaagaca 3301 gctggactgt caatgacata cagaagttag tggggaaatt gaattgggca agtcagattt 3361 acccagggat taaagtaagg caattatgta aactccttag aggaaccaaa gcactaacag 3421 aagtaatacc actaacagaa gaagcagagc tagaactggc agaaaacaga gagattctaa 3481 aagaaccagt acatggagtg tattatgacc catcaaaaga cttaatagca gaaatacaga 3541 agcaggggca aggccaatgg acatatcaaa tttatcaaga gccatttaaa aatctgaaaa 3601 caggaaaata tgcaagaatg aggggtgccc acactaatga tgtaaaacaa ttaacagagg 3661 cagtgcaaaa aataaccaca gaaagcatag taatatgggg aaagactcct aaatttaaac 3721 tgcccataca aaaggaaaca tgggaaacat ggtggacaga gtattggcaa gccacctgga 3781 ttcctgagtg ggagtttgtt aatacccctc ccttagtgaa attatggtac cagttagaga 3841 aagaacccat agtaggagca gaaaccttct atgtagatgg ggcagctaac agggagacta 3901 aattaggaaa agcaggatat gttactaata gaggaagaca aaaagttgtc accctaactg 3961 acacaacaaa tcagaagact gagttacaag caatttatct agctttgcag gattcgggat 4021 tagaagtaaa catagtaaca gactcacaat atgcattagg aatcattcaa gcacaaccag 4081 atcaaagtga atcagagtta gtcaatcaaa taatagagca gttaataaaa aaggaaaagg 4141 tctatctggc atgggtacca gcacacaaag gaattggagg aaatgaacaa gtagataaat 4201 tagtcagtgc tggaatcagg aaagtactat ttttagatgg aatagataag gcccaagatg 4261 aacatgagaa atatcacagt aattggagag caatggctag tgattttaac ctgccacctg 4321 tagtagcaaa agaaatagta gccagctgtg ataaatgtca gctaaaagga gaagccatgc 4381 atggacaagt agactgtagt ccaggaatat ggcaactaga ttgtacacat ttagaaggaa 4441 aagttatcct ggtagcagtt catgtagcca gtggatatat agaagcagaa gttattccag 4501 cagaaacagg gcaggaaaca gcatattttc ttttaaaatt agcaggaaga tggccagtaa 4561 aaacaataca tactgacaat ggcagcaatt tcaccggtgc tacggttagg gccgcctgtt 4621 ggtgggcggg aatcaagcag gaatttggaa ttccctacaa tccccaaagt caaggagtag 4681 tagaatctat gaataaagaa ttaaagaaaa ttataggaca ggtaagagat caggctgaac 4741 atcttaagac agcagtacaa atggcagtat tcatccacaa ttttaaaaga aaagggggga 4801 ttggggggta cagtgcaggg gaaagaatag tagacataat agcaacagac atacaaacta 4861 aagaattaca aaaacaaatt acaaaaattc aaaattttcg ggtttattac agggacagca 4921 gaaatccact ttggaaagga ccagcaaagc tcctctggaa aggtgaaggg gcagtagtaa 4981 tacaagataa tagtgacata aaagtagtgc caagaagaaa agcaaagatc attagggatt 5041 atggaaaaca gatggcaggt gatgattgtg tggcaagtag acaggatgag gattagaaca 5101 tggaaaagtt tagtaaaaca ccatatgtat gtttcaggga aagctagggg atggttttat 5161 agacatcact atgaaagccc tcatccaaga ataagttcag aagtacacat cccactaggg 5221 gatgctagat tggtaataac aacatattgg ggtctgcata caggagaaag agactggcat 5281 ttgggtcagg gagtctccat agaatggagg aaaaagagat atagcacaca agtagaccct 5341 gaactagcag accaactaat tcatctgtat tactttgact gtttttcaga ctctgctata 5401 agaaaggcct tattaggaca catagttagc cctaggtgtg aatatcaagc aggacataac 5461 aaggtaggat ctctacaata cttggcacta gcagcattaa taacaccaaa aaagataaag 5521 ccacctttgc ctagtgttac gaaactgaca gaggatagat ggaacaagcc ccagaagacc 5581 aagggccaca gagggagcca cacaatgaat ggacactaga gcttttagag gagcttaaga 5641 atgaagctgt tagacatttt cctaggattt ggctccatgg cttagggcaa catatctatg 5701 aaacttatgg ggatacttgg gcaggagtgg aagccataat aagaattctg caacaactgc 5761 tgtttatcca ttttcagaat tgggtgtcga catagcagaa taggcgttac tcgacagagg 5821 agagcaagaa atggagccag tagatcctag actagagccc tggaagcatc caggaagtca 5881 gcctaaaact gcttgtacca attgctattg taaaaagtgt tgctttcatt gccaagtttg 5941 tttcataaca aaagccttag gcatctccta tggcaggaag aagcggagac agcgacgaag 6001 agctcatcag aacagtcaga ctcatcaagc ttctctatca aagcagtaag tagtacatgt 6061 aacgcaacct ataccaatag tagcaatagt agcattagta gtagcaataa taatagcaat 6121 agttgtgtgg tccatagtaa tcatagaata taggaaaata ttaagacaaa gaaaaataga 6181 caggttaatt gatagactaa tagaaagagc agaagacagt ggcaatgaga gtgaaggaga 6241 aatatcagca cttgtggaga tgggggtgga gatggggcac catgctcctt gggatgttga 6301 tgatctgtag tgctacagaa aaattgtggg tcacagtcta ttatggggta cctgtgtgga 6361 aggaagcaac caccactcta ttttgtgcat cagatgctaa agcatatgat acagaggtac 6421 ataatgtttg ggccacacat gcctgtgtac ccacagaccc caacccacaa gaagtagtat 6481 tggtaaatgt gacagaaaat tttaacatgt ggaaaaatga catggtagaa cagatgcatg 6541 aggatataat cagtttatgg gatcaaagcc taaagccatg tgtaaaatta accccactct 6601 gtgttagttt aaagtgcact gatttgaaga atgatactaa taccaatagt agtagcggga 6661 gaatgataat ggagaaagga gagataaaaa actgctcttt caatatcagc acaagcataa 6721 gaggtaaggt gcagaaagaa tatgcatttt tttataaact tgatataata ccaatagata 6781 atgatactac cagctataag ttgacaagtt gtaacacctc agtcattaca caggcctgtc 6841 caaaggtatc ctttgagcca attcccatac attattgtgc cccggctggt tttgcgattc 6901 taaaatgtaa taataagacg ttcaatggaa caggaccatg tacaaatgtc agcacagtac 6961 aatgtacaca tggaattagg ccagtagtat caactcaact gctgttaaat ggcagtctag 7021 cagaagaaga ggtagtaatt agatctgtca atttcacgga caatgctaaa accataatag 7081 tacagctgaa cacatctgta gaaattaatt gtacaagacc caacaacaat acaagaaaaa 7141 gaatccgtat ccagagagga ccagggagag catttgttac aataggaaaa ataggaaata 7201 tgagacaagc acattgtaac attagtagag caaaatggaa taacacttta aaacagatag 7261 ctagcaaatt aagagaacaa tttggaaata ataaaacaat aatctttaag caatcctcag 7321 gaggggaccc agaaattgta acgcacagtt ttaattgtgg aggggaattt ttctactgta 7381 attcaacaca actgtttaat agtacttggt ttaatagtac ttggagtact gaagggtcaa 7441 ataacactga aggaagtgac acaatcaccc tcccatgcag aataaaacaa attataaaca 7501 tgtggcagaa agtaggaaaa gcaatgtatg cccctcccat cagtggacaa attagatgtt 7561 catcaaatat tacagggctg ctattaacaa gagatggtgg taatagcaac aatgagtccg 7621 agatcttcag acctggagga ggagatatga gggacaattg gagaagtgaa ttatataaat 7681 ataaagtagt aaaaattgaa ccattaggag tagcacccac caaggcaaag agaagagtgg 7741 tgcagagaga aaaaagagca gtgggaatag gagctttgtt ccttgggttc ttgggagcag 7801 caggaagcac tatgggcgca gcctcaatga cgctgacggt acaggccaga caattattgt 7861 ctggtatagt gcagcagcag aacaatttgc tgagggctat tgaggcgcaa cagcatctgt 7921 tgcaactcac agtctggggc atcaagcagc tccaggcaag aatcctggct gtggaaagat 7981 acctaaagga tcaacagctc ctggggattt ggggttgctc tggaaaactc atttgcacca 8041 ctgctgtgcc ttggaatgct agttggagta ataaatctct ggaacagatt tggaatcaca 8101 cgacctggat ggagtgggac agagaaatta acaattacac aagcttaata cactccttaa 8161 ttgaagaatc gcaaaaccag caagaaaaga atgaacaaga attattggaa ttagataaat 8221 gggcaagttt gtggaattgg tttaacataa caaattggct gtggtatata aaattattca 8281 taatgatagt aggaggcttg gtaggtttaa gaatagtttt tgctgtactt tctatagtga 8341 atagagttag gcagggatat tcaccattat cgtttcagac ccacctccca accccgaggg 8401 gacccgacag gcccgaagga atagaagaag aaggtggaga gagagacaga gacagatcca 8461 ttcgattagt gaacggatcc ttggcactta tctgggacga tctgcggagc ctgtgcctct 8521 tcagctacca ccgcttgaga gacttactct tgattgtaac gaggattgtg gaacttctgg 8581 gacgcagggg gtgggaagcc ctcaaatatt ggtggaatct cctacagtat tggagtcagg 8641 aactaaagaa tagtgctgtt agcttgctca atgccacagc catagcagta gctgagggga 8701 cagatagggt tatagaagta gtacaaggag cttgtagagc tattcgccac atacctagaa 8761 gaataagaca gggcttggaa aggattttgc tataagatgg gtggcaagtg gtcaaaaagt 8821 agtgtgattg gatggcctac tgtaagggaa agaatgagac gagctgagcc agcagcagat 8881 agggtgggag cagcatctcg agacctggaa aaacatggag caatcacaag tagcaataca 8941 gcagctacca atgctgcttg tgcctggcta gaagcacaag aggaggagga ggtgggtttt 9001 ccagtcacac ctcaggtacc tttaagacca atgacttaca aggcagctgt agatcttagc 9061 cactttttaa aagaaaaggg gggactggaa gggctaattc actcccaaag aagacaagat 9121 atccttgatc tgtggatcta ccacacacaa ggctacttcc ctgattagca gaactacaca 9181 ccagggccag gggtcagata tccactgacc tttggatggt gctacaagct agtaccagtt 9241 gagccagata agatagaaga ggccaataaa ggagagaaca ccagcttgtt acaccctgtg 9301 agcctgcatg ggatggatga cccggagaga gaagtgttag agtggaggtt tgacagccgc 9361 ctagcatttc atcacgtggc ccgagagctg catccggagt acttcaagaa ctgctgacat 9421 cgagcttgct acaagggact ttccgctggg gactttccag ggaggcgtgg cctgggcggg 9481 actggggagt ggcgagccct cagatcctgc atataagcag ctgctttttg cctgtactgg 9541 gtctctctgg ttagaccaga tctgagcctg ggagctctct ggctaactag ggaacccact 9601 gcttaagcct caataaagct tgccttgagt gcttcaagta gtgtgtgccc gtctgttgtg 9661 tgactctggt aactagagat ccctcagacc cttttagtca gtgtggaaaa tctctagca //