LOCUS Rb-fetal 4740 bp ss-mRNA PRI 15-JUN-1989 DEFINITION Human retinoblastoma susceptibility mRNA, complete cds. ACCESSION M15400 KEYWORDS retinoblastoma susceptibility. SOURCE Human fetal retina, cDNA to mRNA, clone RB-[1,5]. ORGANISM Homo sapiens Eukaryota; Animalia; Chordata; Vertebrata; Mammalia; Theria; Eutheria; Primates; Haplorhini; Catarrhini; Hominidae. REFERENCE 1 (bases 243 to 4740) AUTHORS Lee,W.H., Bookstein,R., Hong,F., Young,L.J., Shew,J.Y. and Lee,E. TITLE Human retinoblastoma susceptibility gene: Cloning, identification, and sequence JOURNAL Science 235, 1394-1399 (1987) STANDARD full staff_review REFERENCE 2 (bases 1 to 480) AUTHORS Lee,E., Bookstein,R., Young,L.J., Lin,C.-J., Rosenfeld,M.G. and Lee,W.H. TITLE Molecular mechanism of retinoblastoma gene inactivation in retinoblastoma cell line Y79 JOURNAL Proc. Natl. Acad. Sci. U.S.A. 85, 6017-6021 (1988) STANDARD full staff_review REFERENCE 3 AUTHORS Munger,K., Werness,B., Dyson,N., Phelps,W., Harlow,E., and Howley, P.M. TITLE Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product JOURNAL EMBO 8, 4099-4105 (1989) STANDARD full staff_review COMMENT Draft entry and computer-readable copy of sequence in [1] kindly provided by R.Bookstein, 27-APR-1987. The authors [1] identified the retinoblastoma susceptibility (RB) gene encoding a messenger RNA (mRNA) of 4.6 kb on the basis of chromosomal location, homozygous deletion, and tumor-specific alterations in expression. Transcription of the gene was abnormal in 6/6 retinoblastomas while normal in fetal retina and placenta. The sequence presented in this entry is derived from human fetal retina cDNA. The authors [2] also examined cDNA from the retinoblastoma cell line Y79. They found that the mRNA produced was a shortened transcript which reflects a deletion of exons 2-6 and must have ocurred by a mechanism other than recombination of homologous sequences. The Retinoblastoma (RB) susceptibility gene maps to chromosome 13q14 and encodes a nuclear phosphoprotein of 105kD. RB inactivation results in retinoblastomas and osteosarcomas due to germline heterozygosity at the RB locus, and results in retinoblastomas, sarcomas, small cell lung carcinomas, and a portion of bladder, and breast carcinomas presumed due to somatic mutations at the RB locus. RB is a tumor suppressor gene; its nuclear location and ability to bind DNA suggests a role in transcriptional regulation. pRB, on its side, has a complementary oncoprotein-binding pocket that is a common target for the three viral proteins: E1A of adenovirus, large T antigen of SV40, and E7 of HPV. The high risk HPV types such as HPV16 and HPV18 bind to pRB with higher affinity than low risk types 6b and 11. The amino acid locations of the pRB binding site of the HPV16 E7 protein have been mapped to a small stretch of amino acids. Deletion of the amino acid residues between D(21) and C(24) abolish p105-RB binding. L(22) and C(24) are conserved in all HPV E7 sequences and in corresponding parts of the AdE1A and SV40 large T antigen. Mutational analysis of E(26) also reveals that it is necessary for binding pRB. Recently, association with a number of cellular host proteins has been shown to occur at the onco-protein binding site. pRB shows differential phosphorylation at different points within the cell cycle. All three of the viral proteins mentioned above interact with the underphosphorylated form of pRB. FEATURES Location/Qualifiers mRNA <1..4740 /note="RBS MRNA" CDS 139..2925 /note="retinoblastoma susceptibility protein;" /gene="RB1" /map="13q14.2" /codon_start=1 /translation="MPPKTPRKTAATAAAAAAEPPAPPPPPPPEEDPEQDSGPEDLPL VRLEFEETEEPDFTALCQKLKIPDHVRERAWLTWEKVSSVDGVLGGYIQKKKELWGIC IFIARVDLDEMSFTLLSYRKTYEISVHKFFNLLKEIDTSTKVDNAMSRLLKKYDVLFA LFSKLERTCELIYLTQPSSSISTEINSALVLKVSWITFLLAKGEVLQMEDDLVISFQL MLCVLDYFIKLSPPMLLKEPYKTAVIPINGSPRTPRRGQNRSARIAKQLENDTRIIEV LCKEHECNIDEVKNVYFKNFIPFMNSLGLVTSNGLPEVENLSKRYEEIYLKNKDLDRR LFLDHDKTLQTDSIDSFETQRTPRKSNLDEEVNIIPPHTPVRTVMNTIQQLMMILNSA SDQPSENLISYFNNCTVNPKESILKRVKDIGYIFKEKFAKAVGQGCVEIGSQRYKLGV RLYYRVMESMLKSEEERLSIQNFSKLLNDNIFHMSLLACALEVVMATYSRSTSQNLDS GTDLSFPWILNVLNLKAFDFYKVIESFIKAEGNLTREMIKHLERCEHRIMESLAWLSD SPLFDLIKQSKDREGPTDHLESACPLNLPLQNNHTAADMYLSPVRSPKKKGSTTRVNS TANAETQATSAFQTQKPLKSTSLSLFYKKVYRLAYLRLNTLCERLLSEHPELEHIIWT LFQHTLQNEYELMRDRHLDQIMMCSMYGICKVKNIDLKFKIIVTAYKDLPHAVQETFK RVLIKEEEYDSIIVFYNSVFMQRLKTNILQYASTRPPTLSPIPHIPRSPYKFPSSPLR IPGGNIYISPLKSPYKISEGLPTPTKMTPRSRILVSIGESFGTSEKFQKINQMVCNSD RVLKRSAEGSNPPKPLKKLRFDIEGSDEADGSKHLPGESKFQQKLAEMTSTRTRMQKQ KMNDSMDTSNKEEK" source 1..4740 /organism="Homo sapiens" BASE COUNT 1508 a 887 c 862 g 1483 t ORIGIN 1038 bp upstream of EcoRI site; chromosome 13q14.1-q14.2. 1 ttccggtttt tctcagggga cgttgaaatt atttttgtaa cgggagtcgg gagaggacgg 61 ggcgtgcccc gcgtgcgcgc gcgtcgtcct ccccggcgct cctccacagc tcgctggctc 121 ccgccgcgga aaggcgtcat gccgcccaaa accccccgaa aaacggccgc caccgccgcc 181 gctgccgccg cggaaccccc ggcaccgccg ccgccgcccc ctcctgagga ggacccagag 241 caggacagcg gcccggagga cctgcctctc gtcaggcttg agtttgaaga aacagaagaa 301 cctgatttta ctgcattatg tcagaaatta aagataccag atcatgtcag agagagagct 361 tggttaactt gggagaaagt ttcatctgtg gatggagtat tgggaggtta tattcaaaag 421 aaaaaggaac tgtggggaat ctgtatcttt attgcacgag ttgacctaga tgagatgtcg 481 ttcactttac tgagctacag aaaaacatac gaaatcagtg tccataaatt ctttaactta 541 ctaaaagaaa ttgataccag taccaaagtt gataatgcta tgtcaagact gttgaagaag 601 tatgatgtat tgtttgcact cttcagcaaa ttggaaagga catgtgaact tatatatttg 661 acacaaccca gcagttcgat atctactgaa ataaattctg cattggtgct aaaagtttct 721 tggatcacat ttttattagc taaaggggaa gtattacaaa tggaagatga tctggtgatt 781 tcatttcagt taatgctatg tgtccttgac tattttatta aactctcacc tcccatgttg 841 ctcaaagaac catataaaac agctgttata cccattaatg gttcacctcg aacacccagg 901 cgaggtcaga acaggagtgc acggatagca aaacaactag aaaatgatac aagaattatt 961 gaagttctct gtaaagaaca tgaatgtaat atagatgagg tgaaaaatgt ttatttcaaa 1021 aattttatac cttttatgaa ttctcttgga cttgtaacat ctaatggact tccagaggtt 1081 gaaaatcttt ctaaacgata cgaagaaatt tatcttaaaa ataaagatct agatcgaaga 1141 ttatttttgg atcatgataa aactcttcag actgattcta tagacagttt tgaaacacag 1201 agaacaccac gaaaaagtaa ccttgatgaa gaggtgaata taattcctcc acacactcca 1261 gttaggactg ttatgaacac tatccaacaa ttaatgatga ttttaaattc tgcaagtgat 1321 caaccttcag aaaatctgat ttcctatttt aacaactgca cagtgaatcc aaaagaaagt 1381 atactgaaaa gagtgaagga tataggatac atctttaaag agaaatttgc taaagctgtg 1441 ggacagggtt gtgtcgaaat tggatcacag cgatacaaac ttggagttcg cttgtattac 1501 cgagtaatgg aatccatgct taaatcagaa gaagaacgat tatccattca aaattttagc 1561 aaacttctga atgacaacat ttttcatatg tctttattgg cgtgcgctct tgaggttgta 1621 atggccacat atagcagaag tacatctcag aatcttgatt ctggaacaga tttgtctttc 1681 ccatggattc tgaatgtgct taatttaaaa gcctttgatt tttacaaagt gatcgaaagt 1741 tttatcaaag cagaaggcaa cttgacaaga gaaatgataa aacatttaga acgatgtgaa 1801 catcgaatca tggaatccct tgcatggctc tcagattcac ctttatttga tcttattaaa 1861 caatcaaagg accgagaagg accaactgat caccttgaat ctgcttgtcc tcttaatctt 1921 cctctccaga ataatcacac tgcagcagat atgtatcttt ctcctgtaag atctccaaag 1981 aaaaaaggtt caactacgcg tgtaaattct actgcaaatg cagagacaca agcaacctca 2041 gccttccaga cccagaagcc attgaaatct acctctcttt cactgtttta taaaaaagtg 2101 tatcggctag cctatctccg gctaaataca ctttgtgaac gccttctgtc tgagcaccca 2161 gaattagaac atatcatctg gacccttttc cagcacaccc tgcagaatga gtatgaactc 2221 atgagagaca ggcatttgga ccaaattatg atgtgttcca tgtatggcat atgcaaagtg 2281 aagaatatag accttaaatt caaaatcatt gtaacagcat acaaggatct tcctcatgct 2341 gttcaggaga cattcaaacg tgttttgatc aaagaagagg agtatgattc tattatagta 2401 ttctataact cggtcttcat gcagagactg aaaacaaata ttttgcagta tgcttccacc 2461 aggcccccta ccttgtcacc aatacctcac attcctcgaa gcccttacaa gtttcctagt 2521 tcacccttac ggattcctgg agggaacatc tatatttcac ccctgaagag tccatataaa 2581 atttcagaag gtctgccaac accaacaaaa atgactccaa gatcaagaat cttagtatca 2641 attggtgaat cattcgggac ttctgagaag ttccagaaaa taaatcagat ggtatgtaac 2701 agcgaccgtg tgctcaaaag aagtgctgaa ggaagcaacc ctcctaaacc actgaaaaaa 2761 ctacgctttg atattgaagg atcagatgaa gcagatggaa gtaaacatct cccaggagag 2821 tccaaatttc agcagaaact ggcagaaatg acttctactc gaacacgaat gcaaaagcag 2881 aaaatgaatg atagcatgga tacctcaaac aaggaagaga aatgaggatc tcaggacctt 2941 ggtggacact gtgtacacct ctggattcat tgtctctcac agatgtgact gtataacttt 3001 cccaggttct gtttatggcc acatttaata tcttcagctc tttttgtgga tataaaatgt 3061 gcagatgcaa ttgtttgggt gagtcctaag ccacttgaaa tgttagtcat tgttatttat 3121 acaagattga aaatcttgtg taaatcctgc catttaaaaa gttgtagcag attgtttcct 3181 cttccaaagt aaaattgctg tgctttatgg atagtaagaa tggccctaga gtgggagtcc 3241 tgataaccca ggcctgtctg actactttgc cttcttttgt agcatatagg tgatgtttgc 3301 tcttgttttt attaatttat atgtatattt ttttaattta acatgaacac ccttagaaaa 3361 tgtgtcctat ctatcttcca aatgcaattt gattgactgc ccattcacca aaattatcct 3421 gaactcttct gcaaaaatgg atattattag aaattagaaa aaaattacta attttacaca 3481 ttagatttta ttttactatt ggaatctgat atactgtgtg cttgttttat aaaattttgc 3541 ttttaattaa ataaaagctg gaagcaaagt ataaccatat gatactatca tactactgaa 3601 acagatttca tacctcagaa tgtaaaagaa cttactgatt attttcttca tccaacttat 3661 gtttttaaat gaggattatt gatagtactc ttggttttta taccattcag atcactgaat 3721 ttataaagta cccatctagt acttgaaaaa gtaaagtgtt ctgccagatc ttaggtatag 3781 aggaccctaa cacagtatat cccaagtgca ctttctaatg tttctgggtc ctgaagaatt 3841 aagatacaaa ttaattttac tccataaaca gactgttaat tataggagcc ttaatttttt 3901 tttcatagag atttgtctaa ttgcatctca aaattattct gccctcctta atttgggaag 3961 gtttgtgttt tctctggaat ggtacatgtc ttccatgtat cttttgaact ggcaattgtc 4021 tatttatctt ttattttttt aagtcagtat ggtctaacac tggcatgttc aaagccacat 4081 tatttctagt ccaaaattac aagtaatcaa gggtcattat gggttaggca ttaatgtttc 4141 tatctgattt tgtgcaaaag cttcaaatta aaacagctgc attagaaaaa gaggcgcttc 4201 tcccctcccc tacacctaaa ggtgtattta aactatcttg tgtgattaac ttatttagag 4261 atgctgtaac ttaaaatagg ggatatttaa ggtagcttca gctagctttt aggaaaatca 4321 ctttgtctaa ctcagaatta tttttaaaaa gaaatctggt cttgttagaa aacaaaattt 4381 tattttgtgc tcatttaagt ttcaaactta ctattttgac agttattttg ataacaatga 4441 cactagaaaa cttgactcca tttcatcatt gtttctgcat gaatatcata caaatcagtt 4501 agtttttagg tcaagggctt actatttctg ggtcttttgc tactaagttc acattagaat 4561 tagtgccaga attttaggaa cttcagagat cgtgtattga gatttcttaa ataatgcttc 4621 agatattatt gctttattgc ttttttgtat tggttaaaac tgtacattta aaattgctat 4681 gttactattt tctacaatta atagtttgtc tattttaaaa taaattagtt gttaagagtc //