LOCUS c-Ha-ras 6453 bp ds-DNA PRI 15-MAR-1988 DEFINITION Human (genomic clones lambda-[SK2-T2, HS578T]; cDNA clones RS-[3,4, 6]) c-Ha-ras1 proto-oncogene, complete coding sequence. ACCESSION J00277 J00206 J00276 K00954 KEYWORDS H-ras oncogene; c-myc proto-oncogene; consensus sequence; ras oncogene; repeat region; transforming gene. SOURCE Homo sapiens DNA. ORGANISM Homo sapiens Eukaryota; Animalia; Chordata; Vertebrata; Mammalia; Theria; Eutheria; Primates; Haplorhini; Catarrhini; Hominidae. REFERENCE 1 (bases 1638 to 1968) AUTHORS Tabin,C.J., Bradley,S.M., Bargmann,C.I., Weinberg,R.A., Papageorge,A.G., Scolnick,E.M., Dhar,R., Lowy,D.R. and Chang,E.H. TITLE Mechanism of activation of a human oncogene JOURNAL Nature 300, 143-149 (1982) STANDARD full staff_review REFERENCE 2 (bases 1044 to 1973) AUTHORS Reddy,P.E., Reynolds,R.K., Santos,E. and Barbacid,M. TITLE A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene JOURNAL Nature 300, 149-152 (1982) STANDARD full staff_review REFERENCE 3 (bases 1664 to 1774) AUTHORS Taparowsky,E., Suard,Y., Fasano,O., Shimuzu,K., Goldfarb,M. and Wigler,M. TITLE Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change JOURNAL Nature 300, 762-765 (1982) STANDARD full staff_review REFERENCE 4 (bases 1659 to 1774; 2042 to 2220; 2374 to 2533; 3231 to 3355; 3470 to 3749) AUTHORS Fasano,O., Taparowsky,E., Fiddes,J., Wigler,M. and Golfarb,M. TITLE Sequence and structure of the coding region of the human H-ras-1 gene from T24 bladder carcinoma cells JOURNAL J. Mol. Appl. Genet. 2, 173-180 (1983) STANDARD full staff_review REFERENCE 5 (bases 1 to 6453) AUTHORS Capon,D.J., Chen,E.Y., Levinson,A.D., Seeburg,P.H. and Goeddel,D.V. TITLE Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue JOURNAL Nature 302, 33-37 (1983) STANDARD full staff_review REFERENCE 6 (bases 1664 to 1774; 1963 to 2419) AUTHORS Yuasa,Y., Srivastava,S.K., Dunn,C.Y., Rhim,J.S., Reddy,P.E. and Aaronson,S.A. TITLE Acquisition of transforming properties by alternative point mutations within c-bas/has human proto-oncogene JOURNAL Nature 303, 775-779 (1983) STANDARD full staff_review REFERENCE 7 (bases 1 to 4164) AUTHORS Reddy,P.E. TITLE Nucleotide sequence analysis of the T24 human bladder carcinoma oncogene JOURNAL Science 220, 1061-1063 (1983) STANDARD full staff_review REFERENCE 8 (bases 1044 to 3941) AUTHORS Sekiya,T., Fushimi,M., Hori,H., Hirohashi,S., Nishimura,S. and Sugimura,T. TITLE Molecular cloning and the total nucleotide sequence of the human c-Ha-ras-1 gene activated in a melanoma from a Japanese patient JOURNAL Proc. Natl. Acad. Sci. U.S.A. 81, 4771-4775 (1984) STANDARD full staff_review REFERENCE 9 (bases 1664 to 1774) AUTHORS Kraus,M.H., Yuasa,Y. and Aaronson,S.A. TITLE A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient JOURNAL Proc. Natl. Acad. Sci. U.S.A. 81, 5384-5388 (1984) STANDARD full staff_review REFERENCE 10 (bases 2042 to 2220) AUTHORS Kraus,M.H. JOURNAL Unpublished (1985) LCMB, NCI, NIH Bldg.37 Rm.1C03, Bethesda, Md. STANDARD full staff_review COMMENT The human genome contains a family of genes with homology to the Harvey murine sarcoma virus oncogene (c-Ha-ras). Two of these homologues are detectable by high stringency Southern hybridizations; the c-Ha-ras1 and c-Ha-ras2 genes, which occur on BamHI fragments of varying sizes from 3 to 9 kb because of allelic polymorphisms in the flanking regions. Genomic mapping and nucleotide sequencing has shown that c-Ha-ras1 is the normal progenitor of the transforming gene found in several human tumor cell lines (T24 bladder carcinoma; EJ bladder carcinoma; Hs242 lung carcinoma; SK2 melanoma; and HS578T mammary carcinosarcoma). The only difference within the coding exons of the c-Ha-ras1 proto-oncogene and the oncogene of the T24 and EJ cell lines is a 'g' to 't' transversion within codon 12 that results in the substitution of valine for glycine at this position in the p21 protein encoded by c-Ha-ras1. The mutation responsible for transforming ability of the p21 protein in the SK2 and Hs242 cell lines is an 'a' to 't' transversion within codon 61 that results in the substitution of leucine for glutamine at this position. The mutation responsible for transforming ability of the p21 protein in the HS578T cell line is a 'g' to 'a' transition within codon 12 that results in the substitution of Aspartic acid for glycine at this position [9]. Because this 'g' to 'a' transition abolishes a MspI/HpaII site within the transformed allele, [9] was able to determine that both of the H-ras1 alleles found in normal cells from the same individual from which the HS578T cells were obtained, had the normal sequence at this position. A region of repeated DNA consisting of the 28bp consensus sequence 'cactcccccttctctccaggggacgcca' begins at position 4755. The repeat occurs 29 times in the plasmid used for this sequence but may occur more times in the native DNA. This region is known to be unessential for transforming activity [5]. [5] constructs a chimeric SV40 early promoter/human c-Ha-ras1 plasmid to demonstrate that upon transfection transforming activity is unaffected. [2],[5] and [7] discuss the extensive homology with the retroviral onc genes (v-has, v-bas, v-ha-ras). Complete source information: Human genomic DNA [3],[1],[5]; human bladder carcinoma cell line T24 DNA [3],[2],[5],[7]; cDNA to mRNA, clones RS-3, RS-4 and RS-6 [4]; human bladder carcinoma cell line EJ DNA [1]; human lung carcinoma cell line Hs242 DNA [6]; human melanoma cell line SK2 DNA, clone lambda-SK2-T2 [8]; human mammary carcinosarcoma cell line SH578T DNA, clone lambda-HS578T [9],[10] FEATURES Location/Qualifiers conflict replace(675..678,"") /citation=Science 220, 1061-1063 (1983) variation 675..678 /note="cgga in nontransforming cells; taag in T24 [7]" variation 679..680 /note="cg in nontransforming cells; cggcggcg in T24" allele 1654 /note="c in [5],[7]; t in [2],[1],[7] (nontransforming cells)" conflict replace(1654,"") /citation=Nature 300, 143-149 (1982) variation 1654 /note="c in T24; t in EJ [7]" exon <1664..1774 /number=1 /note="c-Ha-ras1 p21 protein" prim_transcript <1664..3744 /note="c-Ha-ras1 mRNA" CDS join(1664..1774,2042..2220,2374..2533,3231..3350) /note="c-Ha-ras1 p21 protein" /codon_start=1 /translation="MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQV VIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHQYREQIKR VKDSDDVPMVLVGNKCDLAARTVESRQAQDLARSYGIPYIETSAKTRQGVEDAFYTLV REIRQHKLRKLNPPDESGPGCMSCKCVLS" mutation 1698 /note="g in nontransforming cells; t in T24 and EJ cells [3],[2],[1],[5],[7],[4]; a" allele 1744 /note="t in one allele; c in two other alleles [3],[5]" intron 1775..2041 /note="c-Ha-ras1 intron a" conflict replace(1783,"") /citation=Proc. Natl. Acad. Sci. U.S.A. 81, 4771-4775 (1984) exon 2042..2220 /number=2 mutation 2112 /note="a in nontransforming cells; t in Hs242 and SK2 transforming cells [6],[8]" intron 2221..2373 /note="c-Ha-ras1 intron b" conflict replace(2328,"") /citation=Nature 303, 775-779 (1983) exon 2374..2533 /number=3 intron 2534..3230 /note="c-Ha-ras1 intron c" conflict replace(2707,"") /citation=Proc. Natl. Acad. Sci. U.S.A. 81, 4771-4775 (1984) variation 2713 /note="a in nontransforming cells; g in T24 and SK2 cells" conflict replace(3117..3120,"") /citation=Science 220, 1061-1063 (1983) exon 3231..>3350 /number=4 /note="c-Ha-ras1 p21 protein" allele 3662 /note="c in two alleles and T24 [5],[7]; t in one allele [7]" conflict replace(4099,"") /citation=Science 220, 1061-1063 (1983) source 1..6453 /organism="Homo sapiens" /sequenced_mol="DNA" BASE COUNT 946 a 2287 c 2113 g 1107 t ORIGIN 1 bp upstream of BamHI site. 1 ggatcccagc ctttccccag cccgtagccc cgggacctcc gcggtgggcg gcgccgcgct 61 gccggcgcag ggagggcctc tggtgcaccg gcaccgctga gtcgggttct ctcgccggcc 121 tgttcccggg agagcccggg gccctgctcg gagatgccgc cccgggcccc cagacaccgg 181 ctccctggcc ttcctcgagc aaccccgagc tcggctccgg tctccagcca agcccaaccc 241 cgagaggccg cggccctact ggctccgcct cccgcgttgc tcccggaagc cccgcccgac 301 cgcggctcct gacagacggg ccgctcagcc aaccggggtg gggcggggcc cgatggcgcg 361 cagccaatgg taggccgcgc ctggcagacg gacgggcgcg gggcggggcg tgcgcaggcc 421 cgcccgagtc tccgccgccc gtgccctgcg cccgcaaccc gagccgcacc cgccgcggac 481 ggagcccatg cgcggggcga accgcgcgcc cccgcccccg ccccgccccg gcctcggccc 541 cggccctggc cccgggggca gtcgcgcctg tgaacggtga gtgcgggcag ggatcggccg 601 ggccgcgcgc cctcctcgcc cccaggcggc agcaatacgc gcggcgcggg ccgggggcgc 661 ggggccggcg ggcgtaagcg gcggcggcgg cggcgggtgg gtggggccgg gcggggcccg 721 cgggcacagg tgagcgggcg tcgggggctg cggcgggcgg gggccccttc ctccctgggg 781 cctgcgggaa tccgggcccc acccgtggcc tcgcgctggg cacggtcccc acgccggcgt 841 acccgggagc ctcgggcccg gcgccctcac acccgggggc gtctgggagg aggcggccgc 901 ggccacggca cgcccgggca cccccgattc agcatcacag gtcgcggacc aggccggggg 961 cctcagcccc agtgcctttt ccctctccgg gtctcccgcg ccgcttctcg gccccttcct 1021 gtcgctcagt ccctgcttcc caggagctcc tctgtcttct ccagctttct gtggctgaaa 1081 gatgcccccg gttccccgcc gggggtgcgg ggcgctgccc gggtctgccc tcccctcggc 1141 ggcgcctagt acgcagtagg cgctcagcaa atacttgtcg gaggcaccag cgccgcgggg 1201 cctgcaggct ggcactagcc tgcccgggca cgccgtggcg cgctccgccg tggccagacc 1261 tgttctggag gacggtaacc tcagccctcg ggcgcctccc tttagccttt ctgccgaccc 1321 agcagcttct aatttgggtg cgtggttgag agcgctcagc tgtcagccct gcctttgagg 1381 gctgggtccc ttttcccatc actgggtcat taagagcaag tgggggcgag gcgacagccc 1441 tcccgcacgc tgggttgcag ctgcacaggt aggcacgctg cagtccttgc tgcctggcgt 1501 tggggcccag ggaccgctgt gggtttgccc ttcagatggc cctgccagca gctgccctgt 1561 ggggcctggg gctgggcctg ggcctggctg agcagggccc tccttggcag gtggggcagg 1621 agaccctgta ggaggacccc gggccgcagg cccctgagga gcgatgacgg aatataagct 1681 ggtggtggtg ggcgccggcg gtgtgggcaa gagtgcgctg accatccagc tgatccagaa 1741 ccattttgtg gacgaatacg accccactat agaggtgagc ctagcgccgc cgtccaggtg 1801 ccagcagctg ctgcgggcga gcccaggaca cagccaggat agggctggct gcagcccctg 1861 gtcccctgca tggtgctgtg gccctgtctc ctgcttcctc tagaggaggg gagtccctcg 1921 tctcagcacc ccaggagagg agggggcatg aggggcatga gaggtaccag ggagaggctg 1981 gctgtgtgaa ctccccccac ggaaggtcct gagggggtcc ctgagccctg tcctcctgca 2041 ggattcctac cggaagcagg tggtcattga tggggagacg tgcctgttgg acatcctgga 2101 taccgccggc caggaggagt acagcgccat gcgggaccag tacatgcgca ccggggaggg 2161 cttcctgtgt gtgtttgcca tcaacaacac caagtctttt gaggacatcc accagtacag 2221 gtgaaccccg tgaggctggc ccgggagccc acgccgcaca ggtggggcca ggccggctgc 2281 gtccaggcag gggcctcctg tcctctctgc gcatgtcctg gatgccgctg cgcctgcagc 2341 ccccgtagcc agctctcgct ttccacctct cagggagcag atcaaacggg tgaaggactc 2401 ggatgacgtg cccatggtgc tggtggggaa caagtgtgac ctggctgcac gcactgtgga 2461 atctcggcag gctcaggacc tcgcccgaag ctacggcatc ccctacatcg agacctcggc 2521 caagacccgg caggtgaggc agctctccac cccacagcta gccagggacc cgccccgccc 2581 cgccccagcc agggagcagc actcactgac cctctccctt gacacagggc agccgctctg 2641 gctctagctc cagctccggg accctctggg accccccggg acccatgtga cccagcggcc 2701 cctcgcactg taggtctccc gggacggcag ggcagtgagg gaggcgaggg ccggggtctg 2761 ggctcacgcc ctgcagtcct gggccgacac agctccgggg aaggcggagg tccttgggga 2821 gagctgccct gagccaggcc ggagcggtga ccctggggcc cggcccctct tgtccccaga 2881 gtgtcccacg ggcacctgtt ggttctgagt cttagtgggg ctactgggga cacgggccgt 2941 agctgagtcg agagctgggt gcagggtggt caaaccctgg ccagacctgg agttcaggag 3001 ggccccgggc caccctgacc tttgaggggc tgctgtagca tgatgcgggt ggccctgggc 3061 acttcgagat ggccagagtc cagcttcccg tgtgtgtggt gggcctgggg aagtggctgg 3121 tggagtcggg agcttcgggc caggcaaggc ttgatcccac agcagggagc ccctcaccca 3181 ggcaggcggc cacaggccgg tccctcctga tcccatccct cctttcccag ggagtggagg 3241 atgccttcta cacgttggtg cgtgagatcc ggcagcacaa gctgcggaag ctgaaccctc 3301 ctgatgagag tggccccggc tgcatgagct gcaagtgtgt gctctcctga cgcaggtgag 3361 ggggactccc agggcggccg ccacgcccac cggatgaccc cggctccccg cccctgccgg 3421 tctcctggcc tgcggtcagc agcctccctt gtgccccgcc cagcacaagc tcaggacatg 3481 gaggtgccgg atgcaggaag gaggtgcaga cggaaggagg aggaaggaag gacggaagca 3541 aggaaggaag gaagggctgc tggagcccag tcaccccggg accgtgggcc gaggtgactg 3601 cagaccctcc cagggaggct gtgcacagac tgtcttgaac atcccaaatg ccaccggaac 3661 cccagccctt agctcccctc ccaggcctct gtgggccctt gtcgggcaca gatgggatca 3721 cagtaaatta ttggatggtc ttgatcttgg ttttcggctg agggtgggac acggtgcgcg 3781 tgtggcctgg catgaggtat gtcggaacct caggcctgtc cagccctggg ctctccatag 3841 cctttgggag ggggaggttg ggagaggccg gtcaggggtc tgggctgtgg tgctctctcc 3901 tcccgcctgc cccagtgtcc acggcttctg gcagagagct ctggacaagc aggcagatca 3961 taaggacaga gagcttactg tgcttctacc aactaggagg gcgtcctggt cctccagagg 4021 gaggtggttt caggggttgg ggatctgtgc cggtggctct ggtctctgct gggagccttc 4081 ttggcggtga gaggcatcac ctttcctgac ttgctcccag cgtgaaatgc acctgccaag 4141 aatggcagac atagggaccc cgcctcctgg gccttcacat gcccagtttt cttcggctct 4201 gtggcctgaa gcggtctgtg gaccttggaa gtagggctcc agcaccgact ggcctcaggc 4261 ctctgcctca ttggtggtcg ggtagcggcc agtagggcgt gggagcctgg ccatccctgc 4321 ctcctggagt ggacgaggtt ggcagctggt ccgtctgctc ctgccccact ctcccccgcc 4381 cctgccctca ccctaccctt gccccacgcc tgcctcatgg ctggttgctc ttggagcctg 4441 gtagtgtcac tggctcagcc ttgctgggta tacacaggct ctgccaccca ctctgctcca 4501 aggggcttgc cctgccttgg gccaagttct aggtctggcc acagccacag acagctcagt 4561 cccctgtgtg gtcatcctgg cttctgctgg gggcccacag cgcccctggt gcccctcccc 4621 tcccagggcc cgggttgagg ctgggccagg ccctctggga cggggacttg tgccctgtca 4681 gggttcccta tccctgaggt tgggggagag ctagcagggc atgccgctgg ctggccaggg 4741 ctgcagggac actccccctt ttgtccaggg aataccacac tcgcccttct ctccagcgaa 4801 caccacactc gcccttctct ccaggggacg ccacactccc ccttctgtcc aggggacgcc 4861 acactccccc ttctctccag gggacgccac actcgccctt ctctccaggg gacgccacac 4921 tcgcccttct ctccagggga cgccacactc gcccttctgt ccaggggacg ccacactcgc 4981 ccttctctcc aggggacgcc acactcgccc ttctctccag gggacgccac actccccctt 5041 ctgtccaggg gacgccacac tcccccttct ctccagggga cgccacactc ccccttctct 5101 ccaggggacg ccacactcgc ccttctctcc aggggacgcc acactccccc ttctgtccag 5161 gggacgccac actcgccctt ctctccaggg gacgccacac tcgcccttct ctccagggga 5221 cgccacactc ccccttctct ccaggggacg ccacactccc ccttctctcc aggggacgcc 5281 acactccccc ttctgtccag gggacgccac actcgccctt ctctccaggg gacgccacac 5341 tcccccttct ctccagggga cgccacactc ccccttctct ccaggggacg ccacactccc 5401 ccttctgtcc aggggacgcc acactcgccc ttctctccag gggacgccac actcgccctt 5461 ctctccaggg gacgccacac tcgcccttct ctccagggga cgccacactt gcccttctgt 5521 ccagggaatg ccacactccc ccttctcccc agcagcctcc gagtgaccag cttccccatc 5581 gatagacttc ccgaggccag gagccctcta gggctgccgg gtgccaccct ggctccttcc 5641 acaccgtgct ggtcactgcc tgctgggggc gtcagatgca ggtgaccctg tgcaggaggt 5701 atctctggac ctgcctcttg gtcattacgg ggctgggcag ggcctggtat cagggccccg 5761 ctggggttgc agggctgggc ctgtgctgtg gtcctggggt gtccaggaca gacgtggagg 5821 ggtcagggcc cagcacccct gctccatgct gaactgtggg aagcatccag gtccctgggt 5881 ggcttcaaca ggagttccag cacgggaacc actggacaac ctggggtgtg tcctgatctg 5941 gggacaggcc agccacaccc cgagtcctag ggactccaga gagcagccca ctgccctggg 6001 ctccacggaa gccccctcat gccgctaggc cttggcctcg gggacagccc agctaggcca 6061 gtgtgtggca ggaccaggcc cccatgtggg agctgacccc ttgggattct ggagctgtgc 6121 tgatgggcag gggagagcca gctcctcccc ttgagggagg gtcttgatgc ctggggttac 6181 ccgcagaggc ctgggtgccg ggacgctccc cggtttggct gaaaggaaag cagatgtggt 6241 cagcttctcc actgagccca tctggtcttc ccggggctgg gccccataga tctgggtccc 6301 tgtgtggccc ccctggtctg atgccgagga tacccctgca aactgccaat cccagaggac 6361 aagactggga agtccctgca gggagagccc atccccgcac cctgacccac aagagggact 6421 cctgctgccc accaggcatc cctccaggga tcc //