NRAS is an enzyme that in humans is encoded by the NRASgene. It was discovered by a small team of researchers led by Robin Weiss at the Institute of Cancer Research in London.[5][6] It was the third RAS gene to be discovered, and was named NRAS, for its initial identification in human neuroblastoma cells.
The N-ras proto-oncogene is a member of the Ras gene family. It is mapped on chromosome 1, and it is activated in HL60, a promyelocytic leukemia line. The order of nearby genes is as follows: cen—CD2—NGFB—NRAS—tel.
The mammalian Ras gene family consists of the Harvey and Kirsten Ras genes (HRAS and KRAS), an inactive pseudogene of each (c-Hras2 and c-Kras1) and the N-Ras gene. They differ significantly only in the C-terminal 40 amino acids. These Ras genes have GTP/GDP binding and GTPase activity, and their normal function may be as G-like regulatory proteins involved in the normal control of cell growth.
The N-Ras gene specifies two main transcripts of 2 kb and 4.3 kb. The difference between the two transcripts is a simple extension through the termination site of the 2 kb transcript. The N-Ras gene consists of seven exons (-I, I, II, III, IV, V, VI). The smaller 2 kb transcript contains the VIa exon, and the larger 4.3 kb transcript contains the VIb exon which is just a longer form of the VIa exon. Both transcripts encode identical proteins as they differ only the 3′ untranslated region.[7]
Mutationsedit
Mutations which change amino acid residues 12, 13 or 61 activate the potential of N-ras to transform cultured cells and are implicated in a variety of human tumors[7] e.g. melanoma.
As a drug targetedit
Binimetinib (MEK162) has had a phase III clinical trial for NRAS Q61 mutant melanoma.[8]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000213281 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000027852 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Marshall CJ, Hall A, Weiss RA (September 1982). "A transforming gene present in human sarcoma cell lines". Nature. 299 (5879): 171–3. Bibcode:1982Natur.299..171M. doi:10.1038/299171a0. PMID 6287287. S2CID 4342747.
^Shimizu K, Goldfarb M, Perucho M, Wigler M (January 1983). "Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line". PNAS. 80 (2): 383–7. Bibcode:1983PNAS...80..383S. doi:10.1073/pnas.80.2.383. PMC393381. PMID 6300838.
^Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma
Further readingedit
McCormick F (1996). "Ras-related proteins in signal transduction and growth control". Mol. Reprod. Dev. 42 (4): 500–6. doi:10.1002/mrd.1080420419. PMID 8607982. S2CID 6507743.
van Elsas A, Scheibenbogen C, van der Minne C, et al. (1998). "UV-induced N-ras mutations are T-cell targets in human melanoma". Melanoma Res. 7 (Suppl 2): S107–13. doi:10.1097/00008390-199708001-00017. PMID 9578425. S2CID 19219505.
Dracopoli NC, Meisler MH (1990). "Mapping the human amylase gene cluster on the proximal short arm of chromosome 1 using a highly informative (CA)n repeat" (PDF). Genomics. 7 (1): 97–102. doi:10.1016/0888-7543(90)90523-W. hdl:2027.42/28584. PMID 1692298.
Yuasa Y, Kamiyama T, Kato M, et al. (1990). "Transforming genes from familial adenomatous polyposis patient cells detected by a tumorigenicity assay". Oncogene. 5 (4): 589–96. PMID 1970154.
Hancock JF, Magee AI, Childs JE, Marshall CJ (1989). "All ras proteins are polyisoprenylated but only some are palmitoylated". Cell. 57 (7): 1167–77. doi:10.1016/0092-8674(89)90054-8. PMID 2661017. S2CID 19292550.
Hall A, Brown R (1985). "Human N-ras: cDNA cloning and gene structure". Nucleic Acids Res. 13 (14): 5255–68. doi:10.1093/nar/13.14.5255. PMC321863. PMID 2991860.
Hirai H, Tanaka S, Azuma M, et al. (1986). "Transforming genes in human leukemia cells". Blood. 66 (6): 1371–8. doi:10.1182/blood.V66.6.1371.1371. PMID 2998510.
Neri A, Knowles DM, Greco A, et al. (1988). "Analysis of RAS oncogene mutations in human lymphoid malignancies". Proc. Natl. Acad. Sci. U.S.A. 85 (23): 9268–72. Bibcode:1988PNAS...85.9268N. doi:10.1073/pnas.85.23.9268. PMC282720. PMID 3057505.
Nitta N, Ochiai M, Nagao M, Sugimura T (1987). "Amino-acid substitution at codon 13 of the N-ras oncogene in rectal cancer in a Japanese patient". Jpn. J. Cancer Res. 78 (1): 21–6. PMID 3102434.
Raybaud F, Noguchi T, Marics I, et al. (1988). "Detection of a low frequency of activated ras genes in human melanomas using a tumorigenicity assay". Cancer Res. 48 (4): 950–3. PMID 3276402.
Hirai H, Kobayashi Y, Mano H, et al. (1987). "A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome". Nature. 327 (6121): 430–2. Bibcode:1987Natur.327..430H. doi:10.1038/327430a0. PMID 3295562. S2CID 4270769.
Gambke C, Hall A, Moroni C (1985). "Activation of an N-ras gene in acute myeloblastic leukemia through somatic mutation in the first exon". Proc. Natl. Acad. Sci. U.S.A. 82 (3): 879–82. Bibcode:1985PNAS...82..879G. doi:10.1073/pnas.82.3.879. PMC397150. PMID 3856237.
Padua RA, Barrass NC, Currie GA (1985). "Activation of N-ras in a human melanoma cell line". Mol. Cell. Biol. 5 (3): 582–5. doi:10.1128/mcb.5.3.582. PMC366752. PMID 3887133.
Brown R, Marshall CJ, Pennie SG, Hall A (1984). "Mechanism of activation of an N-ras gene in the human fibrosarcoma cell line HT1080". EMBO J. 3 (6): 1321–6. doi:10.1002/j.1460-2075.1984.tb01970.x. PMC557516. PMID 6086315.
Yuasa Y, Gol RA, Chang A, et al. (1984). "Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells". Proc. Natl. Acad. Sci. U.S.A. 81 (12): 3670–4. Bibcode:1984PNAS...81.3670Y. doi:10.1073/pnas.81.12.3670. PMC345280. PMID 6587382.
Taparowsky E, Shimizu K, Goldfarb M, Wigler M (1983). "Structure and activation of the human N-ras gene". Cell. 34 (2): 581–6. doi:10.1016/0092-8674(83)90390-2. PMID 6616621. S2CID 39787991.
Mitchell EL, Jones D, White GR, et al. (1995). "Determination of the gene order of the three loci CD2, NGFB, and NRAS at human chromosome band 1p13 and refinement of their localisation at the subband level by fluorescence in situ hybridisation". Cytogenet. Cell Genet. 70 (3–4): 183–5. doi:10.1159/000134028. PMID 7789166.
Kodaki T, Woscholski R, Hallberg B, et al. (1995). "The activation of phosphatidylinositol 3-kinase by Ras". Curr. Biol. 4 (9): 798–806. doi:10.1016/S0960-9822(00)00177-9. PMID 7820549. S2CID 20836474.
Rodriguez-Viciana P, Warne PH, Vanhaesebroeck B, et al. (1996). "Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation". EMBO J. 15 (10): 2442–51. doi:10.1002/j.1460-2075.1996.tb00602.x. PMC450176. PMID 8665852.
External linksedit
GeneReviews/NCBI/NIH/UW entry on Noonan syndrome
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neuroblastoma, viral, oncogene, homolog, nras, enzyme, that, humans, encoded, nras, gene, discovered, small, team, researchers, robin, weiss, institute, cancer, research, london, third, gene, discovered, named, nras, initial, identification, human, neuroblasto. NRAS is an enzyme that in humans is encoded by the NRAS gene It was discovered by a small team of researchers led by Robin Weiss at the Institute of Cancer Research in London 5 6 It was the third RAS gene to be discovered and was named NRAS for its initial identification in human neuroblastoma cells NRASAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes3CON 2N9CIdentifiersAliasesNRAS ALPS4 CMNS N ras NCMS NRAS1 NS6 Neuroblastoma RAS viral oncogene homolog NRAS proto oncogene GTPaseExternal IDsOMIM 164790 MGI 97376 HomoloGene 55661 GeneCards NRASGene location Human Chr Chromosome 1 human 1 Band1p13 2Start114 704 469 bp 1 End114 716 771 bp 1 Gene location Mouse Chr Chromosome 3 mouse 2 Band3 F2 2 3 45 25 cMStart102 965 601 bp 2 End102 975 230 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed insecondary oocyteamniotic fluidgerminal epitheliumganglionic eminenceparietal pleuratibiavisceral pleuraendothelial cellspongy boneislet of LangerhansTop expressed insciatic nerveyolk saccorneal stromamedial ganglionic eminencetrigeminal ganglionhair follicleprimitive streakmedullary collecting ductsecondary oocytespermatocyteMore reference expression dataBioGPSn aGene ontologyMolecular functionnucleotide binding protein containing complex binding GTP binding GTPase activity protein bindingCellular componentGolgi apparatus membrane Golgi membrane plasma membrane extracellular exosome tertiary granule membraneBiological processepidermal growth factor receptor signaling pathway stimulatory C type lectin receptor signaling pathway MAPK cascade axon guidance Fc epsilon receptor signaling pathway Ras protein signal transduction leukocyte migration signal transduction ERBB2 signaling pathway neutrophil degranulation positive regulation of endothelial cell proliferationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez489318176EnsemblENSG00000213281ENSMUSG00000027852UniProtP01111P08556RefSeq mRNA NM 002524NM 010937NM 001368638RefSeq protein NP 002515n aLocation UCSC Chr 1 114 7 114 72 MbChr 3 102 97 102 98 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Mutations 2 1 As a drug target 3 References 4 Further reading 5 External linksFunction editThe N ras proto oncogene is a member of the Ras gene family It is mapped on chromosome 1 and it is activated in HL60 a promyelocytic leukemia line The order of nearby genes is as follows cen CD2 NGFB NRAS tel The mammalian Ras gene family consists of the Harvey and Kirsten Ras genes HRAS and KRAS an inactive pseudogene of each c Hras2 and c Kras1 and the N Ras gene They differ significantly only in the C terminal 40 amino acids These Ras genes have GTP GDP binding and GTPase activity and their normal function may be as G like regulatory proteins involved in the normal control of cell growth The N Ras gene specifies two main transcripts of 2 kb and 4 3 kb The difference between the two transcripts is a simple extension through the termination site of the 2 kb transcript The N Ras gene consists of seven exons I I II III IV V VI The smaller 2 kb transcript contains the VIa exon and the larger 4 3 kb transcript contains the VIb exon which is just a longer form of the VIa exon Both transcripts encode identical proteins as they differ only the 3 untranslated region 7 Mutations editMutations which change amino acid residues 12 13 or 61 activate the potential of N ras to transform cultured cells and are implicated in a variety of human tumors 7 e g melanoma As a drug target edit Binimetinib MEK162 has had a phase III clinical trial for NRAS Q61 mutant melanoma 8 References edit a b c GRCh38 Ensembl release 89 ENSG00000213281 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000027852 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Marshall CJ Hall A Weiss RA September 1982 A transforming gene present in human sarcoma cell lines Nature 299 5879 171 3 Bibcode 1982Natur 299 171M doi 10 1038 299171a0 PMID 6287287 S2CID 4342747 Shimizu K Goldfarb M Perucho M Wigler M January 1983 Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line PNAS 80 2 383 7 Bibcode 1983PNAS 80 383S doi 10 1073 pnas 80 2 383 PMC 393381 PMID 6300838 a b Entrez Gene NRAS neuroblastoma RAS viral v ras oncogene homolog Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation positive MelanomaFurther reading editMcCormick F 1996 Ras related proteins in signal transduction and growth control Mol Reprod Dev 42 4 500 6 doi 10 1002 mrd 1080420419 PMID 8607982 S2CID 6507743 van Elsas A Scheibenbogen C van der Minne C et al 1998 UV induced N ras mutations are T cell targets in human melanoma Melanoma Res 7 Suppl 2 S107 13 doi 10 1097 00008390 199708001 00017 PMID 9578425 S2CID 19219505 Dracopoli NC Meisler MH 1990 Mapping the human amylase gene cluster on the proximal short arm of chromosome 1 using a highly informative CA n repeat PDF Genomics 7 1 97 102 doi 10 1016 0888 7543 90 90523 W hdl 2027 42 28584 PMID 1692298 Yuasa Y Kamiyama T Kato M et al 1990 Transforming genes from familial adenomatous polyposis patient cells detected by a tumorigenicity assay Oncogene 5 4 589 96 PMID 1970154 Hancock JF Magee AI Childs JE Marshall CJ 1989 All ras proteins are polyisoprenylated but only some are palmitoylated Cell 57 7 1167 77 doi 10 1016 0092 8674 89 90054 8 PMID 2661017 S2CID 19292550 Hall A Brown R 1985 Human N ras cDNA cloning and gene structure Nucleic Acids Res 13 14 5255 68 doi 10 1093 nar 13 14 5255 PMC 321863 PMID 2991860 Hirai H Tanaka S Azuma M et al 1986 Transforming genes in human leukemia cells Blood 66 6 1371 8 doi 10 1182 blood V66 6 1371 1371 PMID 2998510 Neri A Knowles DM Greco A et al 1988 Analysis of RAS oncogene mutations in human lymphoid malignancies Proc Natl Acad Sci U S A 85 23 9268 72 Bibcode 1988PNAS 85 9268N doi 10 1073 pnas 85 23 9268 PMC 282720 PMID 3057505 Nitta N Ochiai M Nagao M Sugimura T 1987 Amino acid substitution at codon 13 of the N ras oncogene in rectal cancer in a Japanese patient Jpn J Cancer Res 78 1 21 6 PMID 3102434 Raybaud F Noguchi T Marics I et al 1988 Detection of a low frequency of activated ras genes in human melanomas using a tumorigenicity assay Cancer Res 48 4 950 3 PMID 3276402 Hirai H Kobayashi Y Mano H et al 1987 A point mutation at codon 13 of the N ras oncogene in myelodysplastic syndrome Nature 327 6121 430 2 Bibcode 1987Natur 327 430H doi 10 1038 327430a0 PMID 3295562 S2CID 4270769 Gambke C Hall A Moroni C 1985 Activation of an N ras gene in acute myeloblastic leukemia through somatic mutation in the first exon Proc Natl Acad Sci U S A 82 3 879 82 Bibcode 1985PNAS 82 879G doi 10 1073 pnas 82 3 879 PMC 397150 PMID 3856237 Padua RA Barrass NC Currie GA 1985 Activation of N ras in a human melanoma cell line Mol Cell Biol 5 3 582 5 doi 10 1128 mcb 5 3 582 PMC 366752 PMID 3887133 Brown R Marshall CJ Pennie SG Hall A 1984 Mechanism of activation of an N ras gene in the human fibrosarcoma cell line HT1080 EMBO J 3 6 1321 6 doi 10 1002 j 1460 2075 1984 tb01970 x PMC 557516 PMID 6086315 Yuasa Y Gol RA Chang A et al 1984 Mechanism of activation of an N ras oncogene of SW 1271 human lung carcinoma cells Proc Natl Acad Sci U S A 81 12 3670 4 Bibcode 1984PNAS 81 3670Y doi 10 1073 pnas 81 12 3670 PMC 345280 PMID 6587382 Taparowsky E Shimizu K Goldfarb M Wigler M 1983 Structure and activation of the human N ras gene Cell 34 2 581 6 doi 10 1016 0092 8674 83 90390 2 PMID 6616621 S2CID 39787991 Mitchell EL Jones D White GR et al 1995 Determination of the gene order of the three loci CD2 NGFB and NRAS at human chromosome band 1p13 and refinement of their localisation at the subband level by fluorescence in situ hybridisation Cytogenet Cell Genet 70 3 4 183 5 doi 10 1159 000134028 PMID 7789166 Kodaki T Woscholski R Hallberg B et al 1995 The activation of phosphatidylinositol 3 kinase by Ras Curr Biol 4 9 798 806 doi 10 1016 S0960 9822 00 00177 9 PMID 7820549 S2CID 20836474 Rodriguez Viciana P Warne PH Vanhaesebroeck B et al 1996 Activation of phosphoinositide 3 kinase by interaction with Ras and by point mutation EMBO J 15 10 2442 51 doi 10 1002 j 1460 2075 1996 tb00602 x PMC 450176 PMID 8665852 External links editGeneReviews NCBI NIH UW entry on Noonan syndrome nbsp This protein related article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Neuroblastoma RAS viral oncogene homolog amp oldid 1191281881, wikipedia, wiki, book, books, library,
