GTPase KRas

Details

Name
GTPase KRas
Synonyms
  • c-K-ras
  • c-Ki-ras
  • K-Ras 2
  • Ki-Ras
  • KRAS2
  • RASK2
Gene Name
KRAS
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007775|GTPase KRas
MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAG
QEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDL
PSRTVDTKQAQDLARSYGIPFIETSAKTRQRVEDAFYTLVREIRQYRLKKISKEEKTPGC
VKIKKCIIM
Number of residues
189
Molecular Weight
21655.67
Theoretical pI
6.76
GO Classification
Functions
GDP binding / GMP binding / GTP binding / protein complex binding
Processes
activation of MAPKK activity / axon guidance / blood coagulation / cytokine-mediated signaling pathway / epidermal growth factor receptor signaling pathway / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / innate immune response / insulin receptor signaling pathway / leukocyte migration / MAPK cascade / neurotrophin TRK receptor signaling pathway / positive regulation of cell proliferation / positive regulation of gene expression / positive regulation of MAP kinase activity / positive regulation of NF-kappaB transcription factor activity / positive regulation of nitric-oxide synthase activity / positive regulation of protein phosphorylation / Ras protein signal transduction / response to glucocorticoid / response to mineralocorticoid / small GTPase mediated signal transduction / social behavior / stimulatory C-type lectin receptor signaling pathway / vascular endothelial growth factor receptor signaling pathway
Components
cytoplasm / cytosol / extrinsic component of cytoplasmic side of plasma membrane / focal adhesion / membrane / membrane raft / mitochondrion / plasma membrane
General Function
Protein complex binding
Specific Function
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Plays an important role in the regulation of cell proliferation (PubMed:23698361, PubMed:22711838).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021940|GTPase KRas (KRAS)
ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGGTGGCGTAGGCAAGAGTGCCTTGACG
ATACAGCTAATTCAGAATCATTTTGTGGACGAATATGATCCAACAATAGAGGATTCCTAC
AGGAAGCAAGTAGTAATTGATGGAGAAACCTGTCTCTTGGATATTCTCGACACAGCAGGT
CAAGAGGAGTACAGTGCAATGAGGGACCAGTACATGAGGACTGGGGAGGGCTTTCTTTGT
GTATTTGCCATAAATAATACTAAATCATTTGAAGATATTCACCATTATAGAGAACAAATT
AAAAGAGTTAAGGACTCTGAAGATGTACCTATGGTCCTAGTAGGAAATAAATGTGATTTG
CCTTCTAGAACAGTAGACACAAAACAGGCTCAGGACTTAGCAAGAAGTTATGGAATTCCT
TTTATTGAAACATCAGCAAAGACAAGACAGGGTGTTGATGATGCCTTCTATACATTAGTT
CGAGAAATTCGAAAACATAAAGAAAAGATGAGCAAAGATGGTAAAAAGAAGAAAAAGAAG
TCAAAGACAAAGTGTGTAATTATGTAA
Chromosome Location
12
Locus
12p12.1
External Identifiers
ResourceLink
UniProtKB IDP01116
UniProtKB Entry NameRASK_HUMAN
GenBank Protein ID186764
GenBank Gene IDM54968
HGNC IDHGNC:6407
General References
  1. McGrath JP, Capon DJ, Smith DH, Chen EY, Seeburg PH, Goeddel DV, Levinson AD: Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene. Nature. 1983 Aug 11-17;304(5926):501-6. [Article]
  2. Shimizu K, Birnbaum D, Ruley MA, Fasano O, Suard Y, Edlund L, Taparowsky E, Goldfarb M, Wigler M: Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1. Nature. 1983 Aug 11-17;304(5926):497-500. [Article]
  3. Capon DJ, Seeburg PH, McGrath JP, Hayflick JS, Edman U, Levinson AD, Goeddel DV: Activation of Ki-ras2 gene in human colon and lung carcinomas by two different point mutations. Nature. 1983 Aug 11-17;304(5926):507-13. [Article]
  4. McCoy MS, Bargmann CI, Weinberg RA: Human colon carcinoma Ki-ras2 oncogene and its corresponding proto-oncogene. Mol Cell Biol. 1984 Aug;4(8):1577-82. [Article]
  5. Kahn S, Yamamoto F, Almoguera C, Winter E, Forrester K, Jordano J, Perucho M: The c-K-ras gene and human cancer (review). Anticancer Res. 1987 Jul-Aug;7(4A):639-52. [Article]
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  8. Nakano H, Yamamoto F, Neville C, Evans D, Mizuno T, Perucho M: Isolation of transforming sequences of two human lung carcinomas: structural and functional analysis of the activated c-K-ras oncogenes. Proc Natl Acad Sci U S A. 1984 Jan;81(1):71-5. [Article]
  9. Hirai H, Okabe T, Anraku Y, Fujisawa M, Urabe A, Takaku F: Activation of the c-K-ras oncogene in a human pancreas carcinoma. Biochem Biophys Res Commun. 1985 Feb 28;127(1):168-74. [Article]
  10. Deng GR, Lu YY, Chen SM, Miao J, Lu GR, Li H, Cai H, Xu XL, E Z, Liu PN: Activated c-Ha-ras oncogene with a guanine to thymine transversion at the twelfth codon in a human stomach cancer cell line. Cancer Res. 1987 Jun 15;47(12):3195-8. [Article]
  11. Santos E, Martin-Zanca D, Reddy EP, Pierotti MA, Della Porta G, Barbacid M: Malignant activation of a K-ras oncogene in lung carcinoma but not in normal tissue of the same patient. Science. 1984 Feb 17;223(4637):661-4. [Article]
  12. Sekiya T, Tokunaga A, Fushimi M: Essential region for transforming activity of human c-Ha-ras-1. Jpn J Cancer Res. 1985 Sep;76(9):787-91. [Article]
  13. Yamamoto F, Perucho M: Activation of a human c-K-ras oncogene. Nucleic Acids Res. 1984 Dec 11;12(23):8873-85. [Article]
  14. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  15. Yang MH, Nickerson S, Kim ET, Liot C, Laurent G, Spang R, Philips MR, Shan Y, Shaw DE, Bar-Sagi D, Haigis MC, Haigis KM: Regulation of RAS oncogenicity by acetylation. Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):10843-8. doi: 10.1073/pnas.1201487109. Epub 2012 Jun 18. [Article]
  16. Zimmermann G, Papke B, Ismail S, Vartak N, Chandra A, Hoffmann M, Hahn SA, Triola G, Wittinghofer A, Bastiaens PI, Waldmann H: Small molecule inhibition of the KRAS-PDEdelta interaction impairs oncogenic KRAS signalling. Nature. 2013 May 30;497(7451):638-42. doi: 10.1038/nature12205. Epub 2013 May 22. [Article]
  17. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  18. Sun Q, Burke JP, Phan J, Burns MC, Olejniczak ET, Waterson AG, Lee T, Rossanese OW, Fesik SW: Discovery of small molecules that bind to K-Ras and inhibit Sos-mediated activation. Angew Chem Int Ed Engl. 2012 Jun 18;51(25):6140-3. doi: 10.1002/anie.201201358. Epub 2012 May 8. [Article]
  19. Maurer T, Garrenton LS, Oh A, Pitts K, Anderson DJ, Skelton NJ, Fauber BP, Pan B, Malek S, Stokoe D, Ludlam MJ, Bowman KK, Wu J, Giannetti AM, Starovasnik MA, Mellman I, Jackson PK, Rudolph J, Wang W, Fang G: Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity. Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5299-304. doi: 10.1073/pnas.1116510109. Epub 2012 Mar 19. [Article]
  20. Kozma SC, Bogaard ME, Buser K, Saurer SM, Bos JL, Groner B, Hynes NE: The human c-Kirsten ras gene is activated by a novel mutation in codon 13 in the breast carcinoma cell line MDA-MB231. Nucleic Acids Res. 1987 Aug 11;15(15):5963-71. [Article]
  21. Grimmond SM, Raghavan D, Russell PJ: Detection of a rare point mutation in Ki-ras of a human bladder cancer xenograft by polymerase chain reaction and direct sequencing. Urol Res. 1992;20(2):121-6. [Article]
  22. Motojima K, Urano T, Nagata Y, Shiku H, Tsurifune T, Kanematsu T: Detection of point mutations in the Kirsten-ras oncogene provides evidence for the multicentricity of pancreatic carcinoma. Ann Surg. 1993 Feb;217(2):138-43. [Article]
  23. Lee KH, Lee JS, Suh C, Kim SW, Kim SB, Lee JH, Lee MS, Park MY, Sun HS, Kim SH: Clinicopathologic significance of the K-ras gene codon 12 point mutation in stomach cancer. An analysis of 140 cases. Cancer. 1995 Jun 15;75(12):2794-801. [Article]
  24. Bollag G, Adler F, elMasry N, McCabe PC, Conner E Jr, Thompson P, McCormick F, Shannon K: Biochemical characterization of a novel KRAS insertion mutation from a human leukemia. J Biol Chem. 1996 Dec 20;271(51):32491-4. [Article]
  25. Lee SH, Lee JW, Soung YH, Kim HS, Park WS, Kim SY, Lee JH, Park JY, Cho YG, Kim CJ, Nam SW, Kim SH, Lee JY, Yoo NJ: BRAF and KRAS mutations in stomach cancer. Oncogene. 2003 Oct 9;22(44):6942-5. [Article]
  26. Sharma MK, Zehnbauer BA, Watson MA, Gutmann DH: RAS pathway activation and an oncogenic RAS mutation in sporadic pilocytic astrocytoma. Neurology. 2005 Oct 25;65(8):1335-6. [Article]
  27. Carta C, Pantaleoni F, Bocchinfuso G, Stella L, Vasta I, Sarkozy A, Digilio C, Palleschi A, Pizzuti A, Grammatico P, Zampino G, Dallapiccola B, Gelb BD, Tartaglia M: Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. Am J Hum Genet. 2006 Jul;79(1):129-35. Epub 2006 May 1. [Article]
  28. Tam IY, Chung LP, Suen WS, Wang E, Wong MC, Ho KK, Lam WK, Chiu SW, Girard L, Minna JD, Gazdar AF, Wong MP: Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res. 2006 Mar 1;12(5):1647-53. [Article]
  29. Niihori T, Aoki Y, Narumi Y, Neri G, Cave H, Verloes A, Okamoto N, Hennekam RC, Gillessen-Kaesbach G, Wieczorek D, Kavamura MI, Kurosawa K, Ohashi H, Wilson L, Heron D, Bonneau D, Corona G, Kaname T, Naritomi K, Baumann C, Matsumoto N, Kato K, Kure S, Matsubara Y: Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nat Genet. 2006 Mar;38(3):294-6. Epub 2006 Feb 12. [Article]
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  31. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [Article]
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  33. Bertola DR, Pereira AC, Brasil AS, Albano LM, Kim CA, Krieger JE: Further evidence of genetic heterogeneity in Costello syndrome: involvement of the KRAS gene. J Hum Genet. 2007;52(6):521-6. Epub 2007 Apr 28. [Article]
  34. Zenker M, Lehmann K, Schulz AL, Barth H, Hansmann D, Koenig R, Korinthenberg R, Kreiss-Nachtsheim M, Meinecke P, Morlot S, Mundlos S, Quante AS, Raskin S, Schnabel D, Wehner LE, Kratz CP, Horn D, Kutsche K: Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations. J Med Genet. 2007 Feb;44(2):131-5. Epub 2006 Oct 20. [Article]
  35. Kratz CP, Zampino G, Kriek M, Kant SG, Leoni C, Pantaleoni F, Oudesluys-Murphy AM, Di Rocco C, Kloska SP, Tartaglia M, Zenker M: Craniosynostosis in patients with Noonan syndrome caused by germline KRAS mutations. Am J Med Genet A. 2009 May;149A(5):1036-40. doi: 10.1002/ajmg.a.32786. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB07771[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC ACIDexperimentalunknownDetails
DB07780Farnesyl diphosphateexperimentalunknownDetails
DB15569Sotorasibapproved, investigationalyesinhibitorDetails
DB15568AdagrasibinvestigationalyesinhibitorDetails