You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP01958
Secondary Accession Numbers
  • 7383
Name GTPase HRas
Synonyms
  1. GTPase HRas, N-terminally processed
  2. H-Ras-1
  3. Ha-Ras
  4. Transforming protein p21
  5. c-H-ras
  6. p21ras
Gene Name HRAS
Protein Type Unknown
Biological Properties
General Function Involved in GTP binding
Specific Function Ras proteins bind GDP/GTP and possess intrinsic GTPase activity
Pathways
  • Fc Epsilon Receptor I Signaling in Mast Cells
  • Insulin Signalling
  • Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
  • Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Reactions Not Available
GO Classification
Component
membrane
cell part
intracellular
Function
purine nucleotide binding
binding
nucleotide binding
catalytic activity
hydrolase activity
guanyl nucleotide binding
guanyl ribonucleotide binding
gtp binding
gtpase activity
nucleoside-triphosphatase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
Process
biological regulation
regulation of biological process
regulation of cellular process
signal transduction
intracellular signal transduction
small gtpase mediated signal transduction
Cellular Location
  1. Cell membrane
  2. Lipid-anchor
  3. Lipid-anchor
  4. Golgi apparatus membrane
  5. Cytoplasmic side
Gene Properties
Chromosome Location Chromosome:1
Locus 11p15.5
SNPs HRAS
Gene Sequence
>570 bp
ATGACGGAATATAAGCTGGTGGTGGTGGGCGCCGGCGGTGTGGGCAAGAGTGCGCTGACC
ATCCAGCTGATCCAGAACCATTTTGTGGACGAATACGACCCCACTATAGAGGATTCCTAC
CGGAAGCAGGTGGTCATTGATGGGGAGACGTGCCTGTTGGACATCCTGGATACCGCCGGC
CAGGAGGAGTACAGCGCCATGCGGGACCAGTACATGCGCACCGGGGAGGGCTTCCTGTGT
GTGTTTGCCATCAACAACACCAAGTCTTTTGAGGACATCCACCAGTACAGGGAGCAGATC
AAACGGGTGAAGGACTCGGATGACGTGCCCATGGTGCTGGTGGGGAACAAGTGTGACCTG
GCTGCACGCACTGTGGAATCTCGGCAGGCTCAGGACCTCGCCCGAAGCTACGGCATCCCC
TACATCGAGACCTCGGCCAAGACCCGGCAGGGAGTGGAGGATGCCTTCTACACGTTGGTG
CGTGAGATCCGGCAGCACAAGCTGCGGAAGCTGAACCCTCCTGATGAGAGTGGCCCCGGC
TGCATGAGCTGCAAGTGTGTGCTCTCCTGA
Protein Properties
Number of Residues 189
Molecular Weight 21298.0
Theoretical pI 4.94
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>GTPase HRas
MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAG
QEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHQYREQIKRVKDSDDVPMVLVGNKCDL
AARTVESRQAQDLARSYGIPYIETSAKTRQGVEDAFYTLVREIRQHKLRKLNPPDESGPG
CMSCKCVLS
GenBank ID Protein 20147725
UniProtKB/Swiss-Prot ID P01112
UniProtKB/Swiss-Prot Entry Name RASH_HUMAN
PDB IDs
GenBank Gene ID AF493916
GeneCard ID HRAS
GenAtlas ID HRAS
HGNC ID HGNC:5173
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Topham MK, Prescott SM: Diacylglycerol kinase zeta regulates Ras activation by a novel mechanism. J Cell Biol. 2001 Mar 19;152(6):1135-43. [PubMed:11257115 ]
  3. Goshima N, Kawamura Y, Fukumoto A, Miura A, Honma R, Satoh R, Wakamatsu A, Yamamoto J, Kimura K, Nishikawa T, Andoh T, Iida Y, Ishikawa K, Ito E, Kagawa N, Kaminaga C, Kanehori K, Kawakami B, Kenmochi K, Kimura R, Kobayashi M, Kuroita T, Kuwayama H, Maruyama Y, Matsuo K, Minami K, Mitsubori M, Mori M, Morishita R, Murase A, Nishikawa A, Nishikawa S, Okamoto T, Sakagami N, Sakamoto Y, Sasaki Y, Seki T, Sono S, Sugiyama A, Sumiya T, Takayama T, Takayama Y, Takeda H, Togashi T, Yahata K, Yamada H, Yanagisawa Y, Endo Y, Imamoto F, Kisu Y, Tanaka S, Isogai T, Imai J, Watanabe S, Nomura N: Human protein factory for converting the transcriptome into an in vitro-expressed proteome,. Nat Methods. 2008 Dec;5(12):1011-7. [PubMed:19054851 ]
  4. Scheffzek K, Ahmadian MR, Kabsch W, Wiesmuller L, Lautwein A, Schmitz F, Wittinghofer A: The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants. Science. 1997 Jul 18;277(5324):333-8. [PubMed:9219684 ]
  5. Capon DJ, Chen EY, Levinson AD, Seeburg PH, Goeddel DV: Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature. 1983 Mar 3;302(5903):33-7. [PubMed:6298635 ]
  6. Reddy EP: Nucleotide sequence analysis of the T24 human bladder carcinoma oncogene. Science. 1983 Jun 3;220(4601):1061-3. [PubMed:6844927 ]
  7. Sekiya T, Fushimi M, Hori H, Hirohashi S, Nishimura S, Sugimura T: Molecular cloning and the total nucleotide sequence of the human c-Ha-ras-1 gene activated in a melanoma from a Japanese patient. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4771-5. [PubMed:6087347 ]
  8. Tabin CJ, Bradley SM, Bargmann CI, Weinberg RA, Papageorge AG, Scolnick EM, Dhar R, Lowy DR, Chang EH: Mechanism of activation of a human oncogene. Nature. 1982 Nov 11;300(5888):143-9. [PubMed:6290897 ]
  9. Honkawa H, Masahashi W, Hashimoto S, Hashimoto-Gotoh T: Identification of the principal promoter sequence of the c-H-ras transforming oncogene: deletion analysis of the 5'-flanking region by focus formation assay. Mol Cell Biol. 1987 Aug;7(8):2933-40. [PubMed:3670300 ]
  10. Low A, Sprinzl M, Faulhammer HG: Affinity labeling of c-H-ras p21 consensus elements with periodate-oxidized GDP and GTP. Eur J Biochem. 1993 Jul 15;215(2):473-9. [PubMed:8393791 ]
  11. Feig LA, Pan BT, Roberts TM, Cooper GM: Isolation of ras GTP-binding mutants using an in situ colony-binding assay. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4607-11. [PubMed:3088563 ]
  12. Lacal JC, Anderson PS, Aaronson SA: Deletion mutants of Harvey ras p21 protein reveal the absolute requirement of at least two distant regions for GTP-binding and transforming activities. EMBO J. 1986 Apr;5(4):679-87. [PubMed:3011420 ]
  13. Hancock JF, Magee AI, Childs JE, Marshall CJ: All ras proteins are polyisoprenylated but only some are palmitoylated. Cell. 1989 Jun 30;57(7):1167-77. [PubMed:2661017 ]
  14. Dudler T, Gelb MH: Palmitoylation of Ha-Ras facilitates membrane binding, activation of downstream effectors, and meiotic maturation in Xenopus oocytes. J Biol Chem. 1996 May 10;271(19):11541-7. [PubMed:8626715 ]
  15. Lander HM, Hajjar DP, Hempstead BL, Mirza UA, Chait BT, Campbell S, Quilliam LA: A molecular redox switch on p21(ras). Structural basis for the nitric oxide-p21(ras) interaction. J Biol Chem. 1997 Feb 14;272(7):4323-6. [PubMed:9020151 ]
  16. Song C, Hu CD, Masago M, Kariyai K, Yamawaki-Kataoka Y, Shibatohge M, Wu D, Satoh T, Kataoka T: Regulation of a novel human phospholipase C, PLCepsilon, through membrane targeting by Ras. J Biol Chem. 2001 Jan 26;276(4):2752-7. Epub 2000 Oct 5. [PubMed:11022048 ]
  17. Swarthout JT, Lobo S, Farh L, Croke MR, Greentree WK, Deschenes RJ, Linder ME: DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras. J Biol Chem. 2005 Sep 2;280(35):31141-8. Epub 2005 Jul 6. [PubMed:16000296 ]
  18. Rocks O, Peyker A, Kahms M, Verveer PJ, Koerner C, Lumbierres M, Kuhlmann J, Waldmann H, Wittinghofer A, Bastiaens PI: An acylation cycle regulates localization and activity of palmitoylated Ras isoforms. Science. 2005 Mar 18;307(5716):1746-52. Epub 2005 Feb 10. [PubMed:15705808 ]
  19. Pan F, Sun L, Kardian DB, Whartenby KA, Pardoll DM, Liu JO: Feedback inhibition of calcineurin and Ras by a dual inhibitory protein Carabin. Nature. 2007 Jan 25;445(7126):433-6. Epub 2007 Jan 17. [PubMed:17230191 ]
  20. de Vos AM, Tong L, Milburn MV, Matias PM, Jancarik J, Noguchi S, Nishimura S, Miura K, Ohtsuka E, Kim SH: Three-dimensional structure of an oncogene protein: catalytic domain of human c-H-ras p21. Science. 1988 Feb 19;239(4842):888-93. [PubMed:2448879 ]
  21. Pai EF, Kabsch W, Krengel U, Holmes KC, John J, Wittinghofer A: Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature. 1989 Sep 21;341(6239):209-14. [PubMed:2476675 ]
  22. Pai EF, Krengel U, Petsko GA, Goody RS, Kabsch W, Wittinghofer A: Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis. EMBO J. 1990 Aug;9(8):2351-9. [PubMed:2196171 ]
  23. Tong LA, de Vos AM, Milburn MV, Kim SH: Crystal structures at 2.2 A resolution of the catalytic domains of normal ras protein and an oncogenic mutant complexed with GDP. J Mol Biol. 1991 Feb 5;217(3):503-16. [PubMed:1899707 ]
  24. Kraulis PJ, Domaille PJ, Campbell-Burk SL, Van Aken T, Laue ED: Solution structure and dynamics of ras p21.GDP determined by heteronuclear three- and four-dimensional NMR spectroscopy. Biochemistry. 1994 Mar 29;33(12):3515-31. [PubMed:8142349 ]
  25. Scheidig AJ, Burmester C, Goody RS: The pre-hydrolysis state of p21(ras) in complex with GTP: new insights into the role of water molecules in the GTP hydrolysis reaction of ras-like proteins. Structure. 1999 Nov 15;7(11):1311-24. [PubMed:10574788 ]
  26. Hall BE, Bar-Sagi D, Nassar N: The structural basis for the transition from Ras-GTP to Ras-GDP. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12138-42. Epub 2002 Sep 4. [PubMed:12213964 ]
  27. Williams JG, Pappu K, Campbell SL: Structural and biochemical studies of p21Ras S-nitrosylation and nitric oxide-mediated guanine nucleotide exchange. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6376-81. Epub 2003 May 9. [PubMed:12740440 ]
  28. Buhrman G, Wink G, Mattos C: Transformation efficiency of RasQ61 mutants linked to structural features of the switch regions in the presence of Raf. Structure. 2007 Dec;15(12):1618-29. [PubMed:18073111 ]
  29. Stieglitz B, Bee C, Schwarz D, Yildiz O, Moshnikova A, Khokhlatchev A, Herrmann C: Novel type of Ras effector interaction established between tumour suppressor NORE1A and Ras switch II. EMBO J. 2008 Jul 23;27(14):1995-2005. doi: 10.1038/emboj.2008.125. Epub 2008 Jul 3. [PubMed:18596699 ]
  30. Sakai E, Rikimaru K, Ueda M, Matsumoto Y, Ishii N, Enomoto S, Yamamoto H, Tsuchida N: The p53 tumor-suppressor gene and ras oncogene mutations in oral squamous-cell carcinoma. Int J Cancer. 1992 Dec 2;52(6):867-72. [PubMed:1459726 ]
  31. Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn GW 2nd, Tallini G, Kroll TG, Nikiforov YE: RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003 May;88(5):2318-26. [PubMed:12727991 ]
  32. Aoki Y, Niihori T, Kawame H, Kurosawa K, Ohashi H, Tanaka Y, Filocamo M, Kato K, Suzuki Y, Kure S, Matsubara Y: Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nat Genet. 2005 Oct;37(10):1038-40. Epub 2005 Sep 18. [PubMed:16170316 ]
  33. Gripp KW, Lin AE, Stabley DL, Nicholson L, Scott CI Jr, Doyle D, Aoki Y, Matsubara Y, Zackai EH, Lapunzina P, Gonzalez-Meneses A, Holbrook J, Agresta CA, Gonzalez IL, Sol-Church K: HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation. Am J Med Genet A. 2006 Jan 1;140(1):1-7. [PubMed:16329078 ]
  34. Kerr B, Delrue MA, Sigaudy S, Perveen R, Marche M, Burgelin I, Stef M, Tang B, Eden OB, O'Sullivan J, De Sandre-Giovannoli A, Reardon W, Brewer C, Bennett C, Quarell O, M'Cann E, Donnai D, Stewart F, Hennekam R, Cave H, Verloes A, Philip N, Lacombe D, Levy N, Arveiler B, Black G: Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases. J Med Genet. 2006 May;43(5):401-5. Epub 2006 Jan 27. [PubMed:16443854 ]
  35. Zampino G, Pantaleoni F, Carta C, Cobellis G, Vasta I, Neri C, Pogna EA, De Feo E, Delogu A, Sarkozy A, Atzeri F, Selicorni A, Rauen KA, Cytrynbaum CS, Weksberg R, Dallapiccola B, Ballabio A, Gelb BD, Neri G, Tartaglia M: Diversity, parental germline origin, and phenotypic spectrum of de novo HRAS missense changes in Costello syndrome. Hum Mutat. 2007 Mar;28(3):265-72. [PubMed:17054105 ]
  36. van der Burgt I, Kupsky W, Stassou S, Nadroo A, Barroso C, Diem A, Kratz CP, Dvorsky R, Ahmadian MR, Zenker M: Myopathy caused by HRAS germline mutations: implications for disturbed myogenic differentiation in the presence of constitutive HRas activation. J Med Genet. 2007 Jul;44(7):459-62. Epub 2007 Apr 5. [PubMed:17412879 ]
  37. Gripp KW, Innes AM, Axelrad ME, Gillan TL, Parboosingh JS, Davies C, Leonard NJ, Lapointe M, Doyle D, Catalano S, Nicholson L, Stabley DL, Sol-Church K: Costello syndrome associated with novel germline HRAS mutations: an attenuated phenotype? Am J Med Genet A. 2008 Mar 15;146A(6):683-90. doi: 10.1002/ajmg.a.32227. [PubMed:18247425 ]