[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1038/302033a0; PubMed=6298635 [NCBI, ExPASy, EBI, Israel, Japan] Capon D.J., Chen E.Y., Levinson A.D., Seeburg P.H., Goeddel D.V.; "Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue."; Nature 302:33-37(1983).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1126/science.6844927; PubMed=6844927 [NCBI, ExPASy, EBI, Israel, Japan] Reddy E.P.; "Nucleotide sequence analysis of the T24 human bladder carcinoma oncogene."; Science 220:1061-1063(1983).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1073/pnas.81.15.4771; PubMed=6087347 [NCBI, ExPASy, EBI, Israel, Japan] 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. 81:4771-4775(1984).
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Brain; Puhl H.L. III, Ikeda S.R., Aronstam R.S.; "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."; Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
[5]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.; "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."; Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
[6]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.; "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
[7]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. DOI=10.1038/nmeth.1273; PubMed=19054851 [NCBI, ExPASy, EBI, Israel, Japan] 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 5:1011-1017(2008).
[8]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.; Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[9]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[10]	PROTEIN SEQUENCE OF 1-41; 43-117; 129-161 AND 170-185, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT MET-1 AND THR-2, AND MASS SPECTROMETRY. TISSUE=Cervix carcinoma; Bienvenut W.V., Calvo F., Kolch W.; Submitted (FEB-2008) to UniProtKB.
[11]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37. DOI=10.1038/300143a0; PubMed=6290897 [NCBI, ExPASy, EBI, Israel, Japan] Tabin C.J., Bradley S.M., Bargmann C.I., Weinberg R.A., Papageorge A.G., Scolnick E.M., Dhar R., Lowy D.R., Chang E.H.; "Mechanism of activation of a human oncogene."; Nature 300:143-149(1982).
[12]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16. PubMed=3670300 [NCBI, ExPASy, EBI, Israel, Japan] 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. 7:2933-2940(1987).
[13]	PROTEIN SEQUENCE OF 108-117 AND 132-153. DOI=10.1111/j.1432-1033.1993.tb18056.x; PubMed=8393791 [NCBI, ExPASy, EBI, Israel, Japan] Loew A., Sprinzl M., Faulhammer H.G.; "Affinity labeling of c-H-ras p21 consensus elements with periodate-oxidized GDP and GTP."; Eur. J. Biochem. 215:473-479(1993).
[14]	MUTAGENESIS OF ALA-83; ASP-119 AND THR-144. DOI=10.1073/pnas.83.13.4607; PubMed=3088563 [NCBI, ExPASy, EBI, Israel, Japan] Feig L.A., Pan B.-T., Roberts T.M., Cooper G.M.; "Isolation of ras GTP-binding mutants using an in situ colony-binding assay."; Proc. Natl. Acad. Sci. U.S.A. 83:4607-4611(1986).
[15]	MUTAGENESIS OF 164-ARG-GLN-165. PubMed=3011420 [NCBI, ExPASy, EBI, Israel, Japan] Lacal J.C., Anderson P.S., Aaronson S.A.; "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. 5:679-687(1986).
[16]	PALMITOYLATION AT CYS-181 AND CYS-184. DOI=10.1016/0092-8674(89)90054-8; PubMed=2661017 [NCBI, ExPASy, EBI, Israel, Japan] Hancock J.F., Magee A.I., Childs J.E., Marshall C.J.; "All ras proteins are polyisoprenylated but only some are palmitoylated."; Cell 57:1167-1177(1989).
[17]	PALMITOYLATION AT CYS-181 AND CYS-184, ISOPRENYLATION AT CYS-186, METHYLATION AT CYS-186, AND MUTAGENESIS OF CYS-181 AND CYS-184. DOI=10.1074/jbc.271.19.11541; PubMed=8626715 [NCBI, ExPASy, EBI, Israel, Japan] Dudler T., Gelb M.H.; "Palmitoylation of Ha-Ras facilitates membrane binding, activation of downstream effectors, and meiotic maturation in Xenopus oocytes."; J. Biol. Chem. 271:11541-11547(1996).
[18]	S-NITROSYLATION AT CYS-118, FUNCTION, MASS SPECTROMETRY, AND MUTAGENESIS OF CYS-118. DOI=10.1074/jbc.272.7.4323; PubMed=9020151 [NCBI, ExPASy, EBI, Israel, Japan] Lander H.M., Hajjar D.P., Hempstead B.L., Mirza U.A., Chait B.T., Campbell S., Quilliam L.A.; "A molecular redox switch on p21(ras). Structural basis for the nitric oxide-p21(ras) interaction."; J. Biol. Chem. 272:4323-4326(1997).
[19]	INTERACTION WITH PLCE1, CHARACTERIZATION OF VARIANT VAL-12, AND MUTAGENESIS OF SER-17; ASN-26; VAL-29; TYR-32; PRO-34; THR-35; GLU-37; ASP-38 AND SER-39. DOI=10.1074/jbc.M008324200; PubMed=11022048 [NCBI, ExPASy, EBI, Israel, Japan] Song C., Hu C.-D., Masago M., Kariya 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. 276:2752-2757(2001).
[20]	IDENTIFICATION IN A COMPLEX WITH RASGRP1 AND DGKZ. DOI=10.1083/jcb.152.6.1135; PubMed=11257115 [NCBI, ExPASy, EBI, Israel, Japan] Topham M.K., Prescott S.M.; "Diacylglycerol kinase zeta regulates Ras activation by a novel mechanism."; J. Cell Biol. 152:1135-1143(2001).
[21]	PALMITOYLATION AT CYS-181 AND CYS-184. DOI=10.1074/jbc.M504113200; PubMed=16000296 [NCBI, ExPASy, EBI, Israel, Japan] Swarthout J.T., Lobo S., Farh L., Croke M.R., Greentree W.K., Deschenes R.J., Linder M.E.; "DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras."; J. Biol. Chem. 280:31141-31148(2005).
[22]	PALMITOYLATION AT CYS-181 AND CYS-184, MUTAGENESIS OF CYS-181 AND CYS-184, AND SUBCELLULAR LOCATION. DOI=10.1126/science.1105654; PubMed=15705808 [NCBI, ExPASy, EBI, Israel, Japan] Rocks O., Peyker A., Kahms M., Verveer P.J., Koerner C., Lumbierres M., Kuhlmann J., Waldmann H., Wittinghofer A., Bastiaens P.I.H.; "An acylation cycle regulates localization and activity of palmitoylated Ras isoforms."; Science 307:1746-1752(2005).
[23]	INTERACTION WITH TBC1D10C. DOI=10.1038/nature05476; PubMed=17230191 [NCBI, ExPASy, EBI, Israel, Japan] Pan F., Sun L., Kardian D.B., Whartenby K.A., Pardoll D.M., Liu J.O.; "Feedback inhibition of calcineurin and Ras by a dual inhibitory protein Carabin."; Nature 445:433-436(2007).
[24]	X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). DOI=10.1126/science.2448879; PubMed=2448879 [NCBI, ExPASy, EBI, Israel, Japan] de Vos A.M., Tong L., Milburn M.V., Matias P.M., Jancarik J., Noguchi S., Nishimura S., Miura K., Ohtsuka E., Kim S.-H.; "Three-dimensional structure of an oncogene protein: catalytic domain of human c-H-ras p21."; Science 239:888-893(1988).
[25]	X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS). DOI=10.1038/341209a0; PubMed=2476675 [NCBI, ExPASy, EBI, Israel, Japan] Pai E.F., Kabsch W., Krengel U., Holmes K.C., John J., Wittinghofer A.; "Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation."; Nature 341:209-214(1989).
[26]	X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS). PubMed=2196171 [NCBI, ExPASy, EBI, Israel, Japan] Pai E.F., Krengel U., Petsko G.A., Goody R.S., 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. 9:2351-2359(1990).
[27]	X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). DOI=10.1016/0022-2836(91)90753-S; PubMed=1899707 [NCBI, ExPASy, EBI, Israel, Japan] Tong L.A., de Vos A.M., Milburn M.V., Kim S.H.; "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. 217:503-516(1991).
[28]	STRUCTURE BY NMR OF 1-166. DOI=10.1021/bi00178a008; PubMed=8142349 [NCBI, ExPASy, EBI, Israel, Japan] Kraulis P.J., Domaille P.J., Campbell-Burk S.L., van Aken T., Laue E.D.; "Solution structure and dynamics of ras p21.GDP determined by heteronuclear three- and four-dimensional NMR spectroscopy."; Biochemistry 33:3515-3531(1994).
[29]	X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-166 IN COMPLEX WITH RASGAP. DOI=10.1126/science.277.5324.333; PubMed=9219684 [NCBI, ExPASy, EBI, Israel, Japan] Scheffzek K., Ahmadian M.R., 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 277:333-338(1997).
[30]	X-RAY CRYSTALLOGRAPHY (1.26 ANGSTROMS). DOI=10.1016/S0969-2126(00)80021-0; PubMed=10574788 [NCBI, ExPASy, EBI, Israel, Japan] Scheidig A.J., Burmester C., Goody R.S.; "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 7:1311-1324(1999).
[31]	X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-166 IN COMPLEXES WITH GTP ANALOGS. DOI=10.1073/pnas.192453199; PubMed=12213964 [NCBI, ExPASy, EBI, Israel, Japan] Hall B.E., Bar-Sagi D., Nassar N.; "The structural basis for the transition from Ras-GTP to Ras-GDP."; Proc. Natl. Acad. Sci. U.S.A. 99:12138-12142(2002).
[32]	STRUCTURE BY NMR OF 1-166, MASS SPECTROMETRY, S-NITROSYLATION, FUNCTION, AND MUTAGENESIS OF CYS-118. DOI=10.1073/pnas.1037299100; PubMed=12740440 [NCBI, ExPASy, EBI, Israel, Japan] Williams J.G., Pappu K., Campbell S.L.; "Structural and biochemical studies of p21Ras S-nitrosylation and nitric oxide-mediated guanine nucleotide exchange."; Proc. Natl. Acad. Sci. U.S.A. 100:6376-6381(2003).
[33]	X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-166 IN COMPLEXES WITH GTP ANALOG, CHARACTERIZATION OF VARIANTS LEU-61 AND LYS-61, AND MUTAGENESIS OF GLN-61. DOI=10.1016/j.str.2007.10.011; PubMed=18073111 [NCBI, ExPASy, EBI, Israel, Japan] 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 15:1618-1629(2007).
[34]	X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-166 IN COMPLEX WITH RASSF5. DOI=10.1038/emboj.2008.125; PubMed=18596699 [NCBI, ExPASy, EBI, Israel, Japan] 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. 27:1995-2005(2008).
[35]	VARIANT OSCC SER-12. DOI=10.1002/ijc.2910520606; PubMed=1459726 [NCBI, ExPASy, EBI, Israel, Japan] 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 52:867-872(1992).
[36]	VARIANT LYS-61, AND INVOLVEMENT IN SUSCEPTIBILITY TO HURTHLE CELL THYROID CARCINOMA. DOI=10.1210/jc.2002-021907; PubMed=12727991 [NCBI, ExPASy, EBI, Israel, Japan] Nikiforova M.N., Lynch R.A., Biddinger P.W., Alexander E.K., Dorn G.W. II, Tallini G., Kroll T.G., Nikiforov Y.E.; "RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma."; J. Clin. Endocrinol. Metab. 88:2318-2326(2003).
[37]	VARIANTS COSTELLO SYNDROME ALA-12; SER-12; VAL-12 AND ASP-13. DOI=10.1038/ng1641; PubMed=16170316 [NCBI, ExPASy, EBI, Israel, Japan] 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. 37:1038-1040(2005).
[38]	VARIANTS COSTELLO SYNDROME ALA-12; SER-12 AND CYS-13. DOI=10.1002/ajmg.a.31047; PubMed=16329078 [NCBI, ExPASy, EBI, Israel, Japan] Gripp K.W., Lin A.E., Stabley D.L., Nicholson L., Scott C.I. Jr., Doyle D., Aoki Y., Matsubara Y., Zackai E.H., Lapunzina P., Gonzalez-Meneses A., Holbrook J., Agresta C.A., Gonzalez I.L., Sol-Church K.; "HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation."; Am. J. Med. Genet. A 140:1-7(2006).
[39]	VARIANTS COSTELLO SYNDROME SER-12; CYS-12; GLU-12; ALA-12 AND ARG-117. DOI=10.1136/jmg.2005.040352; PubMed=16443854 [NCBI, ExPASy, EBI, Israel, Japan] Kerr B., Delrue M.-A., Sigaudy S., Perveen R., Marche M., Burgelin I., Stef M., Tang B., Eden O.B., 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. 43:401-405(2006).
[40]	VARIANTS COSTELLO SYNDROME SER-12 AND THR-146. DOI=10.1002/humu.20431; PubMed=17054105 [NCBI, ExPASy, EBI, Israel, Japan] Zampino G., Pantaleoni F., Carta C., Cobellis G., Vasta I., Neri C., Pogna E.A., De Feo E., Delogu A., Sarkozy A., Atzeri F., Selicorni A., Rauen K.A., Cytrynbaum C.S., Weksberg R., Dallapiccola B., Ballabio A., Gelb B.D., Neri G., Tartaglia M.; "Diversity, parental germline origin, and phenotypic spectrum of de novo HRAS missense changes in Costello syndrome."; Hum. Mutat. 28:265-272(2007).
[41]	VARIANTS CMEMS VAL-12; SER-12; LYS-22 AND LYS-63. DOI=10.1136/jmg.2007.049270; PubMed=17412879 [NCBI, ExPASy, EBI, Israel, Japan] van der Burgt I., Kupsky W., Stassou S., Nadroo A., Barroso C., Diem A., Kratz C.P., Dvorsky R., Ahmadian M.R., Zenker M.; "Myopathy caused by HRAS germline mutations: implications for disturbed myogenic differentiation in the presence of constitutive HRas activation."; J. Med. Genet. 44:459-462(2007).
[42]	VARIANTS COSTELLO SYNDROME ILE-58 AND VAL-146. DOI=10.1002/ajmg.a.32227; PubMed=18247425 [NCBI, ExPASy, EBI, Israel, Japan] Gripp K.W., Innes A.M., Axelrad M.E., Gillan T.L., Parboosingh J.S., Davies C., Leonard N.J., Lapointe M., Doyle D., Catalano S., Nicholson L., Stabley D.L., Sol-Church K.; "Costello syndrome associated with novel germline HRAS mutations: an attenuated phenotype?"; Am. J. Med. Genet. A 146:683-690(2008).

Comments

FUNCTION: Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
ENZYME REGULATION: Alternate between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).
SUBUNIT: In its GTP-bound form interacts with PLCE1. Interacts with TBC1D10C. Interacts with RGL3 (By similarity). Forms a signaling complex with RASGRP1 and DGKZ. Interacts with RASSF5.
INTERACTION:
Q7Z569:BRAP; NbExp=3; IntAct=EBI-350145, EBI-349900;
P28829:byr2 (xeno); NbExp=1; IntAct=EBI-350145, EBI-1032333;
P42337:Pik3ca (xeno); NbExp=1; IntAct=EBI-350145, EBI-641748;
P48736:PIK3CG; NbExp=1; IntAct=EBI-350145, EBI-1030384;
Q9Z0S9:Rabac1 (xeno); NbExp=2; IntAct=EBI-350145, EBI-476965;
P04049:RAF1; NbExp=5; IntAct=EBI-350145, EBI-365996;
Q9EQZ6:Rapgef4 (xeno); NbExp=2; IntAct=EBI-350145, EBI-772212;
P20936:RASA1; NbExp=1; IntAct=EBI-350145, EBI-1026476;
Q9NS23-2:RASSF1; NbExp=2; IntAct=EBI-350145, EBI-438698;
Q8WWW0:RASSF5; NbExp=1; IntAct=EBI-350145, EBI-367390;
Q5EBH1-2:Rassf5 (xeno); NbExp=2; IntAct=EBI-350145, EBI-960547;
Q9NZL6:RGL1; NbExp=1; IntAct=EBI-350145, EBI-365926;
Q13671:RIN1; NbExp=2; IntAct=EBI-350145, EBI-366017;
Q13671-1:RIN1; NbExp=1; IntAct=EBI-350145, EBI-366030;
Q07889:SOS1; NbExp=1; IntAct=EBI-350145, EBI-297487;
SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor; Cytoplasmic side. Golgi apparatus membrane; Lipid-anchor. Note=Shuttles between the plasma membrane and the Golgi apparatus.
PTM: Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi.
PTM: S-nitrosylated; critical for redox regulation. Important for stimulating guanine nucleotide exchange. No structural perturbation on nitrosylation.
MASS SPECTROMETRY: Mass=6.223; Mass_error=2; Method=Electrospray; Range=112-166; Source=PubMed:9020151;.
MASS SPECTROMETRY: Mass=6.253; Mass_error=2; Method=Electrospray; Range=112-166; Note=Includes one nitric oxide molecule; Source=PubMed:9020151;.
DISEASE: Defects in HRAS are the cause of Costello syndrome [MIM:218040]; also known as faciocutaneoskeletal syndrome. Costello syndrome is a rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.
DISEASE: Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]. CMEMS is a variant of Costello syndrome.
DISEASE: Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma [MIM:607464]; also known as Hurthle cell thyroid neoplasia. Hurthle cell thyroid carcinoma accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms.
DISEASE: Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors.
DISEASE: Defects in HRAS are a cause of bladder cancer [MIM:109800].
DISEASE: Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC).
SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/HRASID108.html";.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=HRAS";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

J00277; AAB02605.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF493916; AAM12630.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
CR536579; CAG38816.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
CR542271; CAG47067.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BT019421; AAV38228.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB451336; BAG70150.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AB451485; BAG70299.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
CH471158; EAX02337.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC095471; AAH95471.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M17232; AAA35685.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00000006; -.

PIR

A93299; TVHUH.

RefSeq

NP_001123914.1; -.
NP_005334.1; -.

UniGene

Hs.37003

3D structure databases

PDB

121P; X-ray; 1.54 A; A=1-166.	[ExPASy / RCSB / EBI]
1AA9; NMR; -; A=1-171.	[ExPASy / RCSB / EBI]
1AGP; X-ray; 2.30 A; A=1-166.	[ExPASy / RCSB / EBI]
1BKD; X-ray; 2.80 A; R=1-166.	[ExPASy / RCSB / EBI]
1CLU; X-ray; 1.70 A; A=1-166.	[ExPASy / RCSB / EBI]
1CRP; NMR; -; A=1-166.	[ExPASy / RCSB / EBI]
1CRQ; NMR; -; A=1-166.	[ExPASy / RCSB / EBI]
1CRR; NMR; -; A=1-166.	[ExPASy / RCSB / EBI]
1CTQ; X-ray; 1.26 A; A=1-166.	[ExPASy / RCSB / EBI]
1GNP; X-ray; 2.70 A; A=1-166.	[ExPASy / RCSB / EBI]
1GNQ; X-ray; 2.50 A; A=1-166.	[ExPASy / RCSB / EBI]
1GNR; X-ray; 1.85 A; A=1-166.	[ExPASy / RCSB / EBI]
1HE8; X-ray; 3.00 A; B=1-166.	[ExPASy / RCSB / EBI]
1IAQ; X-ray; 2.90 A; A/B/C=1-166.	[ExPASy / RCSB / EBI]
1IOZ; X-ray; 2.00 A; A=1-171.	[ExPASy / RCSB / EBI]
1JAH; X-ray; 1.80 A; A=1-166.	[ExPASy / RCSB / EBI]
1JAI; X-ray; 1.80 A; A=1-166.	[ExPASy / RCSB / EBI]
1K8R; X-ray; 3.00 A; A=1-166.	[ExPASy / RCSB / EBI]
1LF0; X-ray; 1.70 A; A=1-166.	[ExPASy / RCSB / EBI]
1LF5; X-ray; 1.70 A; A=1-166.	[ExPASy / RCSB / EBI]
1LFD; X-ray; 2.10 A; B/D=1-167.	[ExPASy / RCSB / EBI]
1NVU; X-ray; 2.20 A; Q/R=1-166.	[ExPASy / RCSB / EBI]
1NVV; X-ray; 2.18 A; Q=1-166, R=1-166.	[ExPASy / RCSB / EBI]
1NVW; X-ray; 2.70 A; Q/R=1-166.	[ExPASy / RCSB / EBI]
1NVX; X-ray; 3.20 A; Q/R=1-166.	[ExPASy / RCSB / EBI]
1P2S; X-ray; 2.45 A; A=1-166.	[ExPASy / RCSB / EBI]
1P2T; X-ray; 2.00 A; A=1-166.	[ExPASy / RCSB / EBI]
1P2U; X-ray; 2.00 A; A=1-166.	[ExPASy / RCSB / EBI]
1P2V; X-ray; 2.30 A; A=1-166.	[ExPASy / RCSB / EBI]
1PLJ; X-ray; 2.80 A; A=1-166.	[ExPASy / RCSB / EBI]
1PLK; X-ray; 2.80 A; A=1-166.	[ExPASy / RCSB / EBI]
1PLL; X-ray; 2.80 A; A=1-166.	[ExPASy / RCSB / EBI]
1Q21; X-ray; 2.20 A; A=1-171.	[ExPASy / RCSB / EBI]
1QRA; X-ray; 1.60 A; A=1-166.	[ExPASy / RCSB / EBI]
1RVD; X-ray; 1.90 A; A=1-166.	[ExPASy / RCSB / EBI]
1WQ1; X-ray; 2.50 A; R=1-166.	[ExPASy / RCSB / EBI]
1XCM; X-ray; 1.84 A; A=1-167.	[ExPASy / RCSB / EBI]
1XD2; X-ray; 2.70 A; A=1-166, B=1-166.	[ExPASy / RCSB / EBI]
1XJ0; X-ray; 1.70 A; A=1-166.	[ExPASy / RCSB / EBI]
1ZVQ; X-ray; 2.00 A; A=1-166.	[ExPASy / RCSB / EBI]
1ZW6; X-ray; 1.50 A; A=1-166.	[ExPASy / RCSB / EBI]
221P; X-ray; 2.30 A; A=1-166.	[ExPASy / RCSB / EBI]
2C5L; X-ray; 1.90 A; A/B=1-166.	[ExPASy / RCSB / EBI]
2CE2; X-ray; 1.00 A; X=1-166.	[ExPASy / RCSB / EBI]
2CL0; X-ray; 1.80 A; X=1-166.	[ExPASy / RCSB / EBI]
2CL6; X-ray; 1.24 A; X=1-166.	[ExPASy / RCSB / EBI]
2CL7; X-ray; 1.25 A; X=1-166.	[ExPASy / RCSB / EBI]
2CLC; X-ray; 1.30 A; X=1-166.	[ExPASy / RCSB / EBI]
2CLD; X-ray; 1.22 A; X=1-166.	[ExPASy / RCSB / EBI]
2EVW; X-ray; 1.05 A; X=1-166.	[ExPASy / RCSB / EBI]
2GDP; Model; -; A=1-171.	[ExPASy / RCSB / EBI]
2Q21; X-ray; 2.20 A; A=1-171.	[ExPASy / RCSB / EBI]
2QUZ; X-ray; 1.49 A; A=1-166.	[ExPASy / RCSB / EBI]
2RGA; X-ray; 1.90 A; A=1-166.	[ExPASy / RCSB / EBI]
2RGB; X-ray; 1.35 A; A=1-166.	[ExPASy / RCSB / EBI]
2RGC; X-ray; 1.60 A; A=1-166.	[ExPASy / RCSB / EBI]
2RGD; X-ray; 2.00 A; A=1-166.	[ExPASy / RCSB / EBI]
2RGE; X-ray; 1.40 A; A=1-166.	[ExPASy / RCSB / EBI]
2RGG; X-ray; 1.45 A; A=1-166.	[ExPASy / RCSB / EBI]
2UZI; X-ray; 2.00 A; R=1-166.	[ExPASy / RCSB / EBI]
2VH5; X-ray; 2.70 A; R=1-166.	[ExPASy / RCSB / EBI]
3DDC; X-ray; 1.80 A; A=1-166.	[ExPASy / RCSB / EBI]
421P; X-ray; 2.20 A; A=1-166.	[ExPASy / RCSB / EBI]
4Q21; X-ray; 2.00 A; A=1-189.	[ExPASy / RCSB / EBI]
521P; X-ray; 2.60 A; A=1-166.	[ExPASy / RCSB / EBI]
5P21; X-ray; 1.35 A; A=1-166.	[ExPASy / RCSB / EBI]
621P; X-ray; 2.40 A; A=1-166.	[ExPASy / RCSB / EBI]
6Q21; X-ray; 1.95 A; A/B/C/D=1-171.	[ExPASy / RCSB / EBI]
721P; X-ray; 2.00 A; A=1-166.	[ExPASy / RCSB / EBI]
821P; X-ray; 1.50 A; A=1-166.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

121P; -.
1AA9; -.
1AGP; -.
1BKD; -.
1CLU; -.
1CRP; -.
1CRQ; -.
1CRR; -.
1CTQ; -.
1GNP; -.
1GNQ; -.
1GNR; -.
1HE8; -.
1IAQ; -.
1IOZ; -.
1JAH; -.
1JAI; -.
1K8R; -.
1LF0; -.
1LF5; -.
1LFD; -.
1NVU; -.
1NVV; -.
1NVW; -.
1NVX; -.
1P2S; -.
1P2T; -.
1P2U; -.
1P2V; -.
1PLJ; -.
1PLK; -.
1PLL; -.
1Q21; -.
1QRA; -.
1RVD; -.
1WQ1; -.
1XCM; -.
1XD2; -.
1XJ0; -.
1ZVQ; -.
1ZW6; -.
221P; -.
2C5L; -.
2CE2; -.
2CL0; -.
2CL6; -.
2CL7; -.
2CLC; -.
2CLD; -.
2EVW; -.
2GDP; -.
2Q21; -.
2QUZ; -.
2RGA; -.
2RGB; -.
2RGC; -.
2RGD; -.
2RGE; -.
2RGG; -.
2UZI; -.
2VH5; -.
3DDC; -.
421P; -.
4Q21; -.
521P; -.
5P21; -.
621P; -.
6Q21; -.
721P; -.
821P; -.

DisProt

DP00153; -.

ModBase

P01112.

Protein-protein interaction databases

DIP

DIP:1050N; -.

IntAct

P01112; 26.

PTM databases

PhosphoSite

P01112; -.

Enzyme and pathway databases

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway; a6b1 and a6b4 Integrin signaling.
bcr_5pathway; BCR signaling pathway.
pi3kcipathway; Class I PI3K signaling events.
cd8tcrdownstreampathway; Downstream signaling in naive CD8+ T cells.
endothelinpathway; Endothelins.
ephbfwdpathway; EPHB forward signaling.
epopathway; EPO signaling pathway.
fcer1pathway; Fc-epsilon receptor I signaling in mast cells.
igf1_pathway; IGF1 pathway.
il2_1pathway; IL2-mediated signaling events.
insulin_pathway; Insulin Pathway.
lysophospholipid_pathway; LPA receptor mediated events.
trkrpathway; Neurotrophic factor-mediated Trk receptor signaling.
pdgfrbpathway; PDGFR-beta signaling pathway.
er_nongenomic_pathway; Plasma membrane estrogen receptor signaling.
tcrraspathway; Ras signaling in the CD4+ TCR pathway.
met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway; Signaling events mediated by Stem cell factor receptor (c-Kit).
vegfr1_2_pathway; Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway; Signaling events regulated by Ret tyrosine kinase.
syndecan_2_pathway; Syndecan-2-mediated signaling events.
tcrpathway; TCR signaling in naive CD4+ T cells.
cd8tcrpathway; TCR signaling in naive CD8+ T cells.
pi3kplctrkpathway; Trk receptor signaling mediated by PI3K and PLC-gamma.
mapktrkpathway; Trk receptor signaling mediated by the MAPK pathway.

Reactome

REACT_11061; Signalling by NGF.
REACT_498; Signaling by Insulin receptor.
REACT_604; Hemostasis.
REACT_6900; Signaling in Immune system.
REACT_9417; Signaling by EGFR.

Organism-specific databases

GC11M000522; -.

HIX0009354; -.

HGNC:5173; HRAS.

CAB002015; -.

109800; phenotype. [NCBI / EBI]
190020; gene. [NCBI / EBI]
218040; phenotype. [NCBI / EBI]
607464; phenotype. [NCBI / EBI]

Orphanet

3071; Costello syndrome.

PharmGKB

PA29444; -.

Gene expression databases

P01112; -.

P01112; -.

HS_HRAS; -.

ENSG00000174775; Homo sapiens.

Ontologies

GO:0000139;	Cellular component: Golgi membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005886;	Cellular component: plasma membrane (inferred from experiment from Reactome).
GO:0005525;	Molecular function: GTP binding (inferred from electronic annotation from UniProtKB-KW).
GO:0008022;	Molecular function: protein C-terminus binding (inferred from physical interaction from UniProtKB).
GO:0007166;	Biological process: cell surface receptor linked signal transduction (traceable author statement from ProtInc).
GO:0006935;	Biological process: chemotaxis (traceable author statement from ProtInc).
GO:0009887;	Biological process: organ morphogenesis (traceable author statement from ProtInc).
GO:0007265;	Biological process: Ras protein signal transduction (inferred from experiment from Reactome).
QuickGo view.

Family and domain databases

InterPro

IPR003577; GTPase_Ras.
IPR013753; Ras.
IPR001806; Ras_GTPase.
IPR015592; Ras_Ras_related.
IPR005225; Small_GTP_bd.
Graphical view of domain structure.

PANTHER

PTHR11708:SF125; Ras_Ras_related; 1.

Pfam

PF00071; Ras; 1.
Pfam graphical view of domain structure.

PRINTS

PR00449; RASTRNSFRMNG.

SMART

SM00173; RAS; 1.
SMART graphical view of domain structure.

TIGRFAMs

TIGR00231; small_GTP; 1.

PROSITE

PS51421; RAS; 1.
PROSITE graphical view of domain structure (profiles).

Other

SWISS-3DIMAGE

P01112.

Proteomic databases

PRIDE

P01112; -.

Genome annotation databases

Ensembl

ENSG00000174775; Homo sapiens. [Contig view]

GeneID

3265; -.

KEGG

hsa:3265; -.

Phylogenomic databases

HOVERGEN

P01112; -.

OMA

P01112; NCKCVIS.

Other

DB00605; Sulindac.

12961; -.

HRAS; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Acetylation; Cell membrane; Direct protein sequencing; Disease mutation; Golgi apparatus; GTP-binding; Lipoprotein; Membrane; Methylation; Nucleotide-binding; Palmitate; Prenylation; Proto-oncogene; S-nitrosylation.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 186`	`186`	`GTPase HRas.`	`PRO_0000042996`
`INIT_MET`	`1 1`		`Removed; alternate.`
`CHAIN`	`2 186`	`185`	`GTPase HRas, N-terminally processed.`	`PRO_0000326476`
`PROPEP`	`187 189`	`3`	`Removed in mature form.`	`PRO_0000042997`
`NP_BIND`	`10 17`	`8`	`GTP.`
`NP_BIND`	`57 61`	`5`	`GTP.`
`NP_BIND`	`116 119`	`4`	`GTP.`
`REGION`	`166 185`	`20`	`Hypervariable region.`
`MOTIF`	`32 40`	`9`	`Effector region.`
`MOD_RES`	`1 1`		`N-acetylmethionine; in GTPase HRas; alternate.`
`MOD_RES`	`2 2`		`N-acetylthreonine; in GTPase HRas, N-terminally processed.`
`MOD_RES`	`118 118`		`S-nitrosocysteine.`
`MOD_RES`	`186 186`		`Cysteine methyl ester.`
`LIPID`	`181 181`		`S-palmitoyl cysteine.`
`LIPID`	`184 184`		`S-palmitoyl cysteine.`
`LIPID`	`186 186`		`S-farnesyl cysteine.`
`VARIANT`	`12 12`	`1`	`G -> A (in Costello syndrome).`	`VAR_026106 [3D]`
`VARIANT`	`12 12`	`1`	`G -> C (in Costello syndrome).`	`VAR_045975 [3D]`
`VARIANT`	`12 12`	`1`	`G -> E (in Costello syndrome).`	`VAR_045976 [3D]`
`VARIANT`	`12 12`	`1`	`G -> S (in Costello syndrome, OSCC and CMEMS).`	`VAR_006837 [3D]`
`VARIANT`	`12 12`	`1`	`G -> V (in Costello syndrome, bladder carcinoma and CMEMS; constitutively activated; interacts and recruits PLCE1 to plasma membrane; loss of interaction with and recruitment to plasma membrane of PLCE1 when associated with F-32; loss of interaction with PLCE1 when associated with G-26, F-32 and S-35; no effect on interaction with PLCE1 when associated with A-29, G-34, G-37, N-38 and C-39).`	`VAR_006836 [3D]`
`VARIANT`	`13 13`	`1`	`G -> C (in Costello syndrome).`	`VAR_026107 [3D]`
`VARIANT`	`13 13`	`1`	`G -> D (in Costello syndrome).`	`VAR_026108 [3D]`
`VARIANT`	`22 22`	`1`	`Q -> K (in CMEMS).`	`VAR_045977 [3D]`
`VARIANT`	`58 58`	`1`	`T -> I (in Costello syndrome).`	`VAR_045978 [3D]`
`VARIANT`	`61 61`	`1`	`Q -> K (in follicular thyroid carcinoma samples; somatic mutation; increases transformation of cultured cell lines).`	`VAR_045979 [3D]`
`VARIANT`	`61 61`	`1`	`Q -> L (in melanoma; strongly reduced GTP hydrolysis in the presence of RAF1; increases transformation of cultured cell lines).`	`VAR_006838 [3D]`
`VARIANT`	`63 63`	`1`	`E -> K (in CMEMS).`	`VAR_045980 [3D]`
`VARIANT`	`117 117`	`1`	`K -> R (in Costello syndrome).`	`VAR_045981 [3D]`
`VARIANT`	`146 146`	`1`	`A -> T (in Costello syndrome).`	`VAR_045982 [3D]`
`VARIANT`	`146 146`	`1`	`A -> V (in Costello syndrome).`	`VAR_045983 [3D]`
`MUTAGEN`	`17 17`		`S->N: Dominant negative. Prevents PLCE1 EGF-induced recruitment to plasma membrane.`
`MUTAGEN`	`26 26`		`N->G: Loss of interaction with PLCE1; when associated with V-12.`
`MUTAGEN`	`29 29`		`V->A: No effect on interaction with PLCE1; when associated with V-12.`
`MUTAGEN`	`32 32`		`Y->F: Loss of interaction and recruitment to plasma membrane of PLCE1; when associated with V-12.`
`MUTAGEN`	`34 34`		`P->G: No effect on interaction with PLCE1; when associated with V-12.`
`MUTAGEN`	`35 35`		`T->S: Loss of interaction with PLCE1; when associated with V-12.`
`MUTAGEN`	`37 37`		`E->G: No effect on interaction with PLCE1; when associated with V-12.`
`MUTAGEN`	`38 38`		`D->N: No effect on interaction with PLCE1; when associated with V-12.`
`MUTAGEN`	`39 39`		`S->C: No effect on interaction with PLCE1; when associated with V-12.`
`MUTAGEN`	`59 59`		`A->T: Loss of GTPase activity and creation of an autophosphorylation site.`
`MUTAGEN`	`61 61`		`Q->I: Moderately increased transformation of cultured cell lines.`
`MUTAGEN`	`61 61`		`Q->V: Strongly increased transformation of cultured cell lines.`
`MUTAGEN`	`83 83`		`A->T: GTP-binding activity reduced by factor of 30.`
`MUTAGEN`	`118 118`		`C->S: Abolishes S-nitrosylation. No stimulation of guanine nucleotide exchange.`
`MUTAGEN`	`119 119`		`D->N: Loss of GTP-binding activity.`
`MUTAGEN`	`144 144`		`T->I: GTP-binding activity reduced by factor of 25.`
`MUTAGEN`	`164 165`		`RQ->AV: Loss of GTP-binding activity.`
`MUTAGEN`	`181 181`		`C->S: Exclusively localized in Golgi. Non-specifically localized on all endomembranes; when associated with S-184.`
`MUTAGEN`	`184 184`		`C->S: Mainly localized in Golgi. Non-specifically localized on all endomembranes; when associated with S-181.`
`STRAND`	`2 11`	`10`
`HELIX`	`16 25`	`10`
`STRAND`	`36 46`	`11`
`STRAND`	`49 58`	`10`
`HELIX`	`62 64`	`3`
`HELIX`	`65 74`	`10`
`STRAND`	`76 83`	`8`
`HELIX`	`87 91`	`5`
`HELIX`	`93 104`	`12`
`STRAND`	`111 116`	`6`
`HELIX`	`127 137`	`11`
`STRAND`	`141 143`	`3`
`TURN`	`146 148`	`3`
`HELIX`	`152 164`	`13`

Sequence information

Length: 189 AA [This is the length of the unprocessed precursor]

Molecular weight: 21298 Da [This is the MW of the unprocessed precursor]

CRC64: EE6DC2D933E2856A [This is a checksum on the sequence]

        10         20         30         40         50         60 
MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET CLLDILDTAG 

        70         80         90        100        110        120 
QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHQYREQI KRVKDSDDVP MVLVGNKCDL 

       130        140        150        160        170        180 
AARTVESRQA QDLARSYGIP YIETSAKTRQ GVEDAFYTLV REIRQHKLRK LNPPDESGPG 


CMSCKCVLS

P01112 in FASTA format

View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools