ID RASH_HUMAN Reviewed; 189 AA. AC P01112; B5BUA0; Q14080; Q6FHV9; Q9BR65; Q9UCE2; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 02-SEP-2026, entry version 281. DE RecName: Full=GTPase HRas; DE EC=3.6.5.2 {ECO:0000269|PubMed:9020151}; DE AltName: Full=H-Ras-1; DE AltName: Full=Ha-Ras; DE AltName: Full=Transforming protein p21; DE AltName: Full=c-H-ras; DE AltName: Full=p21ras; DE Contains: DE RecName: Full=GTPase HRas, N-terminally processed; DE Flags: Precursor; GN Name=HRAS; Synonyms=HRAS1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INVOLVEMENT IN BLADDER CANCER. RX PubMed=6298635; DOI=10.1038/302033a0; RA Capon D.J., Chen E.Y., Levinson A.D., Seeburg P.H., Goeddel D.V.; RT "Complete nucleotide sequences of the T24 human bladder carcinoma oncogene RT and its normal homologue."; RL Nature 302:33-37(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INVOLVEMENT IN BLADDER CANCER. RX PubMed=6844927; DOI=10.1126/science.6844927; RA Reddy E.P.; RT "Nucleotide sequence analysis of the T24 human bladder carcinoma RT oncogene."; RL Science 220:1061-1063(1983). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6087347; DOI=10.1073/pnas.81.15.4771; RA Sekiya T., Fushimi M., Hori H., Hirohashi S., Nishimura S., Sugimura T.; RT "Molecular cloning and the total nucleotide sequence of the human c-Ha-ras- RT 1 gene activated in a melanoma from a Japanese patient."; RL Proc. Natl. Acad. Sci. U.S.A. 81:4771-4775(1984). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH RACK1, RP SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY, AND RP MUTAGENESIS OF SER-17. RX PubMed=14500341; RA Guil S., de La Iglesia N., Fernandez-Larrea J., Cifuentes D., Ferrer J.C., RA Guinovart J.J., Bach-Elias M.; RT "Alternative splicing of the human proto-oncogene c-H-ras renders a new Ras RT family protein that trafficks to cytoplasm and nucleus."; RL Cancer Res. 63:5178-5187(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=19054851; DOI=10.1038/nmeth.1273; RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B., RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., RA Nomura N.; RT "Human protein factory for converting the transcriptome into an in vitro- RT expressed proteome."; RL Nat. Methods 5:1011-1017(2008). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lung carcinoma; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP PROTEIN SEQUENCE OF 1-41; 43-117; 129-161 AND 170-185, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT MET-1 AND THR-2, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RA Bienvenut W.V., Calvo F., Kolch W.; RL Submitted (FEB-2008) to UniProtKB. RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37. RX PubMed=6290897; DOI=10.1038/300143a0; RA Tabin C.J., Bradley S.M., Bargmann C.I., Weinberg R.A., Papageorge A.G., RA Scolnick E.M., Dhar R., Lowy D.R., Chang E.H.; RT "Mechanism of activation of a human oncogene."; RL Nature 300:143-149(1982). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16. RX PubMed=3670300; DOI=10.1128/mcb.7.8.2933-2940.1987; RA Honkawa H., Masahashi W., Hashimoto S., Hashimoto-Gotoh T.; RT "Identification of the principal promoter sequence of the c-H-ras RT transforming oncogene: deletion analysis of the 5'-flanking region by focus RT formation assay."; RL Mol. Cell. Biol. 7:2933-2940(1987). RN [15] RP PROTEIN SEQUENCE OF 108-117 AND 132-153. RX PubMed=8393791; DOI=10.1111/j.1432-1033.1993.tb18056.x; RA Loew A., Sprinzl M., Faulhammer H.G.; RT "Affinity labeling of c-H-ras p21 consensus elements with periodate- RT oxidized GDP and GTP."; RL Eur. J. Biochem. 215:473-479(1993). RN [16] RP MUTAGENESIS OF ALA-83; ASP-119 AND THR-144. RX PubMed=3088563; DOI=10.1073/pnas.83.13.4607; RA Feig L.A., Pan B.-T., Roberts T.M., Cooper G.M.; RT "Isolation of ras GTP-binding mutants using an in situ colony-binding RT assay."; RL Proc. Natl. Acad. Sci. U.S.A. 83:4607-4611(1986). RN [17] RP MUTAGENESIS OF 164-ARG-GLN-165. RX PubMed=3011420; DOI=10.1002/j.1460-2075.1986.tb04267.x; RA Lacal J.C., Anderson P.S., Aaronson S.A.; RT "Deletion mutants of Harvey ras p21 protein reveal the absolute requirement RT of at least two distant regions for GTP-binding and transforming RT activities."; RL EMBO J. 5:679-687(1986). RN [18] RP PALMITOYLATION AT CYS-181 AND CYS-184. RX PubMed=2661017; DOI=10.1016/0092-8674(89)90054-8; RA Hancock J.F., Magee A.I., Childs J.E., Marshall C.J.; RT "All ras proteins are polyisoprenylated but only some are palmitoylated."; RL Cell 57:1167-1177(1989). RN [19] RP GLYCOSYLATION AT THR-35 (MICROBIAL INFECTION). RX PubMed=8626586; DOI=10.1074/jbc.271.17.10217; RA Popoff M.R., Chaves-Olarte E., Lemichez E., von Eichel-Streiber C., RA Thelestam M., Chardin P., Cussac D., Antonny B., Chavrier P., Flatau G., RA Giry M., de Gunzburg J., Boquet P.; RT "Ras, Rap, and Rac small GTP-binding proteins are targets for Clostridium RT sordellii lethal toxin glucosylation."; RL J. Biol. Chem. 271:10217-10224(1996). RN [20] RP GLYCOSYLATION AT THR-35 (MICROBIAL INFECTION). RX PubMed=8626575; DOI=10.1074/jbc.271.17.10149; RA Just I., Selzer J., Hofmann F., Green G.A., Aktories K.; RT "Inactivation of Ras by Clostridium sordellii lethal toxin-catalyzed RT glucosylation."; RL J. Biol. Chem. 271:10149-10153(1996). RN [21] RP PALMITOYLATION AT CYS-181 AND CYS-184, ISOPRENYLATION AT CYS-186, RP METHYLATION AT CYS-186, AND MUTAGENESIS OF CYS-181 AND CYS-184. RX PubMed=8626715; DOI=10.1074/jbc.271.19.11541; RA Dudler T., Gelb M.H.; RT "Palmitoylation of Ha-Ras facilitates membrane binding, activation of RT downstream effectors, and meiotic maturation in Xenopus oocytes."; RL J. Biol. Chem. 271:11541-11547(1996). RN [22] RP S-NITROSYLATION AT CYS-118, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS RP OF CYS-118. RX PubMed=9020151; DOI=10.1074/jbc.272.7.4323; RA Lander H.M., Hajjar D.P., Hempstead B.L., Mirza U.A., Chait B.T., RA Campbell S., Quilliam L.A.; RT "A molecular redox switch on p21(ras). Structural basis for the nitric RT oxide-p21(ras) interaction."; RL J. Biol. Chem. 272:4323-4326(1997). RN [23] RP GLYCOSYLATION AT THR-35 (MICROBIAL INFECTION). RX PubMed=9632667; DOI=10.1074/jbc.273.26.16134; RA Herrmann C., Ahmadian M.R., Hofmann F., Just I.; RT "Functional consequences of monoglucosylation of Ha-Ras at effector domain RT amino acid threonine 35."; RL J. Biol. Chem. 273:16134-16139(1998). RN [24] RP INTERACTION WITH IKZF3. RX PubMed=10369681; DOI=10.1093/emboj/18.12.3419; RA Romero F., Martinez-A C., Camonis J., Rebollo A.; RT "Aiolos transcription factor controls cell death in T cells by regulating RT Bcl-2 expression and its cellular localization."; RL EMBO J. 18:3419-3430(1999). RN [25] RP INTERACTION WITH RAPGEF2. RX PubMed=10608844; DOI=10.1074/jbc.274.53.37815; RA Liao Y., Kariya K., Hu C.-D., Shibatohge M., Goshima M., Okada T., RA Watari Y., Gao X., Jin T.-G., Yamawaki-Kataoka Y., Kataoka T.; RT "RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a RT Ras/Rap1A-associating domain, is conserved between nematode and humans."; RL J. Biol. Chem. 274:37815-37820(1999). RN [26] RP INTERACTION WITH PLCE1, CHARACTERIZATION OF VARIANT VAL-12, AND MUTAGENESIS RP OF SER-17; ASN-26; VAL-29; TYR-32; PRO-34; THR-35; GLU-37; ASP-38 AND RP SER-39. RX PubMed=11022048; DOI=10.1074/jbc.m008324200; RA Song C., Hu C.-D., Masago M., Kariya K., Yamawaki-Kataoka Y., RA Shibatohge M., Wu D., Satoh T., Kataoka T.; RT "Regulation of a novel human phospholipase C, PLCepsilon, through membrane RT targeting by Ras."; RL J. Biol. Chem. 276:2752-2757(2001). RN [27] RP INTERACTION WITH RAPGEF2. RX PubMed=11598133; DOI=10.1074/jbc.m108373200; RA Pham N., Rotin D.; RT "Nedd4 regulates ubiquitination and stability of the guanine-nucleotide RT exchange factor CNrasGEF."; RL J. Biol. Chem. 276:46995-47003(2001). RN [28] RP IDENTIFICATION IN A COMPLEX WITH RASGRP1 AND DGKZ. RX PubMed=11257115; DOI=10.1083/jcb.152.6.1135; RA Topham M.K., Prescott S.M.; RT "Diacylglycerol kinase zeta regulates Ras activation by a novel RT mechanism."; RL J. Cell Biol. 152:1135-1143(2001). RN [29] RP INTERACTION WITH PDE6D. RX PubMed=11980706; DOI=10.1093/emboj/21.9.2095; RA Hanzal-Bayer M., Renault L., Roversi P., Wittinghofer A., Hillig R.C.; RT "The complex of Arl2-GTP and PDE delta: from structure to function."; RL EMBO J. 21:2095-2106(2002). RN [30] RP LIPIDATION AT CYS-184, AND MUTAGENESIS OF CYS-184. RX PubMed=12684535; DOI=10.1073/pnas.0735842100; RA Oliva J.L., Perez-Sala D., Castrillo A., Martinez N., Canada F.J., RA Bosca L., Rojas J.M.; RT "The cyclopentenone 15-deoxy-delta 12,14-prostaglandin J2 binds to and RT activates H-Ras."; RL Proc. Natl. Acad. Sci. U.S.A. 100:4772-4777(2003). RN [31] RP FUNCTION, VARIANT CYS-89, AND CHARACTERIZATION OF VARIANT CYS-89. RX PubMed=22821884; DOI=10.1002/ajmg.a.35449; RA Gripp K.W., Bifeld E., Stabley D.L., Hopkins E., Meien S., Vinette K., RA Sol-Church K., Rosenberger G.; RT "A novel HRAS substitution (c.266C>G; p.S89C) resulting in decreased RT downstream signaling suggests a new dimension of RAS pathway dysregulation RT in human development."; RL Am. J. Med. Genet. A 158A:2106-2118(2012). RN [32] RP CHARACTERIZATION OF CSTLO VARIANT VAL-12. RX PubMed=15546861; DOI=10.1074/jbc.m410775200; RA Liu F., Iqbal K., Grundke-Iqbal I., Rossie S., Gong C.X.; RT "Dephosphorylation of tau by protein phosphatase 5: impairment in RT Alzheimer's disease."; RL J. Biol. Chem. 280:1790-1796(2005). RN [33] RP PALMITOYLATION AT CYS-181 AND CYS-184. RX PubMed=16000296; DOI=10.1074/jbc.m504113200; RA Swarthout J.T., Lobo S., Farh L., Croke M.R., Greentree W.K., RA Deschenes R.J., Linder M.E.; RT "DHHC9 and GCP16 constitute a human protein fatty acyltransferase with RT specificity for H- and N-Ras."; RL J. Biol. Chem. 280:31141-31148(2005). RN [34] RP PALMITOYLATION AT CYS-181 AND CYS-184, MUTAGENESIS OF CYS-181 AND CYS-184, RP AND SUBCELLULAR LOCATION. RX PubMed=15705808; DOI=10.1126/science.1105654; RA Rocks O., Peyker A., Kahms M., Verveer P.J., Koerner C., Lumbierres M., RA Kuhlmann J., Waldmann H., Wittinghofer A., Bastiaens P.I.H.; RT "An acylation cycle regulates localization and activity of palmitoylated RT Ras isoforms."; RL Science 307:1746-1752(2005). RN [35] RP INTERACTION WITH TBC1D10C. RX PubMed=17230191; DOI=10.1038/nature05476; RA Pan F., Sun L., Kardian D.B., Whartenby K.A., Pardoll D.M., Liu J.O.; RT "Feedback inhibition of calcineurin and Ras by a dual inhibitory protein RT Carabin."; RL Nature 445:433-436(2007). RN [36] RP GLYCOSYLATION AT THR-35 (MICROBIAL INFECTION). RX PubMed=19744486; DOI=10.1016/j.febslet.2009.09.006; RA Huelsenbeck S.C., Klose I., Reichenbach M., Huelsenbeck J., Genth H.; RT "Distinct kinetics of (H/K/N)Ras glucosylation and Rac1 glucosylation RT catalysed by Clostridium sordellii lethal toxin."; RL FEBS Lett. 583:3133-3139(2009). RN [37] RP ACYLATION, AND MUTAGENESIS OF 167-LYS--LYS-185. RX PubMed=29239724; DOI=10.7554/elife.32436; RA Jing H., Zhang X., Wisner S.A., Chen X., Spiegelman N.A., Linder M.E., RA Lin H.; RT "SIRT2 and lysine fatty acylation regulate the transforming activity of K- RT Ras4a."; RL Elife 6:0-0(2017). RN [38] RP UBIQUITINATION AT LYS-170, AND MUTAGENESIS OF LYS-170. RX PubMed=30442762; DOI=10.1126/science.aap7607; RA Steklov M., Pandolfi S., Baietti M.F., Batiuk A., Carai P., Najm P., RA Zhang M., Jang H., Renzi F., Cai Y., Abbasi Asbagh L., Pastor T., RA De Troyer M., Simicek M., Radaelli E., Brems H., Legius E., Tavernier J., RA Gevaert K., Impens F., Messiaen L., Nussinov R., Heymans S., Eyckerman S., RA Sablina A.A.; RT "Mutations in LZTR1 drive human disease by dysregulating RAS RT ubiquitination."; RL Science 362:1177-1182(2018). RN [39] RP INTERACTION WITH PPP1CA; PPP1CB AND SHOC2. RX PubMed=36175670; DOI=10.1038/s41594-022-00841-4; RA Bonsor D.A., Alexander P., Snead K., Hartig N., Drew M., Messing S., RA Finci L.I., Nissley D.V., McCormick F., Esposito D., Rodriguez-Viciana P., RA Stephen A.G., Simanshu D.K.; RT "Structure of the SHOC2-MRAS-PP1c complex provides insights into RAF RT activation and Noonan syndrome."; RL Nat. Struct. Mol. Biol. 29:966-977(2022). RN [40] RP INTERACTION WITH PPP1CA; PPP1CB; PPP1CC AND SHOC2. RX PubMed=35768504; DOI=10.1038/s41586-022-04838-3; RA Liau N.P.D., Johnson M.C., Izadi S., Gerosa L., Hammel M., Bruning J.M., RA Wendorff T.J., Phung W., Hymowitz S.G., Sudhamsu J.; RT "Structural basis for SHOC2 modulation of RAS signalling."; RL Nature 609:400-407(2022). RN [41] RP INTERACTION WITH PPP1CA; PPP1CB; PPP1CC AND SHOC2, AND MUTAGENESIS OF RP GLN-61. RX PubMed=35831509; DOI=10.1038/s41586-022-04928-2; RA Kwon J.J., Hajian B., Bian Y., Young L.C., Amor A.J., Fuller J.R., RA Fraley C.V., Sykes A.M., So J., Pan J., Baker L., Lee S.J., Wheeler D.B., RA Mayhew D.L., Persky N.S., Yang X., Root D.E., Barsotti A.M., Stamford A.W., RA Perry C.K., Burgin A., McCormick F., Lemke C.T., Hahn W.C., Aguirre A.J.; RT "Structure-function analysis of the SHOC2-MRAS-PP1c holophosphatase RT complex."; RL Nature 609:408-415(2022). RN [42] RP FUNCTION, AND INTERACTION WITH LZTR1. RX PubMed=40934300; DOI=10.1126/science.adv7088; RA Dharmaiah S., Bonsor D.A., Mo S.P., Fernandez-Cabrera A., Chan A.H., RA Messing S., Drew M., Vega M., Nissley D.V., Esposito D., Castel P., RA Simanshu D.K.; RT "Structural basis for LZTR1 recognition of RAS GTPases for degradation."; RL Science 389:1112-1117(2025). RN [43] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). RX PubMed=2448879; DOI=10.1126/science.2448879; RA de Vos A.M., Tong L., Milburn M.V., Matias P.M., Jancarik J., Noguchi S., RA Nishimura S., Miura K., Ohtsuka E., Kim S.-H.; RT "Three-dimensional structure of an oncogene protein: catalytic domain of RT human c-H-ras p21."; RL Science 239:888-893(1988). RN [44] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS). RX PubMed=2476675; DOI=10.1038/341209a0; RA Pai E.F., Kabsch W., Krengel U., Holmes K.C., John J., Wittinghofer A.; RT "Structure of the guanine-nucleotide-binding domain of the Ha-ras oncogene RT product p21 in the triphosphate conformation."; RL Nature 341:209-214(1989). RN [45] {ECO:0007744|PDB:5P21} RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS). RX PubMed=2196171; DOI=10.1002/j.1460-2075.1990.tb07409.x; RA Pai E.F., Krengel U., Petsko G.A., Goody R.S., Kabsch W., Wittinghofer A.; RT "Refined crystal structure of the triphosphate conformation of H-ras p21 at RT 1.35-A resolution: implications for the mechanism of GTP hydrolysis."; RL EMBO J. 9:2351-2359(1990). RN [46] {ECO:0007744|PDB:1Q21, ECO:0007744|PDB:2Q21} RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). RX PubMed=1899707; DOI=10.1016/0022-2836(91)90753-s; RA Tong L.A., de Vos A.M., Milburn M.V., Kim S.H.; RT "Crystal structures at 2.2-A resolution of the catalytic domains of normal RT ras protein and an oncogenic mutant complexed with GDP."; RL J. Mol. Biol. 217:503-516(1991). RN [47] {ECO:0007744|PDB:121P} RP STRUCTURE BY NMR OF 1-166. RX PubMed=8142349; DOI=10.1021/bi00178a008; RA Kraulis P.J., Domaille P.J., Campbell-Burk S.L., van Aken T., Laue E.D.; RT "Solution structure and dynamics of ras p21.GDP determined by heteronuclear RT three- and four-dimensional NMR spectroscopy."; RL Biochemistry 33:3515-3531(1994). RN [48] {ECO:0007744|PDB:1WQ1} RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1-166 IN COMPLEX WITH RP RASA1/RASGAP. RX PubMed=9219684; DOI=10.1126/science.277.5324.333; RA Scheffzek K., Ahmadian M.R., Kabsch W., Wiesmuller L., Lautwein A., RA Schmitz F., Wittinghofer A.; RT "The Ras-RasGAP complex: structural basis for GTPase activation and its RT loss in oncogenic Ras mutants."; RL Science 277:333-338(1997). RN [49] {ECO:0007744|PDB:1CTQ, ECO:0007744|PDB:1QRA} RP X-RAY CRYSTALLOGRAPHY (1.26 ANGSTROMS). RX PubMed=10574788; DOI=10.1016/s0969-2126(00)80021-0; RA Scheidig A.J., Burmester C., Goody R.S.; RT "The pre-hydrolysis state of p21(ras) in complex with GTP: new insights RT into the role of water molecules in the GTP hydrolysis reaction of ras-like RT proteins."; RL Structure 7:1311-1324(1999). RN [50] {ECO:0007744|PDB:1LF0, ECO:0007744|PDB:1LF5} RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-166 IN COMPLEXES WITH GTP RP ANALOGS. RX PubMed=12213964; DOI=10.1073/pnas.192453199; RA Hall B.E., Bar-Sagi D., Nassar N.; RT "The structural basis for the transition from Ras-GTP to Ras-GDP."; RL Proc. Natl. Acad. Sci. U.S.A. 99:12138-12142(2002). RN [51] RP STRUCTURE BY NMR OF 1-166, S-NITROSYLATION, FUNCTION, MUTAGENESIS OF RP CYS-118, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12740440; DOI=10.1073/pnas.1037299100; RA Williams J.G., Pappu K., Campbell S.L.; RT "Structural and biochemical studies of p21Ras S-nitrosylation and nitric RT oxide-mediated guanine nucleotide exchange."; RL Proc. Natl. Acad. Sci. U.S.A. 100:6376-6381(2003). RN [52] {ECO:0007744|PDB:2CE2, ECO:0007744|PDB:2CL0, ECO:0007744|PDB:2CL6, ECO:0007744|PDB:2CL7, ECO:0007744|PDB:2CLC, ECO:0007744|PDB:2CLD, ECO:0007744|PDB:2EVW} RP X-RAY CRYSTALLOGRAPHY (1.00 ANGSTROMS) OF 1-166 IN COMPLEX WITH GTP AND RP MAGNESIUM. RX PubMed=16698776; DOI=10.1529/biophysj.105.078931; RA Klink B.U., Goody R.S., Scheidig A.J.; RT "A newly designed microspectrofluorometer for kinetic studies on protein RT crystals in combination with x-ray diffraction."; RL Biophys. J. 91:981-992(2006). RN [53] {ECO:0007744|PDB:2RGA, ECO:0007744|PDB:2RGB, ECO:0007744|PDB:2RGC, ECO:0007744|PDB:2RGD, ECO:0007744|PDB:2RGE, ECO:0007744|PDB:2RGG} RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-166 IN COMPLEXES WITH GTP RP ANALOG, CHARACTERIZATION OF VARIANTS LEU-61 AND LYS-61, AND MUTAGENESIS OF RP GLN-61. RX PubMed=18073111; DOI=10.1016/j.str.2007.10.011; RA Buhrman G., Wink G., Mattos C.; RT "Transformation efficiency of RasQ61 mutants linked to structural features RT of the switch regions in the presence of Raf."; RL Structure 15:1618-1629(2007). RN [54] {ECO:0007744|PDB:3DDC} RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-166 IN COMPLEX WITH RASSF5. RX PubMed=18596699; DOI=10.1038/emboj.2008.125; RA Stieglitz B., Bee C., Schwarz D., Yildiz O., Moshnikova A., RA Khokhlatchev A., Herrmann C.; RT "Novel type of Ras effector interaction established between tumour RT suppressor NORE1A and Ras switch II."; RL EMBO J. 27:1995-2005(2008). RN [55] {ECO:0007744|PDB:7VV8, ECO:0007744|PDB:7VV9, ECO:0007744|PDB:7VVG} RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 1-166 IN COMPLEX WITH MAPKAP1, RP AND INTERACTION WITH MAPKAP1. RX PubMed=35522713; DOI=10.1073/pnas.2119990119; RA Zheng Y., Ding L., Meng X., Potter M., Kearney A.L., Zhang J., Sun J., RA James D.E., Yang G., Zhou C.; RT "Structural insights into Ras regulation by SIN1."; RL Proc. Natl. Acad. Sci. U.S.A. 119:e2119990119-e2119990119(2022). RN [56] RP VARIANT SER-12. RX PubMed=1459726; DOI=10.1002/ijc.2910520606; RA Sakai E., Rikimaru K., Ueda M., Matsumoto Y., Ishii N., Enomoto S., RA Yamamoto H., Tsuchida N.; RT "The p53 tumor-suppressor gene and ras oncogene mutations in oral squamous- RT cell carcinoma."; RL Int. J. Cancer 52:867-872(1992). RN [57] RP INVOLVEMENT IN NMTC2, AND VARIANT NMTC2 LYS-61. RX PubMed=12727991; DOI=10.1210/jc.2002-021907; RA Nikiforova M.N., Lynch R.A., Biddinger P.W., Alexander E.K., Dorn G.W. II, RA Tallini G., Kroll T.G., Nikiforov Y.E.; RT "RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: RT evidence for distinct molecular pathways in thyroid follicular carcinoma."; RL J. Clin. Endocrinol. Metab. 88:2318-2326(2003). RN [58] RP VARIANTS CSTLO ALA-12; SER-12; VAL-12 AND ASP-13. RX PubMed=16170316; DOI=10.1038/ng1641; RA Aoki Y., Niihori T., Kawame H., Kurosawa K., Ohashi H., Tanaka Y., RA Filocamo M., Kato K., Suzuki Y., Kure S., Matsubara Y.; RT "Germline mutations in HRAS proto-oncogene cause Costello syndrome."; RL Nat. Genet. 37:1038-1040(2005). RN [59] RP VARIANTS CSTLO ALA-12; SER-12 AND CYS-13. RX PubMed=16329078; DOI=10.1002/ajmg.a.31047; RA Gripp K.W., Lin A.E., Stabley D.L., Nicholson L., Scott C.I. Jr., Doyle D., RA Aoki Y., Matsubara Y., Zackai E.H., Lapunzina P., Gonzalez-Meneses A., RA Holbrook J., Agresta C.A., Gonzalez I.L., Sol-Church K.; RT "HRAS mutation analysis in Costello syndrome: genotype and phenotype RT correlation."; RL Am. J. Med. Genet. A 140:1-7(2006). RN [60] RP VARIANTS CSTLO SER-12; CYS-12; GLU-12; ALA-12 AND ARG-117. RX PubMed=16443854; DOI=10.1136/jmg.2005.040352; RA Kerr B., Delrue M.-A., Sigaudy S., Perveen R., Marche M., Burgelin I., RA Stef M., Tang B., Eden O.B., O'Sullivan J., De Sandre-Giovannoli A., RA Reardon W., Brewer C., Bennett C., Quarell O., M'Cann E., Donnai D., RA Stewart F., Hennekam R., Cave H., Verloes A., Philip N., Lacombe D., RA Levy N., Arveiler B., Black G.; RT "Genotype-phenotype correlation in Costello syndrome: HRAS mutation RT analysis in 43 cases."; RL J. Med. Genet. 43:401-405(2006). RN [61] RP VARIANTS CSTLO SER-12 AND THR-146. RX PubMed=17054105; DOI=10.1002/humu.20431; RA Zampino G., Pantaleoni F., Carta C., Cobellis G., Vasta I., Neri C., RA Pogna E.A., De Feo E., Delogu A., Sarkozy A., Atzeri F., Selicorni A., RA Rauen K.A., Cytrynbaum C.S., Weksberg R., Dallapiccola B., Ballabio A., RA Gelb B.D., Neri G., Tartaglia M.; RT "Diversity, parental germline origin, and phenotypic spectrum of de novo RT HRAS missense changes in Costello syndrome."; RL Hum. Mutat. 28:265-272(2007). RN [62] RP VARIANTS CMEMS VAL-12; SER-12; LYS-22 AND LYS-63. RX PubMed=17412879; DOI=10.1136/jmg.2007.049270; RA van der Burgt I., Kupsky W., Stassou S., Nadroo A., Barroso C., Diem A., RA Kratz C.P., Dvorsky R., Ahmadian M.R., Zenker M.; RT "Myopathy caused by HRAS germline mutations: implications for disturbed RT myogenic differentiation in the presence of constitutive HRas activation."; RL J. Med. Genet. 44:459-462(2007). RN [63] RP VARIANTS CSTLO ILE-58 AND VAL-146. RX PubMed=18247425; DOI=10.1002/ajmg.a.32227; RA Gripp K.W., Innes A.M., Axelrad M.E., Gillan T.L., Parboosingh J.S., RA Davies C., Leonard N.J., Lapointe M., Doyle D., Catalano S., Nicholson L., RA Stabley D.L., Sol-Church K.; RT "Costello syndrome associated with novel germline HRAS mutations: an RT attenuated phenotype?"; RL Am. J. Med. Genet. A 146:683-690(2008). RN [64] RP VARIANTS CSTLO ASP-12 AND CYS-12. RX PubMed=18039947; DOI=10.1136/jmg.2007.054411; RA Lo I.F., Brewer C., Shannon N., Shorto J., Tang B., Black G., Soo M.T., RA Ng D.K., Lam S.T., Kerr B.; RT "Severe neonatal manifestations of Costello syndrome."; RL J. Med. Genet. 45:167-171(2008). RN [65] RP VARIANT CSTLO GLU-37 INS. RX PubMed=19995790; DOI=10.1093/hmg/ddp548; RA Gremer L., De Luca A., Merbitz-Zahradnik T., Dallapiccola B., Morlot S., RA Tartaglia M., Kutsche K., Ahmadian M.R., Rosenberger G.; RT "Duplication of Glu37 in the switch I region of HRAS impairs effector/GAP RT binding and underlies Costello syndrome by promoting enhanced growth RT factor-dependent MAPK and AKT activation."; RL Hum. Mol. Genet. 19:790-802(2010). RN [66] RP VARIANT SFM ARG-13, AND CHARACTERIZATION OF VARIANT SFM ARG-13. RX PubMed=22683711; DOI=10.1038/ng.2316; RA Groesser L., Herschberger E., Ruetten A., Ruivenkamp C., Lopriore E., RA Zutt M., Langmann T., Singer S., Klingseisen L., Schneider-Brachert W., RA Toll A., Real F.X., Landthaler M., Hafner C.; RT "Postzygotic HRAS and KRAS mutations cause nevus sebaceous and RT Schimmelpenning syndrome."; RL Nat. Genet. 44:783-787(2012). CC -!- FUNCTION: Signal transducer in the Ras-MAPK signaling pathway that CC regulates cell proliferation and survival (PubMed:22821884). Ras CC proteins bind GDP/GTP and possess intrinsic GTPase activity CC (PubMed:12740440, PubMed:14500341, PubMed:9020151). Recognized by LZTR1 CC that mediates its ubiquitination by a BCR (BTB-CUL3-RBX1) E3 ubiquitin- CC protein ligase complex (PubMed:40934300). {ECO:0000269|PubMed:12740440, CC ECO:0000269|PubMed:14500341, ECO:0000269|PubMed:22821884, CC ECO:0000269|PubMed:40934300, ECO:0000269|PubMed:9020151}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2; CC Evidence={ECO:0000269|PubMed:9020151}; CC -!- ACTIVITY REGULATION: Alternates between an inactive form bound to GDP CC and an active form bound to GTP. Activated by a guanine nucleotide- CC exchange factor (GEF) and inactivated by a GTPase-activating protein CC (GAP). CC -!- SUBUNIT: In its GTP-bound form interacts with PLCE1 (PubMed:11022048). CC Interacts with TBC1D10C (PubMed:17230191). Interacts with RGL3 (By CC similarity). Interacts with HSPD1 (By similarity). Found in a complex CC with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14 (By similarity). CC Interacts (active GTP-bound form) with RGS14 (via RBD 1 domain) (By CC similarity). Forms a signaling complex with RASGRP1 and DGKZ CC (PubMed:11257115). Interacts with RASSF5 (PubMed:18596699). Interacts CC with PDE6D (PubMed:11980706). Interacts with IKZF3 (PubMed:10369681). CC Interacts with RACK1 (PubMed:14500341). Interacts with PIK3CG; the CC interaction is required for membrane recruitment and beta-gamma G CC protein dimer-dependent activation of the PI3K gamma complex CC PIK3CG:PIK3R6 (By similarity). Interacts with RAPGEF2 (PubMed:10608844, CC PubMed:11598133). Interacts (active GTP-bound form) with both SHOC2 and CC PP1c (all isoforms) to form a tertiary complex; SHOC2 and PP1c CC preferably bind M-Ras/MRAS, but they also bind K-Ras/KRAS, N-Ras/NRAS CC and H-Ras/HRAS (PubMed:35768504, PubMed:35831509, PubMed:36175670). CC Interacts (GTP-bound form) with MAPKAP1/SIN1; inhibiting H-Ras/HRAS CC activity (PubMed:35522713). Interacts (GDP-bound form) with LZTR1; this CC interaction mediates HRAS ubiquitination by BCR E3 ligase complex CC (PubMed:40934300). {ECO:0000250|UniProtKB:P20171, CC ECO:0000250|UniProtKB:Q61411, ECO:0000269|PubMed:10369681, CC ECO:0000269|PubMed:10608844, ECO:0000269|PubMed:11022048, CC ECO:0000269|PubMed:11257115, ECO:0000269|PubMed:11598133, CC ECO:0000269|PubMed:11980706, ECO:0000269|PubMed:14500341, CC ECO:0000269|PubMed:17230191, ECO:0000269|PubMed:18596699, CC ECO:0000269|PubMed:35522713, ECO:0000269|PubMed:35768504, CC ECO:0000269|PubMed:35831509, ECO:0000269|PubMed:36175670, CC ECO:0000269|PubMed:40934300}. CC -!- INTERACTION: CC P01112; Q99996-3: AKAP9; NbExp=3; IntAct=EBI-350145, EBI-11022349; CC P01112; P53677-2: AP3M2; NbExp=3; IntAct=EBI-350145, EBI-12177015; CC P01112; P10398: ARAF; NbExp=8; IntAct=EBI-350145, EBI-365961; CC P01112; Q9NXL2-1: ARHGEF38; NbExp=3; IntAct=EBI-350145, EBI-18172597; CC P01112; Q9UII2: ATP5IF1; NbExp=3; IntAct=EBI-350145, EBI-718459; CC P01112; Q9H7T9: AUNIP; NbExp=3; IntAct=EBI-350145, EBI-10693257; CC P01112; Q00994: BEX3; NbExp=3; IntAct=EBI-350145, EBI-741753; CC P01112; Q9H2G9: BLZF1; NbExp=4; IntAct=EBI-350145, EBI-2548012; CC P01112; P15056: BRAF; NbExp=10; IntAct=EBI-350145, EBI-365980; CC P01112; Q7Z569: BRAP; NbExp=3; IntAct=EBI-350145, EBI-349900; CC P01112; Q5PSV4: BRMS1L; NbExp=3; IntAct=EBI-350145, EBI-5666615; CC P01112; Q9ULD4-2: BRPF3; NbExp=3; IntAct=EBI-350145, EBI-23662416; CC P01112; Q96LL4: C8orf48; NbExp=3; IntAct=EBI-350145, EBI-751596; CC P01112; Q86X55: CARM1; NbExp=4; IntAct=EBI-350145, EBI-2339854; CC P01112; Q96HB5: CCDC120; NbExp=3; IntAct=EBI-350145, EBI-744556; CC P01112; Q49A88-3: CCDC14; NbExp=3; IntAct=EBI-350145, EBI-12105646; CC P01112; Q96GN5-2: CDCA7L; NbExp=3; IntAct=EBI-350145, EBI-9091443; CC P01112; P24941: CDK2; NbExp=3; IntAct=EBI-350145, EBI-375096; CC P01112; O95674: CDS2; NbExp=3; IntAct=EBI-350145, EBI-3913685; CC P01112; Q9H3R5: CENPH; NbExp=3; IntAct=EBI-350145, EBI-1003700; CC P01112; Q9Y4F5-3: CEP170B; NbExp=3; IntAct=EBI-350145, EBI-12950757; CC P01112; Q86XR8: CEP57; NbExp=3; IntAct=EBI-350145, EBI-308614; CC P01112; Q494V2-2: CFAP100; NbExp=3; IntAct=EBI-350145, EBI-11953200; CC P01112; O14757: CHEK1; NbExp=4; IntAct=EBI-350145, EBI-974488; CC P01112; Q8WUX9: CHMP7; NbExp=4; IntAct=EBI-350145, EBI-749253; CC P01112; Q14117: DPYS; NbExp=3; IntAct=EBI-350145, EBI-12275416; CC P01112; Q9Y6W6: DUSP10; NbExp=3; IntAct=EBI-350145, EBI-3443946; CC P01112; O14641: DVL2; NbExp=3; IntAct=EBI-350145, EBI-740850; CC P01112; A0AVK6: E2F8; NbExp=3; IntAct=EBI-350145, EBI-7779316; CC P01112; Q8NB25: FAM184A; NbExp=3; IntAct=EBI-350145, EBI-9917523; CC P01112; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-350145, EBI-8468186; CC P01112; Q969H0: FBXW7; NbExp=5; IntAct=EBI-350145, EBI-359574; CC P01112; O94868-3: FCHSD2; NbExp=3; IntAct=EBI-350145, EBI-11958845; CC P01112; P49354: FNTA; NbExp=3; IntAct=EBI-350145, EBI-602336; CC P01112; P15407: FOSL1; NbExp=3; IntAct=EBI-350145, EBI-744510; CC P01112; P15408: FOSL2; NbExp=3; IntAct=EBI-350145, EBI-3893419; CC P01112; P52655: GTF2A1; NbExp=3; IntAct=EBI-350145, EBI-389518; CC P01112; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-350145, EBI-2514791; CC P01112; Q9BT25: HAUS8; NbExp=3; IntAct=EBI-350145, EBI-2558143; CC P01112; Q8IV36: HID1; NbExp=3; IntAct=EBI-350145, EBI-743438; CC P01112; O43248: HOXC11; NbExp=3; IntAct=EBI-350145, EBI-2652631; CC P01112; Q53GQ0: HSD17B12; NbExp=3; IntAct=EBI-350145, EBI-2963255; CC P01112; P10809: HSPD1; NbExp=3; IntAct=EBI-350145, EBI-352528; CC P01112; Q8NDH6-2: ICA1L; NbExp=3; IntAct=EBI-350145, EBI-12141931; CC P01112; Q8IY31-2: IFT20; NbExp=3; IntAct=EBI-350145, EBI-11742277; CC P01112; Q8NA54: IQUB; NbExp=3; IntAct=EBI-350145, EBI-10220600; CC P01112; Q13352: ITGB3BP; NbExp=3; IntAct=EBI-350145, EBI-712105; CC P01112; P28290-2: ITPRID2; NbExp=3; IntAct=EBI-350145, EBI-25863618; CC P01112; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-350145, EBI-14069005; CC P01112; Q2M2Z5: KIZ; NbExp=3; IntAct=EBI-350145, EBI-2554344; CC P01112; Q6P597: KLC3; NbExp=3; IntAct=EBI-350145, EBI-1643885; CC P01112; P57682: KLF3; NbExp=3; IntAct=EBI-350145, EBI-8472267; CC P01112; Q9UH77: KLHL3; NbExp=3; IntAct=EBI-350145, EBI-8524663; CC P01112; P08727: KRT19; NbExp=3; IntAct=EBI-350145, EBI-742756; CC P01112; Q14525: KRT33B; NbExp=3; IntAct=EBI-350145, EBI-1049638; CC P01112; Q14847-2: LASP1; NbExp=3; IntAct=EBI-350145, EBI-9088686; CC P01112; Q96LR2: LURAP1; NbExp=3; IntAct=EBI-350145, EBI-741355; CC P01112; P27338: MAOB; NbExp=3; IntAct=EBI-350145, EBI-3911344; CC P01112; Q99558: MAP3K14; NbExp=3; IntAct=EBI-350145, EBI-358011; CC P01112; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-350145, EBI-348259; CC P01112; Q8TAC0: MGC27345; NbExp=3; IntAct=EBI-350145, EBI-25851300; CC P01112; Q5JXC2: MIIP; NbExp=3; IntAct=EBI-350145, EBI-2801965; CC P01112; Q8NEH6: MNS1; NbExp=3; IntAct=EBI-350145, EBI-743811; CC P01112; Q9Y605: MRFAP1; NbExp=4; IntAct=EBI-350145, EBI-995714; CC P01112; Q96HT8: MRFAP1L1; NbExp=3; IntAct=EBI-350145, EBI-748896; CC P01112; Q9GZM8: NDEL1; NbExp=3; IntAct=EBI-350145, EBI-928842; CC P01112; P21359: NF1; NbExp=3; IntAct=EBI-350145, EBI-1172917; CC P01112; Q8N5V2: NGEF; NbExp=3; IntAct=EBI-350145, EBI-718372; CC P01112; Q6PHZ7: NR2C2; NbExp=3; IntAct=EBI-350145, EBI-2802743; CC P01112; Q9BZ95-3: NSD3; NbExp=3; IntAct=EBI-350145, EBI-22002759; CC P01112; A5D8V7: ODAD3; NbExp=3; IntAct=EBI-350145, EBI-8466445; CC P01112; O43482: OIP5; NbExp=3; IntAct=EBI-350145, EBI-536879; CC P01112; Q9BR81: PCDHGC3; NbExp=3; IntAct=EBI-350145, EBI-22012354; CC P01112; O15534: PER1; NbExp=3; IntAct=EBI-350145, EBI-2557276; CC P01112; Q9BUL5: PHF23; NbExp=3; IntAct=EBI-350145, EBI-722852; CC P01112; O00329: PIK3CD; NbExp=2; IntAct=EBI-350145, EBI-718309; CC P01112; O00329-2: PIK3CD; NbExp=2; IntAct=EBI-350145, EBI-6470902; CC P01112; Q9UPR0: PLCL2; NbExp=3; IntAct=EBI-350145, EBI-311059; CC P01112; Q96I34: PPP1R16A; NbExp=3; IntAct=EBI-350145, EBI-710402; CC P01112; Q15435-3: PPP1R7; NbExp=3; IntAct=EBI-350145, EBI-10695066; CC P01112; Q96JH8: RADIL; NbExp=3; IntAct=EBI-350145, EBI-744267; CC P01112; P04049: RAF1; NbExp=30; IntAct=EBI-350145, EBI-365996; CC P01112; P11233: RALA; NbExp=2; IntAct=EBI-350145, EBI-1036803; CC P01112; Q15311: RALBP1; NbExp=3; IntAct=EBI-350145, EBI-749285; CC P01112; Q12967: RALGDS; NbExp=3; IntAct=EBI-350145, EBI-365861; CC P01112; P52306: RAP1GDS1; NbExp=3; IntAct=EBI-350145, EBI-746389; CC P01112; Q9NS23-2: RASSF1; NbExp=2; IntAct=EBI-350145, EBI-438698; CC P01112; Q9NS23-4: RASSF1; NbExp=4; IntAct=EBI-350145, EBI-438710; CC P01112; Q8WWW0: RASSF5; NbExp=2; IntAct=EBI-350145, EBI-367390; CC P01112; Q8TBY0: RBM46; NbExp=3; IntAct=EBI-350145, EBI-12068216; CC P01112; Q9P2K3-2: RCOR3; NbExp=3; IntAct=EBI-350145, EBI-1504830; CC P01112; Q9NZL6: RGL1; NbExp=4; IntAct=EBI-350145, EBI-365926; CC P01112; O15211: RGL2; NbExp=3; IntAct=EBI-350145, EBI-712355; CC P01112; Q8IXN7: RIMKLA; NbExp=3; IntAct=EBI-350145, EBI-21890191; CC P01112; Q13671: RIN1; NbExp=15; IntAct=EBI-350145, EBI-366017; CC P01112; Q13671-1: RIN1; NbExp=2; IntAct=EBI-350145, EBI-366030; CC P01112; Q8WVD3: RNF138; NbExp=3; IntAct=EBI-350145, EBI-749039; CC P01112; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-350145, EBI-25837959; CC P01112; Q13435: SF3B2; NbExp=3; IntAct=EBI-350145, EBI-749111; CC P01112; Q13485: SMAD4; NbExp=5; IntAct=EBI-350145, EBI-347263; CC P01112; Q12824: SMARCB1; NbExp=3; IntAct=EBI-350145, EBI-358419; CC P01112; Q13573: SNW1; NbExp=3; IntAct=EBI-350145, EBI-632715; CC P01112; Q07889: SOS1; NbExp=11; IntAct=EBI-350145, EBI-297487; CC P01112; Q86W54-2: SPATA24; NbExp=3; IntAct=EBI-350145, EBI-12041693; CC P01112; Q92783-2: STAM; NbExp=3; IntAct=EBI-350145, EBI-12025738; CC P01112; O75886: STAM2; NbExp=3; IntAct=EBI-350145, EBI-373258; CC P01112; Q13586: STIM1; NbExp=4; IntAct=EBI-350145, EBI-448878; CC P01112; Q8N4C7: STX19; NbExp=3; IntAct=EBI-350145, EBI-8484990; CC P01112; O75528: TADA3; NbExp=3; IntAct=EBI-350145, EBI-473249; CC P01112; P54274-2: TERF1; NbExp=3; IntAct=EBI-350145, EBI-711018; CC P01112; Q9BXU0: TEX12; NbExp=3; IntAct=EBI-350145, EBI-12090309; CC P01112; Q5T0J7-2: TEX35; NbExp=3; IntAct=EBI-350145, EBI-12833746; CC P01112; Q5T1C6: THEM4; NbExp=3; IntAct=EBI-350145, EBI-7684443; CC P01112; Q8IUR5-4: TMTC1; NbExp=3; IntAct=EBI-350145, EBI-9089156; CC P01112; P36406: TRIM23; NbExp=3; IntAct=EBI-350145, EBI-740098; CC P01112; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-350145, EBI-11525489; CC P01112; Q99598: TSNAX; NbExp=3; IntAct=EBI-350145, EBI-21353855; CC P01112; Q6PF05: TTC23L; NbExp=3; IntAct=EBI-350145, EBI-8656864; CC P01112; Q9UGJ1-2: TUBGCP4; NbExp=3; IntAct=EBI-350145, EBI-10964469; CC P01112; Q9Y5Z9: UBIAD1; NbExp=9; IntAct=EBI-350145, EBI-2819725; CC P01112; P22415: USF1; NbExp=3; IntAct=EBI-350145, EBI-1054489; CC P01112; Q495M9: USH1G; NbExp=3; IntAct=EBI-350145, EBI-8601749; CC P01112; Q9H270: VPS11; NbExp=3; IntAct=EBI-350145, EBI-373380; CC P01112; Q8NEZ2: VPS37A; NbExp=3; IntAct=EBI-350145, EBI-2850578; CC P01112; P19544-6: WT1; NbExp=3; IntAct=EBI-350145, EBI-11745701; CC P01112; O43829: ZBTB14; NbExp=3; IntAct=EBI-350145, EBI-10176632; CC P01112; Q9C0F3: ZNF436; NbExp=3; IntAct=EBI-350145, EBI-8489702; CC P01112; Q7Z637; NbExp=3; IntAct=EBI-350145, EBI-25831475; CC P01112; Q86V28; NbExp=3; IntAct=EBI-350145, EBI-10259496; CC P01112; P42337: Pik3ca; Xeno; NbExp=2; IntAct=EBI-350145, EBI-641748; CC P01112; Q9Z0S9: Rabac1; Xeno; NbExp=4; IntAct=EBI-350145, EBI-476965; CC P01112; Q9EQZ6: Rapgef4; Xeno; NbExp=3; IntAct=EBI-350145, EBI-772212; CC P01112; P27671: Rasgrf1; Xeno; NbExp=2; IntAct=EBI-350145, EBI-645522; CC P01112; Q5EBH1: Rassf5; Xeno; NbExp=13; IntAct=EBI-350145, EBI-960530; CC P01112; Q5EBH1-1: Rassf5; Xeno; NbExp=3; IntAct=EBI-350145, EBI-960543; CC P01112-2; P52306-5: RAP1GDS1; NbExp=5; IntAct=EBI-13290525, EBI-12832744; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P20171}; CC Lipid-anchor; Cytoplasmic side. Golgi apparatus. Golgi apparatus CC membrane; Lipid-anchor. Note=The active GTP-bound form is localized CC most strongly to membranes than the inactive GDP-bound form (By CC similarity). Shuttles between the plasma membrane and the Golgi CC apparatus. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus. Cytoplasm. Cytoplasm, CC perinuclear region. Note=Colocalizes with RACK1 to the perinuclear CC region. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=H-Ras4A, p21; CC IsoId=P01112-1; Sequence=Displayed; CC Name=2; Synonyms=H-RasIDX, p19; CC IsoId=P01112-2; Sequence=VSP_041597; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:14500341}. CC -!- PTM: Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of CC de- and re-palmitoylation regulates rapid exchange between plasma CC membrane and Golgi. CC -!- PTM: S-nitrosylated; critical for redox regulation. Important for CC stimulating guanine nucleotide exchange. No structural perturbation on CC nitrosylation. CC -!- PTM: The covalent modification of cysteine by 15-deoxy-Delta12,14- CC prostaglandin-J2 is autocatalytic and reversible. It may occur as an CC alternative to other cysteine modifications, such as S-nitrosylation CC and S-palmitoylation. CC -!- PTM: Acetylation at Lys-104 prevents interaction with guanine CC nucleotide exchange factors (GEFs). {ECO:0000250}. CC -!- PTM: Fatty-acylated at Lys-170. {ECO:0000269|PubMed:29239724}. CC -!- PTM: Ubiquitinated by the BCR(LZTR1) E3 ubiquitin ligase complex at CC Lys-170 in a non-degradative manner, leading to inhibit Ras signaling CC by decreasing Ras association with membranes. CC {ECO:0000269|PubMed:30442762}. CC -!- PTM: (Microbial infection) Glucosylated at Thr-35 by P.sordellii toxin CC TcsL (PubMed:19744486, PubMed:8626575, PubMed:8626586, PubMed:9632667). CC Monoglucosylation completely prevents the recognition of the downstream CC effector, blocking the GTPases in their inactive form, leading to CC inhibit Ras signaling (PubMed:8626575, PubMed:8626586, PubMed:9632667). CC {ECO:0000269|PubMed:19744486, ECO:0000269|PubMed:8626575, CC ECO:0000269|PubMed:8626586, ECO:0000269|PubMed:9632667}. CC -!- DISEASE: Costello syndrome (CSTLO) [MIM:218040]: A rare condition CC characterized by prenatally increased growth, postnatal growth CC deficiency, intellectual disability, distinctive facial appearance, CC cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic CC cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin CC and musculoskeletal abnormalities. {ECO:0000269|PubMed:16170316, CC ECO:0000269|PubMed:16329078, ECO:0000269|PubMed:16443854, CC ECO:0000269|PubMed:17054105, ECO:0000269|PubMed:18039947, CC ECO:0000269|PubMed:18247425, ECO:0000269|PubMed:19995790}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Congenital myopathy with excess of muscle spindles (CMEMS) CC [MIM:218040]: Variant of Costello syndrome. CC {ECO:0000269|PubMed:17412879}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470]: A form CC of non-medullary thyroid cancer (NMTC), a cancer characterized by CC tumors originating from the thyroid follicular cells. NMTCs represent CC approximately 95% of all cases of thyroid cancer and are classified CC into papillary, follicular, Hurthle cell, and anaplastic neoplasms. CC {ECO:0000269|PubMed:12727991}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Note=Mutations which change positions 12, 13 or 61 activate CC the potential of HRAS to transform cultured cells and are implicated in CC a variety of human tumors. {ECO:0000269|PubMed:3670300}. CC -!- DISEASE: Bladder cancer (BLC) [MIM:109800]: A malignancy originating in CC tissues of the urinary bladder. It often presents with multiple tumors CC appearing at different times and at different sites in the bladder. CC Most bladder cancers are transitional cell carcinomas that begin in CC cells that normally make up the inner lining of the bladder. Other CC types of bladder cancer include squamous cell carcinoma (cancer that CC begins in thin, flat cells) and adenocarcinoma (cancer that begins in CC cells that make and release mucus and other fluids). Bladder cancer is CC a complex disorder with both genetic and environmental influences. CC {ECO:0000269|PubMed:6298635, ECO:0000269|PubMed:6844927}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- DISEASE: Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:163200]: A CC disease characterized by sebaceous nevi, often on the face, associated CC with variable ipsilateral abnormalities of the central nervous system, CC ocular anomalies, and skeletal defects. Many oral manifestations have CC been reported, not only including hypoplastic and malformed teeth, and CC mucosal papillomatosis, but also ankyloglossia, hemihyperplastic CC tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone CC cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous CC nevi follow the lines of Blaschko and these can continue as linear CC intraoral lesions, as in mucosal papillomatosis. CC {ECO:0000269|PubMed:22683711}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/108/HRAS"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J00277; AAB02605.1; -; Genomic_DNA. DR EMBL; AJ437024; CAD24594.1; -; mRNA. DR EMBL; AF493916; AAM12630.1; -; mRNA. DR EMBL; CR536579; CAG38816.1; -; mRNA. DR EMBL; CR542271; CAG47067.1; -; mRNA. DR EMBL; BT019421; AAV38228.1; -; mRNA. DR EMBL; EF015887; ABI97389.1; -; Genomic_DNA. DR EMBL; AB451336; BAG70150.1; -; mRNA. DR EMBL; AB451485; BAG70299.1; -; mRNA. DR EMBL; CH471158; EAX02337.1; -; Genomic_DNA. DR EMBL; CH471158; EAX02338.1; -; Genomic_DNA. DR EMBL; BC006499; AAH06499.1; -; mRNA. DR EMBL; BC095471; AAH95471.1; -; mRNA. DR EMBL; M17232; AAA35685.1; -; Genomic_DNA. DR CCDS; CCDS7698.1; -. [P01112-1] DR CCDS; CCDS7699.1; -. [P01112-2] DR PIR; A93299; TVHUH. DR RefSeq; NP_001123914.1; NM_001130442.3. [P01112-1] DR RefSeq; NP_001304983.1; NM_001318054.2. DR RefSeq; NP_005334.1; NM_005343.4. [P01112-1] DR RefSeq; NP_789765.1; NM_176795.5. [P01112-2] DR RefSeq; XP_054224585.1; XM_054368610.1. [P01112-1] DR PDB; 10DC; X-ray; 2.08 A; A=1-166. DR PDB; 121P; X-ray; 1.54 A; A=1-166. DR PDB; 1AA9; NMR; -; A=1-171. DR PDB; 1AGP; X-ray; 2.30 A; A=1-166. DR PDB; 1BKD; X-ray; 2.80 A; R=1-166. DR PDB; 1CLU; X-ray; 1.70 A; A=1-166. DR PDB; 1CRP; NMR; -; A=1-166. DR PDB; 1CRQ; NMR; -; A=1-166. DR PDB; 1CRR; NMR; -; A=1-166. DR PDB; 1CTQ; X-ray; 1.26 A; A=1-166. DR PDB; 1GNP; X-ray; 2.70 A; A=1-166. DR PDB; 1GNQ; X-ray; 2.50 A; A=1-166. DR PDB; 1GNR; X-ray; 1.85 A; A=1-166. DR PDB; 1HE8; X-ray; 3.00 A; B=1-166. DR PDB; 1IAQ; X-ray; 2.90 A; A/B/C=1-166. DR PDB; 1IOZ; X-ray; 2.00 A; A=1-171. DR PDB; 1JAH; X-ray; 1.80 A; A=1-166. DR PDB; 1JAI; X-ray; 1.80 A; A=1-166. DR PDB; 1K8R; X-ray; 3.00 A; A=1-166. DR PDB; 1LF0; X-ray; 1.70 A; A=1-166. DR PDB; 1LF5; X-ray; 1.70 A; A=1-166. DR PDB; 1LFD; X-ray; 2.10 A; B/D=1-167. DR PDB; 1NVU; X-ray; 2.20 A; Q/R=1-166. DR PDB; 1NVV; X-ray; 2.18 A; Q/R=1-166. DR PDB; 1NVW; X-ray; 2.70 A; Q/R=1-166. DR PDB; 1NVX; X-ray; 3.20 A; Q/R=1-166. DR PDB; 1P2S; X-ray; 2.45 A; A=1-166. DR PDB; 1P2T; X-ray; 2.00 A; A=1-166. DR PDB; 1P2U; X-ray; 2.00 A; A=1-166. DR PDB; 1P2V; X-ray; 2.30 A; A=1-166. DR PDB; 1PLJ; X-ray; 2.80 A; A=1-166. DR PDB; 1PLK; X-ray; 2.80 A; A=1-166. DR PDB; 1PLL; X-ray; 2.80 A; A=1-166. DR PDB; 1Q21; X-ray; 2.20 A; A=1-171. DR PDB; 1QRA; X-ray; 1.60 A; A=1-166. DR PDB; 1RVD; X-ray; 1.90 A; A=1-166. DR PDB; 1WQ1; X-ray; 2.50 A; R=1-166. DR PDB; 1XCM; X-ray; 1.84 A; A=1-167. DR PDB; 1XD2; X-ray; 2.70 A; A/B=1-166. DR PDB; 1XJ0; X-ray; 1.70 A; A=1-166. DR PDB; 1ZVQ; X-ray; 2.00 A; A=1-166. DR PDB; 1ZW6; X-ray; 1.50 A; A=1-166. DR PDB; 221P; X-ray; 2.30 A; A=1-166. DR PDB; 2C5L; X-ray; 1.90 A; A/B=1-166. DR PDB; 2CE2; X-ray; 1.00 A; X=1-166. DR PDB; 2CL0; X-ray; 1.80 A; X=1-166. DR PDB; 2CL6; X-ray; 1.24 A; X=1-166. DR PDB; 2CL7; X-ray; 1.25 A; X=1-166. DR PDB; 2CLC; X-ray; 1.30 A; X=1-166. DR PDB; 2CLD; X-ray; 1.22 A; X=1-166. DR PDB; 2EVW; X-ray; 1.05 A; X=1-166. DR PDB; 2LCF; NMR; -; A=1-166. DR PDB; 2LWI; NMR; -; A=1-166. DR PDB; 2N42; NMR; -; A=1-166. DR PDB; 2N46; NMR; -; A=1-166. DR PDB; 2Q21; X-ray; 2.20 A; A=1-171. DR PDB; 2QUZ; X-ray; 1.49 A; A=1-166. DR PDB; 2RGA; X-ray; 1.90 A; A=1-166. DR PDB; 2RGB; X-ray; 1.35 A; A=1-166. DR PDB; 2RGC; X-ray; 1.60 A; A=1-166. DR PDB; 2RGD; X-ray; 2.00 A; A=1-166. DR PDB; 2RGE; X-ray; 1.40 A; A=1-166. DR PDB; 2RGG; X-ray; 1.45 A; A=1-166. DR PDB; 2UZI; X-ray; 2.00 A; R=1-166. DR PDB; 2VH5; X-ray; 2.70 A; R=1-166. DR PDB; 2X1V; X-ray; 1.70 A; A=1-166. DR PDB; 3DDC; X-ray; 1.80 A; A=1-166. DR PDB; 3I3S; X-ray; 1.36 A; R=1-166. DR PDB; 3K8Y; X-ray; 1.30 A; A=1-166. DR PDB; 3K9L; X-ray; 1.80 A; A/B/C=1-166. DR PDB; 3K9N; X-ray; 2.00 A; A=1-166. DR PDB; 3KKM; X-ray; 1.70 A; A=1-166. DR PDB; 3KKN; X-ray; 2.09 A; A=1-166. DR PDB; 3KUD; X-ray; 2.15 A; A=1-166. DR PDB; 3L8Y; X-ray; 2.02 A; A=1-166. DR PDB; 3L8Z; X-ray; 1.44 A; A=1-166. DR PDB; 3LBH; X-ray; 1.85 A; A=1-166. DR PDB; 3LBI; X-ray; 2.09 A; A=1-166. DR PDB; 3LBN; X-ray; 1.86 A; A=1-166. DR PDB; 3LO5; X-ray; 2.57 A; A/C/E=1-166. DR PDB; 3OIU; X-ray; 1.32 A; A=1-166. DR PDB; 3OIV; X-ray; 1.84 A; A=1-166. DR PDB; 3OIW; X-ray; 1.30 A; A=1-166. DR PDB; 3RRY; X-ray; 1.60 A; A=1-166. DR PDB; 3RRZ; X-ray; 1.60 A; A=1-166. DR PDB; 3RS0; X-ray; 1.40 A; A=1-166. DR PDB; 3RS2; X-ray; 1.84 A; A=1-166. DR PDB; 3RS3; X-ray; 1.52 A; A=1-166. DR PDB; 3RS4; X-ray; 1.70 A; A=1-166. DR PDB; 3RS5; X-ray; 1.68 A; A=1-166. DR PDB; 3RS7; X-ray; 1.70 A; A=1-166. DR PDB; 3RSL; X-ray; 1.70 A; A=1-166. DR PDB; 3RSO; X-ray; 1.60 A; A=1-166. DR PDB; 3TGP; X-ray; 1.31 A; A=1-166. DR PDB; 421P; X-ray; 2.20 A; A=1-166. DR PDB; 4DLR; X-ray; 1.32 A; A=1-166. DR PDB; 4DLS; X-ray; 1.82 A; A=1-166. DR PDB; 4DLT; X-ray; 1.70 A; A=1-166. DR PDB; 4DLU; X-ray; 1.60 A; A=1-166. DR PDB; 4DLV; X-ray; 1.57 A; A=1-166. DR PDB; 4DLW; X-ray; 1.72 A; A=1-166. DR PDB; 4DLX; X-ray; 1.73 A; A=1-166. DR PDB; 4DLY; X-ray; 1.57 A; A=1-166. DR PDB; 4DLZ; X-ray; 1.66 A; A=1-166. DR PDB; 4DST; X-ray; 2.30 A; A=2-167. DR PDB; 4DSU; X-ray; 1.70 A; A=2-167. DR PDB; 4EFL; X-ray; 1.90 A; A=1-166. DR PDB; 4EFM; X-ray; 1.90 A; A=1-166. DR PDB; 4EFN; X-ray; 2.30 A; A=1-166. DR PDB; 4G0N; X-ray; 2.45 A; A=1-166. DR PDB; 4G3X; X-ray; 3.25 A; A=1-166. DR PDB; 4K81; X-ray; 2.40 A; B/D/F/H=1-166. DR PDB; 4L9S; X-ray; 1.61 A; A=1-166. DR PDB; 4L9W; X-ray; 1.95 A; A=1-166. DR PDB; 4NYI; X-ray; 2.96 A; Q/R=1-166. DR PDB; 4NYJ; X-ray; 2.85 A; Q/R=1-166. DR PDB; 4NYM; X-ray; 3.55 A; Q/R=1-166. DR PDB; 4Q21; X-ray; 2.00 A; A=1-189. DR PDB; 4RSG; Neutron; 1.91 A; A=1-166. DR PDB; 4URU; X-ray; 2.83 A; R=1-166. DR PDB; 4URV; X-ray; 2.58 A; R=1-166. DR PDB; 4URW; X-ray; 2.76 A; R=1-166. DR PDB; 4URX; X-ray; 2.49 A; R=1-166. DR PDB; 4URY; X-ray; 2.47 A; R=1-166. DR PDB; 4URZ; X-ray; 2.24 A; R=1-166. DR PDB; 4US0; X-ray; 2.17 A; R=1-166. DR PDB; 4US1; X-ray; 2.65 A; R=1-166. DR PDB; 4US2; X-ray; 2.48 A; R=1-166. DR PDB; 4XVQ; X-ray; 1.89 A; A=1-166. DR PDB; 4XVR; X-ray; 2.03 A; A=1-166. DR PDB; 521P; X-ray; 2.60 A; A=1-166. DR PDB; 5B2Z; X-ray; 1.56 A; A=1-166. DR PDB; 5B30; X-ray; 1.60 A; A=1-166. DR PDB; 5E95; X-ray; 1.40 A; A=1-166. DR PDB; 5P21; X-ray; 1.35 A; A=1-166. DR PDB; 5VBE; X-ray; 1.57 A; A=1-166. DR PDB; 5VBZ; X-ray; 2.20 A; A/B/C=1-166. DR PDB; 5WDO; X-ray; 1.65 A; A=1-166. DR PDB; 5WDP; X-ray; 1.35 A; A=1-166. DR PDB; 5WDQ; X-ray; 1.25 A; A=1-166. DR PDB; 5WFO; X-ray; 1.99 A; Q/R=1-166. DR PDB; 5WFP; X-ray; 2.08 A; Q/R=1-166. DR PDB; 5WFQ; X-ray; 2.26 A; Q/R=1-166. DR PDB; 5WFR; X-ray; 2.46 A; Q/R=1-166. DR PDB; 5WPL; X-ray; 2.15 A; A/D/G/J=1-166. DR PDB; 5X9S; X-ray; 2.50 A; A=1-166. DR PDB; 5ZC6; NMR; -; A=1-166. DR PDB; 621P; X-ray; 2.40 A; A=1-166. DR PDB; 6AMB; X-ray; 2.50 A; A=1-168. DR PDB; 6AXG; X-ray; 3.30 A; B/D/F/H/J/L=1-166. DR PDB; 6BVI; X-ray; 1.75 A; A/C=1-166. DR PDB; 6BVJ; X-ray; 1.75 A; A/C=1-166. DR PDB; 6BVK; X-ray; 1.80 A; A/C=1-166. DR PDB; 6BVL; X-ray; 1.75 A; A/C=1-166. DR PDB; 6BVM; X-ray; 1.80 A; A/C=1-166. DR PDB; 6CUO; X-ray; 1.73 A; A/C=1-166. DR PDB; 6CUP; X-ray; 1.83 A; A/C=1-166. DR PDB; 6CUR; X-ray; 1.73 A; A/C=1-166. DR PDB; 6D55; X-ray; 1.68 A; A/C=1-166. DR PDB; 6D56; X-ray; 1.68 A; A/C=1-166. DR PDB; 6D59; X-ray; 1.70 A; A/C=1-166. DR PDB; 6D5E; X-ray; 1.75 A; A/C=1-166. DR PDB; 6D5G; X-ray; 1.92 A; A/C=1-166. DR PDB; 6D5H; X-ray; 1.80 A; A/C=1-166. DR PDB; 6D5J; X-ray; 1.75 A; A/C=1-166. DR PDB; 6D5L; X-ray; 1.70 A; A/C=1-166. DR PDB; 6D5M; X-ray; 2.08 A; Q/R=1-166. DR PDB; 6D5V; X-ray; 2.04 A; Q/R=1-166. DR PDB; 6D5W; X-ray; 2.48 A; Q/R=1-166. DR PDB; 6DZH; X-ray; 1.95 A; A/B/C=1-166. DR PDB; 6E6C; X-ray; 1.90 A; A=1-166. DR PDB; 6E6P; X-ray; 1.93 A; A/B/C=1-166. DR PDB; 6MQT; X-ray; 1.50 A; A/B/C/D/E/F/G/H=1-166. DR PDB; 6NTC; X-ray; 2.90 A; A=1-166. DR PDB; 6NTD; X-ray; 3.15 A; A=1-166. DR PDB; 6Q21; X-ray; 1.95 A; A/B/C/D=1-171. DR PDB; 6V94; X-ray; 1.80 A; A/C=1-166. DR PDB; 6V9F; X-ray; 1.85 A; A/C=1-166. DR PDB; 6V9J; X-ray; 1.76 A; A/C=1-166. DR PDB; 6V9L; X-ray; 1.70 A; A/C=1-166. DR PDB; 6V9M; X-ray; 1.65 A; A/C=1-166. DR PDB; 6V9N; X-ray; 1.65 A; A/C=1-166. DR PDB; 6V9O; X-ray; 1.80 A; A/C=1-166. DR PDB; 6ZJ0; X-ray; 1.76 A; A=1-166. DR PDB; 6ZL3; X-ray; 2.03 A; A=1-166. DR PDB; 721P; X-ray; 2.00 A; A=1-166. DR PDB; 7DPH; X-ray; 1.54 A; A=1-166. DR PDB; 7DPJ; X-ray; 1.98 A; A=1-166. DR PDB; 7JHP; X-ray; 2.77 A; A=1-166. DR PDB; 7JIF; X-ray; 1.76 A; A=1-166. DR PDB; 7JIG; X-ray; 2.32 A; A=1-166. DR PDB; 7JIH; X-ray; 1.99 A; A/B=1-166. DR PDB; 7JII; X-ray; 1.53 A; A/B=1-166. DR PDB; 7L0F; X-ray; 1.98 A; A/E/G/L=1-166. DR PDB; 7L0G; X-ray; 2.54 A; A/B/E/G=1-166. DR PDB; 7OG9; X-ray; 1.75 A; A=1-166. DR PDB; 7OGA; X-ray; 1.90 A; A=1-166. DR PDB; 7OGB; X-ray; 1.85 A; A=1-166. DR PDB; 7OGC; X-ray; 1.70 A; A=1-166. DR PDB; 7OGD; X-ray; 1.95 A; A=1-166. DR PDB; 7OGE; X-ray; 2.10 A; A=1-166. DR PDB; 7OGF; X-ray; 1.80 A; A=1-166. DR PDB; 7TAM; X-ray; 1.87 A; A=1-166. DR PDB; 7VV8; X-ray; 1.70 A; A=1-166. DR PDB; 7VV9; X-ray; 1.60 A; A=1-170. DR PDB; 7VVG; X-ray; 1.70 A; A=1-166. DR PDB; 821P; X-ray; 1.50 A; A=1-166. DR PDB; 8BE6; X-ray; 2.90 A; R=1-166. DR PDB; 8BE7; X-ray; 3.00 A; R=1-166. DR PDB; 8BE8; X-ray; 2.40 A; R=1-166. DR PDB; 8BE9; X-ray; 2.51 A; R=1-166. DR PDB; 8BEA; X-ray; 2.47 A; R=1-166. DR PDB; 8BOS; X-ray; 2.10 A; R=1-166. DR PDB; 8BWG; X-ray; 1.32 A; R=1-166. DR PDB; 8CNJ; X-ray; 1.35 A; A/B=1-166. DR PDB; 8CNN; X-ray; 1.48 A; A=1-166. DR PDB; 8ELK; X-ray; 1.80 A; A=1-189. DR PDB; 8ELR; X-ray; 2.05 A; A=1-189. DR PDB; 8ELS; X-ray; 2.27 A; A=1-189. DR PDB; 8ELT; X-ray; 1.66 A; A=1-189. DR PDB; 8ELU; X-ray; 1.93 A; A=1-189. DR PDB; 8ELV; X-ray; 2.15 A; A=1-189. DR PDB; 8ELW; X-ray; 1.70 A; A=1-189. DR PDB; 8ELX; X-ray; 1.98 A; A=1-189. DR PDB; 8ELY; X-ray; 1.75 A; A=1-189. DR PDB; 8ELZ; X-ray; 1.96 A; A=1-189. DR PDB; 8EM0; X-ray; 2.11 A; A=1-189. DR PDB; 8FG3; X-ray; 1.49 A; A=1-166. DR PDB; 8FG4; X-ray; 1.85 A; A=1-166. DR PDB; 8OSM; X-ray; 2.05 A; A=1-166. DR PDB; 8OSN; X-ray; 1.80 A; A=1-166. DR PDB; 8OSO; X-ray; 2.50 A; A=1-166. DR PDB; 8TBG; X-ray; 1.20 A; A/B=1-166. DR PDB; 8TLR; X-ray; 1.70 A; A=1-166. DR PDB; 8WWC; X-ray; 2.80 A; A/B=1-166. DR PDB; 9P46; X-ray; 2.02 A; A/B=1-169. DR PDB; 9PU1; X-ray; 1.40 A; A=1-166. DR PDB; 9PU3; X-ray; 1.70 A; A=1-166. DR PDB; 9PU8; X-ray; 1.40 A; A=1-165. DR PDB; 9PUL; X-ray; 2.50 A; A/B/C/D=1-166. DR PDB; 9PUN; X-ray; 2.40 A; A/B/C=1-166. DR PDB; 9PUQ; X-ray; 2.00 A; A/B/C=1-166. DR PDB; 9PUT; X-ray; 2.00 A; A/C=1-166. DR PDB; 9PUZ; X-ray; 2.00 A; A/B/C=1-166. DR PDB; 9PVE; X-ray; 2.00 A; A/B/C/D=1-166. DR AlphaFoldDB; P01112; -. DR BMRB; P01112; -. DR MDposit; P01112; -. DR MDRepo; P01112; -. DR SMR; P01112; -. DR BioGRID; 109501; 711. DR ComplexPortal; CPX-26353; SHOC2-HRAS-PPP1CA complex. DR ComplexPortal; CPX-395; GTPase HRAS - Son of sevenless homolog 1 complex. DR CORUM; P01112; -. DR DIP; DIP-1050N; -. DR ELM; P01112; -. DR FunCoup; P01112; 3079. DR IntAct; P01112; 1037. DR MINT; P01112; -. DR NDEx; IQUERY-CP-HRAS; 142 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000407586; -. DR BindingDB; P01112; -. DR ChEMBL; CHEMBL2167; -. DR DrugBank; DB04315; Guanosine-5'-Diphosphate. DR DrugBank; DB04137; Guanosine-5'-Triphosphate. DR DrugBank; DB02210; Hexane-1,6-Diol. DR DrugBank; DB08751; N,N'-DIMETHYL-N-(ACETYL)-N'-(7-NITROBENZ-2-OXA-1,3-DIAZOL-4-YL)ETHYLENEDIAMINE. DR DrugBank; DB03226; Trifluoroethanol. DR DrugBank; DB15588; Ursolic acid. DR DrugCentral; P01112; -. DR GuidetoPHARMACOLOGY; 2822; -. DR GlyCosmos; P01112; 1 site, No reported glycans. DR GlyGen; P01112; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P01112; -. DR PhosphoSitePlus; P01112; -. DR SwissPalm; P01112; -. DR BioMuta; HRAS; -. DR DMDM; 131869; -. DR CPTAC; CPTAC-1551; -. DR CPTAC; CPTAC-1552; -. DR jPOST; P01112; -. DR MassIVE; P01112; -. DR PaxDb; 9606-ENSP00000407586; -. DR PeptideAtlas; P01112; -. DR ProteomicsDB; 51321; -. [P01112-1] DR ProteomicsDB; 51322; -. [P01112-2] DR Pumba; P01112; -. DR ABCD; P01112; 6 sequenced antibodies. DR Antibodypedia; 22506; 856 antibodies from 40 providers. DR CPTC; P01112; 4 antibodies. DR DNASU; 3265; -. DR Ensembl; ENST00000311189.8; ENSP00000309845.7; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000397594.7; ENSP00000380722.3; ENSG00000174775.19. [P01112-2] DR Ensembl; ENST00000397596.6; ENSP00000380723.2; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000417302.7; ENSP00000388246.1; ENSG00000174775.19. [P01112-2] DR Ensembl; ENST00000451590.5; ENSP00000407586.1; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000493230.5; ENSP00000434023.1; ENSG00000174775.19. [P01112-2] DR Ensembl; ENST00000610977.3; ENSP00000480686.1; ENSG00000276536.4. [P01112-1] DR Ensembl; ENST00000615062.2; ENSP00000482366.1; ENSG00000276536.4. [P01112-1] DR Ensembl; ENST00000616241.4; ENSP00000480317.1; ENSG00000276536.4. [P01112-2] DR Ensembl; ENST00000631404.1; ENSP00000488757.1; ENSG00000276536.4. [P01112-1] DR Ensembl; ENST00000631967.1; ENSP00000488225.1; ENSG00000276536.4. [P01112-2] DR Ensembl; ENST00000634098.1; ENSP00000488296.1; ENSG00000276536.4. [P01112-2] DR Ensembl; ENST00000879221.1; ENSP00000549280.1; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000879222.1; ENSP00000549281.1; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000879223.1; ENSP00000549282.1; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000879224.1; ENSP00000549283.1; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000932528.1; ENSP00000602587.1; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000932529.1; ENSP00000602588.1; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000932530.1; ENSP00000602589.1; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000932531.1; ENSP00000602590.1; ENSG00000174775.19. [P01112-1] DR Ensembl; ENST00000932532.1; ENSP00000602591.1; ENSG00000174775.19. [P01112-1] DR GeneID; 3265; -. DR KEGG; hsa:3265; -. DR MANE-Select; ENST00000311189.8; ENSP00000309845.7; NM_005343.4; NP_005334.1. DR UCSC; uc010qvw.3; human. [P01112-1] DR AGR; HGNC:5173; -. DR CIViC; 3265; 1 clinical assertion and 24 evidence items across 22 molecular profiles. DR ClinPGx; PA29444; -. DR CTD; 3265; -. DR DisGeNET; 3265; -. DR GeneCards; HRAS; -. DR GeneReviews; HRAS; -. DR HGNC; HGNC:5173; HRAS. DR HPA; ENSG00000174775; Tissue enhanced (brain). DR MalaCards; HRAS; -. DR MIM; 109800; phenotype. DR MIM; 163200; phenotype. DR MIM; 188470; phenotype. DR MIM; 190020; gene. DR MIM; 218040; phenotype. DR OpenTargets; ENSG00000174775; -. DR Orphanet; 3071; Costello syndrome. DR Orphanet; 146; Differentiated thyroid carcinoma. DR Orphanet; 2612; Linear nevus sebaceus syndrome. DR Orphanet; 2874; Phakomatosis pigmentokeratotica. DR Orphanet; 79414; Woolly hair nevus. DR VEuPathDB; HostDB:ENSG00000174775; -. DR eggNOG; KOG0395; Eukaryota. DR GeneTree; ENSGT00940000155653; -. DR HOGENOM; CLU_041217_9_8_1; -. DR InParanoid; P01112; -. DR OMA; HYREQIR; -. DR OrthoDB; 5976022at2759; -. DR PAN-GO; P01112; 5 GO annotations based on evolutionary models. DR PhylomeDB; P01112; -. DR BRENDA; 3.6.5.2; 2681. DR PathwayCommons; P01112; -. DR Reactome; R-HSA-112412; SOS-mediated signalling. DR Reactome; R-HSA-1169092; Activation of RAS in B cells. DR Reactome; R-HSA-1236382; Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants. DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling. DR Reactome; R-HSA-1250347; SHC1 events in ERBB4 signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-167044; Signalling to RAS. DR Reactome; R-HSA-171007; p38MAPK events. DR Reactome; R-HSA-179812; GRB2 events in EGFR signaling. DR Reactome; R-HSA-180336; SHC1 events in EGFR signaling. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-1963640; GRB2 events in ERBB2 signaling. DR Reactome; R-HSA-210993; Tie2 Signaling. DR Reactome; R-HSA-2179392; EGFR Transactivation by Gastrin. DR Reactome; R-HSA-2424491; DAP12 signaling. DR Reactome; R-HSA-2428933; SHC-related events triggered by IGF1R. DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. DR Reactome; R-HSA-375165; NCAM signaling for neurite out-growth. DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling. DR Reactome; R-HSA-442982; Ras activation upon Ca2+ influx through NMDA receptor. DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-HSA-5621575; CD209 (DC-SIGN) signaling. DR Reactome; R-HSA-5637810; Constitutive Signaling by EGFRvIII. DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1. DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling. DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2. DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling. DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3. DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling. DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling. DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4. DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease. DR Reactome; R-HSA-5655291; Signaling by FGFR4 in disease. DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease. DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs. DR Reactome; R-HSA-5673000; RAF activation. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-5674135; MAP2K and MAPK activation. DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway. DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants. DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants. DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions. DR Reactome; R-HSA-6802953; RAS signaling downstream of NF1 loss-of-function variants. DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF. DR Reactome; R-HSA-74751; Insulin receptor signalling cascade. DR Reactome; R-HSA-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases. DR Reactome; R-HSA-8851805; MET activates RAS signaling. DR Reactome; R-HSA-9026519; Activated NTRK2 signals through RAS. DR Reactome; R-HSA-9027284; Erythropoietin activates RAS. DR Reactome; R-HSA-9028731; Activated NTRK2 signals through FRS2 and FRS3. DR Reactome; R-HSA-9034864; Activated NTRK3 signals through RAS. DR Reactome; R-HSA-9607240; FLT3 Signaling. DR Reactome; R-HSA-9634285; Constitutive Signaling by Overexpressed ERBB2. DR Reactome; R-HSA-9634635; Estrogen-stimulated signaling through PRKCZ. DR Reactome; R-HSA-9648002; RAS processing. DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants. DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants. DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants. DR Reactome; R-HSA-9665348; Signaling by ERBB2 ECD mutants. DR Reactome; R-HSA-9665686; Signaling by ERBB2 TMD/JMD mutants. DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants. DR Reactome; R-HSA-9673767; Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants. DR Reactome; R-HSA-9673770; Signaling by PDGFRA extracellular domain mutants. DR Reactome; R-HSA-9703465; Signaling by FLT3 fusion proteins. DR Reactome; R-HSA-9703648; Signaling by FLT3 ITD and TKD mutants. DR Reactome; R-HSA-9753510; Signaling by RAS GAP mutants. DR Reactome; R-HSA-9753512; Signaling by RAS GTPase mutants. DR SABIO-RK; P01112; -. DR SignaLink; P01112; -. DR SIGNOR; P01112; -. DR Agora; ENSG00000174775; -. DR BioGRID-ORCS; 3265; 28 hits in 1176 CRISPR screens. DR EvolutionaryTrace; P01112; -. DR GeneWiki; HRAS; -. DR GenomeRNAi; 3265; -. DR Pharos; P01112; Tchem. DR PRO; PR:P01112; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P01112; protein. DR Bgee; ENSG00000174775; Expressed in skin of abdomen and 97 other cell types or tissues. DR ExpressionAtlas; P01112; baseline and differential. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:1905360; C:GTPase complex; IPI:ComplexPortal. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0000164; C:protein phosphatase type 1 complex; IPI:ComplexPortal. DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC. DR GO; GO:0019003; F:GDP binding; IMP:CAFA. DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB. DR GO; GO:0003924; F:GTPase activity; IDA:WormBase. DR GO; GO:0160185; F:phospholipase C activator activity; IDA:UniProtKB. DR GO; GO:0043495; F:protein-membrane adaptor activity; IEA:Ensembl. DR GO; GO:0060612; P:adipose tissue development; IEA:Ensembl. DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0071480; P:cellular response to gamma radiation; IDA:CAFA. DR GO; GO:0090398; P:cellular senescence; IDA:BHF-UCL. DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc. DR GO; GO:0008286; P:insulin receptor signaling pathway; IEA:Ensembl. DR GO; GO:0000165; P:MAPK cascade; TAS:Reactome. DR GO; GO:0042552; P:myelination; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:BHF-UCL. DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:BHF-UCL. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL. DR GO; GO:2000630; P:positive regulation of miRNA metabolic process; IDA:BHF-UCL. DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IMP:UniProtKB. DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; NAS:ComplexPortal. DR GO; GO:1900029; P:positive regulation of ruffle assembly; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0090303; P:positive regulation of wound healing; IDA:BHF-UCL. DR GO; GO:0007265; P:Ras protein signal transduction; IDA:BHF-UCL. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:BHF-UCL. DR GO; GO:0051726; P:regulation of cell cycle; IDA:BHF-UCL. DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:ComplexPortal. DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IDA:SynGO. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:ComplexPortal. DR GO; GO:0014044; P:Schwann cell development; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; NAS:ProtInc. DR CDD; cd04138; H_N_K_Ras_like; 1. DR DisProt; DP00153; -. DR FunFam; 3.40.50.300:FF:000096; KRAS proto-oncogene, GTPase; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005225; Small_GTP-bd. DR InterPro; IPR001806; Small_GTPase. DR InterPro; IPR020849; Small_GTPase_Ras-type. DR NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR24070; RAS, DI-RAS, AND RHEB FAMILY MEMBERS OF SMALL GTPASE SUPERFAMILY; 1. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00175; RAB; 1. DR SMART; SM00173; RAS; 1. DR SMART; SM00174; RHO; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51421; RAS; 1. DR PDBsum; 10DC; -. DR PDBsum; 121P; -. DR PDBsum; 1AA9; -. DR PDBsum; 1AGP; -. DR PDBsum; 1BKD; -. DR PDBsum; 1CLU; -. DR PDBsum; 1CRP; -. DR PDBsum; 1CRQ; -. DR PDBsum; 1CRR; -. DR PDBsum; 1CTQ; -. DR PDBsum; 1GNP; -. DR PDBsum; 1GNQ; -. DR PDBsum; 1GNR; -. DR PDBsum; 1HE8; -. DR PDBsum; 1IAQ; -. DR PDBsum; 1IOZ; -. DR PDBsum; 1JAH; -. DR PDBsum; 1JAI; -. DR PDBsum; 1K8R; -. DR PDBsum; 1LF0; -. DR PDBsum; 1LF5; -. DR PDBsum; 1LFD; -. DR PDBsum; 1NVU; -. DR PDBsum; 1NVV; -. DR PDBsum; 1NVW; -. DR PDBsum; 1NVX; -. DR PDBsum; 1P2S; -. DR PDBsum; 1P2T; -. DR PDBsum; 1P2U; -. DR PDBsum; 1P2V; -. DR PDBsum; 1PLJ; -. DR PDBsum; 1PLK; -. DR PDBsum; 1PLL; -. DR PDBsum; 1Q21; -. DR PDBsum; 1QRA; -. DR PDBsum; 1RVD; -. DR PDBsum; 1WQ1; -. DR PDBsum; 1XCM; -. DR PDBsum; 1XD2; -. DR PDBsum; 1XJ0; -. DR PDBsum; 1ZVQ; -. DR PDBsum; 1ZW6; -. DR PDBsum; 221P; -. DR PDBsum; 2C5L; -. DR PDBsum; 2CE2; -. DR PDBsum; 2CL0; -. DR PDBsum; 2CL6; -. DR PDBsum; 2CL7; -. DR PDBsum; 2CLC; -. DR PDBsum; 2CLD; -. DR PDBsum; 2EVW; -. DR PDBsum; 2LCF; -. DR PDBsum; 2LWI; -. DR PDBsum; 2N42; -. DR PDBsum; 2N46; -. DR PDBsum; 2Q21; -. DR PDBsum; 2QUZ; -. DR PDBsum; 2RGA; -. DR PDBsum; 2RGB; -. DR PDBsum; 2RGC; -. DR PDBsum; 2RGD; -. DR PDBsum; 2RGE; -. DR PDBsum; 2RGG; -. DR PDBsum; 2UZI; -. DR PDBsum; 2VH5; -. DR PDBsum; 2X1V; -. DR PDBsum; 3DDC; -. DR PDBsum; 3I3S; -. DR PDBsum; 3K8Y; -. DR PDBsum; 3K9L; -. DR PDBsum; 3K9N; -. DR PDBsum; 3KKM; -. DR PDBsum; 3KKN; -. DR PDBsum; 3KUD; -. DR PDBsum; 3L8Y; -. DR PDBsum; 3L8Z; -. DR PDBsum; 3LBH; -. DR PDBsum; 3LBI; -. DR PDBsum; 3LBN; -. DR PDBsum; 3LO5; -. DR PDBsum; 3OIU; -. DR PDBsum; 3OIV; -. DR PDBsum; 3OIW; -. DR PDBsum; 3RRY; -. DR PDBsum; 3RRZ; -. DR PDBsum; 3RS0; -. DR PDBsum; 3RS2; -. DR PDBsum; 3RS3; -. DR PDBsum; 3RS4; -. DR PDBsum; 3RS5; -. DR PDBsum; 3RS7; -. DR PDBsum; 3RSL; -. DR PDBsum; 3RSO; -. DR PDBsum; 3TGP; -. DR PDBsum; 421P; -. DR PDBsum; 4DLR; -. DR PDBsum; 4DLS; -. DR PDBsum; 4DLT; -. DR PDBsum; 4DLU; -. DR PDBsum; 4DLV; -. DR PDBsum; 4DLW; -. DR PDBsum; 4DLX; -. DR PDBsum; 4DLY; -. DR PDBsum; 4DLZ; -. DR PDBsum; 4DST; -. DR PDBsum; 4DSU; -. DR PDBsum; 4EFL; -. DR PDBsum; 4EFM; -. DR PDBsum; 4EFN; -. DR PDBsum; 4G0N; -. DR PDBsum; 4G3X; -. DR PDBsum; 4K81; -. DR PDBsum; 4L9S; -. DR PDBsum; 4L9W; -. DR PDBsum; 4NYI; -. DR PDBsum; 4NYJ; -. DR PDBsum; 4NYM; -. DR PDBsum; 4Q21; -. DR PDBsum; 4RSG; -. DR PDBsum; 4URU; -. DR PDBsum; 4URV; -. DR PDBsum; 4URW; -. DR PDBsum; 4URX; -. DR PDBsum; 4URY; -. DR PDBsum; 4URZ; -. DR PDBsum; 4US0; -. DR PDBsum; 4US1; -. DR PDBsum; 4US2; -. DR PDBsum; 4XVQ; -. DR PDBsum; 4XVR; -. DR PDBsum; 521P; -. DR PDBsum; 5B2Z; -. DR PDBsum; 5B30; -. DR PDBsum; 5E95; -. DR PDBsum; 5P21; -. DR PDBsum; 5VBE; -. DR PDBsum; 5VBZ; -. DR PDBsum; 5WDO; -. DR PDBsum; 5WDP; -. DR PDBsum; 5WDQ; -. DR PDBsum; 5WFO; -. DR PDBsum; 5WFP; -. DR PDBsum; 5WFQ; -. DR PDBsum; 5WFR; -. DR PDBsum; 5WPL; -. DR PDBsum; 5X9S; -. DR PDBsum; 5ZC6; -. DR PDBsum; 621P; -. DR PDBsum; 6AMB; -. DR PDBsum; 6AXG; -. DR PDBsum; 6BVI; -. DR PDBsum; 6BVJ; -. DR PDBsum; 6BVK; -. DR PDBsum; 6BVL; -. DR PDBsum; 6BVM; -. DR PDBsum; 6CUO; -. DR PDBsum; 6CUP; -. DR PDBsum; 6CUR; -. DR PDBsum; 6D55; -. DR PDBsum; 6D56; -. DR PDBsum; 6D59; -. DR PDBsum; 6D5E; -. DR PDBsum; 6D5G; -. DR PDBsum; 6D5H; -. DR PDBsum; 6D5J; -. DR PDBsum; 6D5L; -. DR PDBsum; 6D5M; -. DR PDBsum; 6D5V; -. DR PDBsum; 6D5W; -. DR PDBsum; 6DZH; -. DR PDBsum; 6E6C; -. DR PDBsum; 6E6P; -. DR PDBsum; 6MQT; -. DR PDBsum; 6NTC; -. DR PDBsum; 6NTD; -. DR PDBsum; 6Q21; -. DR PDBsum; 6V94; -. DR PDBsum; 6V9F; -. DR PDBsum; 6V9J; -. DR PDBsum; 6V9L; -. DR PDBsum; 6V9M; -. DR PDBsum; 6V9N; -. DR PDBsum; 6V9O; -. DR PDBsum; 6ZJ0; -. DR PDBsum; 6ZL3; -. DR PDBsum; 721P; -. DR PDBsum; 7DPH; -. DR PDBsum; 7DPJ; -. DR PDBsum; 7JHP; -. DR PDBsum; 7JIF; -. DR PDBsum; 7JIG; -. DR PDBsum; 7JIH; -. DR PDBsum; 7JII; -. DR PDBsum; 7L0F; -. DR PDBsum; 7L0G; -. DR PDBsum; 7OG9; -. DR PDBsum; 7OGA; -. DR PDBsum; 7OGB; -. DR PDBsum; 7OGC; -. DR PDBsum; 7OGD; -. DR PDBsum; 7OGE; -. DR PDBsum; 7OGF; -. DR PDBsum; 7TAM; -. DR PDBsum; 7VV8; -. DR PDBsum; 7VV9; -. DR PDBsum; 7VVG; -. DR PDBsum; 821P; -. DR PDBsum; 8BE6; -. DR PDBsum; 8BE7; -. DR PDBsum; 8BE8; -. DR PDBsum; 8BE9; -. DR PDBsum; 8BEA; -. DR PDBsum; 8BOS; -. DR PDBsum; 8BWG; -. DR PDBsum; 8CNJ; -. DR PDBsum; 8CNN; -. DR PDBsum; 8ELK; -. DR PDBsum; 8ELR; -. DR PDBsum; 8ELS; -. DR PDBsum; 8ELT; -. DR PDBsum; 8ELU; -. DR PDBsum; 8ELV; -. DR PDBsum; 8ELW; -. DR PDBsum; 8ELX; -. DR PDBsum; 8ELY; -. DR PDBsum; 8ELZ; -. DR PDBsum; 8EM0; -. DR PDBsum; 8FG3; -. DR PDBsum; 8FG4; -. DR PDBsum; 8OSM; -. DR PDBsum; 8OSN; -. DR PDBsum; 8OSO; -. DR PDBsum; 8TBG; -. DR PDBsum; 8TLR; -. DR PDBsum; 8WWC; -. DR PDBsum; 9P46; -. DR PDBsum; 9PU1; -. DR PDBsum; 9PU3; -. DR PDBsum; 9PU8; -. DR PDBsum; 9PUL; -. DR PDBsum; 9PUN; -. DR PDBsum; 9PUQ; -. DR PDBsum; 9PUT; -. DR PDBsum; 9PUZ; -. DR PDBsum; 9PVE; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell membrane; Cytoplasm; KW Direct protein sequencing; Disease variant; Glycoprotein; Golgi apparatus; KW GTP-binding; Hydrolase; Isopeptide bond; Lipoprotein; Membrane; KW Methylation; Nucleotide-binding; Nucleus; Palmitate; Prenylation; KW Proteomics identification; Proto-oncogene; Reference proteome; KW S-nitrosylation; Ubl conjugation. FT CHAIN 1..186 FT /note="GTPase HRas" FT /id="PRO_0000042996" FT INIT_MET 1 FT /note="Removed; alternate" FT /evidence="ECO:0000269|Ref.12" FT CHAIN 2..186 FT /note="GTPase HRas, N-terminally processed" FT /id="PRO_0000326476" FT PROPEP 187..189 FT /note="Removed in mature form" FT /id="PRO_0000042997" FT REGION 166..185 FT /note="Hypervariable region" FT MOTIF 32..40 FT /note="Effector region" FT BINDING 13..18 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:16698776, FT ECO:0000305|PubMed:35522713" FT BINDING 29..35 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:16698776, FT ECO:0000305|PubMed:35522713" FT BINDING 59..60 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:16698776, FT ECO:0000305|PubMed:35522713" FT BINDING 116..119 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:16698776, FT ECO:0000305|PubMed:35522713" FT BINDING 145..147 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:16698776, FT ECO:0000305|PubMed:35522713" FT MOD_RES 1 FT /note="N-acetylmethionine; in GTPase HRas; alternate" FT /evidence="ECO:0000269|Ref.12" FT MOD_RES 2 FT /note="N-acetylthreonine; in GTPase HRas, N-terminally FT processed" FT /evidence="ECO:0000269|Ref.12" FT MOD_RES 118 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:9020151" FT MOD_RES 186 FT /note="Cysteine methyl ester" FT /evidence="ECO:0000269|PubMed:8626715" FT LIPID 181 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:15705808, FT ECO:0000269|PubMed:16000296, ECO:0000269|PubMed:2661017, FT ECO:0000269|PubMed:8626715" FT LIPID 184 FT /note="S-(15-deoxy-Delta12,14-prostaglandin J2-9- FT yl)cysteine; alternate" FT /evidence="ECO:0000269|PubMed:12684535" FT LIPID 184 FT /note="S-palmitoyl cysteine; alternate" FT /evidence="ECO:0000269|PubMed:15705808, FT ECO:0000269|PubMed:16000296, ECO:0000269|PubMed:2661017, FT ECO:0000269|PubMed:8626715" FT LIPID 186 FT /note="S-farnesyl cysteine" FT /evidence="ECO:0000269|PubMed:8626715" FT CARBOHYD 35 FT /note="(Microbial infection) O-linked (Glc) threonine; by FT P.sordellii toxin TcsL" FT /evidence="ECO:0000269|PubMed:19744486, FT ECO:0000269|PubMed:8626575, ECO:0000269|PubMed:8626586, FT ECO:0000269|PubMed:9632667" FT CROSSLNK 170 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:30442762" FT VAR_SEQ 152..189 FT /note="VEDAFYTLVREIRQHKLRKLNPPDESGPGCMSCKCVLS -> SRSGSSSSSG FT TLWDPPGPM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14500341, FT ECO:0000303|PubMed:15489334" FT /id="VSP_041597" FT VARIANT 12 FT /note="G -> A (in CSTLO; dbSNP:rs104894230)" FT /evidence="ECO:0000269|PubMed:16170316, FT ECO:0000269|PubMed:16329078, ECO:0000269|PubMed:16443854" FT /id="VAR_026106" FT VARIANT 12 FT /note="G -> C (in CSTLO; dbSNP:rs104894229)" FT /evidence="ECO:0000269|PubMed:16443854, FT ECO:0000269|PubMed:18039947" FT /id="VAR_045975" FT VARIANT 12 FT /note="G -> D (in CSTLO; severe mutation; FT dbSNP:rs104894230)" FT /evidence="ECO:0000269|PubMed:18039947" FT /id="VAR_068816" FT VARIANT 12 FT /note="G -> E (in CSTLO)" FT /evidence="ECO:0000269|PubMed:16443854" FT /id="VAR_045976" FT VARIANT 12 FT /note="G -> S (in CSTLO and CMEMS; also found in patients FT with oral squamous cell carcinoma; dbSNP:rs104894229)" FT /evidence="ECO:0000269|PubMed:1459726, FT ECO:0000269|PubMed:16170316, ECO:0000269|PubMed:16329078, FT ECO:0000269|PubMed:16443854, ECO:0000269|PubMed:17054105, FT ECO:0000269|PubMed:17412879" FT /id="VAR_006837" FT VARIANT 12 FT /note="G -> V (in CSTLO, bladder carcinoma and CMEMS; FT constitutively activated; interacts and recruits PLCE1 to FT plasma membrane; dbSNP:rs104894230)" FT /evidence="ECO:0000269|PubMed:11022048, FT ECO:0000269|PubMed:15546861, ECO:0000269|PubMed:16170316, FT ECO:0000269|PubMed:17412879" FT /id="VAR_006836" FT VARIANT 13 FT /note="G -> C (in CSTLO; dbSNP:rs104894228)" FT /evidence="ECO:0000269|PubMed:16329078" FT /id="VAR_026107" FT VARIANT 13 FT /note="G -> D (in CSTLO; dbSNP:rs104894226)" FT /evidence="ECO:0000269|PubMed:16170316" FT /id="VAR_026108" FT VARIANT 13 FT /note="G -> R (in SFM; somatic mutation; shows constitutive FT activation of the MAPK and PI3K-AKT signaling pathways; FT dbSNP:rs104894228)" FT /evidence="ECO:0000269|PubMed:22683711" FT /id="VAR_068817" FT VARIANT 22 FT /note="Q -> K (in CMEMS; dbSNP:rs121917757)" FT /evidence="ECO:0000269|PubMed:17412879" FT /id="VAR_045977" FT VARIANT 37 FT /note="E -> EE (in CSTLO)" FT /evidence="ECO:0000269|PubMed:19995790" FT /id="VAR_068818" FT VARIANT 58 FT /note="T -> I (in CSTLO; dbSNP:rs121917758)" FT /evidence="ECO:0000269|PubMed:18247425" FT /id="VAR_045978" FT VARIANT 61 FT /note="Q -> K (in NMTC2; somatic mutation; increases FT transformation of cultured cell lines; dbSNP:rs28933406)" FT /evidence="ECO:0000269|PubMed:12727991, FT ECO:0000269|PubMed:18073111" FT /id="VAR_045979" FT VARIANT 61 FT /note="Q -> L (in melanoma; strongly reduced GTP hydrolysis FT in the presence of RAF1; increases transformation of FT cultured cell lines; dbSNP:rs121913233)" FT /evidence="ECO:0000269|PubMed:18073111" FT /id="VAR_006838" FT VARIANT 63 FT /note="E -> K (in CMEMS; dbSNP:rs121917756)" FT /evidence="ECO:0000269|PubMed:17412879" FT /id="VAR_045980" FT VARIANT 89 FT /note="S -> C (found in a patient with severe fetal hydrops FT and pleural effusion; uncertain significance; decreased FT activation of Ras protein signal transduction; FT dbSNP:rs755322824)" FT /evidence="ECO:0000269|PubMed:22821884" FT /id="VAR_078259" FT VARIANT 117 FT /note="K -> R (in CSTLO; dbSNP:rs104894227)" FT /evidence="ECO:0000269|PubMed:16443854" FT /id="VAR_045981" FT VARIANT 146 FT /note="A -> T (in CSTLO; dbSNP:rs104894231)" FT /evidence="ECO:0000269|PubMed:17054105" FT /id="VAR_045982" FT VARIANT 146 FT /note="A -> V (in CSTLO; dbSNP:rs121917759)" FT /evidence="ECO:0000269|PubMed:18247425" FT /id="VAR_045983" FT MUTAGEN 17 FT /note="S->N: Dominant negative. Prevents PLCE1 EGF-induced FT recruitment to plasma membrane. No effect on subcellular FT location of isoform 2." FT /evidence="ECO:0000269|PubMed:11022048, FT ECO:0000269|PubMed:14500341" FT MUTAGEN 26 FT /note="N->G: Loss of interaction with PLCE1; when FT associated with V-12." FT /evidence="ECO:0000269|PubMed:11022048" FT MUTAGEN 29 FT /note="V->A: No effect on interaction with PLCE1; when FT associated with V-12." FT /evidence="ECO:0000269|PubMed:11022048" FT MUTAGEN 32 FT /note="Y->F: Loss of interaction and recruitment to plasma FT membrane of PLCE1; when associated with V-12." FT /evidence="ECO:0000269|PubMed:11022048" FT MUTAGEN 34 FT /note="P->G: No effect on interaction with PLCE1; when FT associated with V-12." FT /evidence="ECO:0000269|PubMed:11022048" FT MUTAGEN 35 FT /note="T->S: Loss of interaction with PLCE1; when FT associated with V-12." FT /evidence="ECO:0000269|PubMed:11022048" FT MUTAGEN 37 FT /note="E->G: No effect on interaction with PLCE1; when FT associated with V-12." FT /evidence="ECO:0000269|PubMed:11022048" FT MUTAGEN 38 FT /note="D->N: No effect on interaction with PLCE1; when FT associated with V-12." FT /evidence="ECO:0000269|PubMed:11022048" FT MUTAGEN 39 FT /note="S->C: No effect on interaction with PLCE1; when FT associated with V-12." FT /evidence="ECO:0000269|PubMed:11022048" FT MUTAGEN 59 FT /note="A->T: Loss of GTPase activity and creation of an FT autophosphorylation site." FT MUTAGEN 61 FT /note="Q->I: Moderately increased transformation of FT cultured cell lines." FT /evidence="ECO:0000269|PubMed:18073111" FT MUTAGEN 61 FT /note="Q->R: Promotes interaction with SHOC2 and PP1C." FT /evidence="ECO:0000269|PubMed:35831509" FT MUTAGEN 61 FT /note="Q->V: Strongly increased transformation of cultured FT cell lines." FT /evidence="ECO:0000269|PubMed:18073111" FT MUTAGEN 83 FT /note="A->T: GTP-binding activity reduced by factor of 30." FT /evidence="ECO:0000269|PubMed:3088563" FT MUTAGEN 118 FT /note="C->S: Abolishes S-nitrosylation. No stimulation of FT guanine nucleotide exchange." FT /evidence="ECO:0000269|PubMed:12740440, FT ECO:0000269|PubMed:9020151" FT MUTAGEN 119 FT /note="D->N: Loss of GTP-binding activity." FT /evidence="ECO:0000269|PubMed:3088563" FT MUTAGEN 144 FT /note="T->I: GTP-binding activity reduced by factor of 25." FT /evidence="ECO:0000269|PubMed:3088563" FT MUTAGEN 164..165 FT /note="RQ->AV: Loss of GTP-binding activity." FT /evidence="ECO:0000269|PubMed:3011420" FT MUTAGEN 167..185 FT /note="KLRKLNPPDESGPGCMSCK->RLRRLNPPDESGPGCMSCR: In FT H-Ras-3KR mutant; decreased fatty-acylation." FT /evidence="ECO:0000269|PubMed:29239724" FT MUTAGEN 170 FT /note="K->R: Increased Ras signaling due to impaired FT ubiquitination." FT /evidence="ECO:0000269|PubMed:30442762" FT MUTAGEN 181 FT /note="C->S: Exclusively localized in Golgi. FT Non-specifically localized on all endomembranes; when FT associated with S-184." FT /evidence="ECO:0000269|PubMed:15705808, FT ECO:0000269|PubMed:8626715" FT MUTAGEN 184 FT /note="C->S: Loss of S-(15-deoxy-Delta12,14-prostaglandin FT J2-9-yl)cysteine stimulation of Ras-GTPase activity. Mainly FT localized in Golgi. Non-specifically localized on all FT endomembranes; when associated with S-181." FT /evidence="ECO:0000269|PubMed:12684535, FT ECO:0000269|PubMed:15705808, ECO:0000269|PubMed:8626715" FT STRAND 3..11 FT /evidence="ECO:0007829|PDB:2CE2" FT STRAND 12..15 FT /evidence="ECO:0007829|PDB:6V9M" FT HELIX 16..25 FT /evidence="ECO:0007829|PDB:2CE2" FT STRAND 27..31 FT /evidence="ECO:0007829|PDB:1XCM" FT HELIX 33..35 FT /evidence="ECO:0007829|PDB:3K9L" FT STRAND 38..46 FT /evidence="ECO:0007829|PDB:2CE2" FT STRAND 49..57 FT /evidence="ECO:0007829|PDB:2CE2" FT STRAND 60..63 FT /evidence="ECO:0007829|PDB:2CLD" FT HELIX 66..74 FT /evidence="ECO:0007829|PDB:2CE2" FT STRAND 76..83 FT /evidence="ECO:0007829|PDB:2CE2" FT TURN 84..86 FT /evidence="ECO:0007829|PDB:1CRP" FT HELIX 87..104 FT /evidence="ECO:0007829|PDB:2CE2" FT STRAND 105..107 FT /evidence="ECO:0007829|PDB:7VV9" FT STRAND 111..116 FT /evidence="ECO:0007829|PDB:2CE2" FT STRAND 120..122 FT /evidence="ECO:0007829|PDB:2CLD" FT HELIX 127..137 FT /evidence="ECO:0007829|PDB:2CE2" FT STRAND 141..144 FT /evidence="ECO:0007829|PDB:2CE2" FT TURN 146..148 FT /evidence="ECO:0007829|PDB:2CE2" FT HELIX 152..164 FT /evidence="ECO:0007829|PDB:2CE2" SQ SEQUENCE 189 AA; 21298 MW; EE6DC2D933E2856A CRC64; MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHQYREQI KRVKDSDDVP MVLVGNKCDL AARTVESRQA QDLARSYGIP YIETSAKTRQ GVEDAFYTLV REIRQHKLRK LNPPDESGPG CMSCKCVLS //