ID RRAS2_HUMAN Reviewed; 204 AA. AC P62070; B2R9Z3; B7Z5Z2; B7Z6C4; B7Z7H6; P17082; DT 21-JUN-2004, integrated into UniProtKB/Swiss-Prot. DT 21-JUN-2004, sequence version 1. DT 02-SEP-2026, entry version 203. DE RecName: Full=Ras-related protein R-Ras2; DE EC=3.6.5.2 {ECO:0000269|PubMed:31130282, ECO:0000269|PubMed:39809765}; DE AltName: Full=Ras-like protein TC21; DE AltName: Full=Teratocarcinoma oncogene; DE Flags: Precursor; GN Name=RRAS2 {ECO:0000312|HGNC:HGNC:17271}; Synonyms=TC21; 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 [MRNA] (ISOFORM 1). RX PubMed=2108320; DOI=10.1128/mcb.10.4.1793-1798.1990; RA Drivas G.T., Shih A., Coutavas E., Rush M.G., D'Eustachio P.; RT "Characterization of four novel ras-like genes expressed in a human RT teratocarcinoma cell line."; RL Mol. Cell. Biol. 10:1793-1798(1990). RN [2] RP SEQUENCE REVISION TO 5-11, TISSUE SPECIFICITY, AND VARIANT OVARIAN CANCER RP LEU-72. RX PubMed=8052619; DOI=10.1073/pnas.91.16.7558; RA Chan A.M.-L., Miki T., Meyers K.A., Aaronson S.A.; RT "A human oncogene of the RAS superfamily unmasked by expression cDNA RT cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 91:7558-7562(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Heart; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4). RC TISSUE=Brain, Pericardium, and Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [6] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Bone; 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 [8] RP ISOPRENYLATION AT CYS-201, AND METHYLATION AT CYS-201. RX PubMed=15308774; DOI=10.1073/pnas.0403413101; RA Kho Y., Kim S.C., Jiang C., Barma D., Kwon S.W., Cheng J., Jaunbergs J., RA Weinbaum C., Tamanoi F., Falck J., Zhao Y.; RT "A tagging-via-substrate technology for detection and proteomics of RT farnesylated proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12479-12484(2004). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, INTERACTION WITH RP RASSF5, INVOLVEMENT IN NS12, VARIANTS NS12 VAL-23; GLY-GLY-GLY-24 INS; RP GLY-VAL-GLY-26 INS; THR-70 AND LEU-72, AND CHARACTERIZATION OF VARIANTS RP NS12 VAL-23; GLY-GLY-GLY-24 INS; GLY-VAL-GLY-26 INS; THR-70 AND LEU-72. RX PubMed=31130282; DOI=10.1016/j.ajhg.2019.04.013; RA Capri Y., Flex E., Krumbach O.H.F., Carpentieri G., Cecchetti S., RA Lissewski C., Rezaei Adariani S., Schanze D., Brinkmann J., Piard J., RA Pantaleoni F., Lepri F.R., Goh E.S., Chong K., Stieglitz E., Meyer J., RA Kuechler A., Bramswig N.C., Sacharow S., Strullu M., Vial Y., Vignal C., RA Kensah G., Cuturilo G., Kazemein Jasemi N.S., Dvorsky R., Monaghan K.G., RA Vincent L.M., Cave H., Verloes A., Ahmadian M.R., Tartaglia M., Zenker M.; RT "Activating Mutations of RRAS2 Are a Rare Cause of Noonan Syndrome."; RL Am. J. Hum. Genet. 104:1223-1232(2019). RN [19] RP FUNCTION, INVOLVEMENT IN NS12, VARIANTS NS12 GLY-VAL-GLY-26 INS; HIS-72; RP LEU-72 AND CYS-75, AND CHARACTERIZATION OF VARIANTS NS12 GLY-VAL-GLY-26 RP INS; HIS-72; LEU-72 AND CYS-75. RX PubMed=31130285; DOI=10.1016/j.ajhg.2019.04.014; RA Niihori T., Nagai K., Fujita A., Ohashi H., Okamoto N., Okada S., RA Harada A., Kihara H., Arbogast T., Funayama R., Shirota M., Nakayama K., RA Abe T., Inoue S.I., Tsai I.C., Matsumoto N., Davis E.E., Katsanis N., RA Aoki Y.; RT "Germline-Activating RRAS2 Mutations Cause Noonan Syndrome."; RL Am. J. Hum. Genet. 104:1233-1240(2019). RN [20] RP PALMITOYLATION AT LYS-192; LYS-194; LYS-196; LYS-197 AND CYS-199, RP DEPALMITOYLATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 192-LYS--LYS-197 RP AND CYS-199. RX PubMed=28406396; DOI=10.7554/elife.25158; RA Zhang X., Spiegelman N.A., Nelson O.D., Jing H., Lin H.; RT "SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation."; RL Elife 6:0-0(2017). RN [21] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=39809765; DOI=10.1038/s41467-025-55967-y; RA Bernal Astrain G., Strakhova R., Jo C.H., Teszner E., Killoran R.C., RA Smith M.J.; RT "The small GTPase MRAS is a broken switch."; RL Nat. Commun. 16:647-647(2025). RN [22] {ECO:0007744|PDB:2ERY} RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 10-181 IN COMPLEX WITH GDP. RG Structural genomics consortium (SGC); RT "The crystal structure of the Ras related protein RRAS2 in the GDP bound RT state."; RL Submitted (FEB-2009) to the PDB data bank. CC -!- FUNCTION: GTP-binding protein with GTPase activity, involved in the CC regulation of MAPK signaling pathway and thereby controlling multiple CC cellular processes (PubMed:31130282, PubMed:31130285, PubMed:39809765). CC Regulates craniofacial development (PubMed:31130282, PubMed:31130285). CC {ECO:0000269|PubMed:31130282, ECO:0000269|PubMed:31130285, CC ECO:0000269|PubMed:39809765}. 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:31130282, ECO:0000269|PubMed:39809765}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; CC Evidence={ECO:0000269|PubMed:31130282}; CC -!- SUBUNIT: Interacts with RASSF5. {ECO:0000269|PubMed:31130282}. CC -!- INTERACTION: CC P62070; P10398: ARAF; NbExp=3; IntAct=EBI-491037, EBI-365961; CC P62070; Q8WUI4-6: HDAC7; NbExp=3; IntAct=EBI-491037, EBI-12094670; CC P62070; P52306-5: RAP1GDS1; NbExp=3; IntAct=EBI-491037, EBI-12832744; CC P62070; Q3MIN7: RGL3; NbExp=3; IntAct=EBI-491037, EBI-2856274; CC P62070; Q13671: RIN1; NbExp=6; IntAct=EBI-491037, EBI-366017; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28406396, CC ECO:0000269|PubMed:31130282}; Lipid-anchor CC {ECO:0000269|PubMed:15308774, ECO:0000269|PubMed:28406396}; Cytoplasmic CC side. Golgi apparatus membrane {ECO:0000269|PubMed:31130282}; Lipid- CC anchor {ECO:0000269|PubMed:15308774}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=P62070-1; Sequence=Displayed; CC Name=2; CC IsoId=P62070-2; Sequence=VSP_043066; CC Name=3; CC IsoId=P62070-3; Sequence=VSP_044485; CC Name=4; CC IsoId=P62070-4; Sequence=VSP_055842; CC -!- TISSUE SPECIFICITY: Ubiquitously present in all tissues examined, with CC the highest levels in heart, placenta, and skeletal muscle. Moderate CC levels in lung and liver; low levels in brain, kidney, and pancreas. CC {ECO:0000269|PubMed:8052619}. CC -!- PTM: May be post-translationally modified by both palmitoylation and CC polyisoprenylation. {ECO:0000269|PubMed:15308774}. CC -!- PTM: Fatty-acylation at Lys-192, Lys-194; lys-196 and Lys-197 is CC required for localization to the plasma membrane and activity CC (PubMed:28406396). Defatty-acylated by SIRT6, affecting its CC localization to the plasma membrane (PubMed:28406396). CC {ECO:0000269|PubMed:28406396}. CC -!- DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer CC defines malignancies originating from ovarian tissue. Although many CC histologic types of ovarian tumors have been described, epithelial CC ovarian carcinoma is the most common form. Ovarian cancers are often CC asymptomatic and the recognized signs and symptoms, even of late-stage CC disease, are vague. Consequently, most patients are diagnosed with CC advanced disease. {ECO:0000269|PubMed:8052619}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- DISEASE: Noonan syndrome 12 (NS12) [MIM:618624]: A form of Noonan CC syndrome, a disease characterized by short stature, facial dysmorphic CC features such as hypertelorism, a downward eyeslant and low-set CC posteriorly rotated ears, and a high incidence of congenital heart CC defects and hypertrophic cardiomyopathy. Other features can include a CC short neck with webbing or redundancy of skin, deafness, motor delay, CC variable intellectual deficits, multiple skeletal defects, CC cryptorchidism, and bleeding diathesis. Individuals with Noonan CC syndrome are at risk of juvenile myelomonocytic leukemia, a CC myeloproliferative disorder characterized by excessive production of CC myelomonocytic cells. NS12 inheritance is autosomal dominant. There is CC considerable variability in severity. {ECO:0000269|PubMed:31130282, CC ECO:0000269|PubMed:31130285}. 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 -!- SEQUENCE CAUTION: CC Sequence=AAA36545.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAM12638.1; Type=Frameshift; Evidence={ECO:0000305}; 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; M31468; AAA36545.1; ALT_FRAME; mRNA. DR EMBL; AF493924; AAM12638.1; ALT_FRAME; mRNA. DR EMBL; AK299606; BAH13078.1; -; mRNA. DR EMBL; AK300103; BAH13210.1; -; mRNA. DR EMBL; AK302033; BAH13612.1; -; mRNA. DR EMBL; AK313976; BAG36690.1; -; mRNA. DR EMBL; AC011084; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471064; EAW68487.1; -; Genomic_DNA. DR EMBL; BC013106; AAH13106.1; -; mRNA. DR CCDS; CCDS44544.1; -. [P62070-2] DR CCDS; CCDS53603.1; -. [P62070-3] DR CCDS; CCDS7814.1; -. [P62070-1] DR PIR; B34788; TVHUC2. DR RefSeq; NP_001096139.1; NM_001102669.3. [P62070-2] DR RefSeq; NP_001170785.1; NM_001177314.2. [P62070-3] DR RefSeq; NP_001170786.1; NM_001177315.2. [P62070-2] DR RefSeq; NP_001427641.1; NM_001440712.1. [P62070-2] DR RefSeq; NP_001427642.1; NM_001440713.1. [P62070-2] DR RefSeq; NP_001427643.1; NM_001440714.1. [P62070-2] DR RefSeq; NP_001427644.1; NM_001440715.1. [P62070-2] DR RefSeq; NP_036382.2; NM_012250.6. [P62070-1] DR RefSeq; XP_047282523.1; XM_047426567.1. [P62070-2] DR RefSeq; XP_047282524.1; XM_047426568.1. [P62070-2] DR RefSeq; XP_054224024.1; XM_054368049.1. [P62070-2] DR RefSeq; XP_054224025.1; XM_054368050.1. [P62070-2] DR PDB; 2ERY; X-ray; 1.70 A; A/B=12-181. DR PDB; 9B4Q; X-ray; 1.46 A; A=11-179. DR PDB; 9B4S; X-ray; 3.10 A; B=1-179. DR AlphaFoldDB; P62070; -. DR SMR; P62070; -. DR BioGRID; 116480; 144. DR FunCoup; P62070; 2349. DR IntAct; P62070; 89. DR MINT; P62070; -. DR NDEx; IQUERY-CP-RRAS2; 7 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000256196; -. DR ChEMBL; CHEMBL4879446; -. DR GlyGen; P62070; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P62070; -. DR MetOSite; P62070; -. DR PhosphoSitePlus; P62070; -. DR SwissPalm; P62070; -. DR BioMuta; RRAS2; -. DR DMDM; 49065833; -. DR jPOST; P62070; -. DR MassIVE; P62070; -. DR PaxDb; 9606-ENSP00000256196; -. DR PeptideAtlas; P62070; -. DR ProteomicsDB; 57360; -. [P62070-1] DR ProteomicsDB; 57361; -. [P62070-2] DR ProteomicsDB; 6730; -. DR ProteomicsDB; 6771; -. DR Pumba; P62070; -. DR Antibodypedia; 4173; 271 antibodies from 37 providers. DR DNASU; 22800; -. DR Ensembl; ENST00000256196.9; ENSP00000256196.4; ENSG00000133818.15. [P62070-1] DR Ensembl; ENST00000414023.6; ENSP00000403282.2; ENSG00000133818.15. [P62070-2] DR Ensembl; ENST00000526063.5; ENSP00000434104.1; ENSG00000133818.15. [P62070-2] DR Ensembl; ENST00000529237.5; ENSP00000433230.1; ENSG00000133818.15. [P62070-2] DR Ensembl; ENST00000532814.5; ENSP00000431954.1; ENSG00000133818.15. [P62070-2] DR Ensembl; ENST00000534746.5; ENSP00000437083.1; ENSG00000133818.15. [P62070-2] DR Ensembl; ENST00000537760.5; ENSP00000437547.1; ENSG00000133818.15. [P62070-3] DR GeneID; 22800; -. DR KEGG; hsa:22800; -. DR MANE-Select; ENST00000256196.9; ENSP00000256196.4; NM_012250.6; NP_036382.2. DR UCSC; uc001mlf.5; human. [P62070-1] DR AGR; HGNC:17271; -. DR CIViC; 22800; 1 evidence item across 1 molecular profile. DR ClinPGx; PA34862; -. DR CTD; 22800; -. DR DisGeNET; 22800; -. DR GeneCards; RRAS2; -. DR GeneReviews; RRAS2; -. DR HGNC; HGNC:17271; RRAS2. DR HPA; ENSG00000133818; Low tissue specificity. DR MalaCards; RRAS2; -. DR MIM; 167000; phenotype. DR MIM; 600098; gene. DR MIM; 618624; phenotype. DR OpenTargets; ENSG00000133818; -. DR Orphanet; 648; Noonan syndrome. DR VEuPathDB; HostDB:ENSG00000133818; -. DR eggNOG; KOG0395; Eukaryota. DR GeneTree; ENSGT00940000155328; -. DR InParanoid; P62070; -. DR OMA; NKRGCHC; -. DR OrthoDB; 5976022at2759; -. DR PAN-GO; P62070; 4 GO annotations based on evolutionary models. DR PhylomeDB; P62070; -. DR PathwayCommons; P62070; -. DR Reactome; R-HSA-9696273; RND1 GTPase cycle. DR SignaLink; P62070; -. DR SIGNOR; P62070; -. DR Agora; ENSG00000133818; -. DR BioGRID-ORCS; 22800; 26 hits in 1124 CRISPR screens. DR ChiTaRS; RRAS2; human. DR EvolutionaryTrace; P62070; -. DR GeneWiki; RRAS2; -. DR GenomeRNAi; 22800; -. DR Pharos; P62070; Tbio. DR PRO; PR:P62070; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P62070; protein. DR Bgee; ENSG00000133818; Expressed in secondary oocyte and 204 other cell types or tissues. DR ExpressionAtlas; P62070; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; NAS:ProtInc. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; EXP:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProt. DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC. DR GO; GO:0005525; F:GTP binding; IEA:InterPro. DR GO; GO:0003924; F:GTPase activity; IDA:UniProt. DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IBA:GO_Central. DR GO; GO:0001649; P:osteoblast differentiation; HDA:UniProtKB. DR GO; GO:0007265; P:Ras protein signal transduction; IDA:UniProt. DR CDD; cd04145; M_R_Ras_like; 1. DR FunFam; 3.40.50.300:FF:000080; Ras-like GTPase Ras1; 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; SM00176; RAN; 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; 2ERY; -. DR PDBsum; 9B4Q; -. DR PDBsum; 9B4S; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell membrane; KW Disease variant; Golgi apparatus; GTP-binding; Hydrolase; Lipoprotein; KW Membrane; Methylation; Nucleotide-binding; Palmitate; Phosphoprotein; KW Prenylation; Proteomics identification; Proto-oncogene; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..201 FT /note="Ras-related protein R-Ras2" FT /id="PRO_0000082652" FT PROPEP 202..204 FT /note="Removed in mature form" FT /evidence="ECO:0000250|UniProtKB:P10114" FT /id="PRO_0000281302" FT MOTIF 43..51 FT /note="Effector region" FT BINDING 21..29 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.22, ECO:0007744|PDB:2ERY" FT BINDING 68..72 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P01112" FT BINDING 127..130 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.22, ECO:0007744|PDB:2ERY" FT BINDING 157..159 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|Ref.22, ECO:0007744|PDB:2ERY" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 186 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 201 FT /note="Cysteine methyl ester" FT /evidence="ECO:0000305|PubMed:15308774" FT LIPID 192 FT /note="N6-palmitoyl lysine" FT /evidence="ECO:0000305|PubMed:28406396" FT LIPID 194 FT /note="N6-palmitoyl lysine" FT /evidence="ECO:0000305|PubMed:28406396" FT LIPID 196 FT /note="N6-palmitoyl lysine" FT /evidence="ECO:0000305|PubMed:28406396" FT LIPID 197 FT /note="N6-palmitoyl lysine" FT /evidence="ECO:0000305|PubMed:28406396" FT LIPID 199 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:28406396" FT LIPID 201 FT /note="S-farnesyl cysteine" FT /evidence="ECO:0000269|PubMed:15308774" FT VAR_SEQ 1..77 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043066" FT VAR_SEQ 1..36 FT /note="MAAAGWRDGSGQEKYRLVVVGGGGVGKSALTIQFIQ -> M (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044485" FT VAR_SEQ 36 FT /note="Q -> QFFLFLQ (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055842" FT VARIANT 23 FT /note="G -> V (in NS12; increased MAPK signaling; FT dbSNP:rs1591495779)" FT /evidence="ECO:0000269|PubMed:31130282" FT /id="VAR_083149" FT VARIANT 24 FT /note="G -> GGGG (in NS12; increased MAPK signaling)" FT /evidence="ECO:0000269|PubMed:31130282" FT /id="VAR_083150" FT VARIANT 26 FT /note="G -> GGVG (in NS12; increased MAPK signaling; FT results in craniofacial patterning defects when expressed FT in zebrafish)" FT /evidence="ECO:0000269|PubMed:31130282, FT ECO:0000269|PubMed:31130285" FT /id="VAR_083151" FT VARIANT 70 FT /note="A -> T (in NS12; decreased GAP-stimulated GTPase FT activity leading to an accumulation of RRAS2 in its FT GTP-bound active state; increased MAPK signaling; loss of FT interaction with RASSF5; dbSNP:rs782457908)" FT /evidence="ECO:0000269|PubMed:31130282" FT /id="VAR_083152" FT VARIANT 72 FT /note="Q -> H (in NS12; associated in cis with C-75; FT increased MAPK signaling; results in craniofacial FT patterning defects when expressed in zebrafish; results in FT craniofacial patterning defects in zebrafish when FT associated with C-75)" FT /evidence="ECO:0000269|PubMed:31130285" FT /id="VAR_083153" FT VARIANT 72 FT /note="Q -> L (in NS12; also found as somatic mutation in FT ovarian cancer; increased MAPK signaling; results in FT craniofacial patterning defects when expressed in FT zebrafish; dbSNP:rs113954997)" FT /evidence="ECO:0000269|PubMed:31130282, FT ECO:0000269|PubMed:31130285, ECO:0000269|PubMed:8052619" FT /id="VAR_006848" FT VARIANT 75 FT /note="F -> C (likely benign; associated in cis with H-72 FT in a patient with Noonan syndrome; has no effect on MAPK FT signaling; has no effect on craniofacial patterning when FT expressed in zebrafish; results in craniofacial patterning FT defects in zebrafish when associated with H-72)" FT /evidence="ECO:0000269|PubMed:31130285" FT /id="VAR_083154" FT MUTAGEN 192..197 FT /note="KEKDKK->RERDRR: Strongly decreased lysine FT fatty-acylation." FT /evidence="ECO:0000269|PubMed:28406396" FT MUTAGEN 199 FT /note="C->S: Does not affect lysine fatty-acylation." FT /evidence="ECO:0000269|PubMed:28406396" FT STRAND 14..20 FT /evidence="ECO:0007829|PDB:9B4Q" FT HELIX 27..36 FT /evidence="ECO:0007829|PDB:9B4Q" FT STRAND 47..57 FT /evidence="ECO:0007829|PDB:9B4Q" FT STRAND 60..69 FT /evidence="ECO:0007829|PDB:9B4Q" FT HELIX 73..78 FT /evidence="ECO:0007829|PDB:9B4Q" FT HELIX 79..85 FT /evidence="ECO:0007829|PDB:9B4Q" FT STRAND 87..94 FT /evidence="ECO:0007829|PDB:9B4Q" FT HELIX 98..115 FT /evidence="ECO:0007829|PDB:9B4Q" FT STRAND 121..127 FT /evidence="ECO:0007829|PDB:9B4Q" FT HELIX 132..134 FT /evidence="ECO:0007829|PDB:9B4Q" FT HELIX 139..148 FT /evidence="ECO:0007829|PDB:9B4Q" FT STRAND 151..155 FT /evidence="ECO:0007829|PDB:9B4Q" FT TURN 158..161 FT /evidence="ECO:0007829|PDB:9B4Q" FT HELIX 164..178 FT /evidence="ECO:0007829|PDB:9B4Q" SQ SEQUENCE 204 AA; 23400 MW; BA7D4759DC49446F CRC64; MAAAGWRDGS GQEKYRLVVV GGGGVGKSAL TIQFIQSYFV TDYDPTIEDS YTKQCVIDDR AARLDILDTA GQEEFGAMRE QYMRTGEGFL LVFSVTDRGS FEEIYKFQRQ ILRVKDRDEF PMILIGNKAD LDHQRQVTQE EGQQLARQLK VTYMEASAKI RMNVDQAFHE LVRVIRKFQE QECPPSPEPT RKEKDKKGCH CVIF //