RRAS2_HUMAN
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 03-AUG-2022, entry version 184.
DE RecName: Full=Ras-related protein R-Ras2;
DE EC=3.6.5.- {ECO:0000269|PubMed:31130282};
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 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, thereby controlling multiple
CC cellular processes (PubMed:31130282). Involved in the regulation of
CC MAPK signaling pathway (PubMed:31130282, PubMed:31130285). Regulation
CC of craniofacial development (PubMed:31130282, PubMed:31130285).
CC {ECO:0000269|PubMed:31130282, ECO:0000269|PubMed:31130285}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000269|PubMed:31130282};
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=4; 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};
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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_001102669.2. [P62070-2]
DR RefSeq; NP_001170785.1; NM_001177314.1. [P62070-3]
DR RefSeq; NP_001170786.1; NM_001177315.1. [P62070-2]
DR RefSeq; NP_036382.2; NM_012250.5. [P62070-1]
DR PDB; 2ERY; X-ray; 1.70 A; A/B=12-181.
DR PDBsum; 2ERY; -.
DR AlphaFoldDB; P62070; -.
DR SMR; P62070; -.
DR BioGRID; 116480; 106.
DR IntAct; P62070; 47.
DR MINT; P62070; -.
DR STRING; 9606.ENSP00000256196; -.
DR iPTMnet; P62070; -.
DR MetOSite; P62070; -.
DR PhosphoSitePlus; P62070; -.
DR SwissPalm; P62070; -.
DR BioMuta; RRAS2; -.
DR DMDM; 49065833; -.
DR EPD; P62070; -.
DR jPOST; P62070; -.
DR MassIVE; P62070; -.
DR MaxQB; P62070; -.
DR PaxDb; P62070; -.
DR PeptideAtlas; P62070; -.
DR PRIDE; P62070; -.
DR ProteomicsDB; 57360; -. [P62070-1]
DR ProteomicsDB; 57361; -. [P62070-2]
DR ProteomicsDB; 6730; -.
DR ProteomicsDB; 6771; -.
DR Antibodypedia; 4173; 274 antibodies from 36 providers.
DR DNASU; 22800; -.
DR Ensembl; ENST00000256196.9; ENSP00000256196.4; ENSG00000133818.14. [P62070-1]
DR Ensembl; ENST00000414023.6; ENSP00000403282.2; ENSG00000133818.14. [P62070-2]
DR Ensembl; ENST00000526063.5; ENSP00000434104.1; ENSG00000133818.14. [P62070-2]
DR Ensembl; ENST00000529237.5; ENSP00000433230.1; ENSG00000133818.14. [P62070-2]
DR Ensembl; ENST00000532814.5; ENSP00000431954.1; ENSG00000133818.14. [P62070-2]
DR Ensembl; ENST00000534746.5; ENSP00000437083.1; ENSG00000133818.14. [P62070-2]
DR Ensembl; ENST00000537760.5; ENSP00000437547.1; ENSG00000133818.14. [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 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 neXtProt; NX_P62070; -.
DR OpenTargets; ENSG00000133818; -.
DR Orphanet; 648; Noonan syndrome.
DR PharmGKB; PA34862; -.
DR VEuPathDB; HostDB:ENSG00000133818; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000155328; -.
DR InParanoid; P62070; -.
DR OMA; KNKRGCH; -.
DR OrthoDB; 1259506at2759; -.
DR PhylomeDB; P62070; -.
DR TreeFam; TF312796; -.
DR PathwayCommons; P62070; -.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; P62070; -.
DR SIGNOR; P62070; -.
DR BioGRID-ORCS; 22800; 16 hits in 1041 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 202 other tissues.
DR ExpressionAtlas; P62070; baseline and differential.
DR Genevisible; P62070; HS.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0019003; F:GDP binding; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0001649; P:osteoblast differentiation; HDA:UniProtKB.
DR GO; GO:1900149; P:positive regulation of Schwann cell migration; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:1901214; P:regulation of neuron death; IMP:UniProtKB.
DR GO; GO:0036135; P:Schwann cell migration; IEA:Ensembl.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras-type.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
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; 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.21, 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.21, ECO:0007744|PDB:2ERY"
FT BINDING 157..159
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|Ref.21, 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 GTP-
FT 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 variant; associated in cis
FT with H-72 in a patient with Noonan syndrome; has no effect
FT on MAPK signaling; has no effect on craniofacial patterning
FT when expressed in zebrafish; results in craniofacial
FT patterning 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 fatty-
FT 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..21
FT /evidence="ECO:0007829|PDB:2ERY"
FT HELIX 27..36
FT /evidence="ECO:0007829|PDB:2ERY"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:2ERY"
FT STRAND 60..68
FT /evidence="ECO:0007829|PDB:2ERY"
FT HELIX 77..85
FT /evidence="ECO:0007829|PDB:2ERY"
FT STRAND 87..94
FT /evidence="ECO:0007829|PDB:2ERY"
FT HELIX 98..102
FT /evidence="ECO:0007829|PDB:2ERY"
FT HELIX 104..115
FT /evidence="ECO:0007829|PDB:2ERY"
FT STRAND 121..127
FT /evidence="ECO:0007829|PDB:2ERY"
FT HELIX 139..148
FT /evidence="ECO:0007829|PDB:2ERY"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:2ERY"
FT TURN 158..161
FT /evidence="ECO:0007829|PDB:2ERY"
FT HELIX 164..178
FT /evidence="ECO:0007829|PDB:2ERY"
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
