RRAS_HUMAN
ID RRAS_HUMAN Reviewed; 218 AA.
AC P10301; Q6FH12;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Ras-related protein R-Ras;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:P62070};
DE AltName: Full=p23;
DE Flags: Precursor;
GN Name=RRAS;
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].
RX PubMed=3098437; DOI=10.1016/0092-8674(87)90364-3;
RA Lowe D.G., Capon D.J., Delwart E., Sakaguchi A.Y., Naylor S.L.,
RA Goeddel D.V.;
RT "Structure of the human and murine R-ras genes, novel genes closely related
RT to ras proto-oncogenes.";
RL Cell 48:137-146(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
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 [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Uterus;
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 [7]
RP PROTEIN SEQUENCE OF 177-188.
RC TISSUE=Adipocyte;
RX PubMed=15242332; DOI=10.1042/bj20040647;
RA Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.;
RT "Vectorial proteomics reveal targeting, phosphorylation and specific
RT fragmentation of polymerase I and transcript release factor (PTRF) at the
RT surface of caveolae in human adipocytes.";
RL Biochem. J. 383:237-248(2004).
RN [8]
RP FUNCTION, AND INTERACTION WITH PLCE1.
RX PubMed=16537651; DOI=10.1242/jcs.02835;
RA Ada-Nguema A.S., Xenias H., Sheetz M.P., Keely P.J.;
RT "The small GTPase R-Ras regulates organization of actin and drives membrane
RT protrusions through the activity of PLCepsilon.";
RL J. Cell Sci. 119:1307-1319(2006).
RN [9]
RP FUNCTION, INTERACTION WITH OSBPL3, AND MUTAGENESIS OF GLY-38 AND SER-43.
RX PubMed=18270267; DOI=10.1242/jcs.016964;
RA Lehto M., Maeyraenpaeae M.I., Pellinen T., Ihalmo P., Lehtonen S.,
RA Kovanen P.T., Groop P.H., Ivaska J., Olkkonen V.M.;
RT "The R-Ras interaction partner ORP3 regulates cell adhesion.";
RL J. Cell Sci. 121:695-705(2008).
RN [10]
RP INTERACTION WITH ZDHHC19, AND PALMITOYLATION.
RX PubMed=20074548; DOI=10.1016/j.bbamem.2010.01.002;
RA Baumgart F., Corral-Escariz M., Perez-Gil J., Rodriguez-Crespo I.;
RT "Palmitoylation of R-Ras by human DHHC19, a palmitoyl transferase with a
RT CaaX box.";
RL Biochim. Biophys. Acta 1798:592-604(2010).
RN [11]
RP IDENTIFICATION BY 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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 23-201 IN COMPLEX WITH GDP.
RX PubMed=16773572; DOI=10.1086/504394;
RA Carta C., Pantaleoni F., Bocchinfuso G., Stella L., Vasta I., Sarkozy A.,
RA Digilio C., Palleschi A., Pizzuti A., Grammatico P., Zampino G.,
RA Dallapiccola B., Gelb B.D., Tartaglia M.;
RT "Germline missense mutations affecting KRAS Isoform B are associated with a
RT severe Noonan syndrome phenotype.";
RL Am. J. Hum. Genet. 79:129-135(2006).
CC -!- FUNCTION: Regulates the organization of the actin cytoskeleton
CC (PubMed:16537651, PubMed:18270267). With OSPBL3, modulates integrin
CC beta-1 (ITGB1) activity (PubMed:18270267).
CC {ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:18270267}.
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:0000250|UniProtKB:P62070};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P62070};
CC -!- SUBUNIT: Interacts with PLCE1 (PubMed:16537651). Interacts (active GTP-
CC bound form preferentially) with RGS14 (By similarity). Interacts with
CC OSBPL3 (PubMed:18270267, PubMed:16537651, PubMed:20074548) (By
CC similarity). Interacts with ZDHHC19 (PubMed:20074548).
CC {ECO:0000250|UniProtKB:D3Z8L7, ECO:0000269|PubMed:16537651,
CC ECO:0000269|PubMed:18270267, ECO:0000269|PubMed:20074548}.
CC -!- INTERACTION:
CC P10301; P16333: NCK1; NbExp=3; IntAct=EBI-968703, EBI-389883;
CC P10301; P52306-5: RAP1GDS1; NbExp=3; IntAct=EBI-968703, EBI-12832744;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Note=Inner surface of
CC plasma membrane possibly with attachment requiring acylation of the C-
CC terminal cysteine (By similarity with RAS).
CC -!- PTM: S-palmitoylated by ZDHHC19, leading to increased association with
CC membranes and with rafts/caveolae as well as enhanced cell viability.
CC {ECO:0000269|PubMed:20074548}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC {ECO:0000305}.
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DR EMBL; M14949; AAA60256.1; -; Genomic_DNA.
DR EMBL; M14948; AAA60256.1; JOINED; Genomic_DNA.
DR EMBL; AF493920; AAM12634.1; -; mRNA.
DR EMBL; BT006805; AAP35451.1; -; mRNA.
DR EMBL; CR541944; CAG46742.1; -; mRNA.
DR EMBL; CR541967; CAG46765.1; -; mRNA.
DR EMBL; CH471177; EAW52506.1; -; Genomic_DNA.
DR EMBL; BC016286; AAH16286.1; -; mRNA.
DR EMBL; BC016318; AAH16318.1; -; mRNA.
DR CCDS; CCDS12774.1; -.
DR PIR; A26159; TVHURR.
DR RefSeq; NP_006261.1; NM_006270.4.
DR PDB; 2FN4; X-ray; 1.65 A; A=23-201.
DR PDB; 7S0Z; X-ray; 2.34 A; C/D=23-201.
DR PDBsum; 2FN4; -.
DR PDBsum; 7S0Z; -.
DR AlphaFoldDB; P10301; -.
DR SMR; P10301; -.
DR BioGRID; 112151; 59.
DR IntAct; P10301; 41.
DR MINT; P10301; -.
DR STRING; 9606.ENSP00000246792; -.
DR iPTMnet; P10301; -.
DR MetOSite; P10301; -.
DR PhosphoSitePlus; P10301; -.
DR SwissPalm; P10301; -.
DR BioMuta; RRAS; -.
DR DMDM; 133486; -.
DR SWISS-2DPAGE; P10301; -.
DR EPD; P10301; -.
DR jPOST; P10301; -.
DR MassIVE; P10301; -.
DR MaxQB; P10301; -.
DR PaxDb; P10301; -.
DR PeptideAtlas; P10301; -.
DR PRIDE; P10301; -.
DR ProteomicsDB; 52595; -.
DR Antibodypedia; 32074; 240 antibodies from 32 providers.
DR DNASU; 6237; -.
DR Ensembl; ENST00000246792.4; ENSP00000246792.2; ENSG00000126458.4.
DR GeneID; 6237; -.
DR KEGG; hsa:6237; -.
DR MANE-Select; ENST00000246792.4; ENSP00000246792.2; NM_006270.5; NP_006261.1.
DR UCSC; uc002pop.2; human.
DR CTD; 6237; -.
DR DisGeNET; 6237; -.
DR GeneCards; RRAS; -.
DR GeneReviews; RRAS; -.
DR HGNC; HGNC:10447; RRAS.
DR HPA; ENSG00000126458; Low tissue specificity.
DR MalaCards; RRAS; -.
DR MIM; 165090; gene.
DR neXtProt; NX_P10301; -.
DR OpenTargets; ENSG00000126458; -.
DR Orphanet; 86834; Juvenile myelomonocytic leukemia.
DR Orphanet; 648; Noonan syndrome.
DR PharmGKB; PA34861; -.
DR VEuPathDB; HostDB:ENSG00000126458; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000160972; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; P10301; -.
DR OMA; GCPCILL; -.
DR OrthoDB; 1259506at2759; -.
DR PhylomeDB; P10301; -.
DR TreeFam; TF312796; -.
DR PathwayCommons; P10301; -.
DR Reactome; R-HSA-399955; SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
DR Reactome; R-HSA-416550; Sema4D mediated inhibition of cell attachment and migration.
DR SignaLink; P10301; -.
DR SIGNOR; P10301; -.
DR BioGRID-ORCS; 6237; 9 hits in 1076 CRISPR screens.
DR ChiTaRS; RRAS; human.
DR EvolutionaryTrace; P10301; -.
DR GeneWiki; RRAS; -.
DR GenomeRNAi; 6237; -.
DR Pharos; P10301; Tbio.
DR PRO; PR:P10301; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P10301; protein.
DR Bgee; ENSG00000126458; Expressed in right coronary artery and 159 other tissues.
DR ExpressionAtlas; P10301; baseline and differential.
DR Genevisible; P10301; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:MGI.
DR GO; GO:0060325; P:face morphogenesis; IMP:UniProtKB.
DR GO; GO:0002521; P:leukocyte differentiation; IMP:UniProtKB.
DR GO; GO:1900148; P:negative regulation of Schwann cell migration; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:CACAO.
DR GO; GO:1904906; P:positive regulation of endothelial cell-matrix adhesion via fibronectin; IMP:CACAO.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; IMP:CACAO.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; 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; Cell membrane; Direct protein sequencing; GTP-binding;
KW Hydrolase; Lipoprotein; Membrane; Methylation; Nucleotide-binding;
KW Palmitate; Prenylation; Reference proteome.
FT CHAIN 1..215
FT /note="Ras-related protein R-Ras"
FT /id="PRO_0000082650"
FT PROPEP 216..218
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281300"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 58..66
FT /note="Effector region"
FT BINDING 36..44
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16773572"
FT BINDING 83..87
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 142..145
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16773572"
FT BINDING 172..174
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:16773572"
FT MOD_RES 215
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 215
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT MUTAGEN 38
FT /note="G->V: No effect on interaction with OSBPL3."
FT /evidence="ECO:0000269|PubMed:18270267"
FT MUTAGEN 43
FT /note="S->N: No effect on interaction with OSBPL3."
FT /evidence="ECO:0000269|PubMed:18270267"
FT STRAND 29..36
FT /evidence="ECO:0007829|PDB:2FN4"
FT HELIX 42..51
FT /evidence="ECO:0007829|PDB:2FN4"
FT STRAND 64..72
FT /evidence="ECO:0007829|PDB:2FN4"
FT STRAND 75..83
FT /evidence="ECO:0007829|PDB:2FN4"
FT TURN 87..90
FT /evidence="ECO:0007829|PDB:2FN4"
FT HELIX 94..100
FT /evidence="ECO:0007829|PDB:2FN4"
FT STRAND 102..109
FT /evidence="ECO:0007829|PDB:2FN4"
FT HELIX 113..130
FT /evidence="ECO:0007829|PDB:2FN4"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:2FN4"
FT HELIX 144..149
FT /evidence="ECO:0007829|PDB:2FN4"
FT HELIX 154..163
FT /evidence="ECO:0007829|PDB:2FN4"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:2FN4"
FT TURN 173..176
FT /evidence="ECO:0007829|PDB:2FN4"
FT HELIX 179..193
FT /evidence="ECO:0007829|PDB:2FN4"
SQ SEQUENCE 218 AA; 23480 MW; 437F73170670EB28 CRC64;
MSSGAASGTG RGRPRGGGPG PGDPPPSETH KLVVVGGGGV GKSALTIQFI QSYFVSDYDP
TIEDSYTKIC SVDGIPARLD ILDTAGQEEF GAMREQYMRA GHGFLLVFAI NDRQSFNEVG
KLFTQILRVK DRDDFPVVLV GNKADLESQR QVPRSEASAF GASHHVAYFE ASAKLRLNVD
EAFEQLVRAV RKYQEQELPP SPPSAPRKKG GGCPCVLL
