RHES_RAT
ID RHES_RAT Reviewed; 266 AA.
AC P63033; Q9WVD3;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=GTP-binding protein Rhes;
DE AltName: Full=Ras homolog enriched in striatum;
DE AltName: Full=SE6C;
DE Flags: Precursor;
GN Name=Rasd2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND GTP-BINDING.
RC STRAIN=Sprague-Dawley; TISSUE=Corpus striatum;
RX PubMed=10467249;
RX DOI=10.1002/(sici)1097-4547(19990915)57:6<782::aid-jnr3>3.0.co;2-9;
RA Falk J.D., Vargiu P., Foye P.E., Usui H., Perez J., Danielson P.E.,
RA Lerner D.L., Bernal J., Sutcliffe J.G.;
RT "Rhes: a striatal-specific Ras homolog related to Dexras1.";
RL J. Neurosci. Res. 57:782-788(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=11976265; DOI=10.1038/sj.bjp.0704680;
RA Chan S.L.F., Monks L.K., Gao H., Deaville P., Morgan N.G.;
RT "Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated
RT protein in the pancreatic beta-cell.";
RL Br. J. Pharmacol. 136:31-36(2002).
RN [3]
RP TISSUE SPECIFICITY, AND INDUCTION BY THYROID HORMONE.
RX PubMed=11597759; DOI=10.1016/s0169-328x(01)00140-1;
RA Vargiu P., Morte B., Manzano J., Perez J., de Abajo R., Sutcliffe J.G.,
RA Bernal J.;
RT "Thyroid hormone regulation of rhes, a novel Ras homolog gene expressed in
RT the striatum.";
RL Brain Res. Mol. Brain Res. 94:1-8(2001).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=15199135; DOI=10.1128/mcb.24.13.5788-5796.2004;
RA Spano D., Branchi I., Rosica A., Pirro M.T., Riccio A., Mithbaokar P.,
RA Affuso A., Arra C., Campolongo P., Terracciano D., Macchia V., Bernal J.,
RA Alleva E., Di Lauro R.;
RT "Rhes is involved in striatal function.";
RL Mol. Cell. Biol. 24:5788-5796(2004).
RN [5]
RP FUNCTION, GTP-BINDING, SUBCELLULAR LOCATION, ISOPRENYLATION AT CYS-263,
RP MUTAGENESIS OF CYS-263, AND INTERACTION WITH PIK3CA.
RX PubMed=14724584; DOI=10.1038/sj.onc.1207161;
RA Vargiu P., De Abajo R., Garcia-Ranea J.A., Valencia A., Santisteban P.,
RA Crespo P., Bernal J.;
RT "The small GTP-binding protein, Rhes, regulates signal transduction from G
RT protein-coupled receptors.";
RL Oncogene 23:559-568(2004).
RN [6]
RP TISSUE SPECIFICITY, AND INDUCTION BY EFAROXAN AND GLIBENCLAMIDE.
RX PubMed=16945334; DOI=10.1016/j.bbrc.2006.08.102;
RA Taylor J.P., Jackson D.A., Morgan N.G., Chan S.L.;
RT "Rhes expression in pancreatic beta-cells is regulated by efaroxan in a
RT calcium-dependent process.";
RL Biochem. Biophys. Res. Commun. 349:809-815(2006).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18929545; DOI=10.1016/j.brainres.2008.09.066;
RA Harrison L.M., Lahoste G.J., Ruskin D.N.;
RT "Ontogeny and dopaminergic regulation in brain of Ras homolog enriched in
RT striatum (Rhes).";
RL Brain Res. 1245:16-25(2008).
RN [8]
RP FUNCTION, INTERACTION WITH UBE2I, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP CYS-263.
RX PubMed=19498170; DOI=10.1126/science.1172871;
RA Subramaniam S., Sixt K.M., Barrow R., Snyder S.H.;
RT "Rhes, a striatal specific protein, mediates mutant-huntingtin
RT cytotoxicity.";
RL Science 324:1327-1330(2009).
CC -!- FUNCTION: GTPase signaling protein that binds to and hydrolyzes GTP.
CC Regulates signaling pathways involving G-proteins-coupled receptor and
CC heterotrimeric proteins such as GNB1, GNB2 and GNB3. May be involved in
CC selected striatal competencies, mainly locomotor activity and motor
CC coordination. {ECO:0000269|PubMed:10467249,
CC ECO:0000269|PubMed:11976265, ECO:0000269|PubMed:14724584,
CC ECO:0000269|PubMed:18929545, ECO:0000269|PubMed:19498170}.
CC -!- SUBUNIT: Monomer (Potential). Interacts with GNB1, GNB2 and GNB3 (By
CC similarity). Interacts with PIK3CA and UBE2I. {ECO:0000250,
CC ECO:0000269|PubMed:14724584, ECO:0000269|PubMed:19498170, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14724584,
CC ECO:0000269|PubMed:19498170}; Lipid-anchor
CC {ECO:0000269|PubMed:14724584, ECO:0000269|PubMed:19498170}. Note=Found
CC in granular structures throughout the cytosol.
CC -!- TISSUE SPECIFICITY: Prominently expressed in the striatum, weakly in
CC the cerebral cortex and the CA fields of the hippocampus. Highly
CC expressed in the hippocampus and cerebellum, only during the postnatal
CC period. Also expressed in pancreatic endocrine cells (islets of
CC Langerhans), adrenal gland and stomach and in a thyroid cell line.
CC {ECO:0000269|PubMed:10467249, ECO:0000269|PubMed:11597759,
CC ECO:0000269|PubMed:15199135, ECO:0000269|PubMed:16945334,
CC ECO:0000269|PubMed:18929545}.
CC -!- DEVELOPMENTAL STAGE: Low levels detected at E16 through P10, and
CC increased between P10 and P15 during the development of brain; the
CC amount did decrease in the adult brain.
CC -!- INDUCTION: By thyroid hormone, efaroxan and glibenclamide.
CC {ECO:0000269|PubMed:11597759, ECO:0000269|PubMed:16945334}.
CC -!- PTM: Farnesylated. Farnesylation is required for membrane targeting.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. RasD family.
CC {ECO:0000305}.
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DR EMBL; AF134409; AAD38928.1; -; mRNA.
DR RefSeq; NP_598252.1; NM_133568.1.
DR AlphaFoldDB; P63033; -.
DR SMR; P63033; -.
DR STRING; 10116.ENSRNOP00000020017; -.
DR PaxDb; P63033; -.
DR Ensembl; ENSRNOT00000020017; ENSRNOP00000020017; ENSRNOG00000014761.
DR GeneID; 171099; -.
DR KEGG; rno:171099; -.
DR UCSC; RGD:628594; rat.
DR CTD; 23551; -.
DR RGD; 628594; Rasd2.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000161129; -.
DR HOGENOM; CLU_041217_9_3_1; -.
DR InParanoid; P63033; -.
DR OMA; EREKCTI; -.
DR OrthoDB; 1398885at2759; -.
DR PhylomeDB; P63033; -.
DR TreeFam; TF316238; -.
DR PRO; PR:P63033; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000014761; Expressed in frontal cortex and 17 other tissues.
DR Genevisible; P63033; RN.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0031681; F:G-protein beta-subunit binding; ISO:RGD.
DR GO; GO:0005525; F:GTP binding; IDA:MGI.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:UniProtKB.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IPI:UniProtKB.
DR GO; GO:0007626; P:locomotory behavior; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; IDA:UniProtKB.
DR GO; GO:0043949; P:regulation of cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0001963; P:synaptic transmission, dopaminergic; ISO:RGD.
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 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 Cell membrane; GTP-binding; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Prenylation; Reference proteome.
FT CHAIN 1..263
FT /note="GTP-binding protein Rhes"
FT /id="PRO_0000082722"
FT PROPEP 264..266
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281377"
FT REGION 189..235
FT /note="Interaction with GNB1, GNB2 and GNB3"
FT /evidence="ECO:0000250"
FT MOTIF 48..56
FT /note="Effector region"
FT BINDING 26..33
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 73..77
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 140..143
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 263
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 263
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:14724584"
FT MUTAGEN 263
FT /note="C->A: Loss of plasma membrane localization."
FT /evidence="ECO:0000269|PubMed:14724584,
FT ECO:0000269|PubMed:19498170"
FT MUTAGEN 263
FT /note="C->S: Rather found in granular structures
FT translocated to the nucleus."
FT /evidence="ECO:0000269|PubMed:14724584,
FT ECO:0000269|PubMed:19498170"
SQ SEQUENCE 266 AA; 30197 MW; 21B00C11CADD40B0 CRC64;
MMKTLSSGNC TLNVPAKNSY RMVVLGASRV GKSSIVSRFL NGRFEDQYTP TIEDFHRKVY
NIHGDMYQLD ILDTSGNHPF PAMRRLSILT GDVFILVFSL DSRESFDEVK RLQKQILEVK
SCLKNKTKEA AELPMVICGN KNDHSELCRQ VPAMEAELLV SGDENCAYFE VSAKKNTNVN
EMFYVLFSMA KLPHEMSPAL HHKISVQYGD AFHPRPFCMR RTKVAGAYGM VSPFARRPSV
NSDLKYIKAK VLREGQARER DKCSIQ