RHES_MOUSE
ID RHES_MOUSE Reviewed; 266 AA.
AC P63032; Q9WVD3;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 31-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=GTP-binding protein Rhes;
DE AltName: Full=Ras homolog enriched in striatum;
DE Flags: Precursor;
GN Name=Rasd2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-266.
RC TISSUE=Salivary gland;
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 [3]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
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 [4]
RP INDUCTION BY EFAROXAN AND GLIBENCLAMIDE, AND TISSUE SPECIFICITY.
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 [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18035555; DOI=10.1016/j.mcn.2007.10.007;
RA Errico F., Santini E., Migliarini S., Borgkvist A., Centonze D., Nasti V.,
RA Carta M., De Chiara V., Prosperetti C., Spano D., Herve D., Pasqualetti M.,
RA Di Lauro R., Fisone G., Usiello A.;
RT "The GTP-binding protein Rhes modulates dopamine signalling in striatal
RT medium spiny neurons.";
RL Mol. Cell. Neurosci. 37:335-345(2008).
RN [6]
RP INDUCTION BY HYPOTHYROIDISM.
RX PubMed=18585460; DOI=10.1016/j.nbd.2008.05.015;
RA Vallortigara J., Alfos S., Micheau J., Higueret P., Enderlin V.;
RT "T3 administration in adult hypothyroid mice modulates expression of
RT proteins involved in striatal synaptic plasticity and improves motor
RT behavior.";
RL Neurobiol. Dis. 31:378-385(2008).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=18845937; DOI=10.1097/wnr.0b013e3283118434;
RA Quintero G.C., Spano D., Lahoste G.J., Harrison L.M.;
RT "The Ras homolog Rhes affects dopamine D1 and D2 receptor-mediated behavior
RT in mice.";
RL NeuroReport 19:1563-1566(2008).
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:15199135,
CC ECO:0000269|PubMed:18035555}.
CC -!- SUBUNIT: Monomer (Potential). Interacts with PIK3CA and UBE2I.
CC Interacts with GNB1, GNB2 and GNB3 (By similarity). {ECO:0000250,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain; prominently in the
CC striatum and weakly in kidney, thyroid, lung, heart and testis. Not
CC expressed in liver. Expressed in pancreatic cell lines and in a
CC embryonic stem cell line. {ECO:0000269|PubMed:15199135,
CC ECO:0000269|PubMed:16945334}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the brain from 13.5 dpc.
CC {ECO:0000269|PubMed:15199135}.
CC -!- INDUCTION: Down-regulated in hypothyroid conditions and up-regulated by
CC glibenclamide. {ECO:0000269|PubMed:16945334,
CC ECO:0000269|PubMed:18585460}.
CC -!- PTM: Farnesylated. Farnesylation is required for membrane targeting (By
CC similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Shows behavioral abnormalities, displaying a
CC gender-dependent increase in anxiety levels and a clear motor
CC coordination deficit and a mild hyperactive phenotype. Mice are more
CC sensitive to D2 receptor stimulation and have decreased body weight.
CC {ECO:0000269|PubMed:15199135, ECO:0000269|PubMed:18035555,
CC ECO:0000269|PubMed:18845937}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. RasD family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH26377.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence.; Evidence={ECO:0000305};
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DR EMBL; AK015898; BAB30023.1; -; mRNA.
DR EMBL; BC026377; AAH26377.1; ALT_SEQ; mRNA.
DR CCDS; CCDS52602.1; -.
DR RefSeq; NP_083458.1; NM_029182.1.
DR AlphaFoldDB; P63032; -.
DR SMR; P63032; -.
DR BioGRID; 217250; 8.
DR IntAct; P63032; 1.
DR MINT; P63032; -.
DR STRING; 10090.ENSMUSP00000118070; -.
DR iPTMnet; P63032; -.
DR PhosphoSitePlus; P63032; -.
DR PaxDb; P63032; -.
DR PRIDE; P63032; -.
DR ProteomicsDB; 255257; -.
DR Antibodypedia; 205; 392 antibodies from 33 providers.
DR Ensembl; ENSMUST00000132133; ENSMUSP00000120717; ENSMUSG00000034472.
DR Ensembl; ENSMUST00000139848; ENSMUSP00000118070; ENSMUSG00000034472.
DR GeneID; 75141; -.
DR KEGG; mmu:75141; -.
DR UCSC; uc009mhg.2; mouse.
DR CTD; 23551; -.
DR MGI; MGI:1922391; Rasd2.
DR VEuPathDB; HostDB:ENSMUSG00000034472; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000161129; -.
DR HOGENOM; CLU_041217_9_3_1; -.
DR InParanoid; P63032; -.
DR OMA; EREKCTI; -.
DR OrthoDB; 1398885at2759; -.
DR PhylomeDB; P63032; -.
DR TreeFam; TF316238; -.
DR BioGRID-ORCS; 75141; 2 hits in 73 CRISPR screens.
DR PRO; PR:P63032; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P63032; protein.
DR Bgee; ENSMUSG00000034472; Expressed in superior frontal gyrus and 122 other tissues.
DR Genevisible; P63032; MM.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0031681; F:G-protein beta-subunit binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISO:MGI.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; ISO:MGI.
DR GO; GO:0007626; P:locomotory behavior; IDA:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; ISO:MGI.
DR GO; GO:0043949; P:regulation of cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0001963; P:synaptic transmission, dopaminergic; IMP:UniProtKB.
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 2: Evidence at transcript level;
KW Behavior; 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_0000082721"
FT PROPEP 264..266
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281376"
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:0000250"
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
