RHES_HUMAN
ID RHES_HUMAN Reviewed; 266 AA.
AC Q96D21; O95520; Q5THY8;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=GTP-binding protein Rhes;
DE AltName: Full=Ras homolog enriched in striatum;
DE AltName: Full=Tumor endothelial marker 2;
DE Flags: Precursor;
GN Name=RASD2; Synonyms=TEM2;
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].
RC TISSUE=Endothelial cell;
RX PubMed=10947988; DOI=10.1126/science.289.5482.1197;
RA St Croix B., Rago C., Velculescu V.E., Traverso G., Romans K.E.,
RA Montgomery E., Lal A., Riggins G.J., Lengauer C., Vogelstein B.,
RA Kinzler K.W.;
RT "Genes expressed in human tumor endothelium.";
RL Science 289:1197-1202(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [6]
RP FUNCTION, AND INTERACTION WITH GNB1; GNB2 AND GNB3.
RX PubMed=19255495; DOI=10.1159/000204075;
RA Hill C., Goddard A., Ladds G., Davey J.;
RT "The cationic region of Rhes mediates its interactions with specific Gbeta
RT subunits.";
RL Cell. Physiol. Biochem. 23:1-8(2009).
RN [7]
RP INTERACTION WITH HTT, AND INVOLVEMENT IN CELL SURVIVAL.
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:11976265,
CC ECO:0000269|PubMed:19255495}.
CC -!- SUBUNIT: Monomer (Potential). Interacts with PIK3CA and UBE2I (By
CC similarity). Interacts with GNB1, GNB2 and GNB3. Interacts with HTT;
CC interacts with mutant HTT (mHTT) with a much higher affinity than wild
CC type HTT. {ECO:0000250, ECO:0000269|PubMed:19255495,
CC ECO:0000269|PubMed:19498170, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Pancreatic endocrine cells (islets of Langerhans).
CC {ECO:0000269|PubMed:11976265}.
CC -!- PTM: Farnesylated. Farnesylation is required for membrane targeting (By
CC similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Reduces cell survival in striatal cells with Huntington
CC disease by binding to mutant Huntington disease protein (mHTT; poly-Gln
CC region with 82 repeats) and inducing sumoylation of mHTT.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. RasD family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG00868.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF279143; AAG00868.1; ALT_INIT; mRNA.
DR EMBL; CR456477; CAG30363.1; -; mRNA.
DR EMBL; AL022334; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013419; AAH13419.1; -; mRNA.
DR CCDS; CCDS13916.1; -.
DR RefSeq; NP_055125.2; NM_014310.3.
DR RefSeq; XP_005261499.1; XM_005261442.4.
DR RefSeq; XP_011528342.1; XM_011530040.2.
DR RefSeq; XP_016884190.1; XM_017028701.1.
DR RefSeq; XP_016884191.1; XM_017028702.1.
DR AlphaFoldDB; Q96D21; -.
DR SMR; Q96D21; -.
DR BioGRID; 117095; 13.
DR IntAct; Q96D21; 5.
DR MINT; Q96D21; -.
DR STRING; 9606.ENSP00000216127; -.
DR iPTMnet; Q96D21; -.
DR PhosphoSitePlus; Q96D21; -.
DR BioMuta; RASD2; -.
DR DMDM; 21362868; -.
DR jPOST; Q96D21; -.
DR MassIVE; Q96D21; -.
DR PaxDb; Q96D21; -.
DR PeptideAtlas; Q96D21; -.
DR PRIDE; Q96D21; -.
DR ProteomicsDB; 76247; -.
DR Antibodypedia; 205; 392 antibodies from 33 providers.
DR DNASU; 23551; -.
DR Ensembl; ENST00000216127.5; ENSP00000216127.4; ENSG00000100302.7.
DR GeneID; 23551; -.
DR KEGG; hsa:23551; -.
DR MANE-Select; ENST00000216127.5; ENSP00000216127.4; NM_014310.4; NP_055125.2.
DR UCSC; uc003anx.4; human.
DR CTD; 23551; -.
DR DisGeNET; 23551; -.
DR GeneCards; RASD2; -.
DR HGNC; HGNC:18229; RASD2.
DR HPA; ENSG00000100302; Tissue enriched (brain).
DR MIM; 612842; gene.
DR neXtProt; NX_Q96D21; -.
DR OpenTargets; ENSG00000100302; -.
DR PharmGKB; PA34237; -.
DR VEuPathDB; HostDB:ENSG00000100302; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000161129; -.
DR HOGENOM; CLU_041217_9_3_1; -.
DR InParanoid; Q96D21; -.
DR OMA; EREKCTI; -.
DR OrthoDB; 1398885at2759; -.
DR PhylomeDB; Q96D21; -.
DR TreeFam; TF316238; -.
DR PathwayCommons; Q96D21; -.
DR SignaLink; Q96D21; -.
DR BioGRID-ORCS; 23551; 18 hits in 1066 CRISPR screens.
DR GeneWiki; RASD2; -.
DR GenomeRNAi; 23551; -.
DR Pharos; Q96D21; Tbio.
DR PRO; PR:Q96D21; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q96D21; protein.
DR Bgee; ENSG00000100302; Expressed in putamen and 106 other tissues.
DR Genevisible; Q96D21; HS.
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; IPI:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; NAS:UniProtKB.
DR GO; GO:0007626; P:locomotory behavior; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; ISS:UniProtKB.
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; 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 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_0000082720"
FT PROPEP 264..266
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281375"
FT REGION 189..235
FT /note="Interaction with GNB1, GNB2 and GNB3"
FT /evidence="ECO:0000269|PubMed:19255495"
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; 30366 MW; 2E23A76F346F9EDD CRC64;
MMKTLSSGNC TLSVPAKNSY RMVVLGASRV GKSSIVSRFL NGRFEDQYTP TIEDFHRKVY
NIRGDMYQLD ILDTSGNHPF PAMRRLSILT GDVFILVFSL DNRESFDEVK RLQKQILEVK
SCLKNKTKEA AELPMVICGN KNDHGELCRQ VPTTEAELLV SGDENCAYFE VSAKKNTNVD
EMFYVLFSMA KLPHEMSPAL HRKISVQYGD AFHPRPFCMR RVKEMDAYGM VSPFARRPSV
NSDLKYIKAK VLREGQARER DKCTIQ
