Affinage

RASD2

GTP-binding protein Rhes · UniProt Q96D21

Length
266 aa
Mass
30.4 kDa
Annotated
2026-04-28
73 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RASD2 (Rhes) is a striatum-enriched, farnesylated small GTPase that functions as a SUMO E3 ligase and integrates multiple signaling cascades—including mTOR activation, PI3K/AKT signaling, cAMP/PKA suppression via Gαi/Gβγ, and autophagy—to regulate striatal neuron physiology, motor behavior, and cell survival (PMID:14724584, PMID:22179112, PMID:24324270, PMID:20424159). Rhes binds directly to SUMO E1 and Ubc9 (E2) enzymes to enhance global sumoylation, and it selectively binds and SUMOylates mutant huntingtin (mHTT), increasing its solubility and cytotoxicity, thereby accounting for the striatal selectivity of Huntington's disease neurodegeneration (PMID:19498170, PMID:20424159, PMID:26048156). Rhes induces tunneling nanotube-like protrusions through a farnesylation- and SUMO-dependent mechanism involving the plasma membrane partner Slc4a7 and intracellular pH modulation, enabling intercellular transport of mHTT between striatal neurons and from striatum to cortex in vivo (PMID:31076452, PMID:35319973, PMID:41861004). Rhes also promotes mitophagy through direct interaction with Nix/BNIP3L via its SUMO E3-ligase domain, and its SUMO ligase activity extends to non-neuronal substrates such as CTPS1, linking RASD2 to endometriosis progression (PMID:31676548, PMID:39672102).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 Medium

    Identification of Rhes as a novel striatum-enriched, thyroid-hormone-dependent Ras-family GTPase established a previously unknown signaling node specific to the postnatal striatum.

    Evidence GTP-binding assay with bacterially expressed protein; subtractive hybridization in rat brain

    PMID:10467249

    Open questions at the time
    • No GEF or GAP identified
    • Intrinsic GTPase rate not measured
    • Endogenous protein not visualized
  2. 2004 High

    Demonstration that Rhes is plasma-membrane-targeted by farnesylation, constitutively GTP-loaded (~30%), activates PI3K, and suppresses cAMP/PKA signaling defined its first effector pathways and distinguished it from classical Ras oncogenes.

    Evidence Farnesylation inhibitor assay, PI3K binding/activity assay, cAMP/PKA signaling assay in PC12 cells, ERK assay, transformation assay

    PMID:14724584

    Open questions at the time
    • Direct structural basis for constitutive GTP loading unknown
    • PI3K binding interface not mapped at residue level
  3. 2004 Medium

    Rhes knockout mice displayed motor coordination deficits and anxiety, establishing in vivo necessity for striatal behavioral functions and providing a genetic model.

    Evidence Homologous recombination KO mice; rotarod, anxiety, and learning behavioral tests

    PMID:15199135

    Open questions at the time
    • Electrophysiological basis of motor deficits not determined
    • Cell-type-specific contribution (D1 vs. D2 MSNs) not resolved
  4. 2008 Medium

    Electrophysiological reconstitution showed Rhes triggers tonic Gβγ signaling from PTX-sensitive Gi proteins to modulate CaV2.2 channels, clarifying how Rhes suppresses receptor-coupled signaling.

    Evidence Whole-cell patch-clamp in HEK293 cells; pertussis toxin; Gβγ-sequestering peptide

    PMID:18815223

    Open questions at the time
    • Not confirmed in striatal neurons
    • Stoichiometry of Rhes–Gαi interaction undefined
  5. 2009 High

    The discovery that Rhes selectively binds mutant huntingtin (mHTT) and promotes its SUMOylation, leading to cytotoxicity, provided a molecular explanation for the long-standing puzzle of striatal selectivity in Huntington's disease.

    Evidence Co-immunoprecipitation; sumoylation assay; cytotoxicity assay in cultured cells

    PMID:19498170

    Open questions at the time
    • Structural basis for mHTT selectivity over wtHTT not resolved
    • In vivo sumoylation of endogenous mHTT by Rhes not directly shown at this point
  6. 2010 High

    Biochemical reconstitution and Rhes-KO mice established Rhes as a bona fide SUMO E3 ligase that bridges E1 and Ubc9 to enhance global striatal sumoylation, expanding its function beyond canonical GTPase signaling.

    Evidence In vivo sumoylation in Rhes-KO striatum; in vitro reconstitution with purified E1, Ubc9, and Rhes

    PMID:20424159

    Open questions at the time
    • Full substrate repertoire of Rhes SUMO ligase activity unknown
    • Crystal structure of Rhes–E1–Ubc9 complex lacking
  7. 2011 High

    Demonstration that Rhes directly binds and activates mTOR in the striatum, and that Rhes deletion suppresses L-DOPA-induced dyskinesia while preserving therapeutic benefit, placed Rhes upstream of mTOR in a clinically relevant pathway.

    Evidence Co-immunoprecipitation; mTOR activity assay; Rhes KO with L-DOPA challenge; pharmacological epistasis

    PMID:22179112

    Open questions at the time
    • Whether Rhes activates mTORC1 vs. mTORC2 not distinguished
    • Mechanism of mTOR activation by Rhes (direct allosteric vs. scaffold) unresolved
  8. 2013 High

    Rhes was shown to bind Beclin-1, freeing it from Bcl-2 inhibition to activate mTOR-independent autophagy—an activity blocked by co-expression of mHTT, linking impaired autophagy to HD pathogenesis.

    Evidence Co-immunoprecipitation; autophagy flux assay; mTOR inhibitor controls in PC12 cells

    PMID:24324270

    Open questions at the time
    • Relative contribution of Rhes-driven autophagy vs. mTOR-driven autophagy in vivo not quantified
    • Mechanism by which mHTT blocks Rhes–Beclin-1 interaction not defined
  9. 2015 High

    Ectopic Rhes expression in the cerebellum caused mHTT-dependent neurodegeneration, and reintroduction into Rhes-deleted HD striatum restored disease phenotype, providing causal gain-of-function evidence that Rhes mediates mHTT toxicity through its GTPase and SUMO E3 ligase activities.

    Evidence Stereotaxic viral injection; Purkinje neuron loss; caspase-3 activation; mHTT solubility analysis; behavioral rescue

    PMID:26048156

    Open questions at the time
    • Relative contribution of GTPase vs. SUMO ligase activity to toxicity not fully separated
    • Long-term neurodegeneration kinetics not tracked
  10. 2016 High

    Proteomic identification of the striatal Rhes interactome ('Rhesactome') and demonstration that RasGRP1 stabilizes Rhes at synapses revealed an upstream regulatory mechanism and expanded the network of Rhes effectors.

    Evidence Mass spectrometry of striatal lysates; Co-IP; RasGRP1 KO × Rhes heterozygote genetic epistasis; behavioral assays

    PMID:27902448

    Open questions at the time
    • Whether RasGRP1 acts as a GEF for Rhes or only as a stabilizer not resolved
    • Functional validation of most Rhesactome members pending
  11. 2019 High

    Discovery that Rhes induces tunneling nanotube (TNT)-like protrusions and selectively transports SUMOylated mHTT between cells revealed a novel mechanism for prion-like spreading of HD pathology, dependent on SUMO E3 ligase activity and farnesylation.

    Evidence Live-cell imaging; electron microscopy; CRISPR SUMO depletion; domain mutagenesis

    PMID:31076452

    Open questions at the time
    • TNT structural composition not fully defined
    • Whether TNTs form in vivo brain tissue not yet shown at this point
  12. 2019 High

    Rhes was established as a mitophagy regulator that interacts with Nix/BNIP3L via its SUMO E3-ligase domain to recruit lysosomes to mitochondria; Nix depletion abolished Rhes-mediated mitophagy and cell death, and Rhes KO mice were resistant to 3-NP-induced striatal lesions.

    Evidence Density fractionation; Co-IP; live-cell imaging; mitochondrial membrane potential; EM; Nix depletion; Rhes KO with 3-NP challenge

    PMID:31676548

    Open questions at the time
    • Whether Rhes-driven mitophagy is protective or pathological in physiological context unclear
    • Relationship between mitophagy and mHTT toxicity not integrated
  13. 2022 High

    In vivo confirmation that Rhes moves between D1R and D2R MSNs via TNT-like protrusions and transports mHTT from striatum to cortex established the physiological relevance of Rhes-mediated intercellular transfer in the intact brain.

    Evidence In vivo imaging; organotypic brain slices; genetic tracing in Rhes KO mice

    PMID:35319973

    Open questions at the time
    • Quantitative contribution of TNT-mediated spread vs. exosomal or synaptic spread not compared
    • Whether blocking TNT formation in vivo slows HD progression not tested
  14. 2024 Medium

    RASD2 overexpression in NAcc DRD2+ neurons activates DRD2-cAMP-PKA-DARPP-32 signaling and alleviates stress-induced depression, extending Rhes function to affective circuitry beyond motor control.

    Evidence Viral overexpression; DREADD chemogenetics; Drd2-Cre mice; behavioral assays

    PMID:39097664

    Open questions at the time
    • Mechanism by which Rhes activates rather than suppresses cAMP/PKA in this context not reconciled with earlier suppressive role
    • Endogenous Rhes levels in NAcc under stress not measured
  15. 2024 Medium

    Rhes SUMO E3-ligase activity was shown to stabilize CTPS1 via SUMOylation in endometriosis, demonstrating that Rhes SUMO ligase function operates in non-neuronal tissues and on novel substrates.

    Evidence Co-IP; IP-mass spectrometry; in vivo mouse endometriosis model; ChIP-qPCR for RASD2 transcription

    PMID:39672102

    Open questions at the time
    • Whether RASD2 expression is physiologically relevant in endometrial tissue beyond disease unclear
    • Generalizability of SUMO-mediated substrate stabilization to other Rhes targets not tested
  16. 2026 High

    Identification of Slc4a7 as a direct plasma-membrane partner of Rhes that modulates intracellular pH to facilitate TNT biogenesis provided the first mechanistic link between Rhes membrane anchoring, pH sensing, and intercellular mHTT transfer.

    Evidence LC-MS/MS membrane-associated complex proteomics; siRNA and pharmacological inhibition of Slc4a7; domain binding assays; farnesylation inhibitor; Slc4a7 KO mouse in vivo mHTT transmission

    PMID:41861004

    Open questions at the time
    • How pH changes mechanistically drive TNT formation not elucidated
    • Whether other Slc4a family members compensate in vivo not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of Rhes dual GTPase/SUMO-ligase activity, the identity of its GEF and GAP, whether therapeutic targeting of Rhes TNT formation can slow HD progression in vivo, and how Rhes switches between mTOR-activating and autophagy-promoting modes in different cellular contexts.
  • No crystal or cryo-EM structure available
  • No GEF or GAP definitively identified
  • No therapeutic intervention targeting Rhes tested in HD animal models for disease modification

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0016874 ligase activity 4 GO:0003924 GTPase activity 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-112316 Neuronal System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
BECN1BNIP3LHTTMTORPIK3R1RASGRP1SLC4A7UBE2I

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Rhes (RASD2) is a small GTP-binding protein of the Ras family that binds GTP, as demonstrated by bacterially expressed Rhes; it shares 62% identity with Dexras1 and has a substantially longer C-terminus than typical Ras-like proteins. Its expression is dependent on thyroid hormone availability and is postnatal. GTP-binding assay with bacterially expressed protein; subtractive hybridization; sequence analysis Journal of neuroscience research Medium 10467249
2001 Rhes mRNA and protein in the striatum are strongly dependent on thyroid hormone (T3) status; a single T3 dose normalizes rhes mRNA in hypothyroid rats within 8 hours, establishing Rhes as a direct thyroid hormone-regulated gene. In situ hybridization; T3 administration to hypothyroid rats; double in situ hybridization Brain research. Molecular brain research Medium 11597759
2004 Rhes is targeted to the plasma membrane by farnesylation; approximately 30% of native Rhes is constitutively bound to GTP; Rhes binds to and activates PI3K; Rhes impairs cAMP/PKA pathway activation by G protein-coupled receptors (TSH receptor, β2 adrenergic receptor), suggesting uncoupling of receptor from its heterotrimeric G-protein complex; Rhes does not stimulate the ERK pathway and is not transforming. Farnesylation inhibitor assay; GTP-binding assay; PI3K binding and activity assay; cAMP/PKA signaling assay in PC12 cells; ERK assay; fibroblast transformation assay Oncogene High 14724584
2004 Genetic deletion of Rhes in mice causes behavioral abnormalities including gender-dependent increased anxiety and motor coordination deficits, establishing Rhes as necessary for normal striatal motor and affective function in vivo. Homologous recombination knockout mice; behavioral testing (rotarod, anxiety, learning/memory) Molecular and cellular biology Medium 15199135
2007 Rhes modulates cAMP/PKA signaling in striatopallidal and striatonigral projection neurons by increasing Golf protein levels in Rhes null mice; Rhes is required for correct dopamine-mediated GTP binding associated with D2 receptor stimulation. Rhes null mouse model; biochemical measurement of Golf levels; GTP binding assay; motor behavior assays Molecular and cellular neurosciences Medium 18035555
2008 Rhes and AGS1 both trigger tonic Gβγ signaling and attenuate receptor-initiated signaling by Gβγ subunits of PTX-sensitive G proteins to modulate N-type Ca2+ channels (CaV2.2); the effects of both proteins are blocked by pertussis toxin or Gβγ-sequestering peptide. Whole-cell patch-clamp recording in HEK293 cells; pertussis toxin treatment; Gβγ-sequestering peptide expression American journal of physiology. Cell physiology Medium 18815223
2009 Rhes binds physiologically to mutant huntingtin (mHtt) but not to wild-type Htt; Rhes induces sumoylation of mHtt, which disaggregates mHtt and leads to cytotoxicity; this interaction accounts for the selective striatal neuropathology of Huntington's disease. Co-immunoprecipitation; sumoylation assay; cytotoxicity assay in cultured cells; binding assay Science (New York, N.Y.) High 19498170
2009 Rhes binds selectively to Gβ1, Gβ2, and Gβ3 subunits of heterotrimeric G proteins; this binding is mediated by the cationic region of Rhes, and Rhes-AGS1 chimeras showed that their different cationic regions determine Gβ-subunit specificity. Yeast two-hybrid; Rhes-AGS1 chimera construction and binding assays Cellular physiology and biochemistry Medium 19255495
2010 Rhes acts as a physiologic SUMO E3 ligase in the striatum; Rhes-deleted mice show markedly reduced striatal sumoylation; Rhes binds directly to both E1 and Ubc9 (E2) sumoylation enzymes, enhancing cross-sumoylation (intermolecular SUMO transfer between E1 and Ubc9) as well as thioester transfer from E1 to Ubc9. In vivo sumoylation assay in Rhes-KO mice; in vitro binding assays; biochemical sumoylation reconstitution The Journal of biological chemistry High 20424159
2011 Rhes binds to and activates mTOR in the striatum; Rhes-/- mice show reduced striatal mTOR signaling and diminished L-DOPA-induced dyskinesia while maintaining motor improvement, placing Rhes upstream of mTOR in the dyskinesia pathway. Co-immunoprecipitation; mTOR activity assay; Rhes knockout mouse model with L-DOPA treatment; pharmacological/genetic epistasis Nature neuroscience High 22179112
2011 Rhes decreases dopamine D1 receptor agonist-stimulated cAMP accumulation in a pertussis toxin-sensitive manner; both Rhes and AGS1/Dexras1 associate with GTP-bound Gαi in pull-down assays; neither protein interacts with the D1 receptor directly. cAMP accumulation assay; pertussis toxin treatment; GST pull-down with GTP-bound Gαi Journal of neuroscience research Medium 21374700
2012 Rhes interacts with p85, the regulatory subunit of PI3K, via its C-terminal unique tail region; this interaction is enhanced upon growth factor treatment; Rhes or the Rhes-p85 complex facilitates AKT translocation to the membrane, establishing Rhes as a striatal regulator of the AKT pathway. Co-immunoprecipitation; domain mapping with C-terminal deletion mutants; AKT membrane translocation assay Neuroscience letters Medium 22683505
2013 Rhes binds the autophagy regulator Beclin-1, decreasing its inhibitory interaction with Bcl-2 independent of JNK-1 signaling; Rhes overexpression activates autophagy independently of mTOR in PC12 cells; co-expression of mHtt blocks Rhes-induced autophagy activation. Co-immunoprecipitation; autophagy flux assays; Rhes KD/OE in PC12 cells; mTOR inhibitor controls The Journal of biological chemistry High 24324270
2013 Rhes is necessary for Akt dephosphorylation by the striatal multi-protein β-arrestin2/PP2A/Akt complex; Rhes co-immunoprecipitates with β-arrestins; in Rhes-/- mice, basally increased Akt and GSK3β phosphorylation is observed, and apomorphine causes further increases, phenocopying lithium treatment. Co-immunoprecipitation; Western blot of phospho-Akt/GSK3β in KO mice; drug challenge with apomorphine and lithium Neuroscience Medium 23380502
2013 Rhes participates in iron uptake via DMT1 by interacting with PAP7 (Peripheral benzodiazepine receptor-associated protein 7); Rhes is phosphorylated by PKA at serine-239; phosphomimetic (S239D) and constitutively active (A173V) Rhes mutants show increased iron uptake; unlike its close homolog Dexras1, Rhes is not S-nitrosylated by nitric oxide. Co-immunoprecipitation; iron uptake assay; site-directed mutagenesis; S-nitrosylation assay Neuroscience Medium 23999124
2015 Ectopic Rhes expression in the cerebellum of HD (N171-82Q) mice elicits cerebellar degeneration, Purkinje neuron loss, caspase-3 activation, and enhanced soluble mHtt; reintroduction of Rhes into Rhes-deleted knock-in HD striatum restores rotarod deficits; these gain-of-function experiments confirm Rhes as a causal mediator of mHtt toxicity requiring its GTPase and SUMO E3-ligase activities. Stereotaxic viral vector injection (ectopic expression); behavioral testing; immunohistochemistry; caspase-3 assay; biochemical analysis of mHtt solubility Neurobiology of disease High 26048156
2016 RasGRP1 (a guanine nucleotide exchange factor) stabilizes Rhes and increases its synaptic accumulation in the striatum; RasGRP1 depletion attenuates Rhes-mediated control of striatal motor activity; proteomic analysis identified the Rhes interactome ('Rhesactome'), which includes PDE2A, LRRC7, and DLG2, and is altered by RasGRP1 and amphetamine. Co-immunoprecipitation; proteomic mass spectrometry of striatal lysates; genetic epistasis (Rhes+/- × Rasgrp1 KO); behavioral assays Science signaling High 27902448
2019 Rhes induces the biogenesis of tunneling nanotube (TNT)-like cellular protrusions ('Rhes tunnels') through which it moves from cell to cell and transports mHTT (but not normal HTT, mTOR, or wtTau); TNT formation requires Rhes serine-33, C-terminal CAAX motif, and SUMO E3-ligase domain; mHTT transport requires SUMOylation since SUMOylation-defective mHTT or Rhes C263S mutation diminishes transport; CRISPR depletion of SUMO isoforms abrogates mHTT transport. Live-cell imaging; electron microscopy; CRISPR/Cas9 SUMO depletion; site-directed mutagenesis; vesicle tracking; domain deletion mapping The Journal of cell biology High 31076452
2019 Rhes is a critical regulator of mitophagy; Rhes co-immunoprecipitates and co-sediments with mitochondrial and lysosomal proteins; Rhes surrounds globular mitochondria, recruits lysosomes, and degrades mitochondria; Rhes promotes excessive mitophagy via direct interaction with Nix (BNIP3L) through its SUMO E3-ligase domain; Nix depletion abrogates Rhes-mediated mitophagy and cell death; in vivo, systemic 3-NP promotes globular mitochondria and striatal lesion only in WT but not Rhes KO mice. In vivo interactome/density fractionation; Co-IP; live-cell imaging; mitochondrial membrane potential assay; ultrastructural EM; Rhes KO mouse model; Nix depletion Proceedings of the National Academy of Sciences of the United States of America High 31676548
2022 Rhes moves between neurons (D1R-MSNs to D2R-MSNs) in the intact striatum and organotypic brain slices via TNT-like protrusions; mHTT is robustly transported within the striatum and from striatum to cortex, and Rhes deletion diminishes such transport; Rhes restricted to MSNs was also detected in cortical regions. In vivo imaging; organotypic slice preparation; genetic tracing with Rhes KO mice; fluorescence microscopy Science advances High 35319973
2024 RASD2 overexpression in the NAcc activates the DRD2-cAMP-PKA-DARPP-32 signaling pathway and alleviates stress-induced depression-like behaviors; activation of the PrL-NAcc glutamatergic circuit increases DRD2- and RASD2-positive neurons in NAcc; Rasd2 overexpression specifically in DRD2+ PrL-NAcc neurons ameliorates depression-like behaviors. Viral vector-mediated overexpression; DREADD chemogenetics; Drd2-Cre transgenic mice; Western blot; co-immunoprecipitation; behavioral assays Molecular psychiatry Medium 39097664
2024 Histone lactylation (H3K18la) promotes RASD2 transcription in endometriosis; RASD2 in turn increases CTPS1 stability by promoting its SUMOylation and inhibiting its ubiquitination, thereby promoting endometriosis progression. ChIP-qPCR; Co-immunoprecipitation; IP-mass spectrometry; Western blot; in vivo mouse endometriosis model American journal of physiology. Cell physiology Medium 39672102
2026 Rhes directly interacts with Slc4a7 (an intracellular pH sensor/solute carrier) through both its N- and C-terminal domains at the plasma membrane; Rhes modulates intracellular pH via this interaction to facilitate TNT formation; siRNA depletion or pharmacological inhibition of Slc4a7 substantially reduces Rhes-induced TNT formation and mHTT intercellular transfer; Rhes farnesylation (membrane anchoring) is required for Slc4a7 binding and TNT formation; Slc4a7 KO mice show markedly reduced mHTT cell-to-cell transmission in striatum. LC-MS/MS membrane-associated complex proteomics; siRNA knockdown; pharmacological inhibition; domain binding assays; farnesylation inhibitor; Slc4a7 KO mouse model; in vivo mHTT transmission assay Science advances High 41861004

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity. Science (New York, N.Y.) 260 19498170
2013 Rhes, a striatal-selective protein implicated in Huntington disease, binds beclin-1 and activates autophagy. The Journal of biological chemistry 96 24324270
1996 Inhibition of TEM-2 beta-lactamase from Escherichia coli by clavulanic acid: observation of intermediates by electrospray ionization mass spectrometry. Biochemistry 91 8823177
2011 Rhes, a striatal-enriched small G protein, mediates mTOR signaling and L-DOPA-induced dyskinesia. Nature neuroscience 86 22179112
1999 Rhes: A striatal-specific Ras homolog related to Dexras1. Journal of neuroscience research 82 10467249
2004 The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors. Oncogene 80 14724584
2010 Rhes, a physiologic regulator of sumoylation, enhances cross-sumoylation between the basic sumoylation enzymes E1 and Ubc9. The Journal of biological chemistry 68 20424159
2007 The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons. Molecular and cellular neurosciences 60 18035555
2019 Rhes travels from cell to cell and transports Huntington disease protein via TNT-like protrusion. The Journal of cell biology 59 31076452
2001 Thyroid hormone regulation of rhes, a novel Ras homolog gene expressed in the striatum. Brain research. Molecular brain research 56 11597759
2004 Rhes is involved in striatal function. Molecular and cellular biology 55 15199135
2008 RASD2, MYH9, and CACNG2 genes at chromosome 22q12 associated with the subgroup of schizophrenia with non-deficit in sustained attention and executive function. Biological psychiatry 49 18571626
2014 Trihelix transcription factor GT-4 mediates salt tolerance via interaction with TEM2 in Arabidopsis. BMC plant biology 48 25465615
2010 Huntington's disease is a disorder of the corpus striatum: focus on Rhes (Ras homologue enriched in the striatum). Neuropharmacology 47 21044641
2013 Rhes deletion is neuroprotective in the 3-nitropropionic acid model of Huntington's disease. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 23447628
1996 Characterization of an inhibitor-resistant enzyme IRT-2 derived from TEM-2 beta-lactamase produced by Proteus mirabilis strains. The Journal of antimicrobial chemotherapy 44 8877532
2019 Rhes, a striatal-enriched protein, promotes mitophagy via Nix. Proceedings of the National Academy of Sciences of the United States of America 38 31676548
2015 Ectopic expression of the striatal-enriched GTPase Rhes elicits cerebellar degeneration and an ataxia phenotype in Huntington's disease. Neurobiology of disease 37 26048156
2005 Rhes, the Ras homolog enriched in striatum, is reduced under conditions of dopamine supersensitivity. Neuroscience 35 16352400
2015 Rhes influences striatal cAMP/PKA-dependent signaling and synaptic plasticity in a gender-sensitive fashion. Scientific reports 34 26190541
2011 Rhes and AGS1/Dexras1 affect signaling by dopamine D1 receptors through adenylyl cyclase. Journal of neuroscience research 33 21374700
1985 [Distinction between the primary structures of TEM-1 and TEM-2 beta-lactamases]. Annales de l'Institut Pasteur. Microbiologie 33 3901878
2013 Attenuation of Rhes activity significantly delays the appearance of behavioral symptoms in a mouse model of Huntington's disease. PloS one 32 23349722
2016 RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network ("Rhesactome") in the striatum. Science signaling 28 27902448
2015 Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and 'Schizophrenia-Like Behaviors' in Mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 28 26228524
2008 The monomeric G proteins AGS1 and Rhes selectively influence Galphai-dependent signaling to modulate N-type (CaV2.2) calcium channels. American journal of physiology. Cell physiology 27 18815223
2015 Rhes regulates dopamine D2 receptor transmission in striatal cholinergic interneurons. Neurobiology of disease 25 25818655
2012 Striatum specific protein, Rhes regulates AKT pathway. Neuroscience letters 25 22683505
2022 Rhes protein transits from neuron to neuron and facilitates mutant huntingtin spreading in the brain. Science advances 24 35319973
2013 Effects of the Ras homolog Rhes on Akt/protein kinase B and glycogen synthase kinase 3 phosphorylation in striatum. Neuroscience 22 23380502
2018 The Thyroid Hormone-target Gene Rhes a Novel Crossroad for Neurological and Psychiatric Disorders: New Insights from Animal Models. Neuroscience 21 29857029
1987 Oligonucleotide probes for the detection of TEM-1 and TEM-2 beta-lactamase genes and their transposons. Canadian journal of microbiology 21 3032386
2008 The Ras homolog Rhes affects dopamine D1 and D2 receptor-mediated behavior in mice. Neuroreport 20 18845937
2019 Lack of Rhes Increases MDMA-Induced Neuroinflammation and Dopamine Neuron Degeneration: Role of Gender and Age. International journal of molecular sciences 19 30925704
2013 PKA modulates iron trafficking in the striatum via small GTPase, Rhes. Neuroscience 19 23999124
2008 Ontogeny and dopaminergic regulation in brain of Ras homolog enriched in striatum (Rhes). Brain research 19 18929545
2015 Genetic deletion of Rhes or pharmacological blockade of mTORC1 prevent striato-nigral neurons activation in levodopa-induced dyskinesia. Neurobiology of disease 18 26522958
2012 Rhes: a GTP-binding protein integral to striatal physiology and pathology. Cellular and molecular neurobiology 18 22450871
2014 Rhes suppression enhances disease phenotypes in Huntington's disease mice. Journal of Huntington's disease 17 25062765
2013 The role of Rhes, Ras homolog enriched in striatum, in neurodegenerative processes. Experimental cell research 17 23583659
2016 The Small GTP-Binding Protein Rhes Influences Nigrostriatal-Dependent Motor Behavior During Aging. Movement disorders : official journal of the Movement Disorder Society 15 26853527
2014 Small G Proteins Dexras1 and RHES and Their Role in Pathophysiological Processes. International journal of cell biology 15 24817889
2017 Decreased Rhes mRNA levels in the brain of patients with Parkinson's disease and MPTP-treated macaques. PloS one 14 28742811
2020 Rhes Tunnels: A Radical New Way of Communication in the Brain's Striatum? BioEssays : news and reviews in molecular, cellular and developmental biology 13 32236969
2013 Study on lung cancer cells expressing VEGFR2 and the impact on the effect of RHES combined with radiotherapy in the treatment of brain metastases. Clinical lung cancer 13 24374073
2002 Identification of the monomeric G-protein, Rhes, as an efaroxan-regulated protein in the pancreatic beta-cell. British journal of pharmacology 13 11976265
2019 The striatal-enriched protein Rhes is a critical modulator of cocaine-induced molecular and behavioral responses. Scientific reports 12 31653935
2024 Rasd2 regulates depression-like behaviors via DRD2 neurons in the prelimbic cortex afferent to nucleus accumbens core circuit. Molecular psychiatry 11 39097664
2021 Involvement of the Protein Ras Homolog Enriched in the Striatum, Rhes, in Dopaminergic Neurons' Degeneration: Link to Parkinson's Disease. International journal of molecular sciences 11 34070217
2021 Nano-ivabradine averts behavioral anomalies in Huntington's disease rat model via modulating Rhes/m-tor pathway. Progress in neuro-psychopharmacology & biological psychiatry 10 34087391
2010 Mice lacking rhes show altered morphine analgesia, tolerance, and dependence. Neuroscience letters 10 21163334
1986 Lincomycin stimulates synthesis of TEM-2 beta-lactamase by Escherichia coli. Antimicrobial agents and chemotherapy 10 3530127
2022 RASD2 promotes the development and metastasis of uveal melanoma via enhancing glycolysis. Biochemical and biophysical research communications 9 35461072
2022 Striatal Induction and Spread of the Huntington's Disease Protein: A Novel Rhes Route. Journal of Huntington's disease 9 35871361
2009 The cationic region of Rhes mediates its interactions with specific Gbeta subunits. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 9 19255495
2021 Patterns of neuronal Rhes as a novel hallmark of tauopathies. Acta neuropathologica 8 33677647
2018 Rhes Counteracts Dopamine Neuron Degeneration and Neuroinflammation Depending on Gender and Age. Frontiers in aging neuroscience 8 29904346
2011 Exploration of sex differences in Rhes effects in dopamine mediated behaviors. Neuropsychiatric disease and treatment 8 22128255
2006 Analysis of Rhes activation state and effector function. Methods in enzymology 8 16757351
2005 Monomeric G-protein, Rhes, is not an imidazoline-regulated protein in pancreatic beta-cells. Biochemical and biophysical research communications 8 16277977
2023 Rasd2 Mediates Acute Fasting-Induced Antidepressant-Like Effects via Dopamine D2 Receptor Activation in Ovariectomized Mice. The international journal of neuropsychopharmacology 7 36566472
2021 Global Rhes knockout in the Q175 Huntington's disease mouse model. PloS one 6 34648564
2018 MicroRNA-101 inhibits the expression of Rhes, a striatal-enriched small G-protein, at the post-transcriptional level in vitro. BMC research notes 5 30064488
2022 Construction and Evaluation of Traceable rhES-QDs-M-MS Protein Delivery System: Sustained-Release Properties, Targeted Effect, and Antitumor Activity. AAPS PharmSciTech 4 35896916
2006 Rhes expression in pancreatic beta-cells is regulated by efaroxan in a calcium-dependent process. Biochemical and biophysical research communications 3 16945334
2025 Modulation of RASD2 by miRNA-485-5p Drives Thyroid Cancer Progression and Metastasis. The Kaohsiung journal of medical sciences 2 40289764
2024 Curbing Rhes Actions: Mechanism-based Molecular Target for Huntington's Disease and Tauopathies. CNS & neurological disorders drug targets 2 36959146
2024 Histone lactylation-mediated overexpression of RASD2 promotes endometriosis progression via upregulating the SUMOylation of CTPS1. American journal of physiology. Cell physiology 2 39672102
1994 Val-237 for Ala substitution in the TEM-2 beta-lactamase dramatically alters the catalytic efficiencies towards carbenicillin and ticarcillin. FEMS microbiology letters 2 8200509
2026 Rasd2 Knockout Exaggerates the Hearing Loss Phenotype of Tsc1-Deficient Mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41537759
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