Affinage

RASD2

GTP-binding protein Rhes · UniProt Q96D21

Length
266 aa
Mass
30.4 kDa
Annotated
2026-06-10
73 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/8 claims corpus-supported (75%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RASD2 (Rhes) is a striatum-enriched, farnesylated small GTPase that serves as a hub coupling G-protein signaling, protein SUMOylation, and selective neuronal vulnerability in Huntington's disease (PMID:10467249, PMID:19498170, PMID:26048156). It binds GTP and is constitutively partly GTP-loaded, anchoring to the plasma membrane through farnesylation, and modulates GPCR signaling by uncoupling receptors from heterotrimeric G proteins and engaging Gαi and Gβ subunits to attenuate cAMP/PKA output and tonic Gβγ signaling at CaV2.2 channels (PMID:14724584, PMID:19255495, PMID:21374700, PMID:18815223). Beyond G-protein modulation, Rhes activates PI3K/AKT through the p85 regulatory subunit and binds and activates mTORC1, a function linked in vivo to L-DOPA-induced dyskinesia (PMID:22179112, PMID:22683505). Rhes functions as a SUMO E3 ligase that binds SUMO E1 and the E2 Ubc9 and is the principal regulator of striatal SUMOylation (PMID:20424159). Through this activity it binds preferentially to mutant huntingtin (mHtt), promotes its SUMOylation and disaggregation, and confers cytotoxicity, and genetic loss or ectopic re-expression of Rhes establishes it as the causative factor for the striatal selectivity of mHtt toxicity in vivo (PMID:19498170, PMID:23447628, PMID:26048156). Rhes also controls catabolic pathways, binding Beclin-1 to activate mTOR-independent autophagy and interacting with Nix (BNIP3L) through its SUMO E3-like domain to drive mitophagy and cell death (PMID:24324270, PMID:31676548). A distinctive activity is the biogenesis of tunneling-nanotube-like "Rhes tunnels" that transport mHtt between neurons in a SUMOylation- and farnesylation-dependent manner, requiring a membrane-associated complex with the pH sensor Slc4a7 and validated by intercellular mHtt transfer in intact striatum (PMID:31076452, PMID:35319973, PMID:41861004). Outside the nervous system, RASD2 promotes target-protein SUMOylation (CTPS1 in endometriosis) and activates RAF1-Ser338/MAPK signaling in renal carcinoma (PMID:39672102, PMID:42226617).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 Medium

    Establishing that Rhes is a genuine GTP-binding protein defined a new membrane-targeted Ras subfamily and set the molecular starting point for all downstream signaling work.

    Evidence GTP-binding assay with bacterially expressed protein and sequence analysis

    PMID:10467249

    Open questions at the time
    • No GTPase regulator (GEF/GAP) identified
    • Intrinsic hydrolysis rate not quantified
  2. 2004 Medium

    Biochemical dissection showed Rhes is constitutively partly GTP-bound and acts on PI3K and GPCR-cAMP signaling rather than the classical Ras-ERK/transformation axis, distinguishing it functionally from oncogenic Ras.

    Evidence GTP-loading, PI3K activation, cAMP accumulation assays and membrane fractionation in PC12/fibroblasts; plus in vivo knockout behavioral phenotyping

    PMID:14724584 PMID:15199135

    Open questions at the time
    • Mechanism of constitutive GTP loading not resolved
    • Receptor-uncoupling stoichiometry undefined
  3. 2007 Medium

    Knockout studies tied Rhes to dopaminergic signaling, showing it raises Golf levels and is required for D2-associated dopamine-mediated GTP binding, embedding it in striatal cAMP/PKA control.

    Evidence Rhes null mice with cAMP/PKA and GTP-binding measurements plus dopaminergic pharmacological challenges

    PMID:18035555

    Open questions at the time
    • Direct Rhes-Golf interaction not shown
    • Cell-type resolution within striatum limited
  4. 2009 High

    Discovery that Rhes binds preferentially to mutant huntingtin and induces its SUMOylation with disaggregation and cytotoxicity provided the first molecular link explaining striatal selectivity in Huntington's disease.

    Evidence Co-immunoprecipitation, sumoylation and cell-viability assays in cultured cells; yeast two-hybrid mapping of Gβ-subunit binding

    PMID:19255495 PMID:19498170

    Open questions at the time
    • SUMO acceptor sites on mHtt not all mapped
    • Link between disaggregation and toxicity mechanistically incomplete
  5. 2010 High

    Reconstitution established Rhes as a bona fide SUMO E3 ligase that binds E1 and Ubc9 and is the dominant regulator of striatal SUMOylation, defining the enzymatic basis for its mHtt action.

    Evidence In vitro sumoylation and direct E1/Ubc9 binding assays plus Rhes KO striatum analysis and mass spectrometry

    PMID:20424159

    Open questions at the time
    • Full striatal SUMO substrate repertoire incomplete
    • How GTPase state gates E3 activity unknown
  6. 2011 High

    Identification of Rhes as a direct activator of striatal mTORC1 and a modulator of Gαi/PI3K-coupled receptor signaling connected its biochemistry to L-DOPA-induced dyskinesia and cholinergic excitability.

    Evidence Co-IP with mTOR and Gαi pull-downs, cAMP/PTX-sensitivity assays, and Rhes-/- mice with 6-OHDA/L-DOPA paradigms

    PMID:21374700 PMID:22179112

    Open questions at the time
    • Direct vs indirect mTORC1 activation mechanism not fully resolved
    • Relationship between mTOR activation and SUMO ligase activity unclear
  7. 2012 Medium

    Mapping the Rhes-p85 interaction to the unique C-terminal tail and showing growth-factor-enhanced AKT membrane translocation positioned Rhes as a striatal PI3K/AKT regulator.

    Evidence Co-IP with deletion-mutant domain mapping and AKT translocation assays

    PMID:22683505

    Open questions at the time
    • Single-lab, single-study interaction
    • In vivo relevance of p85 binding not tested
  8. 2013 Medium

    A cluster of studies expanded Rhes function to catabolic and signaling control: Beclin-1-dependent mTOR-independent autophagy, β-arrestin2/PP2A-mediated Akt dephosphorylation, PAP7/DMT1 iron uptake regulated by PKA phosphorylation at Ser239, and protection in the 3-NP striatal HD model.

    Evidence Co-IP of Beclin-1/Bcl-2 and β-arrestin/PP2A, autophagy flux assays, iron-uptake and mutagenesis assays, and Rhes KO mice in the 3-NP toxicity model

    PMID:23380502 PMID:23447628 PMID:23999124 PMID:24324270

    Open questions at the time
    • How one protein balances autophagy, Akt, and iron functions in vivo unclear
    • Tissue/cell context dependence of each interaction unresolved
  9. 2015 High

    Gain-of-function ectopic expression with loss-of-function striatal rescue formally established Rhes as the causative determinant of selective mHtt toxicity, and electrophysiology localized PI3K-dependent D2R modulation to cholinergic interneurons.

    Evidence AAV ectopic Rhes expression and striatal re-introduction in HD mouse models; patch-clamp recordings with Cav2.2/PI3K pharmacology in Rhes KO ChIs

    PMID:25818655 PMID:26048156

    Open questions at the time
    • Molecular event converting Rhes presence into selective vulnerability not pinpointed
    • Generalizability beyond modeled HD alleles untested
  10. 2016 Medium

    Defining the striatal 'Rhesactome' and the RasGRP1 stabilizing interaction revealed how Rhes protein levels, synaptic localization, and interactome are dynamically regulated, including by amphetamine.

    Evidence Co-IP, protein-stabilization Westerns, LC-MS/MS striatal proteomics, and Rhes+/- / Rasgrp1 KO behavioral epistasis

    PMID:27902448

    Open questions at the time
    • Functional roles of most Rhesactome partners (PDE2A, LRRC7, DLG2) untested
    • Whether RasGRP1 acts as a true GEF for Rhes unresolved
  11. 2019 High

    Discovery of Rhes-induced tunneling-nanotube biogenesis and Nix-dependent mitophagy revealed two new membrane-based functions—intercellular mHtt transport and selective mitochondrial degradation—both requiring the SUMO E3-like domain and farnesylation.

    Evidence Live-cell imaging, EM, CRISPR SUMO depletion and domain mutagenesis for TNTs; Co-IP, fractionation, mitochondrial potential and Nix-depletion assays plus 3-NP KO mice for mitophagy

    PMID:31076452 PMID:31676548

    Open questions at the time
    • Structural basis of TNT membrane deformation unknown
    • How SUMO ligase activity mechanistically links to both processes unresolved
  12. 2022 High

    Demonstrating Rhes-driven mHtt transport between MSN subtypes and from striatum to cortex in intact and organotypic brain established intercellular spread as an in vivo mechanism of HD pathology propagation.

    Evidence Organotypic slice imaging and in vivo AAV tracking with Rhes KO validation

    PMID:35319973

    Open questions at the time
    • Quantitative contribution of spread to disease progression undefined
    • Directionality determinants of transport unclear
  13. 2026 High

    Identification of the membrane-associated Rhes-Slc4a7 complex provided the molecular machinery for TNT formation, showing pH modulation and Rhes farnesylation—but not Slc4a7 transport activity—drive intercellular mHtt transfer in vivo.

    Evidence LC-MS/MS of membrane Rhes complexes, Co-IP, domain mapping, Slc4a7 siRNA/pharmacology, pH measurements, farnesylation mutants, and Slc4a7 KO mice with in vivo mHTT transmission

    PMID:41861004

    Open questions at the time
    • How local pH change physically promotes TNT membrane biogenesis unresolved
    • Whether other carriers substitute for Slc4a7 untested
  14. 2024 Medium

    Studies outside the striatal HD context showed RASD2 modulates NAcc DRD2-cAMP-PKA-DARPP-32 circuitry to influence depression-like behavior and acts as a SUMOylation-promoting oncogenic factor (CTPS1 stabilization in endometriosis).

    Evidence AAV/Drd2-cre circuit manipulation with DREADDs and pathway Westerns; ChIP, IP-MS, SUMOylation/ubiquitination assays and mouse models in endometriosis

    PMID:39097664 PMID:39672102

    Open questions at the time
    • Mechanistic overlap between neuronal and tumor SUMO functions untested
    • Whether GTPase/farnesylation are required in these contexts unknown
  15. 2026 Medium

    Extending RASD2 into cancer signaling, it was shown to bind RAF1 and enhance Ser338 phosphorylation to activate P38/ERK-MAPK in clear cell renal carcinoma.

    Evidence Co-IP, LC-MS/MS, phospho-RAF1 Westerns, RAF1 inhibitor and xenograft experiments

    PMID:42226617

    Open questions at the time
    • Reconciliation with earlier finding that Rhes does not stimulate ERK/transformation unresolved
    • Direct vs scaffold role in RAF1 activation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Rhes's GTP-loading state, farnesylation, and SUMO E3 activity are integrated to select among its many effectors (G proteins, mTORC1, autophagy, mitophagy, TNT transport) in a given cell remains unresolved.
  • No structural model coordinating GTPase and SUMO-ligase domains
  • Upstream signals switching Rhes between functions unknown
  • Endogenous GEF/GAP regulation of Rhes not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 4 GO:0098772 molecular function regulator activity 4 GO:0003924 GTPase activity 2 GO:0060089 molecular transducer activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 3 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5 R-HSA-112316 Neuronal System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-9612973 Autophagy 2
Partners
BECN1BNIP3LHTTMTORRAF1RASGRP1SLC4A7UBE2I
Complex memberships
Rhes-Slc4a7 membrane complexβ-arrestin2/PP2A/Akt complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Bacterially expressed Rhes binds GTP, demonstrating GTPase functionality. Rhes is targeted to the plasma membrane by farnesylation and shares ~62% identity with Dexras1, defining a novel Ras subfamily with extended C-termini. GTP-binding assay with bacterially expressed protein; sequence analysis Journal of neuroscience research Medium 10467249
2004 Rhes is targeted to the plasma membrane via farnesylation. Approximately 30% of native Rhes is constitutively GTP-bound, and this proportion is not altered by typical Ras nucleotide exchange factors. Rhes binds to and activates PI3K, and impairs cAMP/PKA pathway activation by G protein-coupled receptors (TSH receptor, β2-adrenergic receptor) by uncoupling receptor from its cognate heterotrimeric G protein complex. Rhes does not stimulate the ERK pathway and is not transforming in fibroblasts. GTP-loading assays, PI3K activation assay, cAMP accumulation assays, cell-based signaling in PC12 cells, membrane fractionation Oncogene Medium 14724584
2004 Rhes knockout mice display behavioral abnormalities (gender-dependent increased anxiety, motor coordination deficits) without learning/memory impairment, establishing a role for Rhes in striatal motor function in vivo. Homologous recombination knockout, behavioral testing (rotarod, anxiety assays) Molecular and cellular biology Medium 15199135
2007 Rhes modulates cAMP/PKA signaling in both striatopallidal and striatonigral projection neurons by increasing Golf protein levels. Rhes is required for correct dopamine-mediated GTP binding associated mainly with D2 receptor stimulation. Rhes null mutant mice, cAMP/PKA signaling measurements, GTP binding assays, dopaminergic agonist/antagonist behavioral challenges Molecular and cellular neurosciences Medium 18035555
2009 Rhes binds physically and preferentially to mutant huntingtin (mHtt) over wild-type Htt. Rhes induces sumoylation of mHtt, which disaggregates mHtt inclusions and leads to cytotoxicity in cultured cells. Co-immunoprecipitation, sumoylation assays, cell viability assays, transfection in cultured cells Science High 19498170
2009 Rhes binds selectively to Gbeta1, Gbeta2, and Gbeta3 subunits of heterotrimeric G proteins via its cationic region. Rhes-AGS1 chimera studies showed that different cationic regions of Rhes and AGS1 determine their distinct Gbeta-subunit binding specificities. Yeast two-hybrid assays, Rhes-AGS1 chimera constructs Cellular physiology and biochemistry Medium 19255495
2010 Rhes acts as a SUMO E3 ligase and is a physiologic regulator of sumoylation in the striatum; sumoylation is markedly reduced in the corpus striatum of Rhes-deleted mice. Rhes binds directly to both SUMO E1 and Ubc9 (E2), enhancing cross-sumoylation (intermolecular SUMO transfer between E1 and Ubc9) as well as thioester transfer from E1 to Ubc9. In vitro sumoylation assays, direct binding assays between Rhes and E1/Ubc9, Rhes knockout mouse striatum analysis, mass spectrometry The Journal of biological chemistry High 20424159
2011 Rhes binds to and activates mTOR (mTORC1) in the striatum. Rhes-/- mice show reduced striatal mTOR signaling and diminished L-DOPA-induced dyskinesia while maintaining motor improvement on L-DOPA, demonstrating Rhes is a key regulator of striatal mTOR activation relevant to dyskinesia. Co-immunoprecipitation, mTOR signaling assays, Rhes-/- mice with 6-OHDA lesion and L-DOPA treatment, behavioral assessment Nature neuroscience High 22179112
2011 Rhes decreases dopamine D1 receptor agonist-stimulated cAMP accumulation in a pertussis toxin-sensitive manner, suggesting interaction with Gαi. Rhes associates with GTP-bound Gαi in pull-down assays but does not interact with the D1 receptor directly and has no effect on D2 receptor-mediated inhibition of cAMP. cAMP accumulation assays, pertussis toxin treatment, Gαi pull-down assays, transfection in cell lines Journal of neuroscience research Medium 21374700
2012 Rhes interacts with p85, the regulatory subunit of PI3K; this interaction involves the C-terminal unique tail region of Rhes and is enhanced upon growth factor treatment. The Rhes-p85 complex facilitates AKT translocation to the membrane, indicating Rhes is a striatal regulator of the AKT pathway. Co-immunoprecipitation, domain-mapping with deletion mutants, AKT membrane translocation assays Neuroscience letters Medium 22683505
2013 Rhes binds Beclin-1 and activates autophagy in a mTOR-independent manner. Rhes decreases the inhibitory interaction between Beclin-1 and Bcl-2 independently of JNK-1 signaling. Rhes overexpression activates autophagy; deletion decreases autophagy. Co-expression of mHtt blocks Rhes-induced autophagy activation. Co-immunoprecipitation of Rhes-Beclin-1 and Beclin-1/Bcl-2, autophagy flux assays, Rhes overexpression and knockdown in PC12 cells The Journal of biological chemistry Medium 24324270
2013 Rhes-/- mice are dramatically protected from neurotoxicity and motor dysfunction in the 3-nitropropionic acid (3-NP) striatal model of Huntington's disease, placing Rhes as a critical mediator of striatal selective vulnerability. Rhes knockout mice, 3-NP systemic injection, behavioral and neuropathological assessment The Journal of neuroscience Medium 23447628
2013 Rhes co-immunoprecipitates with β-arrestins and is necessary for Akt dephosphorylation by the striatal multi-protein complex (β-arrestin2/PP2A/Akt). In Rhes-/- mice, basal Akt and GSK3β phosphorylation are increased and apomorphine treatment causes increased Akt/GSK3 phosphorylation, mimicking a lithium-treated phenotype. Co-immunoprecipitation of Rhes with β-arrestins and PP2A-C, phospho-Akt/GSK3β Western blotting in Rhes KO mice, pharmacological challenges Neuroscience Medium 23380502
2013 Rhes participates in iron uptake via divalent metal transporter 1 (DMT1) by interacting with PAP7 (peripheral benzodiazepine receptor-associated protein 7), similar to Dexras1. Unlike Dexras1, Rhes is not S-nitrosylated by NO; instead, it is phosphorylated by PKA at Ser-239. Phosphomimetic (S239D) and constitutively active (A173V) Rhes mutants show increased iron uptake. Co-immunoprecipitation, iron uptake assays, site-directed mutagenesis, S-nitrosylation and phosphorylation assays Neuroscience Medium 23999124
2015 Ectopic expression of Rhes in the cerebellum of HD mice (N171-82Q) during the asymptomatic period causes exacerbated motor deficits with ataxia features, cerebellar Purkinje neuron loss, caspase-3 activation, and enhanced soluble mHtt forms. Re-introducing Rhes into the striatum of Rhes-/-/Hdh150Q/150Q knock-in mice restores progressive rotarod deficits, establishing Rhes as the causative factor for selective mHtt toxicity in vivo. Adeno-associated virus (AAV)-mediated ectopic Rhes expression in cerebellum, behavioral testing, immunohistochemistry, Western blotting Neurobiology of disease High 26048156
2015 Rhes modulates D2 receptor (D2R) signaling specifically in striatal cholinergic interneurons (ChIs); Rhes KO mice show aberrant excitatory rather than expected inhibitory D2R responses in ChIs. This abnormal D2R response requires Cav2.2 calcium channels and is rescued by selective PI3K inhibition, linking Rhes to PI3K/Akt modulation of cholinergic excitability. Electrophysiology (patch clamp) in ChIs from Rhes KO mice, pharmacological isolation, intrapipette BAPTA and GDP-β-S, Cav2.2 channel blockade, PI3K inhibition Neurobiology of disease Medium 25818655
2016 RasGRP1 (a guanine nucleotide exchange factor) interacts with Rhes, stabilizes Rhes protein, and increases its synaptic accumulation in the striatum. Partial Rhes deficiency (Rhes+/-) enhances the locomotor response to amphetamine, which is attenuated by coincident RasGRP1 depletion. Proteomic analysis identified the 'Rhesactome' — a set of Rhes-interacting proteins in the striatum that includes PDE2A, LRRC7, and DLG2, and whose composition is modulated by RasGRP1 and amphetamine. Co-immunoprecipitation, Western blotting (protein stabilization), Rhes+/- and Rasgrp1 KO mouse behavioral studies, LC-MS/MS proteomics of striatal lysates Science signaling Medium 27902448
2019 Rhes induces the biogenesis of tunneling nanotube (TNT)-like cellular protrusions ('Rhes tunnels') through which it moves between cells and transports mHtt (poly-Q expanded mutant huntingtin), but not normal HTT, mTOR, or wtTau. TNT formation requires Rhes's Ser33, C-terminal CAAX motif, and SUMO E3-like domain. Rhes tunnels carry Rab5a/Lyso20-positive vesicles. SUMOylation-defective mHtt, Rhes C263S (cannot SUMOylate mHtt), or CRISPR/Cas9 depletion of SUMO isoforms diminishes Rhes-mediated mHtt transport. Live-cell imaging, electron microscopy, CRISPR/Cas9 SUMO depletion, site-directed mutagenesis (Rhes C263S, S33A, CAAX deletion), cargo transport assays 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 in vivo. Rhes surrounds globular mitochondria, recruits lysosomes, and degrades mitochondria in live-cell imaging. Rhes disrupts mitochondrial membrane potential and promotes mitophagy and cell death via interaction with Nix (BNIP3L) through its SUMO E3-ligase domain. Nix depletion abrogates Rhes-mediated mitophagy. Rhes KO striatum is protected from 3-NP-induced mitophagosomes and striatal lesion in vivo. Co-immunoprecipitation, density fractionation, live-cell imaging, mitochondrial membrane potential assays, Nix depletion, Rhes KO mice with 3-NP injection and ultrastructural analysis Proceedings of the National Academy of Sciences of the United States of America High 31676548
2022 Rhes transports between D1R-MSNs and D2R-MSNs of intact striatum and organotypic brain slices via TNT-like protrusions. mHtt is robustly transported within the striatum and from striatum to cortical areas in the brain; Rhes deletion diminishes this transport. Rhes restricted to MSNs also moves to cortical regions in vivo. Organotypic brain slice imaging, in vivo Rhes-tagged AAV injections, Rhes KO mice, fluorescence tracking Science advances High 35319973
2008 Rhes and AGS1 trigger nearly identical modulation of N-type Ca2+ channels (CaV2.2) by selectively altering Gαi-dependent signaling: both reduce basal CaV2.2 current densities, trigger tonic voltage-dependent inhibition, and attenuate agonist-initiated Gαi-coupled receptor inhibition. These effects are blocked by pertussis toxin or Gβγ-sequestering peptide, indicating Rhes mediates tonic Gβγ signaling through PTX-sensitive G proteins. Whole-cell patch-clamp recording in HEK293 cells expressing CaV2.2, pertussis toxin treatment, Gβγ sequestration, comparison with multiple other Ras-family members American journal of physiology. Cell physiology Medium 18815223
2024 RASD2 overexpression in the nucleus accumbens core (NAcc) alleviates stress-induced depression-like behaviors and activates the DRD2-cAMP-PKA-DARPP-32 signaling pathway. Rasd2 overexpression in DRD2-expressing PrL-NAcc neurons (using Drd2-cre mice) ameliorates depression-like behaviors, placing RASD2 as a modulator of DRD2-dependent signaling in NAcc circuits. AAV-mediated overexpression, Drd2-cre transgenic mice, DREADD chemogenetics, retrograde tracing, Western blotting for cAMP-PKA-DARPP-32 pathway Molecular psychiatry Medium 39097664
2024 Histone lactylation (H3K18la) promotes transcription of RASD2 in endometriosis. RASD2 increases the stability of CTPS1 by promoting CTPS1 SUMOylation and inhibiting its ubiquitination, thereby promoting endometriosis progression. This was established via the RASD2/CTPS1 axis. ChIP-qPCR, Co-immunoprecipitation, IP-MS, SUMOylation/ubiquitination assays, cell proliferation/invasion assays, endometriosis mouse models 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. This Rhes-Slc4a7 complex is membrane-associated and modulates intracellular pH to facilitate TNT formation and mHTT intercellular transfer. Farnesylation of Rhes is required for its binding to Slc4a7 and for TNT formation. Slc4a7 KO mice show reduced cell-to-cell mHTT transmission in the striatum in vivo. The transporter activity of Slc4a7 is not required for this interaction. LC-MS/MS of membrane-associated Rhes complexes, Co-immunoprecipitation, siRNA depletion of Slc4a7, pharmacological inhibition of Slc4a7, intracellular pH measurements, Rhes farnesylation mutants, Slc4a7 KO mice with in vivo mHTT transmission assay Science advances High 41861004
2026 RASD2 binds RAF1 and enhances RAF1 phosphorylation at Ser338, thereby activating the P38/ERK-MAPK pathway in clear cell renal cell carcinoma cells. This interaction was identified by Co-immunoprecipitation and LC-MS/MS. Co-immunoprecipitation, LC-MS/MS proteomics, phospho-RAF1 (Ser338) Western blotting, RAF1 inhibitor (BAY43-9006) experiments, xenograft models Cancer science Medium 42226617

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 92 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 69 20424159
2019 Rhes travels from cell to cell and transports Huntington disease protein via TNT-like protrusion. The Journal of cell biology 60 31076452
2007 The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons. Molecular and cellular neurosciences 60 18035555
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
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 39 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
2022 Rhes protein transits from neuron to neuron and facilitates mutant huntingtin spreading in the brain. Science advances 25 35319973
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
2018 The Thyroid Hormone-target Gene Rhes a Novel Crossroad for Neurological and Psychiatric Disorders: New Insights from Animal Models. Neuroscience 22 29857029
2013 Effects of the Ras homolog Rhes on Akt/protein kinase B and glycogen synthase kinase 3 phosphorylation in striatum. Neuroscience 22 23380502
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
2014 Small G Proteins Dexras1 and RHES and Their Role in Pathophysiological Processes. International journal of cell biology 16 24817889
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
2024 Rasd2 regulates depression-like behaviors via DRD2 neurons in the prelimbic cortex afferent to nucleus accumbens core circuit. Molecular psychiatry 14 39097664
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
2022 Striatal Induction and Spread of the Huntington's Disease Protein: A Novel Rhes Route. Journal of Huntington's disease 11 35871361
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
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
2024 Histone lactylation-mediated overexpression of RASD2 promotes endometriosis progression via upregulating the SUMOylation of CTPS1. American journal of physiology. Cell physiology 3 39672102
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
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
2026 Membrane-associated Rhes-Slc4a7 complex orchestrates tunneling nanotube formation and mutant Huntingtin spread. Science advances 0 41861004
2026 RASD2 Drives Renal Clear Cell Carcinoma Progression via RAF1 (Ser338) Phosphorylation. Cancer science 0 42226617
2023 Rhes depletion promotes striatal accumulation and aggregation of mutant huntingtin in a presymptomatic HD mouse model. Frontiers in aging neuroscience 0 37637962
1993 [Oligonucleotide probes for the characterization of TEM-1 and TEM-2 beta lactamases in Salmonella strains]. Enfermedades infecciosas y microbiologia clinica 0 8324021

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