Affinage

RGS3

Regulator of G-protein signaling 3 · UniProt P49796

Length
1198 aa
Mass
132.3 kDa
Annotated
2026-06-10
49 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RGS3 is a multi-isoform regulator of G protein signaling that terminates GPCR cascades by acting as a GTPase-activating protein (GAP) for Gαi (excluding Gαz) and Gαq, accelerating GTP hydrolysis, while sparing Gαs and Gα12 (PMID:10999941). Beyond its catalytic GAP function, RGS3 antagonizes Gαq-driven PLC-β activation as an effector antagonist (PMID:10999941) and independently binds Gβ1γ2 through regions outside the RGS domain to block Gβγ-mediated inositol phosphate, Akt, and MAPK signaling (PMID:11294858). RGS3 controls signaling at endogenous receptors, negatively modulating Gq/11-coupled muscarinic m3 responses in vascular smooth muscle (PMID:12006602) and Gq-coupled GnRH receptor desensitization that suppresses LH secretion (PMID:9003025, PMID:11716781). Its activity is spatially and post-translationally tuned: it translocates from cytosol to plasma membrane upon G protein activation via both RGS and N-terminal domains (PMID:9858594), undergoes agonist-dependent palmitoylation (PMID:11897687), and is sequestered by 14-3-3 binding at Ser264, which both sterically occludes and conformationally distorts the Gα-interaction surface of the RGS domain (PMID:11985497, PMID:20347994, PMID:22027839). In sensory neurons, an EF-hand-containing isoform binds calcium entering through voltage-gated channels to drive rapid, calcium-dependent desensitization of Go-mediated N-type Ca2+ channel inhibition (PMID:12771384). RGS3 also operates outside canonical G protein biology: it binds Smad2/3/4 to block Smad heteromerization and inhibit TGF-β transcription (PMID:18287247), and through its PDZ-RGS3 isoform links phospho-ephrin-B reverse signaling to neural progenitor self-renewal (PMID:20629178, PMID:15096211) and enhances canonical Wnt/β-catenin signaling by binding and inhibiting GSK3β (PMID:22859293). Most unexpectedly, RGS3 directly enhances GTPase activity of wild-type and mutant KRAS, including KRASG12C, promoting its inactive GDP-bound state (PMID:34618566).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 Medium

    Established the founding question of which G protein classes RGS3 acts on, showing isoform-specific suppression of Gq, Gs, and Gi signaling and that the C-terminal RGS domain carries the inhibitory function.

    Evidence Transfection of RGS3/RGS3T into BHK and COS-1 cells with IP, cAMP, ERK, and IP3 readouts plus GST pulldown of Gqα

    PMID:9003025 PMID:9182581

    Open questions at the time
    • Cellular assays did not distinguish GAP catalysis from effector antagonism
    • No in vitro GTPase reconstitution at this stage
  2. 1999 High

    Resolved how RGS3 reaches its target, demonstrating activation-dependent cytosol-to-membrane translocation driven by both the RGS and N-terminal domains.

    Evidence Co-IP with AlF4-activated Gα subunits, subcellular fractionation, immunofluorescence, and deletion mutants

    PMID:9858594

    Open questions at the time
    • Calcium-dependent N-terminal translocation mechanism not molecularly defined here
    • Endogenous translocation dynamics not measured
  3. 2000 High

    Defined RGS3 biochemically as a bona fide GAP for Gαi/Gαq with active-site residues homologous to RGS4, and uncovered a distinct Gαq effector-antagonist activity.

    Evidence In vitro GTPase assays, active-site mutagenesis, CREB reporter, and IP production assays

    PMID:10999941

    Open questions at the time
    • Structural basis of effector antagonism not resolved
    • Selectivity rules against Gαz/Gαs/Gα12 not mechanistically explained
  4. 2001 High

    Extended RGS3 function beyond GAP activity by showing direct Gβγ binding and inhibition of Gβγ effector signaling through domains outside the RGS module.

    Evidence Co-expression with Gβ1γ2 in COS-7/HEK293, deletion mapping, in vitro PLC-β assay, and Akt/MAPK readouts

    PMID:11294858

    Open questions at the time
    • Structure of the RGS3-Gβγ complex unknown
    • Physiological contribution of Gβγ inhibition versus GAP activity not dissected
  5. 2002 High

    Identified post-translational and regulatory control of RGS3 — 14-3-3 sequestration at Ser264 and agonist-dependent palmitoylation — and confirmed non-redundant control of endogenous Gq/11 muscarinic signaling.

    Evidence Yeast two-hybrid, in vitro binding, co-IP, S264A mutagenesis, palmitate incorporation assays, and ribozyme knockdown in vascular smooth muscle

    PMID:11897687 PMID:11985497 PMID:12006602

    Open questions at the time
    • Kinase responsible for Ser264 phosphorylation not identified
    • Palmitoylation site and enzyme not mapped
    • Functional interplay between palmitoylation and 14-3-3 sequestration unresolved
  6. 2003 High

    Revealed a calcium-sensing function: an EF-hand isoform of RGS3 binds calcium entering through voltage-gated channels to mediate rapid feedback desensitization of Go signaling in neurons.

    Evidence Retroviral isoform/EF-hand-deletion expression in DRG neurons, electrophysiology of N-type Ca2+ channels, and gel-shift calcium binding

    PMID:12771384

    Open questions at the time
    • Structural detail of EF-hand calcium coordination not determined
    • Whether EF-hand isoform contributes to other GPCR pathways unknown
  7. 2004 Medium

    Mechanistically detailed PDZ-RGS3 recruitment to ephrin-B reverse signaling, showing a single ephrin-B2 phosphotyrosine enables simultaneous Grb4 and PDZ-RGS3 binding.

    Evidence NMR HSQC binding experiments, phosphopeptide binding assays, and three-component complex reconstitution

    PMID:15096211

    Open questions at the time
    • Downstream signaling output of the ternary complex not defined here
    • In vivo relevance established only later
  8. 2006 Medium

    Refined isoform/domain logic in channel modulation, showing the short RGS3 isoform regulates GIRK channels by collision rather than precoupling and that the N-terminal domain restricts cytoplasmic localization.

    Evidence Co-IP and electrophysiology of GPCR-Kir3/Cav2.3 complexes in CHO-K1/HEK293 with chimeric and deletion constructs and EGFP imaging

    PMID:16855219 PMID:16973624

    Open questions at the time
    • Quantitative kinetic comparison limited to specific channel/receptor pairs
    • Structural basis for collision versus precoupling not established
  9. 2008 Medium

    Connected RGS3 to TGF-β signaling, demonstrating a non-RGS region binds the Smad MH2 domain to block Smad3-Smad4 heteromerization and inhibit transcription independent of receptor phosphorylation.

    Evidence Co-IP, domain mapping, Smad reporter and heteromerization assays, and myofibroblast differentiation assay

    PMID:18287247

    Open questions at the time
    • Single-lab finding without reciprocal in vivo validation
    • Reconciliation with later report of RGS3 enhancing SMAD2/3 phosphorylation unaddressed
  10. 2010 High

    Provided structural mechanism for 14-3-3 inhibition and an in vivo role for PDZ-RGS3, solving the RGS domain crystal structure and showing 14-3-3 binding distorts the Gα-interaction surface, while PDZ-RGS3 knockout phenocopies ephrin-B1 loss in cortical neurogenesis.

    Evidence X-ray crystallography at 2.3 Å, time-resolved tryptophan fluorescence with single-Trp mutants, and PDZ-RGS3 knockout mouse neurogenesis analysis

    PMID:20347994 PMID:20629178

    Open questions at the time
    • Full-length RGS3 structure not solved
    • Molecular signaling linking PDZ-RGS3 to progenitor cell cycle not fully defined
  11. 2011 High

    Completed the structural model of 14-3-3 regulation, showing the RGS domain docks on the outer surface of the 14-3-3ζ dimer to both occlude and conformationally impair Gα binding.

    Evidence SAXS solution structure, H/D exchange kinetics, and FRET

    PMID:22027839

    Open questions at the time
    • Atomic-resolution structure of the complex not obtained
    • Cellular stoichiometry of 14-3-3-RGS3 regulation unmeasured
  12. 2012 Medium

    Linked PDZ-RGS3 to canonical Wnt signaling and EMT, showing Wnt-induced PDZ-RGS3 binds and inhibits GSK3β to stabilize β-catenin and promote Snail1-driven EMT.

    Evidence Co-IP, GSK3β kinase activity assay, β-catenin reporter, Wnt3a stimulation, and EMT analysis

    PMID:22859293

    Open questions at the time
    • Single-lab study without in vivo confirmation
    • Mechanism of GSK3β inhibition (direct versus complex-mediated) not resolved
  13. 2013 High

    Demonstrated a non-redundant in vivo immune function, with RGS-domain deletion increasing T cell accumulation in lung and altering migration, establishing RGS3's GAP function in restricting T cell trafficking.

    Evidence RGS3ΔRGS knock-in mice in an asthma model, T cell enumeration, and in vitro migration with RGS3-knockdown thymoma cells

    PMID:24077945

    Open questions at the time
    • Specific chemokine receptors/Gα targets in T cells not identified
    • Cell-intrinsic versus extrinsic effects not fully separated
  14. 2020 Medium

    Identified a spindle-orientation-independent mode of progenitor fate control, with RGS3 partnering KIF20A to balance proliferative versus differentiative divisions.

    Evidence Loss-of-function genetics in mice, spindle orientation measurement, and progenitor fate analysis

    PMID:32864611

    Open questions at the time
    • Biochemical nature of the RGS3-KIF20A interaction undefined
    • Molecular pathway downstream of the pairing unresolved
  15. 2021 High

    Overturned the GPCR-exclusive view of RGS3 by showing it directly acts as a GAP for KRAS, including KRASG12C, promoting GDP-bound inactivation and enabling inhibitor efficacy.

    Evidence In vitro GTPase assays with recombinant RGS3 and KRAS mutants plus cellular KRASG12C inhibitor sensitivity experiments

    PMID:34618566

    Open questions at the time
    • Structural basis of RGS3 engagement of KRAS not determined
    • Selectivity over other small GTPases unexplored
  16. 2025 Medium

    Implicated RGS3 in ovarian cancer, showing it binds ARID3B and promotes SMAD2/3 phosphorylation to drive TGF-β-dependent proliferation and metastasis.

    Evidence Co-IP with ARID3B, SMAD2/3 phosphorylation assays, and siRNA knockdown with proliferation, apoptosis, and metastasis readouts

    PMID:40456746

    Open questions at the time
    • Single-lab finding without reciprocal validation
    • Apparent contradiction with earlier inhibition of Smad signaling (#12) not reconciled
    • Direct ARID3B-RGS3 binding interface unmapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how RGS3's diverse activities — GAP toward Gα and KRAS, Gβγ binding, Smad and GSK3β regulation — are partitioned across its isoforms and integrated in a single cell context.
  • No unified isoform-resolved map of which domains/isoforms execute each function
  • Opposite effects on TGF-β/Smad signaling across studies unreconciled
  • No full-length structure to relate domains spatially

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140299 molecular sensor activity 1 GO:0140313 molecular sequestering activity 1
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 1
Partners
GNAI3GNAQGNB1GSK3BKRASSMAD3SMAD4YWHAZ

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 A truncated C-terminal form of RGS3 (RGS3T) inhibits Gq-mediated inositol phosphate production and Gs-mediated cAMP production in intact cells, while both full-length RGS3 and RGS3T impair Gi-mediated ERK1/2 phosphorylation, demonstrating that the C-terminal RGS domain is sufficient for Gq/Gs inhibition and that both forms regulate Gi signaling. Transient transfection of BHK cells with RGS3 or RGS3T cDNA followed by inositol phosphate, cAMP, and ERK phosphorylation assays The Journal of biological chemistry Medium 9182581
1997 RGS3 binds Gq-alpha protein in vitro; recombinant RGS3-GST fusion protein bound ~5-fold more 35S-labeled Gqα than GST alone, and RGS3 expression suppressed GnRH-stimulated IP3 responses by 75% in COS-1 cells, identifying Gqα as the mechanistic target mediating GnRH desensitization. GST pulldown with 35S-met labeled Gqα; co-transfection of GnRH receptor and RGS3 in COS-1 cells with IP3 measurement Endocrinology Medium 9003025
1999 RGS3 inhibits G protein-coupled receptor signaling by translocating from the cytosol to the plasma membrane upon G protein activation; this translocation is mediated by a dual mechanism involving both the C-terminal RGS domain (which binds activated Gα11-QL constitutively) and the N-terminal domain (which translocates in response to agonist stimulation via a calcium-dependent mechanism). RGS3 co-immunoprecipitates with AlF4-activated Gα11 and, to a lesser extent, Gαi3, through its RGS domain. Co-immunoprecipitation of RGS3 with activated Gα subunits; Western blotting of cytosolic and particulate fractions; immunofluorescence microscopy; calcium ionophore experiments; deletion mutant analysis Molecular and cellular biology High 9858594
2000 RGS3 functions as a GTPase-activating protein (GAP) for Gαi (except Gαz) and Gαq subunits but not Gαs or Gα12, with Gαq GAP activity comparable to RGS4. Mutation of residues in the RGS domain analogous to those required for RGS4 Gαi GAP activity impaired RGS3 function. RGS3 also acts as a potent Gαq effector antagonist blocking PLC-β activation, an activity that distinguishes it from RGS4. In vitro GTPase assay; active-site mutagenesis; reporter gene assay (CREB); inositol phosphate production assay in intact cells Molecular pharmacology High 10999941
2001 RGS3 directly binds Gβ1γ2 subunits and inhibits Gβγ-mediated signaling (inositol phosphate production, Akt activation, and MAPK activation) independently of its GAP activity; inhibition requires two regions (residues 313–390 and 391–458) outside the RGS domain. RGS3 also inhibits Gβγ-mediated PLC-β activation in vitro. Co-expression of RGS3 with Gβ1γ2 in COS-7 and HEK293 cells; deletion mutant analysis; in vitro PLC-β activation assay; inositol phosphate and Akt/MAPK assays The Journal of biological chemistry High 11294858
2001 Adenoviral-mediated RGS3 gene transfer in rat pituitary gonadotropes inhibits GnRH-stimulated LH secretion in a dose-dependent manner, consistent with RGS3 acting at Gqα to suppress inositol phosphate accumulation and downstream LH release. Adenoviral transduction of rat pituitary cells; LH secretion assay; 3H-inositol phosphate accumulation assay BMC cell biology Medium 11716781
2002 RGS3 interacts with 14-3-3 protein via a single binding site at Ser264 in its N-terminal region (outside the RGS domain); the S264A mutation abolishes 14-3-3 binding without affecting Gαq binding. 14-3-3-bound RGS3 cannot interact with G proteins, so 14-3-3 acts as a negative regulator of RGS3 by sequestering it away from Gα subunits. The S264A mutant is more potent than wild-type RGS3 in inhibiting G protein signaling. Yeast two-hybrid screening; in vitro binding assays; co-immunoprecipitation; site-directed mutagenesis (S264A); signaling assays The Biochemical journal High 11985497
2002 Endogenous RGS3 specifically negatively modulates muscarinic m3 receptor (carbachol)-stimulated MAP kinase activity through Gq/11 (pertussis toxin-insensitive) in rat vascular smooth muscle cells, as demonstrated by ribozyme-mediated knockdown of RGS3 but not RGS2, RGS5, or RGS7. Synthetic ribozymes targeting RGS3 transfected into rat aorta smooth muscle cells; MAP kinase activation assay; pertussis toxin treatment The Journal of biological chemistry Medium 12006602
2002 RGS3 undergoes agonist-dependent palmitoylation: palmitic acid incorporation into RGS3 is dependent on agonist occupancy of the GnRH receptor, whereas RGS10 palmitoylation is constitutive. This ligand-regulated palmitoylation represents a novel post-translational regulatory mechanism for RGS3. Overexpression in GGH3 cells with palmitic acid incorporation assay; site-directed mutagenesis of palmitoylation site in RGS10 as comparison Endocrinology Medium 11897687
2003 RGS3 mediates calcium-dependent rapid termination of G protein (Go) signaling in dorsal root ganglion neurons; calcium influx through voltage-gated channels directly binds to an EF-hand domain of RGS3. Deletion of the EF-hand domain abolishes both the calcium-RGS3 interaction (gel-shift assay) and the rapid desensitization of Go-mediated N-type Ca2+ channel inhibition. A naturally occurring RGS3 variant lacking the EF hand produces slower, calmodulin-dependent desensitization instead. Retroviral overexpression of RGS3 isoforms and EF-hand deletion mutants in dorsal root ganglion neurons; electrophysiological recording of N-type Ca2+ channel inhibition; gel-shift calcium-binding assay Proceedings of the National Academy of Sciences of the United States of America High 12771384
2004 RGS3 (short isoform RGS3s) does not interact with GPCR-Kir3 channel complexes, in contrast to RGS4. RGS3s modulates m2 receptor-coupled GIRK channels by 'collision coupling' rather than 'precoupling', reducing maximal ACh-evoked GIRK current amplitude ~45% and shifting the dose-response relation, while RGS4 precouples to the receptor complex with ~100-fold greater potency in accelerating Kir3 channel-gating kinetics. Co-immunoprecipitation of RGS constructs with GPCR-Kir3 complexes in CHO-K1 cells; deletion and chimeric RGS constructs; electrophysiological recording of GIRK channel gating kinetics The Journal of biological chemistry Medium 16973624
2006 Full-length RGS3 and its native isoform RGS3T antagonize muscarinic M2 receptor-mediated inhibition of Cav2.3 (R-type) Ca2+ channels equally effectively; the core RGS domain alone is sufficient for this activity and the extended N-terminal domain does not enhance signaling function. The N-terminal domain of RGS3 restricts its localization to the cytoplasm as shown by confocal microscopy of GFP fusion proteins. Whole-cell patch-clamp recordings in HEK293 cells expressing Cav2.3, M2R, and RGS3 deletion mutants; confocal microscopy of RGS3-EGFP fusion proteins American journal of physiology. Cell physiology Medium 16855219
2008 RGS3 interacts with Smad2, Smad3, and Smad4 via a region outside its RGS domain binding to the Smad MH2 domain. RGS3 overexpression inhibits TGF-β-induced Smad-mediated gene transcription by preventing Smad3-Smad4 heteromerization without affecting TGF-β-induced Smad phosphorylation, and inhibits TGF-β-induced myofibroblast differentiation. Co-immunoprecipitation of RGS3 with Smad proteins; domain mapping; reporter gene transcription assay; Smad heteromerization assay; myofibroblast differentiation assay Molecular pharmacology Medium 18287247
2010 14-3-3 protein binding induces structural changes in both the N-terminal region and the C-terminal RGS domain of phosphorylated RGS3, affecting the Gα-interacting portion of the RGS domain. The crystal structure of the RGS domain of RGS3 was solved at 2.3 Å resolution. The isolated RGS domain can interact with 14-3-3 in a phosphorylation-independent manner. Time-resolved tryptophan fluorescence spectroscopy with single-tryptophan mutants; X-ray crystallography of RGS domain at 2.3 Å resolution Journal of structural biology High 20347994
2010 Knockout of PDZ-RGS3 in mice causes early cell cycle exit and precocious differentiation of neural progenitor cells in the developing cerebral cortex, resulting in loss of cortical neural progenitor cells and impaired production of late-born cortical neurons, phenocopying ephrin-B1 knockout, thereby placing PDZ-RGS3 downstream of ephrin-B reverse signaling in neural progenitor maintenance. Genetic knockout (PDZ-RGS3 null mice); cortical neurogenesis analysis; comparison with ephrin-B1 knockout phenotype; cell cycle analysis Stem cells (Dayton, Ohio) High 20629178
2011 The 14-3-3ζ protein forms a complex with RGS3 in which the RGS domain of RGS3 binds to the outer surface of the 14-3-3ζ dimer (outside its central channel), and this binding both sterically occludes the Gα interaction surface of the RGS domain and induces conformational changes that impair its Gα binding. Small angle X-ray scattering (SAXS); hydrogen/deuterium exchange kinetics; FRET measurements; low-resolution solution structure determination The Journal of biological chemistry High 22027839
2012 PDZ-RGS3 (isoform 1) is upregulated by Wnt signaling, binds GSK3β, and decreases GSK3β catalytic activity toward β-catenin, thereby enhancing canonical Wnt/β-catenin signaling. PDZ-RGS3 overexpression enhances Snail1 expression and promotes epithelial-mesenchymal transition (EMT). Co-immunoprecipitation of PDZ-RGS3 with GSK3β; kinase activity assay for GSK3β toward β-catenin; β-catenin reporter assay; Wnt3a stimulation; EMT morphological and biochemical analysis The Journal of biological chemistry Medium 22859293
2013 Endogenous RGS3 controls T cell migration in a non-redundant manner; mice with RGS domain deletion (RGS3ΔRGS) show increased T cell numbers and formation of perivascular lymphoid structures in the lung in an asthma model, with reduced T cell numbers in draining lymph nodes, demonstrating RGS3 restricts T cell migration via its G protein regulatory (RGS) domain. Generation of RGS3ΔRGS knock-in mice; experimental asthma model; T cell enumeration in lungs and draining lymph nodes; in vitro T cell migration assay with RGS3-knockdown thymoma cells American journal of physiology. Lung cellular and molecular physiology High 24077945
2021 RGS3, previously known only as a regulator of GPCR/G protein signaling, can also directly enhance the GTPase activity of both wild-type and mutant KRAS proteins (including KRASG12C), thereby inactivating KRAS and enabling KRASG12C inhibitor efficacy by promoting GTP hydrolysis and accumulation of the GDP-bound inactive state. GTPase activity assays with recombinant RGS3 and KRAS proteins; biochemical and cellular studies of KRAS inactivation; KRASG12C inhibitor sensitivity experiments Science (New York, N.Y.) High 34618566
2020 RGS3 interacts with KIF20A and together they regulate the balance between proliferative and differentiative divisions of neural progenitor cells in the developing cortex independently of spindle/cleavage plane orientation, revealing a spindle orientation-independent mechanism of cell fate determination. Loss-of-function genetic experiments in mice (RGS3 and KIF20A inactivation); spindle orientation measurement; neural progenitor cell fate analysis Cerebral cortex communications Medium 32864611
2004 Single phosphorylation of Tyr304 on ephrin-B2 enables bifunctional binding to both the SH2 domain of Grb4 and the PDZ domain of PDZ-RGS3 simultaneously, forming a three-component molecular complex, as determined by NMR HSQC experiments and binding assays. NMR (1H-15N HSQC) binding experiments; in vitro binding assays with phosphopeptides; three-component complex reconstitution European journal of biochemistry Medium 15096211
2025 RGS3 directly interacts with ARID3B and facilitates phosphorylation of SMAD2/3, thereby enhancing TGF-β pathway activity and driving ovarian cancer cell proliferation and metastasis through EMT. Silencing RGS3 promotes apoptosis and inhibits tumor growth in ovarian cancer cells. Co-immunoprecipitation of RGS3 with ARID3B; SMAD2/3 phosphorylation assay; siRNA knockdown with proliferation, apoptosis, and metastasis readouts Cell death discovery Medium 40456746

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 A truncated form of RGS3 negatively regulates G protein-coupled receptor stimulation of adenylyl cyclase and phosphoinositide phospholipase C. The Journal of biological chemistry 110 9182581
2002 Receptor-selective effects of endogenous RGS3 and RGS5 to regulate mitogen-activated protein kinase activation in rat vascular smooth muscle cells. The Journal of biological chemistry 99 12006602
1999 RGS3 inhibits G protein-mediated signaling via translocation to the membrane and binding to Galpha11. Molecular and cellular biology 97 9858594
1997 Potential role for a regulator of G protein signaling (RGS3) in gonadotropin-releasing hormone (GnRH) stimulated desensitization. Endocrinology 91 9003025
2000 RGS3 is a GTPase-activating protein for g(ialpha) and g(qalpha) and a potent inhibitor of signaling by GTPase-deficient forms of g(qalpha) and g(11alpha). Molecular pharmacology 73 10999941
2021 The G protein signaling regulator RGS3 enhances the GTPase activity of KRAS. Science (New York, N.Y.) 70 34618566
2006 Possible involvement of CCT5, RGS3, and YKT6 genes up-regulated in p53-mutated tumors in resistance to docetaxel in human breast cancers. Breast cancer research and treatment 69 16821082
2004 Regulators of G-protein signaling 3 and 4 (RGS3, RGS4) are associated with glioma cell motility. Journal of neuropathology and experimental neurology 64 15055445
2001 Expression of RGS3, RGS4 and Gi alpha 2 in acutely failing donor hearts and end-stage heart failure. European heart journal 63 11428836
1998 RGS3 and RGS4 are GTPase activating proteins in the heart. Journal of molecular and cellular cardiology 61 9515003
2007 C. elegans G protein regulator RGS-3 controls sensitivity to sensory stimuli. Neuron 55 17196529
2006 RGS3 and RGS4 differentially associate with G protein-coupled receptor-Kir3 channel signaling complexes revealing two modes of RGS modulation. Precoupling and collision coupling. The Journal of biological chemistry 44 16973624
2001 Regulator of G-protein signaling 3 (RGS3) inhibits Gbeta1gamma 2-induced inositol phosphate production, mitogen-activated protein kinase activation, and Akt activation. The Journal of biological chemistry 43 11294858
2002 RGS3 interacts with 14-3-3 via the N-terminal region distinct from the RGS (regulator of G-protein signalling) domain. The Biochemical journal 41 11985497
2019 MicroRNA‑126‑3p inhibits the proliferation, migration, invasion, and angiogenesis of triple‑negative breast cancer cells by targeting RGS3. Oncology reports 39 31364749
2010 14-3-3 protein interacts with and affects the structure of RGS domain of regulator of G protein signaling 3 (RGS3). Journal of structural biology 36 20347994
2002 Regulation of RGS3 and RGS10 palmitoylation by GnRH. Endocrinology 34 11897687
2015 Elevated microRNA-25 inhibits cell apoptosis in lung cancer by targeting RGS3. In vitro cellular & developmental biology. Animal 29 26416661
2002 Additional 5' exons in the RGS3 locus generate multiple mRNA transcripts, one of which accounts for the origin of human PDZ-RGS3. Genomics 28 12036301
2011 Structural basis for the 14-3-3 protein-dependent inhibition of the regulator of G protein signaling 3 (RGS3) function. The Journal of biological chemistry 27 22027839
2010 Essential role of PDZ-RGS3 in the maintenance of neural progenitor cells. Stem cells (Dayton, Ohio) 24 20629178
2004 Single phosphorylation of Tyr304 in the cytoplasmic tail of ephrin B2 confers high-affinity and bifunctional binding to both the SH2 domain of Grb4 and the PDZ domain of the PDZ-RGS3 protein. European journal of biochemistry 21 15096211
2003 High basal expression and injury-induced down regulation of two regulator of G-protein signaling transcripts, RGS3 and RGS4 in primary sensory neurons. Molecular and cellular neurosciences 20 14550772
2001 Evidence for a short form of RGS3 preferentially expressed in the human heart. Naunyn-Schmiedeberg's archives of pharmacology 19 11330340
2008 Regulation of Smad-mediated gene transcription by RGS3. Molecular pharmacology 18 18287247
2005 Neuronal Kir3.1/Kir3.2a channels coupled to serotonin 1A and muscarinic m2 receptors are differentially modulated by the "short" RGS3 isoform. Neuropharmacology 18 15935408
2003 RGS3 mediates a calcium-dependent termination of G protein signaling in sensory neurons. Proceedings of the National Academy of Sciences of the United States of America 18 12771384
2013 RGS3 controls T lymphocyte migration in a model of Th2-mediated airway inflammation. American journal of physiology. Lung cellular and molecular physiology 14 24077945
2012 Regulator of G-protein signaling 3 isoform 1 (PDZ-RGS3) enhances canonical Wnt signaling and promotes epithelial mesenchymal transition. The Journal of biological chemistry 14 22859293
2008 Lack of receptor-selective effects of either RGS2, RGS3 or RGS4 on muscarinic M3- and gonadotropin-releasing hormone receptor-mediated signalling through G alpha q/11. European journal of pharmacology 14 18457830
1997 Genomic organization, 5'-flanking region, and chromosomal localization of the human RGS3 gene. Genomics 13 9344672
2022 Pseudogene UBE2MP1 derived transcript enhances in vitro cell proliferation and apoptosis resistance of hepatocellular carcinoma cells through miR-145-5p/RGS3 axis. Aging 12 36214767
2025 RGS3 acts as a tumor promoter by facilitating the regulation of the TGF-β signaling pathway and promoting EMT in ovarian cancer. Cell death discovery 11 40456746
2017 RGS3 inhibits TGF-β1/Smad signalling in adventitial fibroblasts. Cell biochemistry and function 11 28845525
2001 A regulator of G protein signaling, RGS3, inhibits gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion. BMC cell biology 11 11716781
1999 Modulation of renal tubular cell function by RGS3. The American journal of physiology 11 10198412
2004 Analysis of PDZ-RGS3 function in ephrin-B reverse signaling. Methods in enzymology 9 15488174
2025 Exosomal mir-126-3p derived from endothelial cells induces ion channel dysfunction by targeting RGS3 signaling in cardiomyocytes: a novel mechanism in Takotsubo cardiomyopathy. Stem cell research & therapy 8 39901299
2022 RGS3 and IL1RAPL1 missense variants implicate defective neurotransmission in early-onset inherited schizophrenias. Journal of psychiatry & neuroscience : JPN 8 36318984
2000 C2PA, a new protein expressed during mouse spermatogenesis. FEBS letters 8 11034339
2019 A Multi-Trait Approach Identified Genetic Variants Including a Rare Mutation in RGS3 with Impact on Abnormalities of Cardiac Structure/Function. Scientific reports 4 30971721
2006 Muscarinic modulation of Cav2.3 (R-type) calcium channels is antagonized by RGS3 and RGS3T. American journal of physiology. Cell physiology 4 16855219
2022 Inhibition of the expression of rgs-3 alleviates propofol-induced decline in learning and memory in Caenorhabditis elegans. CNS neuroscience & therapeutics 3 36284438
2003 A Galphas mutation (D229S) differentially effects gonadotropin-releasing hormone receptor regulation by RGS10, RGS3 and RGS3T. Molecular and cellular endocrinology 3 12644305
2004 Assays of RGS3 activation and modulation. Methods in enzymology 2 15488173
2002 C2PA is a nuclear protein implicated in the heat shock response. Journal of cellular biochemistry 2 12210723
2022 Exploring the expression and preliminary function of chicken regulator of G protein signalling 3 (RGS3) gene in follicular development. British poultry science 1 35522181
2026 BMSCs regulate RGS3 expression in ovarian stromal cells to improve ovarian stromal fibrosis and angiogenic microenvironment in cyclophosphamide-induced premature ovarian failure. Stem cell research & therapy 0 42002799
2020 Spindle Orientation-Independent Control of Cell Fate Determination by RGS3 and KIF20A. Cerebral cortex communications 0 32864611

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