RGS2 is a regulator of heterotrimeric G protein signaling that accelerates GTP hydrolysis on G alpha subunits, particularly Gq, thereby limiting receptor-driven signaling. It associates with the cytoplasmic surface of the plasma membrane and also occupies cytoplasmic and nuclear compartments; alternative translation initiation generates a shorter product with mitochondrial localization. RGS2 regulates vascular and cardiac signaling and can inhibit adenylyl cyclase and translation through mechanisms distinct from its GAP activity. Its physiological effects depend on receptor, cell type, expression level and protein isoform.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001965 G-protein alpha-subunit binding | IPI PMID:19478087 Structural determinants of G-protein alpha subunit selectivi... | ACCEPT | Summary: RGS2 binds activated G alpha and accelerates its intrinsic GTP hydrolysis. Reason: Wild-type biochemical selectivity favors Gq; the engineered Gi-binding mutants in PMID:19478087 must not be presented as wild-type Gi specificity. Cell-based beta2-adrenergic Gi regulation is a distinct demonstrated context. Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:0001975 response to amphetamine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Rat source PMID:26321241 reports RGS2 expression changes correlated with amphetamine intake in VTA and nucleus accumbens. Reason: Retain a contextual orthology-based stimulus-response annotation, not a claim that human RGS2 metabolizes amphetamine or necessarily drives addiction. Supporting Evidence: |
| GO:0003924 GTPase activity | IEA GO_REF:0000117 | MODIFY | Summary: RGS2 is the GTPase-activating regulator, whereas G alpha binds and hydrolyzes GTP. Reason: Refine the assigned enzyme role to the existing GAP activity; this is not removal of RGS2 from the GTPase cycle. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: ARBA:ARBA00026818 UNRESOLVED RGS2 is the GTPase-activating regulator, whereas G alpha binds and hydrolyzes GTP. Refine the assigned enzyme role to the existing GAP activity; this is not removal of RGS2 from the GTPase cycle. Proposed replacements: GTPase activator activity Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits |
| GO:0003924 GTPase activity | TAS Reactome:R-HSA-8982025 | MODIFY | Summary: RGS2 is the GTPase-activating regulator, whereas G alpha binds and hydrolyzes GTP. Reason: Refine the assigned enzyme role to the existing GAP activity; this is not removal of RGS2 from the GTPase cycle. Proposed replacements: GTPase activator activity Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits |
| GO:0005096 GTPase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: RGS2 binds activated G alpha and accelerates its intrinsic GTP hydrolysis. Reason: Wild-type biochemical selectivity favors Gq; the engineered Gi-binding mutants in PMID:19478087 must not be presented as wild-type Gi specificity. Cell-based beta2-adrenergic Gi regulation is a distinct demonstrated context. Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:0005096 GTPase activator activity | IMP PMID:19478087 Structural determinants of G-protein alpha subunit selectivi... | ACCEPT | Summary: RGS2 binds activated G alpha and accelerates its intrinsic GTP hydrolysis. Reason: Wild-type biochemical selectivity favors Gq; the engineered Gi-binding mutants in PMID:19478087 must not be presented as wild-type Gi specificity. Cell-based beta2-adrenergic Gi regulation is a distinct demonstrated context. Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:0005096 GTPase activator activity | TAS PMID:10747990 Ca2+/Calmodulin reverses phosphatidylinositol 3,4, 5-trispho... | ACCEPT | Summary: RGS2 binds activated G alpha and accelerates its intrinsic GTP hydrolysis. Reason: Wild-type biochemical selectivity favors Gq; the engineered Gi-binding mutants in PMID:19478087 must not be presented as wild-type Gi specificity. Cell-based beta2-adrenergic Gi regulation is a distinct demonstrated context. Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:0005515 protein binding | IPI PMID:14608379 Regulator of G-protein signaling-2 mediates vascular smooth ... | REMOVE | Summary: The interaction claim is not denied, but bare protein binding is uninformative under the project protein-binding policy. Reason: Specific G alpha binding and the independently established signaling functions are retained. |
| GO:0005515 protein binding | IPI PMID:17464283 Spinophilin/neurabin reciprocally regulate signaling intensi... | REMOVE | Summary: The interaction claim is not denied, but bare protein binding is uninformative under the project protein-binding policy. Reason: Specific G alpha binding and the independently established signaling functions are retained. |
| GO:0005515 protein binding | IPI PMID:24794857 A Parkinson's disease gene regulatory network identifies the... | REMOVE | Summary: The interaction claim is not denied, but bare protein binding is uninformative under the project protein-binding policy. Reason: Specific G alpha binding and the independently established signaling functions are retained. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: The interaction claim is not denied, but bare protein binding is uninformative under the project protein-binding policy. Reason: Specific G alpha binding and the independently established signaling functions are retained. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: The interaction claim is not denied, but bare protein binding is uninformative under the project protein-binding policy. Reason: Specific G alpha binding and the independently established signaling functions are retained. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The interaction claim is not denied, but bare protein binding is uninformative under the project protein-binding policy. Reason: Specific G alpha binding and the independently established signaling functions are retained. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: The interaction claim is not denied, but bare protein binding is uninformative under the project protein-binding policy. Reason: Specific G alpha binding and the independently established signaling functions are retained. |
| GO:0005516 calmodulin binding | TAS PMID:10747990 Ca2+/Calmodulin reverses phosphatidylinositol 3,4, 5-trispho... | UNDECIDED | Summary: The accessible PMID:10747990 abstract establishes calmodulin binding to tested RGS proteins and explicitly discusses RGS4, but does not identify whether RGS2 was one of the individually assayed proteins. Reason: Full target-level results could not be recovered. RGS2 calmodulin binding is therefore unresolved rather than rejected from a paralog-focused abstract. Supporting Evidence: PMID:10747990 Ca(2+)/calmodulin binds a complex of RGS4 |
| GO:0005634 nucleus | IDA PMID:10791963 Cytoplasmic, nuclear, and golgi localization of RGS proteins... | KEEP AS NON CORE | Summary: Nuclear and nucleolar pools are supported for the longer human translation products by localization experiments and curated isoform-specific UniProt statements. Reason: These locations are retained as contextual pools, without asserting that every RGS2 isoform is nuclear. |
| GO:0005634 nucleus | IDA PMID:11278586 Mechanisms governing subcellular localization and function o... | KEEP AS NON CORE | Summary: Nuclear and nucleolar pools are supported for the longer human translation products by localization experiments and curated isoform-specific UniProt statements. Reason: These locations are retained as contextual pools, without asserting that every RGS2 isoform is nuclear. |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear and nucleolar pools are supported for the longer human translation products by localization experiments and curated isoform-specific UniProt statements. Reason: These locations are retained as contextual pools, without asserting that every RGS2 isoform is nuclear. |
| GO:0005737 cytoplasm | EXP PMID:17901199 Alternative translation initiation of human regulators of G-... | ACCEPT | Summary: RGS2 has an experimentally supported cytoplasmic/cytosolic pool in addition to its membrane-associated signaling pool. Reason: The isoform-localization experiments and cell imaging support soluble localization; no exclusivity is inferred. |
| GO:0005737 cytoplasm | IDA PMID:11278586 Mechanisms governing subcellular localization and function o... | ACCEPT | Summary: RGS2 has an experimentally supported cytoplasmic/cytosolic pool in addition to its membrane-associated signaling pool. Reason: The isoform-localization experiments and cell imaging support soluble localization; no exclusivity is inferred. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: RGS2 has an experimentally supported cytoplasmic/cytosolic pool in addition to its membrane-associated signaling pool. Reason: The isoform-localization experiments and cell imaging support soluble localization; no exclusivity is inferred. |
| GO:0005739 mitochondrion | EXP PMID:17901199 Alternative translation initiation of human regulators of G-... | KEEP AS NON CORE | Summary: The shorter translation product beginning at the fourth initiation site has curated experimentally supported mitochondrial localization in PMID:17901199. Reason: Retain the root organelle assertion separately from the membrane/nuclear distributions of other isoforms; no submitochondrial topology is claimed. Supporting Evidence: |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The shorter translation product beginning at the fourth initiation site has curated experimentally supported mitochondrial localization in PMID:17901199. Reason: Retain the root organelle assertion separately from the membrane/nuclear distributions of other isoforms; no submitochondrial topology is claimed. Supporting Evidence: |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: RGS2 has an experimentally supported cytoplasmic/cytosolic pool in addition to its membrane-associated signaling pool. Reason: The isoform-localization experiments and cell imaging support soluble localization; no exclusivity is inferred. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: RGS2 has an experimentally supported cytoplasmic/cytosolic pool in addition to its membrane-associated signaling pool. Reason: The isoform-localization experiments and cell imaging support soluble localization; no exclusivity is inferred. |
| GO:0005829 cytosol | ISS GO_REF:0000024 | ACCEPT | Summary: RGS2 has an experimentally supported cytoplasmic/cytosolic pool in addition to its membrane-associated signaling pool. Reason: The isoform-localization experiments and cell imaging support soluble localization; no exclusivity is inferred. |
| GO:0005886 plasma membrane | EXP PMID:17901199 Alternative translation initiation of human regulators of G-... | MODIFY | Summary: RGS2 is a peripheral intracellular regulator recruited to the cytoplasmic face of the plasma membrane, not a transmembrane receptor. Reason: Refine to the already asserted cytoplasmic-side location, supported by its membrane targeting and Gq interaction. Proposed replacements: cytoplasmic side of plasma membrane |
| GO:0005886 plasma membrane | EXP PMID:28784619 Human Missense Mutations in Regulator of G Protein Signaling... | MODIFY | Summary: RGS2 is a peripheral intracellular regulator recruited to the cytoplasmic face of the plasma membrane, not a transmembrane receptor. Reason: Refine to the already asserted cytoplasmic-side location, supported by its membrane targeting and Gq interaction. Proposed replacements: cytoplasmic side of plasma membrane |
| GO:0005886 plasma membrane | IDA PMID:11278586 Mechanisms governing subcellular localization and function o... | MODIFY | Summary: RGS2 is a peripheral intracellular regulator recruited to the cytoplasmic face of the plasma membrane, not a transmembrane receptor. Reason: Refine to the already asserted cytoplasmic-side location, supported by its membrane targeting and Gq interaction. Proposed replacements: cytoplasmic side of plasma membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | MODIFY | Summary: RGS2 is a peripheral intracellular regulator recruited to the cytoplasmic face of the plasma membrane, not a transmembrane receptor. Reason: Refine to the already asserted cytoplasmic-side location, supported by its membrane targeting and Gq interaction. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:O08849 SUPPORTS TRANSFER RGS2 is a peripheral intracellular regulator recruited to the cytoplasmic face of the plasma membrane, not a transmembrane receptor. Refine to the already asserted cytoplasmic-side location, supported by its membrane targeting and Gq interaction. UniProtKB-SubCell:SL-0039 SUPPORTS TRANSFER RGS2 is a peripheral intracellular regulator recruited to the cytoplasmic face of the plasma membrane, not a transmembrane receptor. Refine to the already asserted cytoplasmic-side location, supported by its membrane targeting and Gq interaction. Proposed replacements: cytoplasmic side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982017 | MODIFY | Summary: RGS2 is a peripheral intracellular regulator recruited to the cytoplasmic face of the plasma membrane, not a transmembrane receptor. Reason: Refine to the already asserted cytoplasmic-side location, supported by its membrane targeting and Gq interaction. Proposed replacements: cytoplasmic side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982025 | MODIFY | Summary: RGS2 is a peripheral intracellular regulator recruited to the cytoplasmic face of the plasma membrane, not a transmembrane receptor. Reason: Refine to the already asserted cytoplasmic-side location, supported by its membrane targeting and Gq interaction. Proposed replacements: cytoplasmic side of plasma membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982026 | MODIFY | Summary: RGS2 is a peripheral intracellular regulator recruited to the cytoplasmic face of the plasma membrane, not a transmembrane receptor. Reason: Refine to the already asserted cytoplasmic-side location, supported by its membrane targeting and Gq interaction. Proposed replacements: cytoplasmic side of plasma membrane |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS Reactome:R-HSA-388396 | ACCEPT | Summary: RGS2 performs signal termination within GPCR signaling by accelerating G alpha GTP hydrolysis. Reason: This is direct regulatory participation rather than a mere expression association. Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The traced mouse source PMID:14581517 is a differential-expression survey of germ-cell stages. Reason: Expression during spermatogenesis alone does not establish that RGS2 performs a spermatogenic step, and no independent RGS2-specific functional mechanism was identified in this review. The transfer is over-specific for the demonstrated expression evidence, not proof that a reproductive role is impossible. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:O08849 UNRESOLVED The traced mouse source PMID:14581517 is a differential-expression survey of germ-cell stages. Expression during spermatogenesis alone does not establish that RGS2 performs a spermatogenic step, and no independent RGS2-specific functional mechanism was identified in this review. The transfer is over-specific for the demonstrated expression evidence, not proof that a reproductive role is impossible. Supporting Evidence: |
| GO:0008277 regulation of G protein-coupled receptor signaling pathway | TAS PMID:10747990 Ca2+/Calmodulin reverses phosphatidylinositol 3,4, 5-trispho... | MODIFY | Summary: The principal demonstrated regulatory action is attenuation of G protein signaling. Reason: Refine the unsigned regulation term to the existing negative-regulation term, while preserving separately supported context-specific downstream effects. Proposed replacements: negative regulation of G protein-coupled receptor signaling pathway Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:0009898 cytoplasmic side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The intracellular membrane-associated pool positions RGS2 to bind and inactivate receptor-activated Gq. Reason: Membrane targeting of RGS2 is experimentally supported; this does not exclude its soluble or isoform-specific organellar pools. |
| GO:0009898 cytoplasmic side of plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The intracellular membrane-associated pool positions RGS2 to bind and inactivate receptor-activated Gq. Reason: Membrane targeting of RGS2 is experimentally supported; this does not exclude its soluble or isoform-specific organellar pools. |
| GO:0009898 cytoplasmic side of plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The intracellular membrane-associated pool positions RGS2 to bind and inactivate receptor-activated Gq. Reason: Membrane targeting of RGS2 is experimentally supported; this does not exclude its soluble or isoform-specific organellar pools. |
| GO:0010614 negative regulation of cardiac muscle hypertrophy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Native mouse Rgs2 deletion under pressure overload increases Gq-linked hypertrophy and JNK activation, prevents adaptive increases in contractility and impairs relaxation (PMID:19127022). Reason: These support the specific cardiac regulatory processes as comparative physiological functions, not constitutive human myocardial phenotypes or direct kinase activity. Supporting Evidence: PMID:19127022 RGS2 principally suppresses G q signaling |
| GO:0010614 negative regulation of cardiac muscle hypertrophy | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Native mouse Rgs2 deletion under pressure overload increases Gq-linked hypertrophy and JNK activation, prevents adaptive increases in contractility and impairs relaxation (PMID:19127022). Reason: These support the specific cardiac regulatory processes as comparative physiological functions, not constitutive human myocardial phenotypes or direct kinase activity. Supporting Evidence: PMID:19127022 RGS2 principally suppresses G q signaling |
| GO:0010855 adenylate cyclase inhibitor activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Alternative-initiation experiments directly show RGS2-dependent inhibition of adenylyl cyclase V with reduced efficacy of the shorter products. Reason: This secondary effector-inhibitory capability is retained independently of Gq GAP activity and is not evidence that RGS2 hydrolyzes cAMP. Supporting Evidence: |
| GO:0010976 positive regulation of neuron projection development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PMID:16820281 reports direct RGS2βtubulin interaction through residues 41β60, stimulation of microtubule polymerization, and gain/loss effects on NGF-induced neurites in PC12 cells. Reason: Retain the binding and neurite functions with this comparative cellular scope; they are distinct from the main GAP mechanism. Supporting Evidence: PMID:16820281 RGS2 directly interacted with tubulin via a short region at the N-terminus |
| GO:0017148 negative regulation of translation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RGS2 directly interacts with eIF2B epsilon and inhibits translation through a region distinct from the determinants of G protein regulation. Reason: The independent primary evidence supports a secondary translation-control role rather than inferring it from altered proliferation. Supporting Evidence: PMID:19736320 RGS2 was found to bind to eIF2Bepsilon |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Chronic intermittent ethanol and withdrawal increased rat prefrontal RGS2 mRNA and protein. Reason: This supports a bounded conserved response annotation, not ethanol metabolism or a proven causal role in dependence. Supporting Evidence: |
| GO:0045744 negative regulation of G protein-coupled receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: RGS2 accelerates G alpha inactivation and limits receptor signaling. Reason: Its biochemical Gq preference and cell-specific Gi-linked beta2-adrenergic termination are compatible; neither implies universal inhibition of every GPCR output. Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:0045744 negative regulation of G protein-coupled receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: RGS2 accelerates G alpha inactivation and limits receptor signaling. Reason: Its biochemical Gq preference and cell-specific Gi-linked beta2-adrenergic termination are compatible; neither implies universal inhibition of every GPCR output. Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:0045744 negative regulation of G protein-coupled receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: RGS2 accelerates G alpha inactivation and limits receptor signaling. Reason: Its biochemical Gq preference and cell-specific Gi-linked beta2-adrenergic termination are compatible; neither implies universal inhibition of every GPCR output. Supporting Evidence: PMID:19478087 RGS2 is unique in its in vitro potency and selectivity as a GAP for Galpha(q) subunits PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:0046329 negative regulation of JNK cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Native mouse Rgs2 deletion under pressure overload increases Gq-linked hypertrophy and JNK activation, prevents adaptive increases in contractility and impairs relaxation (PMID:19127022). Reason: These support the specific cardiac regulatory processes as comparative physiological functions, not constitutive human myocardial phenotypes or direct kinase activity. Supporting Evidence: PMID:19127022 RGS2 principally suppresses G q signaling |
| GO:0046329 negative regulation of JNK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Native mouse Rgs2 deletion under pressure overload increases Gq-linked hypertrophy and JNK activation, prevents adaptive increases in contractility and impairs relaxation (PMID:19127022). Reason: These support the specific cardiac regulatory processes as comparative physiological functions, not constitutive human myocardial phenotypes or direct kinase activity. Supporting Evidence: PMID:19127022 RGS2 principally suppresses G q signaling |
| GO:0048487 beta-tubulin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PMID:16820281 reports direct RGS2βtubulin interaction through residues 41β60, stimulation of microtubule polymerization, and gain/loss effects on NGF-induced neurites in PC12 cells. Reason: Retain the binding and neurite functions with this comparative cellular scope; they are distinct from the main GAP mechanism. Supporting Evidence: PMID:16820281 RGS2 directly interacted with tubulin via a short region at the N-terminus |
| GO:0055119 relaxation of cardiac muscle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Native mouse Rgs2 deletion under pressure overload increases Gq-linked hypertrophy and JNK activation, prevents adaptive increases in contractility and impairs relaxation (PMID:19127022). Reason: These support the specific cardiac regulatory processes as comparative physiological functions, not constitutive human myocardial phenotypes or direct kinase activity. Supporting Evidence: PMID:19127022 RGS2 principally suppresses G q signaling |
| GO:0055119 relaxation of cardiac muscle | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Native mouse Rgs2 deletion under pressure overload increases Gq-linked hypertrophy and JNK activation, prevents adaptive increases in contractility and impairs relaxation (PMID:19127022). Reason: These support the specific cardiac regulatory processes as comparative physiological functions, not constitutive human myocardial phenotypes or direct kinase activity. Supporting Evidence: PMID:19127022 RGS2 principally suppresses G q signaling |
| GO:0060087 relaxation of vascular associated smooth muscle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PKGI-alpha binding and phosphorylation enhance RGS2-mediated restraint of vascular Gq signaling, supporting vascular smooth-muscle relaxation. Reason: This is signaling-mediated regulation, not a structural contractile role. Supporting Evidence: |
| GO:0060135 maternal process involved in female pregnancy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The original rat myometrial study measured pregnancy-dependent expression and explicitly left its physiological role unknown. Reason: Independent mouse knockout experiments in PMID:31030617 demonstrate RGS2-dependent uterine vascular remodeling and blood flow during pregnancy, supporting the conserved maternal process with a vascular, rather than proven direct parturition, mechanism. Supporting Evidence: PMID:12712095 the specific role of myometrial RGS2 remains unknown PMID:31030617 RGS 2 plays a critical role in the structural and functional remodeling of uterine arteries |
| GO:0060452 positive regulation of cardiac muscle contraction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Native mouse Rgs2 deletion under pressure overload increases Gq-linked hypertrophy and JNK activation, prevents adaptive increases in contractility and impairs relaxation (PMID:19127022). Reason: These support the specific cardiac regulatory processes as comparative physiological functions, not constitutive human myocardial phenotypes or direct kinase activity. Supporting Evidence: PMID:19127022 RGS2 principally suppresses G q signaling |
| GO:0060452 positive regulation of cardiac muscle contraction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Native mouse Rgs2 deletion under pressure overload increases Gq-linked hypertrophy and JNK activation, prevents adaptive increases in contractility and impairs relaxation (PMID:19127022). Reason: These support the specific cardiac regulatory processes as comparative physiological functions, not constitutive human myocardial phenotypes or direct kinase activity. Supporting Evidence: PMID:19127022 RGS2 principally suppresses G q signaling |
| GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RGS2 loss enhances agonist-induced cardiomyocyte hypertrophy and cell growth in the native rat study; mouse pressure-overload genetics independently corroborates the antihypertrophic function. Reason: Retain the contextual cardiac growth regulation. |
| GO:0071877 regulation of adenylate cyclase-inhibiting adrenergic receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: RGS2 ablation and overexpression identify it as a terminator of beta2-adrenergic Gi signaling in adult mouse cardiomyocytes and HEK293 assays. Reason: Retain this specific receptor/cell context without converting it into indiscriminate Gi GAP activity. Supporting Evidence: PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:0071877 regulation of adenylate cyclase-inhibiting adrenergic receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: RGS2 ablation and overexpression identify it as a terminator of beta2-adrenergic Gi signaling in adult mouse cardiomyocytes and HEK293 assays. Reason: Retain this specific receptor/cell context without converting it into indiscriminate Gi GAP activity. Supporting Evidence: PMID:21291891 RGS2 ablation, similar to Ξ²AR agonist stimulation, sustains the Ξ²(2)AR-G(i) signaling |
| GO:1900738 positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway | IEA GO_REF:0000107 | MODIFY | Summary: The traced mouse source PMID:19127022 shows the opposite regulatory sign: Rgs2 loss enhances Gq signaling and PLCbeta inhibition rescues the exaggerated hypertrophy. Reason: RGS2 suppresses this PLC-activating branch; improved contractility is a downstream benefit of negative signaling regulation, not positive regulation of the GqβPLC pathway. Propagation Review Root cause: SOURCE BAD Failure modes: REGULATORY SIGN INVERSION Sources checked: UniProtKB:O08849 SOURCE BAD The traced mouse source PMID:19127022 shows the opposite regulatory sign: Rgs2 loss enhances Gq signaling and PLCbeta inhibition rescues the exaggerated hypertrophy. RGS2 suppresses this PLC-activating branch; improved contractility is a downstream benefit of negative signaling regulation, not positive regulation of the GqβPLC pathway. Proposed replacements: negative regulation of phospholipase C-activating G protein-coupled receptor signaling pathway Supporting Evidence: PMID:19127022 RGS2 principally suppresses G q signaling |
| GO:1900738 positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway | ISS GO_REF:0000024 | MODIFY | Summary: The traced mouse source PMID:19127022 shows the opposite regulatory sign: Rgs2 loss enhances Gq signaling and PLCbeta inhibition rescues the exaggerated hypertrophy. Reason: RGS2 suppresses this PLC-activating branch; improved contractility is a downstream benefit of negative signaling regulation, not positive regulation of the GqβPLC pathway. Propagation Review Root cause: SOURCE BAD Failure modes: REGULATORY SIGN INVERSION Sources checked: UniProtKB:O08849 SOURCE BAD The traced mouse source PMID:19127022 shows the opposite regulatory sign: Rgs2 loss enhances Gq signaling and PLCbeta inhibition rescues the exaggerated hypertrophy. RGS2 suppresses this PLC-activating branch; improved contractility is a downstream benefit of negative signaling regulation, not positive regulation of the GqβPLC pathway. Proposed replacements: negative regulation of phospholipase C-activating G protein-coupled receptor signaling pathway Supporting Evidence: PMID:19127022 RGS2 principally suppresses G q signaling |
| GO:1900924 negative regulation of glycine import across plasma membrane | IEA GO_REF:0000107 | UNDECIDED | Summary: The traced rat source PMID:21798518 measures glycine-evoked electrical currents by whole-cell patch clamp, not glycine uptake. Reason: The live GO definition requires reduction of glycine import into the cell. This is a specific mismatch between the measured endpoint and the transferred transport claim; the inaccessible full text and lack of independent uptake evidence leave an actual RGS2 glycine-import mechanism unresolved. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q9JHX0 UNRESOLVED The traced rat source PMID:21798518 measures glycine-evoked electrical currents by whole-cell patch clamp, not glycine uptake. The live GO definition requires reduction of glycine import into the cell. This is a specific mismatch between the measured endpoint and the transferred transport claim; the inaccessible full text and lack of independent uptake evidence leave an actual RGS2 glycine-import mechanism unresolved. Supporting Evidence: PMID:21798518 using immunohistochemistry, Western blot analysis and whole-cell patch-clamp techniques |
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Q: Does wild-type human RGS2 directly bind calmodulin under the conditions used in PMID:10747990?
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