GNAI2 encodes G alpha i2, a heterotrimeric G protein alpha subunit that transmits receptor signals through guanine-nucleotide exchange and hydrolysis. Activated Gi2 can inhibit selected adenylyl cyclases and also regulate channel, kinase and secretory pathways in a receptor- and cell-dependent manner. It functions at the cytoplasmic plasma-membrane surface, with additional cytosolic, mitotic and neuronal secretory-vesicle pools. Its physiological roles include immune and vascular signaling, endocrine secretion and synaptic regulation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001525 angiogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Human endothelial GNAI2 perturbation and complementary mouse vascular experiments support a signaling requirement in angiogenesis. Reason: Retain this defined physiological role without assigning Gi2 direct extracellular matrix or vessel structural activity. Supporting Evidence: |
| GO:0001525 angiogenesis | IMP PMID:38505600 G protein subunit alpha i2's pivotal role in angiogenesis. | KEEP AS NON CORE | Summary: Human endothelial GNAI2 perturbation and complementary mouse vascular experiments support a signaling requirement in angiogenesis. Reason: Retain this defined physiological role without assigning Gi2 direct extracellular matrix or vessel structural activity. Supporting Evidence: |
| GO:0001973 G protein-coupled adenosine receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The traced native-neuron study uses PTX-insensitive alpha-subunit replacement to establish adenosine and GABAB receptor-dependent presynaptic inhibition. Reason: Retain these conserved receptor-context capabilities with engineered rescue scope; the experiments do not mean every inhibitory receptor selects Gi2. Supporting Evidence: |
| GO:0001973 G protein-coupled adenosine receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The traced native-neuron study uses PTX-insensitive alpha-subunit replacement to establish adenosine and GABAB receptor-dependent presynaptic inhibition. Reason: Retain these conserved receptor-context capabilities with engineered rescue scope; the experiments do not mean every inhibitory receptor selects Gi2. Supporting Evidence: |
| GO:0003924 GTPase activity | EXP PMID:12359238 Modulation of G(ialpha(2)) signaling by the axonal guidance ... | ACCEPT | Summary: GNAI2 is a guanine-nucleotide-binding G alpha subunit that switches between GDP- and GTP-bound states and hydrolyzes bound GTP. Reason: Receptor/effector biochemistry and nucleotide-state experiments support the intrinsic molecular switch. This is distinct from the GAP activity of RGS proteins; activated or nucleotide-defective mutants are controls, not substitutes for the wild-type function. Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. |
| GO:0003924 GTPase activity | IEA GO_REF:0000120 | ACCEPT | Summary: GNAI2 is a guanine-nucleotide-binding G alpha subunit that switches between GDP- and GTP-bound states and hydrolyzes bound GTP. Reason: Receptor/effector biochemistry and nucleotide-state experiments support the intrinsic molecular switch. This is distinct from the GAP activity of RGS proteins; activated or nucleotide-defective mutants are controls, not substitutes for the wild-type function. Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. |
| GO:0003924 GTPase activity | TAS PMID:9637720 Right ventricular outflow tract tachycardia due to a somatic... | ACCEPT | Summary: GNAI2 is a guanine-nucleotide-binding G alpha subunit that switches between GDP- and GTP-bound states and hydrolyzes bound GTP. Reason: Receptor/effector biochemistry and nucleotide-state experiments support the intrinsic molecular switch. This is distinct from the GAP activity of RGS proteins; activated or nucleotide-defective mutants are controls, not substitutes for the wild-type function. Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. |
| GO:0003925 G protein activity | IBA GO_REF:0000033 | ACCEPT | Summary: GNAI2 is a guanine-nucleotide-binding G alpha subunit that switches between GDP- and GTP-bound states and hydrolyzes bound GTP. Reason: Receptor/effector biochemistry and nucleotide-state experiments support the intrinsic molecular switch. This is distinct from the GAP activity of RGS proteins; activated or nucleotide-defective mutants are controls, not substitutes for the wild-type function. Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:16782902 Activation state-dependent interaction between Galphai and p... | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:16782902 Activation state-dependent interaction between Galphai and p... | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:16782902 Activation state-dependent interaction between Galphai and p... | MODIFY | Summary: Interaction with a G-protein beta subunit (UniProtKB:P62873) reported in PMID:16782902. GΞ²Ξ³ binding is the defining heterotrimer interaction of GΞ± subunits. Reason: Generic protein binding is uninformative. Binding of GΞ±i2-GDP to GΞ²Ξ³ forms the inactive heterotrimer (UniProt subunit statement; Reactome R-HSA-751001), so the more informative existing term G-protein beta/gamma-subunit complex binding is proposed. Proposed replacements: G-protein beta/gamma-subunit complex binding Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt In this context, forms a complex with the beta subunit GNB1 and the gamma subunit GNG2 Reactome:R-HSA-751001 The inactive G alpha (i):GDP complex has much higher affinity for the G beta:gamma complex and consequently reassociates. |
| GO:0005515 protein binding | IPI PMID:18599439 Agonist-selective signaling is determined by the receptor lo... | MODIFY | Summary: Co-immunoprecipitation/association of GΞ±i2 with the mu-opioid receptor (mouse Oprm1) whose dissociation from GΞ±i2 governs agonist-selective receptor translocation (PMID:18599439). Reason: Generic protein binding is uninformative; the partner is a Gi-coupled GPCR and the paper shows agonist-regulated receptorβGΞ±i2 association. G protein-coupled receptor binding captures the functional interaction. Proposed replacements: G protein-coupled receptor binding Supporting Evidence: PMID:18599439 The etorphine-induced MOR translocation required the dissociation of the receptor from Galphai2 first and then the binding of beta-arrestin. |
| GO:0005515 protein binding | IPI PMID:23773523 Differential G protein subunit expression by prostate cancer... | MODIFY | Summary: GΞ±i2 co-immunoprecipitated with the chemokine receptor CXCR5 in resting PCa cells and dissociated after CXCL13 stimulation (PMID:23773523). Reason: Generic protein binding is uninformative; the interaction is ligand-regulated GPCRβG protein coupling, better described by G protein-coupled receptor binding. Proposed replacements: G protein-coupled receptor binding Supporting Evidence: PMID:23773523 GΞ±q/11/GΞ²3/GΞ³9 in LNCaP and GΞ±i2/GΞ²3/GΞ³9 in C4-2B and PC3 cell lines, were coupled to CXCR5 and disassociated following CXCL13 stimulation. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: In situ proximity ligation assay detected endogenous GNAI2βCXCR5 proximity in HeLa cells (PMID:25241761; abstract only cached). Reason: Generic protein binding is uninformative. The partner is the Gi-coupled chemokine receptor CXCR5, and independent co-immunoprecipitation work shows ligand-regulated CXCR5βGΞ±i2 coupling (PMID:23773523), so G protein-coupled receptor binding is the informative replacement. Proposed replacements: G protein-coupled receptor binding Supporting Evidence: PMID:23773523 GΞ±q/11/GΞ²3/GΞ³9 in LNCaP and GΞ±i2/GΞ²3/GΞ³9 in C4-2B and PC3 cell lines, were coupled to CXCR5 and disassociated following CXCL13 stimulation. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:28219978 A Mutation in the G-Protein Gene GNB2 Causes Familial Sinus ... | MODIFY | Summary: Interaction with a G-protein beta subunit (UniProtKB:P62879) reported in PMID:28219978. GΞ²Ξ³ binding is the defining heterotrimer interaction of GΞ± subunits. Reason: Generic protein binding is uninformative. Binding of GΞ±i2-GDP to GΞ²Ξ³ forms the inactive heterotrimer (UniProt subunit statement; Reactome R-HSA-751001), so the more informative existing term G-protein beta/gamma-subunit complex binding is proposed. Proposed replacements: G-protein beta/gamma-subunit complex binding Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt In this context, forms a complex with the beta subunit GNB1 and the gamma subunit GNG2 Reactome:R-HSA-751001 The inactive G alpha (i):GDP complex has much higher affinity for the G beta:gamma complex and consequently reassociates. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Interaction with a G-protein beta subunit (UniProtKB:P62873) reported in PMID:33961781. GΞ²Ξ³ binding is the defining heterotrimer interaction of GΞ± subunits. Reason: Generic protein binding is uninformative. Binding of GΞ±i2-GDP to GΞ²Ξ³ forms the inactive heterotrimer (UniProt subunit statement; Reactome R-HSA-751001), so the more informative existing term G-protein beta/gamma-subunit complex binding is proposed. Proposed replacements: G-protein beta/gamma-subunit complex binding Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt In this context, forms a complex with the beta subunit GNB1 and the gamma subunit GNG2 Reactome:R-HSA-751001 The inactive G alpha (i):GDP complex has much higher affinity for the G beta:gamma complex and consequently reassociates. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: Interaction with a G-protein beta subunit (UniProtKB:P62873) reported in PMID:35271311. GΞ²Ξ³ binding is the defining heterotrimer interaction of GΞ± subunits. Reason: Generic protein binding is uninformative. Binding of GΞ±i2-GDP to GΞ²Ξ³ forms the inactive heterotrimer (UniProt subunit statement; Reactome R-HSA-751001), so the more informative existing term G-protein beta/gamma-subunit complex binding is proposed. Proposed replacements: G-protein beta/gamma-subunit complex binding Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt In this context, forms a complex with the beta subunit GNB1 and the gamma subunit GNG2 Reactome:R-HSA-751001 The inactive G alpha (i):GDP complex has much higher affinity for the G beta:gamma complex and consequently reassociates. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: The physical interactions are not denied. Reason: Remove bare protein binding under the project policy while retaining specific receptor, beta/gamma and effector functions supported independently. |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: GNAI2 is a guanine-nucleotide-binding G alpha subunit that switches between GDP- and GTP-bound states and hydrolyzes bound GTP. Reason: Receptor/effector biochemistry and nucleotide-state experiments support the intrinsic molecular switch. This is distinct from the GAP activity of RGS proteins; activated or nucleotide-defective mutants are controls, not substitutes for the wild-type function. Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: The G alpha protein is an intracellular peripheral-membrane signaling component with a cytoplasmic pool. Reason: Cytoplasm is compatible with membrane association and, where demonstrated, other intracellular pools; no exclusive localization is inferred. Supporting Evidence: PMID:17635935 We show expression of G(ialpha1), G(ialpha2), and G(ialpha3) in the centrosomes and at the midbody |
| GO:0005737 cytoplasm | IDA PMID:17635935 Localization of Gi alpha proteins in the centrosomes and at ... | ACCEPT | Summary: The G alpha protein is an intracellular peripheral-membrane signaling component with a cytoplasmic pool. Reason: Cytoplasm is compatible with membrane association and, where demonstrated, other intracellular pools; no exclusive localization is inferred. Supporting Evidence: PMID:17635935 We show expression of G(ialpha1), G(ialpha2), and G(ialpha3) in the centrosomes and at the midbody |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: The G alpha protein is an intracellular peripheral-membrane signaling component with a cytoplasmic pool. Reason: Cytoplasm is compatible with membrane association and, where demonstrated, other intracellular pools; no exclusive localization is inferred. Supporting Evidence: PMID:17635935 We show expression of G(ialpha1), G(ialpha2), and G(ialpha3) in the centrosomes and at the midbody |
| GO:0005813 centrosome | IDA PMID:17635935 Localization of Gi alpha proteins in the centrosomes and at ... | KEEP AS NON CORE | Summary: Cell imaging directly identifies Gi2 at centrosomes and the midbody during division. Reason: Retain these cell-cycle-specific locations independently of its plasma-membrane pool. Supporting Evidence: |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cell imaging directly identifies Gi2 at centrosomes and the midbody during division. Reason: Retain these cell-cycle-specific locations independently of its plasma-membrane pool. Supporting Evidence: |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: The intracellular soluble pool is compatible with direct localization experiments and the dynamic membrane/mitotic distributions of Gi2. Reason: Retain the cytosolic assignment without implying exclusive solubility. Supporting Evidence: |
| GO:0005834 heterotrimeric G-protein complex | IBA GO_REF:0000033 | ACCEPT | Summary: The GDP-state G alpha subunit associates with a G beta/gamma dimer to form a functional heterotrimer. Reason: Receptor-coupling and structural/reconstitution experiments support this assembly and beta/gamma binding as integral functions. A particular experimental beta/gamma combination does not imply universal interchangeability. Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt In this context, forms a complex with the beta subunit GNB1 and the gamma subunit GNG2 |
| GO:0005886 plasma membrane | EXP PMID:17635935 Localization of Gi alpha proteins in the centrosomes and at ... | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:P04897 SUPPORTS TRANSFER The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. UniProtKB-SubCell:SL-0039 SUPPORTS TRANSFER The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-170666 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-170671 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-170674 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-170686 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-380073 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-392187 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-392195 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-392202 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749454 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749456 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-751001 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8964242 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8964329 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982012 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982019 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982020 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9021600 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9021601 | MODIFY | Summary: The independently supported plasma-membrane signaling pool lies on the cytoplasmic side, already represented separately in this record. Reason: Refine this general membrane location while retaining other independently supported intracellular locations; the refinement does not assert exclusive residence. Proposed replacements: cytoplasmic side of plasma membrane Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | MODIFY | Summary: The protein directly transduces signals through heterotrimeric G protein-coupled receptor signaling. Reason: Refine generic signal transduction to the established receptor pathway without excluding additional receptor-independent functions. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: InterPro:IPR011025 SUPPORTS TRANSFER The protein directly transduces signals through heterotrimeric G protein-coupled receptor signaling. Refine generic signal transduction to the established receptor pathway without excluding additional receptor-independent functions. Proposed replacements: G protein-coupled receptor signaling pathway Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades |
| GO:0007165 signal transduction | TAS PMID:7961880 Regulation of cAMP-mediated gene transcription by wild type ... | MODIFY | Summary: The protein directly transduces signals through heterotrimeric G protein-coupled receptor signaling. Reason: Refine generic signal transduction to the established receptor pathway without excluding additional receptor-independent functions. Proposed replacements: G protein-coupled receptor signaling pathway Supporting Evidence: PMID:7961880 G2A Gi alpha-2 was unable to couple the m4 mAChR to inhibition of AC |
| GO:0007165 signal transduction | TAS PMID:9637720 Right ventricular outflow tract tachycardia due to a somatic... | MODIFY | Summary: The protein directly transduces signals through heterotrimeric G protein-coupled receptor signaling. Reason: Refine generic signal transduction to the established receptor pathway without excluding additional receptor-independent functions. Proposed replacements: G protein-coupled receptor signaling pathway Supporting Evidence: PMID:9637720 This mutation was shown to increase intracellular cAMP concentration and inhibit suppression of cAMP by adenosine |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Receptor-dependent nucleotide exchange and effector coupling establish direct participation in GPCR signaling. Reason: Individual receptor preferences and physiological contexts must be established separately rather than inferred from the whole G protein family. Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt Signaling by an activated GPCR promotes GDP release and GTP binding |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS PMID:8587610 Insulin action impaired by deficiency of the G-protein subun... | ACCEPT | Summary: Receptor-dependent nucleotide exchange and effector coupling establish direct participation in GPCR signaling. Reason: Individual receptor preferences and physiological contexts must be established separately rather than inferred from the whole G protein family. Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt Signaling by an activated GPCR promotes GDP release and GTP binding |
| GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: Gi2 modulates cyclase output with enzyme-isoform and concentration dependence. Reason: Purified inhibition is strong for selected isoforms, while high-concentration activation of others is reported; the unsigned pathway term preserves this documented context dependence. Supporting Evidence: PMID:8119955 Type II adenylyl cyclase appears to be immune to inhibition by these proteins PMID:8119955 High concentrations of Gi alpha can interact with site 1 on types I and II adenylyl cyclase and activate the enzymes. |
| GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway | IEA GO_REF:0000107 | MODIFY | Summary: The traced rat source PMID:27912212 directly measures oxotremorine-dependent inhibition of adenylyl cyclase; Gi2 knockdown attenuates that inhibition. Reason: Its activating-pathway transfer reverses the measured sign. Refine to the independently supported inhibitory pathway while acknowledging that high-concentration stimulation of other purified cyclases is a different biochemical context. Propagation Review Root cause: SOURCE BAD Failure modes: REGULATORY SIGN INVERSION Sources checked: UniProtKB:P04897 SOURCE BAD The traced rat source PMID:27912212 directly measures oxotremorine-dependent inhibition of adenylyl cyclase; Gi2 knockdown attenuates that inhibition. Its activating-pathway transfer reverses the measured sign. Refine to the independently supported inhibitory pathway while acknowledging that high-concentration stimulation of other purified cyclases is a different biochemical context. Proposed replacements: adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway Supporting Evidence: PMID:8119955 Types V and VI adenylyl cyclase are most sensitive to inhibition by Gi alpha 1, Gi alpha 2, and Gi alpha 3 |
| GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Native receptor signaling, human Gi2 mutation studies and purified cyclase reconstitution establish inhibitory regulation of cAMP production. Reason: This is direct effector regulation with cyclase-isoform dependence, not a blanket claim that every Gi2 output is inhibitory. Supporting Evidence: PMID:8119955 Types V and VI adenylyl cyclase are most sensitive to inhibition by Gi alpha 1, Gi alpha 2, and Gi alpha 3 |
| GO:0007194 negative regulation of adenylate cyclase activity | TAS PMID:9637720 Right ventricular outflow tract tachycardia due to a somatic... | ACCEPT | Summary: Native receptor signaling, human Gi2 mutation studies and purified cyclase reconstitution establish inhibitory regulation of cAMP production. Reason: This is direct effector regulation with cyclase-isoform dependence, not a blanket claim that every Gi2 output is inhibitory. Supporting Evidence: PMID:8119955 Types V and VI adenylyl cyclase are most sensitive to inhibition by Gi alpha 1, Gi alpha 2, and Gi alpha 3 |
| GO:0007214 gamma-aminobutyric acid signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The traced native-neuron study uses PTX-insensitive alpha-subunit replacement to establish adenosine and GABAB receptor-dependent presynaptic inhibition. Reason: Retain these conserved receptor-context capabilities with engineered rescue scope; the experiments do not mean every inhibitory receptor selects Gi2. Supporting Evidence: |
| GO:0007214 gamma-aminobutyric acid signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The traced native-neuron study uses PTX-insensitive alpha-subunit replacement to establish adenosine and GABAB receptor-dependent presynaptic inhibition. Reason: Retain these conserved receptor-context capabilities with engineered rescue scope; the experiments do not mean every inhibitory receptor selects Gi2. Supporting Evidence: |
| GO:0007584 response to nutrient | TAS PMID:8587610 Insulin action impaired by deficiency of the G-protein subun... | KEEP AS NON CORE | Summary: Mouse Gi2-targeted antisense produces insulin resistance and altered metabolic responses, supporting a conserved nutrient-response role. Reason: This is endocrine signaling participation rather than direct nutrient transport or catalysis. Supporting Evidence: |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GNAI2-specific perturbation in human tongue-cancer cells supports positive regulation of proliferation, with separate vascular and neural models providing contextual corroboration. Reason: Retain the phenotype as secondary signaling activity, not universal promotion of growth. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:21079996 Identification and experimental validation of G protein alph... | KEEP AS NON CORE | Summary: GNAI2-specific perturbation in human tongue-cancer cells supports positive regulation of proliferation, with separate vascular and neural models providing contextual corroboration. Reason: Retain the phenotype as secondary signaling activity, not universal promotion of growth. |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:17635935 Localization of Gi alpha proteins in the centrosomes and at ... | ACCEPT | Summary: The intracellular G alphaβbeta/gamma complex contacts the cytoplasmic receptor surface and intracellular effectors. Reason: Receptor-complex structures, membrane targeting and signaling experiments support the cytoplasmic plasma-membrane face. Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0009898 cytoplasmic side of plasma membrane | IEA GO_REF:0000117 | ACCEPT | Summary: The intracellular G alphaβbeta/gamma complex contacts the cytoplasmic receptor surface and intracellular effectors. Reason: Receptor-complex structures, membrane targeting and signaling experiments support the cytoplasmic plasma-membrane face. Supporting Evidence: PMID:17635935 Imaging of live cells transfected with the GiΞ±-YFP constructs demonstrated that the fusion proteins were predominantly localized at the plasma membrane in most cells |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MODIFY | Summary: Independent membrane targeting identifies a cytoplasmic plasma-membrane pool. Reason: Refine the generic membrane assertion to that directly supported membrane surface, while retaining the separately asserted neuronal dense-core-vesicle pool; this is not exclusive localization. Proposed replacements: cytoplasmic side of plasma membrane |
| GO:0016020 membrane | IEA GO_REF:0000044 | MODIFY | Summary: Independent membrane targeting identifies a cytoplasmic plasma-membrane pool. Reason: Refine the generic membrane assertion to that directly supported membrane surface, while retaining the separately asserted neuronal dense-core-vesicle pool; this is not exclusive localization. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB-SubCell:SL-0162 SUPPORTS TRANSFER Independent membrane targeting identifies a cytoplasmic plasma-membrane pool. Refine the generic membrane assertion to that directly supported membrane surface, while retaining the separately asserted neuronal dense-core-vesicle pool; this is not exclusive localization. Proposed replacements: cytoplasmic side of plasma membrane |
| GO:0019001 guanyl nucleotide binding | IEA GO_REF:0000002 | MODIFY | Summary: The conserved guanine-nucleotide pocket binds GTP during activation and GDP in the inactive state. Reason: Refine the generic nucleotide-binding term to these two chemically defined ligands, preserving both halves of the switch. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: InterPro:IPR001019 SUPPORTS TRANSFER The conserved guanine-nucleotide pocket binds GTP during activation and GDP in the inactive state. Refine the generic nucleotide-binding term to these two chemically defined ligands, preserving both halves of the switch. Proposed replacements: GTP binding GDP binding Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state |
| GO:0030335 positive regulation of cell migration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Human prostate cancer cell Gi2 knockdown, PTX-resistant rescue and siRNA-resistant rescue directly support oxytocin/EGF-induced migration. Reason: Retain this specific signaling contribution rather than infer migration from expression alone. Supporting Evidence: |
| GO:0030425 dendrite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Native mouse cerebellar immunolocalization places Gi2 in neuronal somata and transiently in developing Purkinje dendrites. Reason: Retain the conserved locations with developmental-stage limits; this is not constitutive localization in all adult neurons. Supporting Evidence: |
| GO:0030496 midbody | IDA PMID:17635935 Localization of Gi alpha proteins in the centrosomes and at ... | KEEP AS NON CORE | Summary: Cell imaging directly identifies Gi2 at centrosomes and the midbody during division. Reason: Retain these cell-cycle-specific locations independently of its plasma-membrane pool. Supporting Evidence: |
| GO:0031683 G-protein beta/gamma-subunit complex binding | IEA GO_REF:0000002 | ACCEPT | Summary: The GDP-state G alpha subunit associates with a G beta/gamma dimer to form a functional heterotrimer. Reason: Receptor-coupling and structural/reconstitution experiments support this assembly and beta/gamma binding as integral functions. A particular experimental beta/gamma combination does not imply universal interchangeability. Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt In this context, forms a complex with the beta subunit GNB1 and the gamma subunit GNG2 |
| GO:0032930 positive regulation of superoxide anion generation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Gi2 antisense in hypertensive rats reduces enhanced superoxide/NADPH-oxidase outputs and vascular smooth-muscle hyperproliferation. Reason: Retain the positive regulatory functions in that disease-model context, not direct oxidase catalysis or universal vascular growth promotion. Supporting Evidence: |
| GO:0035810 positive regulation of urine volume | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Brain Gi2 downregulation disrupts volume-expansion renal responses in rats, supporting a conserved central signaling contribution to fluid excretion. Reason: The mechanism is sympathoinhibitory control, not direct renal water transport by Gi2. Supporting Evidence: |
| GO:0044297 cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Native mouse cerebellar immunolocalization places Gi2 in neuronal somata and transiently in developing Purkinje dendrites. Reason: Retain the conserved locations with developmental-stage limits; this is not constitutive localization in all adult neurons. Supporting Evidence: |
| GO:0045955 negative regulation of calcium ion-dependent exocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Rat alpha-cell capacitance assays and Gi2-directed antisense demonstrate somatostatin-dependent inhibition of calcium-triggered exocytosis via calcineurin/depriming. Reason: Retain this defined endocrine context without attributing vesicle fusion catalysis to Gi2. Supporting Evidence: |
| GO:0050804 modulation of chemical synaptic transmission | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse expression of constitutively active Gi2 modifies mGluR2-dependent transmission and plasticity at mossy-fiberβCA3 synapses. Reason: Retain the contextual signaling/site inference with the activated-transgene limitation; it is not proof that unmodified Gi2 alone mediates every mGluR2 response. Supporting Evidence: |
| GO:0050805 negative regulation of synaptic transmission | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The traced native-neuron study uses PTX-insensitive alpha-subunit replacement to establish adenosine and GABAB receptor-dependent presynaptic inhibition. Reason: Retain these conserved receptor-context capabilities with engineered rescue scope; the experiments do not mean every inhibitory receptor selects Gi2. Supporting Evidence: |
| GO:0051301 cell division | IMP PMID:17635935 Localization of Gi alpha proteins in the centrosomes and at ... | KEEP AS NON CORE | Summary: Direct cell-cycle localization and perturbation implicate Gi2 in cytokinetic regulation. Reason: This secondary division role is distinct from its receptor-transducer mechanism. Supporting Evidence: |
| GO:0051924 regulation of calcium ion transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Defined PTX-resistant Gi2 heterotrimers restore receptor-dependent N-type calcium-current inhibition in rat sympathetic neurons. Reason: Retain channel-regulatory participation with heterologous replacement and receptor-specific efficiency limits. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:12519789 Proteomic and biochemical analyses of human B cell-derived e... | KEEP AS NON CORE | Summary: The B-cell exosome study explicitly detects Gi2 among vesicular signaling proteins, independently supporting extracellular-vesicle localization. Reason: Retain this secondary cargo pool across the broader proteomics rows without claiming that every individual survey resolves vesicle topology or a functional extracellular Gi2 signal. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: The B-cell exosome study explicitly detects Gi2 among vesicular signaling proteins, independently supporting extracellular-vesicle localization. Reason: Retain this secondary cargo pool across the broader proteomics rows without claiming that every individual survey resolves vesicle topology or a functional extracellular Gi2 signal. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: The B-cell exosome study explicitly detects Gi2 among vesicular signaling proteins, independently supporting extracellular-vesicle localization. Reason: Retain this secondary cargo pool across the broader proteomics rows without claiming that every individual survey resolves vesicle topology or a functional extracellular Gi2 signal. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: The B-cell exosome study explicitly detects Gi2 among vesicular signaling proteins, independently supporting extracellular-vesicle localization. Reason: Retain this secondary cargo pool across the broader proteomics rows without claiming that every individual survey resolves vesicle topology or a functional extracellular Gi2 signal. Supporting Evidence: |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A Gi2-specific ribozyme reduces PGF2alpha-induced ERK activation in hepatocytes with specificity controls. Reason: Retain this positive signaling contribution rather than assign Gi2 direct MAP kinase activity. Supporting Evidence: |
| GO:0071878 negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The transferred study supports Gi2-dependent restraint of adrenergic cAMP signaling. Reason: Retain this receptor-context regulatory sign as consistent with independently demonstrated inhibitory cyclase activity, without assuming all adrenergic pathways are Gi2 substrates. Supporting Evidence: file:human/GNAI2/GNAI2-uniprot.txt The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli |
| GO:0098686 hippocampal mossy fiber to CA3 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse expression of constitutively active Gi2 modifies mGluR2-dependent transmission and plasticity at mossy-fiberβCA3 synapses. Reason: Retain the contextual signaling/site inference with the activated-transgene limitation; it is not proof that unmodified Gi2 alone mediates every mGluR2 response. Supporting Evidence: |
| GO:0098992 neuronal dense core vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The target-specific primary explicitly localizes Gi2 to substance-P-positive large dense-core vesicles and shows DOR1/Gi2 interaction-dependent recruitment and surface delivery. Reason: Retain this transport pool rather than infer membrane exclusivity from plasma-membrane function. Supporting Evidence: |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | KEEP AS NON CORE | Summary: The B-cell exosome study explicitly detects Gi2 among vesicular signaling proteins, independently supporting extracellular-vesicle localization. Reason: Retain this secondary cargo pool across the broader proteomics rows without claiming that every individual survey resolves vesicle topology or a functional extracellular Gi2 signal. Supporting Evidence: |
| GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Gi2 antisense in hypertensive rats reduces enhanced superoxide/NADPH-oxidase outputs and vascular smooth-muscle hyperproliferation. Reason: Retain the positive regulatory functions in that disease-model context, not direct oxidase catalysis or universal vascular growth promotion. Supporting Evidence: |
| GO:2000179 positive regulation of neural precursor cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The comparative developmental study combines Gi2 localization, PTX-sensitive neural-progenitor mitogenic signaling and endothelin stimulation. Reason: Retain the conserved proliferation role while noting that PTX is not Gi2-selective and the target assignment is less direct than a Gi2-specific knockout/rescue. Supporting Evidence: |
| GO:2001234 negative regulation of apoptotic signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: LPA protection of marrow stromal cells implicates Gi2/Gi3-dependent ERK and PI3K signaling in suppression of peroxide-induced apoptosis. Reason: Retain this conditional conserved survival response without assigning an intrinsic anti-apoptotic function in every cell. Supporting Evidence: |
| GO:0010855 adenylate cyclase inhibitor activity | IDA PMID:8119955 Distinct patterns of bidirectional regulation of mammalian a... | NEW | Summary: Purified, activated GΞ±i2 directly inhibits membrane adenylyl cyclases, most potently types V and VI (PMID:8119955; PMID:8327893). Reason: GΞ±i2-GTP is itself the effector-regulating entity: it binds adenylyl cyclase at an inhibitory site distinct from the GsΞ± site and reduces catalytic activity. Comparator check: human GNAI1 carries GO:0010855 by IDA from the same paper, which reports Gi alpha 1, 2 and 3 alike, and mouse Gnaz carries it by IMP; GNAI2 lacks it. This MF captures the effector activity that underlies the accepted adenylate cyclase-inhibiting GPCR signaling pathway and negative regulation of adenylate cyclase activity annotations. Supporting Evidence: PMID:8119955 Types V and VI adenylyl cyclase are most sensitive to inhibition by Gi alpha 1, Gi alpha 2, and Gi alpha 3 PMID:8327893 Concentration-dependent inhibition of adenylyl cyclases by purified Gi alpha subunits is described. PMID:12359238 The interaction of G(ialpha(2)) and UNC5H2 liberated adenylyl cyclase from G(ialpha(2)) inhibition. |
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