GNA11 encodes G alpha 11, a Gq-family heterotrimeric G protein alpha subunit. Receptor-stimulated GDP/GTP exchange activates PLC beta signaling, linking extracellular stimuli to inositol trisphosphate, diacylglycerol and calcium-dependent responses. G11 acts on the cytoplasmic plasma-membrane surface and shares some physiological roles with Gq, including endocrine, vascular and developmental signaling. Receptor specificity, cellular expression and compensatory overlap determine which paralog contributes in each tissue.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001508 action potential | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The PAINT node PTN008303190 is seeded by native mouse Gna11 evidence for action-potential modulation. Reason: Retain this conserved signaling role as contextual, not direct pore-forming activity or a claim that human G11 is required for all action potentials. Supporting Evidence: |
| GO:0001664 G protein-coupled receptor binding | IEA GO_REF:0000002 | ACCEPT | Summary: Receptor coupling and the M1–G11 structure support GPCR recognition and PLC-activating signaling. Reason: The 6OIJ structural G11 construct is predominantly human P29992 but contains a Gi1 N-terminal segment; it is direct mechanistic evidence with that construct limit, not a fully native sequence assay. |
| GO:0001750 photoreceptor outer segment | ISS GO_REF:0000024 | UNDECIDED | Summary: Mouse retinal evidence does not resolve the precise transferred human outer-segment location. Reason: The precise human GNA11 outer-segment localization remains unresolved. PMID:12196552 reports chicken Gq/11 immunolocalization with G11-associated opsin signaling. Full PMID:24958088 adds adult mouse retinal localization, including Gnaq-selective cone-photoreceptor staining and cross-reactive Gnaq/11 staining, but the reported cone/photoreceptor-layer signal does not independently resolve this exact human subcompartment for each isoform. Its melanopsin experiments concern inner-retinal ganglion cells, not rod/cone outer segments. PMID:24870805 examines neonatal ipRGC expression and function, which likewise does not settle outer-segment residence. These limitations do not demonstrate absence. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q5F3B5 UNRESOLVED The precise human GNA11 outer-segment localization remains unresolved. PMID:12196552 reports chicken Gq/11 immunolocalization with G11-associated opsin signaling. Full PMID:24958088 adds adult mouse retinal localization, including Gnaq-selective cone-photoreceptor staining and cross-reactive Gnaq/11 staining, but the reported cone/photoreceptor-layer signal does not independently resolve this exact human subcompartment for each isoform. Its melanopsin experiments concern inner-retinal ganglion cells, not rod/cone outer segments. PMID:24870805 examines neonatal ipRGC expression and function, which likewise does not settle outer-segment residence. These limitations do not demonstrate absence. Supporting Evidence: PMID:24958088 These data confirm that Gnaq and Gna11 convey the melanopsin signal in Neuro-2A cells. PMID:24870805 Another possibility is that there is compensatory upregulation from other remaining Gq/11 family members in the tested mutant lines. |
| GO:0001750 photoreceptor outer segment | ISS GO_REF:0000024 | UNDECIDED | Summary: Mouse retinal evidence does not resolve the precise transferred human outer-segment location. Reason: The precise human GNA11 outer-segment localization remains unresolved. PMID:12196552 reports chicken Gq/11 immunolocalization with G11-associated opsin signaling. Full PMID:24958088 adds adult mouse retinal localization, including Gnaq-selective cone-photoreceptor staining and cross-reactive Gnaq/11 staining, but the reported cone/photoreceptor-layer signal does not independently resolve this exact human subcompartment for each isoform. Its melanopsin experiments concern inner-retinal ganglion cells, not rod/cone outer segments. PMID:24870805 examines neonatal ipRGC expression and function, which likewise does not settle outer-segment residence. These limitations do not demonstrate absence. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q71RI7 UNRESOLVED The precise human GNA11 outer-segment localization remains unresolved. PMID:12196552 reports chicken Gq/11 immunolocalization with G11-associated opsin signaling. Full PMID:24958088 adds adult mouse retinal localization, including Gnaq-selective cone-photoreceptor staining and cross-reactive Gnaq/11 staining, but the reported cone/photoreceptor-layer signal does not independently resolve this exact human subcompartment for each isoform. Its melanopsin experiments concern inner-retinal ganglion cells, not rod/cone outer segments. PMID:24870805 examines neonatal ipRGC expression and function, which likewise does not settle outer-segment residence. These limitations do not demonstrate absence. Supporting Evidence: PMID:24958088 These data confirm that Gnaq and Gna11 convey the melanopsin signal in Neuro-2A cells. PMID:24870805 Another possibility is that there is compensatory upregulation from other remaining Gq/11 family members in the tested mutant lines. |
| GO:0003924 GTPase activity | IEA GO_REF:0000002 | ACCEPT | Summary: GNA11 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. |
| GO:0003924 GTPase activity | ISS GO_REF:0000024 | ACCEPT | Summary: GNA11 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. |
| GO:0003924 GTPase activity | TAS PMID:8530500 Interaction between G proteins and tyrosine kinases upon T c... | ACCEPT | Summary: GNA11 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. |
| GO:0003924 GTPase activity | TAS Reactome:R-HSA-167415 | ACCEPT | Summary: GNA11 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. |
| GO:0003925 G protein activity | IBA GO_REF:0000033 | ACCEPT | Summary: GNA11 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. |
| GO:0003925 G protein activity | IDA PMID:15331768 Signaling and ligand binding by recombinant neuromedin U rec... | ACCEPT | Summary: GNA11 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. |
| GO:0003925 G protein activity | IDA PMID:31073061 Structures of the M1 and M2 muscarinic acetylcholine recepto... | ACCEPT | Summary: GNA11 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. |
| GO:0003925 G protein activity | IEA GO_REF:0000120 | ACCEPT | Summary: GNA11 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. |
| GO:0005515 protein binding | IPI PMID:18703424 RGS22, a novel testis-specific regulator of G-protein signal... | 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:0000117 | ACCEPT | Summary: GNA11 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. |
| GO:0005525 GTP binding | TAS Reactome:R-HSA-167429 | ACCEPT | Summary: GNA11 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. |
| 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. |
| GO:0005737 cytoplasm | IDA PMID:18703424 RGS22, a novel testis-specific regulator of G-protein signal... | 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. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | 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. |
| GO:0005737 cytoplasm | TAS PMID:9175863 Interaction of the G-protein G11alpha with receptors and pho... | 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. |
| GO:0005765 lysosomal membrane | HDA PMID:17897319 Integral and associated lysosomal membrane proteins. | UNDECIDED | Summary: The placental lysosome-proteomics citation remains original provenance, but target-specific GNA11 enrichment/topology has not been resolved from the available source. Reason: Plasma-membrane signaling does not exclude an additional lysosomal pool. 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. |
| GO:0005886 plasma membrane | IDA PMID:18703424 RGS22, a novel testis-specific regulator of G-protein signal... | 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 |
| 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:P21278 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 |
| GO:0005886 plasma membrane | TAS PMID:9175863 Interaction of the G-protein G11alpha with receptors and pho... | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-111879 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-112037 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-112271 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-114558 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-114688 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167408 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167415 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167419 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167429 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167433 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-379048 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-396996 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-397835 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-400586 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-416358 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-416516 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-418576 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-418582 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-428749 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-428750 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-428752 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-428941 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749448 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749452 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-750993 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8850560 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8964280 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8964284 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8964340 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982017 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982025 | 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 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8982026 | 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 |
| 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 |
| GO:0007165 signal transduction | TAS PMID:8530500 Interaction between G proteins and tyrosine kinases upon T c... | 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 |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000002 | 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. |
| GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the ancestral cyclase-modulating pathway capability in its broader sense: Gq/11-dependent PLC/calcium signaling can influence cAMP without direct Gs-like stimulation of adenylyl cyclase. Reason: This is a conserved pathway inference, not a claim that every G11 receptor directly regulates every cyclase isoform. |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | IDA PMID:15331768 Signaling and ligand binding by recombinant neuromedin U rec... | ACCEPT | Summary: Receptor coupling and the M1–G11 structure support GPCR recognition and PLC-activating signaling. Reason: The 6OIJ structural G11 construct is predominantly human P29992 but contains a Gi1 N-terminal segment; it is direct mechanistic evidence with that construct limit, not a fully native sequence assay. |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | IDA PMID:31073061 Structures of the M1 and M2 muscarinic acetylcholine recepto... | ACCEPT | Summary: Receptor coupling and the M1–G11 structure support GPCR recognition and PLC-activating signaling. Reason: The 6OIJ structural G11 construct is predominantly human P29992 but contains a Gi1 N-terminal segment; it is direct mechanistic evidence with that construct limit, not a fully native sequence assay. |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Receptor coupling and the M1–G11 structure support GPCR recognition and PLC-activating signaling. Reason: The 6OIJ structural G11 construct is predominantly human P29992 but contains a Gi1 N-terminal segment; it is direct mechanistic evidence with that construct limit, not a fully native sequence assay. |
| GO:0007207 phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: M1–G11 structural/coupling evidence supports the specific PLC-linked muscarinic pathway. Reason: The structure uses human G11 with a Gi1 N-terminal segment, and native mouse Gq/G11 beta-cell genetics provides complementary physiological evidence. |
| GO:0007213 G protein-coupled acetylcholine receptor signaling pathway | ISS GO_REF:0000024 | MODIFY | Summary: The demonstrated muscarinic implementation is specifically PLC-activating and is already annotated separately. Reason: Refine the broad cholinergic pathway to that supported route, without suggesting G11 binds extracellular acetylcholine. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:Q5F3B5 SUPPORTS TRANSFER The demonstrated muscarinic implementation is specifically PLC-activating and is already annotated separately. Refine the broad cholinergic pathway to that supported route, without suggesting G11 binds extracellular acetylcholine. Proposed replacements: phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway |
| GO:0007213 G protein-coupled acetylcholine receptor signaling pathway | ISS GO_REF:0000024 | MODIFY | Summary: The demonstrated muscarinic implementation is specifically PLC-activating and is already annotated separately. Reason: Refine the broad cholinergic pathway to that supported route, without suggesting G11 binds extracellular acetylcholine. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:Q71RI7 SUPPORTS TRANSFER The demonstrated muscarinic implementation is specifically PLC-activating and is already annotated separately. Refine the broad cholinergic pathway to that supported route, without suggesting G11 binds extracellular acetylcholine. Proposed replacements: phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway |
| GO:0007603 phototransduction, visible light | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Comparative mammalian experiments support a secondary phototransduction role with overlapping G-protein contributions. Reason: Retain a secondary visible-light phototransduction role for human GNA11 as comparative functional inference, not a direct human retinal assay. Full PMID:24958088 Fig. 4 isolates endogenous mouse Gnaq and Gna11 contributions in melanopsin-expressing Neuro-2A cells: either supports the calcium response, whereas joint silencing eliminates it. Fig. 5 combines native retinal knockdown with pupil measurements and supports overlapping Gnaq/Gna11/Gna14 participation without separately establishing each isoform as necessary in vivo. This mammalian evidence supplements the older chicken source PMID:12196552. PMID:24870805 preserves responses in tested single/double knockout combinations and discusses compensation or alternative signaling; this limits necessity claims, not the demonstrated participation capacity. Neither experiment establishes an exclusive human isoform assignment or every ipRGC subtype. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5F3B5 UNRESOLVED The original chicken-source transfer is retained in light of independent mammalian functional evidence, not relabeled as a direct human experiment. Retain a secondary visible-light phototransduction role for human GNA11 as comparative functional inference, not a direct human retinal assay. Full PMID:24958088 Fig. 4 isolates endogenous mouse Gnaq and Gna11 contributions in melanopsin-expressing Neuro-2A cells: either supports the calcium response, whereas joint silencing eliminates it. Fig. 5 combines native retinal knockdown with pupil measurements and supports overlapping Gnaq/Gna11/Gna14 participation without separately establishing each isoform as necessary in vivo. This mammalian evidence supplements the older chicken source PMID:12196552. PMID:24870805 preserves responses in tested single/double knockout combinations and discusses compensation or alternative signaling; this limits necessity claims, not the demonstrated participation capacity. Neither experiment establishes an exclusive human isoform assignment or every ipRGC subtype. Supporting Evidence: PMID:24958088 These data confirm that Gnaq and Gna11 convey the melanopsin signal in Neuro-2A cells. PMID:24870805 Another possibility is that there is compensatory upregulation from other remaining Gq/11 family members in the tested mutant lines. |
| GO:0007603 phototransduction, visible light | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Comparative mammalian experiments support a secondary phototransduction role with overlapping G-protein contributions. Reason: Retain a secondary visible-light phototransduction role for human GNA11 as comparative functional inference, not a direct human retinal assay. Full PMID:24958088 Fig. 4 isolates endogenous mouse Gnaq and Gna11 contributions in melanopsin-expressing Neuro-2A cells: either supports the calcium response, whereas joint silencing eliminates it. Fig. 5 combines native retinal knockdown with pupil measurements and supports overlapping Gnaq/Gna11/Gna14 participation without separately establishing each isoform as necessary in vivo. This mammalian evidence supplements the older chicken source PMID:12196552. PMID:24870805 preserves responses in tested single/double knockout combinations and discusses compensation or alternative signaling; this limits necessity claims, not the demonstrated participation capacity. Neither experiment establishes an exclusive human isoform assignment or every ipRGC subtype. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q71RI7 UNRESOLVED The original chicken-source transfer is retained in light of independent mammalian functional evidence, not relabeled as a direct human experiment. Retain a secondary visible-light phototransduction role for human GNA11 as comparative functional inference, not a direct human retinal assay. Full PMID:24958088 Fig. 4 isolates endogenous mouse Gnaq and Gna11 contributions in melanopsin-expressing Neuro-2A cells: either supports the calcium response, whereas joint silencing eliminates it. Fig. 5 combines native retinal knockdown with pupil measurements and supports overlapping Gnaq/Gna11/Gna14 participation without separately establishing each isoform as necessary in vivo. This mammalian evidence supplements the older chicken source PMID:12196552. PMID:24870805 preserves responses in tested single/double knockout combinations and discusses compensation or alternative signaling; this limits necessity claims, not the demonstrated participation capacity. Neither experiment establishes an exclusive human isoform assignment or every ipRGC subtype. Supporting Evidence: PMID:24958088 These data confirm that Gnaq and Gna11 convey the melanopsin signal in Neuro-2A cells. PMID:24870805 Another possibility is that there is compensatory upregulation from other remaining Gq/11 family members in the tested mutant lines. |
| GO:0008217 regulation of blood pressure | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Native vascular Gq/G11 signaling studies support blood-pressure regulation. Reason: Retain this orthology-based physiological role while distinguishing combined-pathway dependence from proof that human G11 alone is indispensable. Supporting Evidence: |
| GO:0009649 entrainment of circadian clock | ISS GO_REF:0000024 | UNDECIDED | Summary: Mammalian circadian assays limit necessity claims but do not independently resolve this human entrainment assignment. Reason: The precise human GNA11 contribution to circadian entrainment remains unresolved after mammalian source review. Chicken pineal phase shifting in PMID:12196552 is a different photoreceptive implementation. PMID:24958088 measures cellular phototransduction and pupillary responses, not circadian entrainment. Full PMID:24870805 actually tests mouse wheel-running rhythms: the tested mutant combinations retain light-dark entrainment and light-pulse phase shifting; Gnaq/Gna11 double mutants show a small reduction of period lengthening in constant light. That combined-genotype effect does not separately establish human GNA11 entrainment, and normal entrainment does not demonstrate absence of a redundant contribution. Do not equate melanopsin participation with proof of every downstream circadian role. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q5F3B5 UNRESOLVED The precise human GNA11 contribution to circadian entrainment remains unresolved after mammalian source review. Chicken pineal phase shifting in PMID:12196552 is a different photoreceptive implementation. PMID:24958088 measures cellular phototransduction and pupillary responses, not circadian entrainment. Full PMID:24870805 actually tests mouse wheel-running rhythms: the tested mutant combinations retain light-dark entrainment and light-pulse phase shifting; Gnaq/Gna11 double mutants show a small reduction of period lengthening in constant light. That combined-genotype effect does not separately establish human GNA11 entrainment, and normal entrainment does not demonstrate absence of a redundant contribution. Do not equate melanopsin participation with proof of every downstream circadian role. Supporting Evidence: PMID:24958088 These data confirm that Gnaq and Gna11 convey the melanopsin signal in Neuro-2A cells. PMID:24870805 Another possibility is that there is compensatory upregulation from other remaining Gq/11 family members in the tested mutant lines. |
| GO:0009649 entrainment of circadian clock | ISS GO_REF:0000024 | UNDECIDED | Summary: Mammalian circadian assays limit necessity claims but do not independently resolve this human entrainment assignment. Reason: The precise human GNA11 contribution to circadian entrainment remains unresolved after mammalian source review. Chicken pineal phase shifting in PMID:12196552 is a different photoreceptive implementation. PMID:24958088 measures cellular phototransduction and pupillary responses, not circadian entrainment. Full PMID:24870805 actually tests mouse wheel-running rhythms: the tested mutant combinations retain light-dark entrainment and light-pulse phase shifting; Gnaq/Gna11 double mutants show a small reduction of period lengthening in constant light. That combined-genotype effect does not separately establish human GNA11 entrainment, and normal entrainment does not demonstrate absence of a redundant contribution. Do not equate melanopsin participation with proof of every downstream circadian role. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q71RI7 UNRESOLVED The precise human GNA11 contribution to circadian entrainment remains unresolved after mammalian source review. Chicken pineal phase shifting in PMID:12196552 is a different photoreceptive implementation. PMID:24958088 measures cellular phototransduction and pupillary responses, not circadian entrainment. Full PMID:24870805 actually tests mouse wheel-running rhythms: the tested mutant combinations retain light-dark entrainment and light-pulse phase shifting; Gnaq/Gna11 double mutants show a small reduction of period lengthening in constant light. That combined-genotype effect does not separately establish human GNA11 entrainment, and normal entrainment does not demonstrate absence of a redundant contribution. Do not equate melanopsin participation with proof of every downstream circadian role. Supporting Evidence: PMID:24958088 These data confirm that Gnaq and Gna11 convey the melanopsin signal in Neuro-2A cells. PMID:24870805 Another possibility is that there is compensatory upregulation from other remaining Gq/11 family members in the tested mutant lines. |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:18703424 RGS22, a novel testis-specific regulator of G-protein signal... | ACCEPT | Summary: The intracellular G alpha–beta/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. |
| GO:0009898 cytoplasmic side of plasma membrane | IEA GO_REF:0000117 | ACCEPT | Summary: The intracellular G alpha–beta/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. |
| 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 |
| 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. |
| GO:0045202 synapse | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Native neuronal Gq/G11 signaling and electrophysiology support a synaptic signaling pool as a conserved location. Reason: Retain the broad synapse assertion without inventing a specific human synaptic ultrastructural compartment. Supporting Evidence: |
| GO:0060158 phospholipase C-activating dopamine receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The PAINT assertion at PTN000026396 is grounded in mouse Gq/G11-dependent dopamine signaling. Reason: Retain this receptor-context capability without describing it as the canonical mechanism of every D1 or D2 receptor or a direct assay of human G11. Supporting Evidence: |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | UNDECIDED | Summary: The original extracellular-vesicle proteomics citations do not provide independently inspected GNA11-specific enrichment in the accessible material. Reason: Retain uncertainty about this additional compartment rather than infer absence from its intracellular function. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | UNDECIDED | Summary: The original extracellular-vesicle proteomics citations do not provide independently inspected GNA11-specific enrichment in the accessible material. Reason: Retain uncertainty about this additional compartment rather than infer absence from its intracellular function. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | UNDECIDED | Summary: The original extracellular-vesicle proteomics citations do not provide independently inspected GNA11-specific enrichment in the accessible material. Reason: Retain uncertainty about this additional compartment rather than infer absence from its intracellular function. |
| GO:0086100 endothelin receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse endothelin–Gq/G11 genetics supports a developmental signaling contribution to craniofacial patterning. Reason: Retain conserved endothelin signaling and cranial development with explicit paralog-overlap and animal-model limits; G11 is a transducer, not a skeletal structural protein. Supporting Evidence: |
| GO:1904888 cranial skeletal system development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse endothelin–Gq/G11 genetics supports a developmental signaling contribution to craniofacial patterning. Reason: Retain conserved endothelin signaling and cranial development with explicit paralog-overlap and animal-model limits; G11 is a transducer, not a skeletal structural protein. Supporting Evidence: |
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