Chrm2 encodes the M2 muscarinic acetylcholine receptor, a seven-transmembrane GPCR that couples acetylcholine recognition to Gi/o-family signaling. It inhibits adenylyl cyclase in appropriate signaling contexts and regulates ion channels through G protein subunits. M2 receptors slow cardiac pacemaker activity and act as inhibitory presynaptic autoreceptors in selected brain regions, including hippocampus and cerebral cortex. Receptor localization and downstream effects vary by cell type, and M4 has the predominant autoreceptor role in mouse striatum.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004930 G protein-coupled receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: The receptor is specifically an acetylcholine-activated muscarinic GPCR. Reason: Refine generic GPCR activity to the existing acetylcholine-receptor activity supported by native M2 knockout studies. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: InterPro:IPR000276 SUPPORTS TRANSFER The receptor is specifically an acetylcholine-activated muscarinic GPCR. Refine generic GPCR activity to the existing acetylcholine-receptor activity supported by native M2 knockout studies. Proposed replacements: G protein-coupled acetylcholine receptor activity Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0005730 nucleolus | ISO GO_REF:0000119 | UNDECIDED | Summary: This location is transferred from human CHRM2 (UniProtKB:P08172), but the current human source review and curated record do not recover the specific nucleolar/Golgi/ciliary localization evidence. Reason: The historical experimental source and target-level localization assay remain unresolved. Plasma-membrane localization does not disprove an additional intracellular pool; the organelle assertion is therefore neither removed nor narrowed. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08172 UNRESOLVED This location is transferred from human CHRM2 (UniProtKB:P08172), but the current human source review and curated record do not recover the specific nucleolar/Golgi/ciliary localization evidence. The historical experimental source and target-level localization assay remain unresolved. Plasma-membrane localization does not disprove an additional intracellular pool; the organelle assertion is therefore neither removed nor narrowed. |
| GO:0005794 Golgi apparatus | ISO GO_REF:0000119 | UNDECIDED | Summary: This location is transferred from human CHRM2 (UniProtKB:P08172), but the current human source review and curated record do not recover the specific nucleolar/Golgi/ciliary localization evidence. Reason: The historical experimental source and target-level localization assay remain unresolved. Plasma-membrane localization does not disprove an additional intracellular pool; the organelle assertion is therefore neither removed nor narrowed. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08172 UNRESOLVED This location is transferred from human CHRM2 (UniProtKB:P08172), but the current human source review and curated record do not recover the specific nucleolar/Golgi/ciliary localization evidence. The historical experimental source and target-level localization assay remain unresolved. Plasma-membrane localization does not disprove an additional intracellular pool; the organelle assertion is therefore neither removed nor narrowed. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: M2 is a functional cell-surface muscarinic receptor, with receptor-mediated acetylcholine responses and membrane receptor localization. Reason: Native cardiac and brain knockout experiments independently support the membrane signaling role. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: M2 is a functional cell-surface muscarinic receptor, with receptor-mediated acetylcholine responses and membrane receptor localization. Reason: Native cardiac and brain knockout experiments independently support the membrane signaling role. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0005886 plasma membrane | ISO GO_REF:0000119 | ACCEPT | Summary: M2 is a functional cell-surface muscarinic receptor, with receptor-mediated acetylcholine responses and membrane receptor localization. Reason: Native cardiac and brain knockout experiments independently support the membrane signaling role. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0005886 plasma membrane | ISO GO_REF:0000119 | ACCEPT | Summary: M2 is a functional cell-surface muscarinic receptor, with receptor-mediated acetylcholine responses and membrane receptor localization. Reason: Native cardiac and brain knockout experiments independently support the membrane signaling role. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: M2 is a functional cell-surface muscarinic receptor, with receptor-mediated acetylcholine responses and membrane receptor localization. Reason: Native cardiac and brain knockout experiments independently support the membrane signaling role. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0005929 cilium | ISO GO_REF:0000119 | UNDECIDED | Summary: This location is transferred from human CHRM2 (UniProtKB:P08172), but the current human source review and curated record do not recover the specific nucleolar/Golgi/ciliary localization evidence. Reason: The historical experimental source and target-level localization assay remain unresolved. Plasma-membrane localization does not disprove an additional intracellular pool; the organelle assertion is therefore neither removed nor narrowed. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08172 UNRESOLVED This location is transferred from human CHRM2 (UniProtKB:P08172), but the current human source review and curated record do not recover the specific nucleolar/Golgi/ciliary localization evidence. The historical experimental source and target-level localization assay remain unresolved. Plasma-membrane localization does not disprove an additional intracellular pool; the organelle assertion is therefore neither removed nor narrowed. |
| GO:0006940 regulation of smooth muscle contraction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: M2 contributes to muscarinic control of smooth-muscle contraction as a Gi/o-coupled receptor; the effect is context-dependent and need not be the primary contractile M3 pathway. Reason: Retain the conserved regulatory role rather than describe M2 as a contractile structural protein. Native tissue specificity must be distinguished from a universal receptor hierarchy. Supporting Evidence: |
| GO:0006940 regulation of smooth muscle contraction | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: M2 contributes to muscarinic control of smooth-muscle contraction as a Gi/o-coupled receptor; the effect is context-dependent and need not be the primary contractile M3 pathway. Reason: Retain the conserved regulatory role rather than describe M2 as a contractile structural protein. Native tissue specificity must be distinguished from a universal receptor hierarchy. Supporting Evidence: |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: M2 directly receives cholinergic signals and activates G proteins. Reason: Native knockout evidence establishes cardiac and brain functions, with hippocampal/cortical autoreceptor use distinct from the predominantly M4 striatal implementation. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | IBA GO_REF:0000033 | MODIFY | Summary: For this receptor the specific represented cyclic-nucleotide pathway is acetylcholine receptor-mediated inhibition of adenylyl cyclase. Reason: Refine to the existing M2-compatible pathway without implying that cyclic-nucleotide regulation is its only output. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000664111 SUPPORTS TRANSFER For this receptor the specific represented cyclic-nucleotide pathway is acetylcholine receptor-mediated inhibition of adenylyl cyclase. Refine to the existing M2-compatible pathway without implying that cyclic-nucleotide regulation is its only output. Proposed replacements: adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway |
| GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | IEA GO_REF:0000107 | MODIFY | Summary: For this receptor the specific represented cyclic-nucleotide pathway is acetylcholine receptor-mediated inhibition of adenylyl cyclase. Reason: Refine to the existing M2-compatible pathway without implying that cyclic-nucleotide regulation is its only output. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:P08172 SUPPORTS TRANSFER For this receptor the specific represented cyclic-nucleotide pathway is acetylcholine receptor-mediated inhibition of adenylyl cyclase. Refine to the existing M2-compatible pathway without implying that cyclic-nucleotide regulation is its only output. Proposed replacements: adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway |
| GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | ISO GO_REF:0000119 | MODIFY | Summary: For this receptor the specific represented cyclic-nucleotide pathway is acetylcholine receptor-mediated inhibition of adenylyl cyclase. Reason: Refine to the existing M2-compatible pathway without implying that cyclic-nucleotide regulation is its only output. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:P08172 SUPPORTS TRANSFER For this receptor the specific represented cyclic-nucleotide pathway is acetylcholine receptor-mediated inhibition of adenylyl cyclase. Refine to the existing M2-compatible pathway without implying that cyclic-nucleotide regulation is its only output. Proposed replacements: adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway |
| GO:0007197 adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: M2 couples to inhibitory Gi/o signaling and participates in the adenylyl-cyclase-inhibiting muscarinic pathway. Reason: Cardiac GIRK regulation is a parallel G protein output, not evidence that all M2 effects require direct G alpha inhibition of one adenylyl cyclase isoform. |
| GO:0007197 adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: M2 couples to inhibitory Gi/o signaling and participates in the adenylyl-cyclase-inhibiting muscarinic pathway. Reason: Cardiac GIRK regulation is a parallel G protein output, not evidence that all M2 effects require direct G alpha inhibition of one adenylyl cyclase isoform. |
| GO:0007197 adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: M2 couples to inhibitory Gi/o signaling and participates in the adenylyl-cyclase-inhibiting muscarinic pathway. Reason: Cardiac GIRK regulation is a parallel G protein output, not evidence that all M2 effects require direct G alpha inhibition of one adenylyl cyclase isoform. |
| GO:0007197 adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: M2 couples to inhibitory Gi/o signaling and participates in the adenylyl-cyclase-inhibiting muscarinic pathway. Reason: Cardiac GIRK regulation is a parallel G protein output, not evidence that all M2 effects require direct G alpha inhibition of one adenylyl cyclase isoform. |
| GO:0007213 G protein-coupled acetylcholine receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: M2 directly receives cholinergic signals and activates G proteins. Reason: Native knockout evidence establishes cardiac and brain functions, with hippocampal/cortical autoreceptor use distinct from the predominantly M4 striatal implementation. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0007213 G protein-coupled acetylcholine receptor signaling pathway | IMP PMID:9990086 Pronounced pharmacologic deficits in M2 muscarinic acetylcho... | ACCEPT | Summary: M2 directly receives cholinergic signals and activates G proteins. Reason: Native knockout evidence establishes cardiac and brain functions, with hippocampal/cortical autoreceptor use distinct from the predominantly M4 striatal implementation. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0007213 G protein-coupled acetylcholine receptor signaling pathway | ISO GO_REF:0000096 | ACCEPT | Summary: M2 directly receives cholinergic signals and activates G proteins. Reason: Native knockout evidence establishes cardiac and brain functions, with hippocampal/cortical autoreceptor use distinct from the predominantly M4 striatal implementation. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0007213 G protein-coupled acetylcholine receptor signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: M2 directly receives cholinergic signals and activates G proteins. Reason: Native knockout evidence establishes cardiac and brain functions, with hippocampal/cortical autoreceptor use distinct from the predominantly M4 striatal implementation. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0007213 G protein-coupled acetylcholine receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: M2 directly receives cholinergic signals and activates G proteins. Reason: Native knockout evidence establishes cardiac and brain functions, with hippocampal/cortical autoreceptor use distinct from the predominantly M4 striatal implementation. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0007268 chemical synaptic transmission | IBA GO_REF:0000033 | ACCEPT | Summary: Native M2 regulates acetylcholine release as a presynaptic autoreceptor in hippocampus and cerebral cortex. Reason: This is direct receptor participation in synaptic transmission, with region-specific division of labor from M4. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0008016 regulation of heart contraction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: M2 receptor deletion alters cholinergic control of cardiac responses; Rgs6/Gnb5 experiments further establish the regulated M2–GIRK branch in pacemaker cells. Reason: Retain the organ-level physiological role, distinct from the receptor molecular activity. |
| GO:0009615 response to virus | IEA GO_REF:0000107 | UNDECIDED | Summary: The transferred human stimulus-response annotation lacks a resolved target-specific viral exposure or receptor-function source in the available donor record. Reason: Viral modulation of cholinergic physiology would not alone establish Chrm2 participation in the response, but the absence of a recovered source does not establish a false claim. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08172 UNRESOLVED The transferred human stimulus-response annotation lacks a resolved target-specific viral exposure or receptor-function source in the available donor record. Viral modulation of cholinergic physiology would not alone establish Chrm2 participation in the response, but the absence of a recovered source does not establish a false claim. |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: M2 is a membrane-spanning cell-surface receptor, and plasma membrane is directly supported and already annotated. Reason: Refine the general membrane term to that compartment without denying internalized receptor pools. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:P08172 SUPPORTS TRANSFER M2 is a membrane-spanning cell-surface receptor, and plasma membrane is directly supported and already annotated. Refine the general membrane term to that compartment without denying internalized receptor pools. InterPro:IPR000276 SUPPORTS TRANSFER M2 is a membrane-spanning cell-surface receptor, and plasma membrane is directly supported and already annotated. Refine the general membrane term to that compartment without denying internalized receptor pools. InterPro:IPR001065 SUPPORTS TRANSFER M2 is a membrane-spanning cell-surface receptor, and plasma membrane is directly supported and already annotated. Refine the general membrane term to that compartment without denying internalized receptor pools. InterPro:IPR017452 SUPPORTS TRANSFER M2 is a membrane-spanning cell-surface receptor, and plasma membrane is directly supported and already annotated. Refine the general membrane term to that compartment without denying internalized receptor pools. Proposed replacements: plasma membrane Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0016020 membrane | ISO GO_REF:0000119 | MODIFY | Summary: M2 is a membrane-spanning cell-surface receptor, and plasma membrane is directly supported and already annotated. Reason: Refine the general membrane term to that compartment without denying internalized receptor pools. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: UniProtKB:P08172 SUPPORTS TRANSFER M2 is a membrane-spanning cell-surface receptor, and plasma membrane is directly supported and already annotated. Refine the general membrane term to that compartment without denying internalized receptor pools. Proposed replacements: plasma membrane Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0016907 G protein-coupled acetylcholine receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Native M2 knockout removes specific muscarinic responses and alters acetylcholine autoregulation. Reason: These results support the acetylcholine-activated GPCR molecular function independently of each individual transferred row. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0016907 G protein-coupled acetylcholine receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: Native M2 knockout removes specific muscarinic responses and alters acetylcholine autoregulation. Reason: These results support the acetylcholine-activated GPCR molecular function independently of each individual transferred row. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0016907 G protein-coupled acetylcholine receptor activity | IMP PMID:9990086 Pronounced pharmacologic deficits in M2 muscarinic acetylcho... | ACCEPT | Summary: Native M2 knockout removes specific muscarinic responses and alters acetylcholine autoregulation. Reason: These results support the acetylcholine-activated GPCR molecular function independently of each individual transferred row. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0016907 G protein-coupled acetylcholine receptor activity | ISO GO_REF:0000096 | ACCEPT | Summary: Native M2 knockout removes specific muscarinic responses and alters acetylcholine autoregulation. Reason: These results support the acetylcholine-activated GPCR molecular function independently of each individual transferred row. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0016907 G protein-coupled acetylcholine receptor activity | ISO GO_REF:0000119 | ACCEPT | Summary: Native M2 knockout removes specific muscarinic responses and alters acetylcholine autoregulation. Reason: These results support the acetylcholine-activated GPCR molecular function independently of each individual transferred row. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0016907 G protein-coupled acetylcholine receptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: Native M2 knockout removes specific muscarinic responses and alters acetylcholine autoregulation. Reason: These results support the acetylcholine-activated GPCR molecular function independently of each individual transferred row. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0030425 dendrite | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Muscarinic receptor localization and native neurotransmitter-release experiments support neuronal somatodendritic/synaptic pools. Reason: Retain the anatomical inference with the donor context distinguished from exact mouse subcellular topology. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0030425 dendrite | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Muscarinic receptor localization and native neurotransmitter-release experiments support neuronal somatodendritic/synaptic pools. Reason: Retain the anatomical inference with the donor context distinguished from exact mouse subcellular topology. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0032279 asymmetric synapse | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rat M2 is directly localized to terminals at asymmetric synapses. Reason: The recovered abstract reports subtype-specific rat M2 electron microscopy, not a direct mouse assay. Retain the conserved secondary localization as an orthology inference; native mouse autoreceptor experiments provide complementary functional context, not the ultrastructural observation itself. PMID:8182478 explicitly identifies many M2-immunoreactive terminals forming asymmetric synapses, independently corroborated in monkey cortex by PMID:8389473. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: RGD:620023 SUPPORTS TRANSFER The recovered abstract reports subtype-specific rat M2 electron microscopy, not a direct mouse assay. Retain the conserved secondary localization as an orthology inference; native mouse autoreceptor experiments provide complementary functional context, not the ultrastructural observation itself. PMID:8182478 explicitly identifies many M2-immunoreactive terminals forming asymmetric synapses, independently corroborated in monkey cortex by PMID:8389473. Supporting Evidence: PMID:8182478 many m2-immunoreactive axon terminals formed asymmetrical synapses with spines or dendrites. |
| GO:0032280 symmetric synapse | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rat M2 is directly localized to terminals at symmetric synapses. Reason: The recovered abstract reports subtype-specific rat M2 electron microscopy, not a direct mouse assay. Retain the conserved secondary localization as an orthology inference; native mouse autoreceptor experiments provide complementary functional context, not the ultrastructural observation itself. PMID:8182478 explicitly finds that most M2-positive axon terminals make symmetric synapses. This is a location inference, not proof of identical transmitter identity or proportions in every mouse region. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: RGD:620023 SUPPORTS TRANSFER The recovered abstract reports subtype-specific rat M2 electron microscopy, not a direct mouse assay. Retain the conserved secondary localization as an orthology inference; native mouse autoreceptor experiments provide complementary functional context, not the ultrastructural observation itself. PMID:8182478 explicitly finds that most M2-positive axon terminals make symmetric synapses. This is a location inference, not proof of identical transmitter identity or proportions in every mouse region. Supporting Evidence: PMID:8182478 Most axon terminals containing m2 make symmetrical synapses with somata, and dendritic shafts and spines. |
| GO:0036064 ciliary basal body | ISO GO_REF:0000119 | UNDECIDED | Summary: This location is transferred from human CHRM2 (UniProtKB:P08172), but the current human source review and curated record do not recover the specific nucleolar/Golgi/ciliary localization evidence. Reason: The historical experimental source and target-level localization assay remain unresolved. Plasma-membrane localization does not disprove an additional intracellular pool; the organelle assertion is therefore neither removed nor narrowed. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:P08172 UNRESOLVED This location is transferred from human CHRM2 (UniProtKB:P08172), but the current human source review and curated record do not recover the specific nucleolar/Golgi/ciliary localization evidence. The historical experimental source and target-level localization assay remain unresolved. Plasma-membrane localization does not disprove an additional intracellular pool; the organelle assertion is therefore neither removed nor narrowed. |
| GO:0042734 presynaptic membrane | ISO GO_REF:0000096 | ACCEPT | Summary: Native mouse brain-slice experiments identify M2 as a presynaptic inhibitory autoreceptor controlling acetylcholine release in hippocampus and cortex. Reason: Retain the presynaptic-membrane pool without extending it to every cholinergic terminal. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0043025 neuronal cell body | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Muscarinic receptor localization and native neurotransmitter-release experiments support neuronal somatodendritic/synaptic pools. Reason: Retain the anatomical inference with the donor context distinguished from exact mouse subcellular topology. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0043679 axon terminus | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rat and primate M2 electron microscopy establishes axon-terminal localization. Reason: The recovered abstract reports subtype-specific rat M2 electron microscopy, not a direct mouse assay. Retain the conserved secondary localization as an orthology inference; native mouse autoreceptor experiments provide complementary functional context, not the ultrastructural observation itself. Both primary abstracts explicitly identify M2-positive axon terminals, resolving the previous access-limited uncertainty about this compartment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: RGD:620023 SUPPORTS TRANSFER The recovered abstract reports subtype-specific rat M2 electron microscopy, not a direct mouse assay. Retain the conserved secondary localization as an orthology inference; native mouse autoreceptor experiments provide complementary functional context, not the ultrastructural observation itself. Both primary abstracts explicitly identify M2-positive axon terminals, resolving the previous access-limited uncertainty about this compartment. Supporting Evidence: PMID:8182478 m2 immunocytochemistry labeled somata, aspiny dendrites, and many axon terminals. PMID:8389473 the m2 receptor is also found in presynaptic axon terminals |
| GO:0045202 synapse | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Muscarinic receptor localization and native neurotransmitter-release experiments support neuronal somatodendritic/synaptic pools. Reason: Retain the anatomical inference with the donor context distinguished from exact mouse subcellular topology. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The curated receptor record and transferred localization support a postsynaptic M2 pool in addition to the directly established presynaptic autoreceptor. Reason: Retain the nonexclusive anatomical assignment; autoreceptor physiology does not imply that all M2 is presynaptic. Supporting Evidence: file:mouse/Chrm2/Chrm2-uniprot.txt |
| GO:0045211 postsynaptic membrane | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: The curated receptor record and transferred localization support a postsynaptic M2 pool in addition to the directly established presynaptic autoreceptor. Reason: Retain the nonexclusive anatomical assignment; autoreceptor physiology does not imply that all M2 is presynaptic. Supporting Evidence: file:mouse/Chrm2/Chrm2-uniprot.txt |
| GO:0045211 postsynaptic membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The curated receptor record and transferred localization support a postsynaptic M2 pool in addition to the directly established presynaptic autoreceptor. Reason: Retain the nonexclusive anatomical assignment; autoreceptor physiology does not imply that all M2 is presynaptic. Supporting Evidence: file:mouse/Chrm2/Chrm2-uniprot.txt |
| GO:0098978 glutamatergic synapse | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Comparative M2 localization supports a secondary excitatory/glutamatergic synaptic pool. Reason: The rat source establishes M2-positive asymmetric contacts, while PMID:8389473 explicitly places primate M2 at pre- and postsynaptic compartments of asymmetric pathways using excitatory amino acids. Together these support the conserved glutamatergic-synapse assignment as an anatomical and orthology inference, not direct glutamate colabeling of mouse M2 in the present sources. A muscarinic receptor can modulate a glutamatergic synapse without becoming a glutamate receptor; not every asymmetric synapse is being equated with a chemically verified glutamatergic contact. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: RGD:620023 SUPPORTS TRANSFER The rat source establishes M2-positive asymmetric contacts, while PMID:8389473 explicitly places primate M2 at pre- and postsynaptic compartments of asymmetric pathways using excitatory amino acids. Together these support the conserved glutamatergic-synapse assignment as an anatomical and orthology inference, not direct glutamate colabeling of mouse M2 in the present sources. A muscarinic receptor can modulate a glutamatergic synapse without becoming a glutamate receptor; not every asymmetric synapse is being equated with a chemically verified glutamatergic contact. Supporting Evidence: PMID:8389473 The association of m1 and m2 receptors with asymmetric synapses in central pathways, which use excitatory amino acids as neurotransmitters, |
| GO:0098981 cholinergic synapse | EXP PMID:11880500 Characterization of central inhibitory muscarinic autorecept... | ACCEPT | Summary: M2 single- and M2/M4 double-knockout brain slices directly establish muscarinic autoinhibition of acetylcholine release. Reason: M2 predominates in hippocampus/cortex whereas M4 predominates in striatum, so retain cholinergic-synapse and presynaptic-modulation claims with this regional scope. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0098981 cholinergic synapse | IMP PMID:11880500 Characterization of central inhibitory muscarinic autorecept... | ACCEPT | Summary: M2 single- and M2/M4 double-knockout brain slices directly establish muscarinic autoinhibition of acetylcholine release. Reason: M2 predominates in hippocampus/cortex whereas M4 predominates in striatum, so retain cholinergic-synapse and presynaptic-modulation claims with this regional scope. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0099171 presynaptic modulation of chemical synaptic transmission | EXP PMID:11880500 Characterization of central inhibitory muscarinic autorecept... | ACCEPT | Summary: M2 single- and M2/M4 double-knockout brain slices directly establish muscarinic autoinhibition of acetylcholine release. Reason: M2 predominates in hippocampus/cortex whereas M4 predominates in striatum, so retain cholinergic-synapse and presynaptic-modulation claims with this regional scope. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:0099171 presynaptic modulation of chemical synaptic transmission | IMP PMID:11880500 Characterization of central inhibitory muscarinic autorecept... | ACCEPT | Summary: M2 single- and M2/M4 double-knockout brain slices directly establish muscarinic autoinhibition of acetylcholine release. Reason: M2 predominates in hippocampus/cortex whereas M4 predominates in striatum, so retain cholinergic-synapse and presynaptic-modulation claims with this regional scope. Supporting Evidence: PMID:11880500 primarily by the M2 receptor in hippocampus and cerebral cortex, but predominantly by the M4 receptor in the striatum |
| GO:1990763 arrestin family protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Arrestin association is part of muscarinic receptor regulation and is supported by conserved M2 receptor evidence, including phosphorylation-site-dependent M2–arrestin interaction in PMID:10952973. Reason: Retain the specific partner-class binding function rather than treating it as generic protein binding. |
| GO:1990763 arrestin family protein binding | ISO GO_REF:0000119 | ACCEPT | Summary: Arrestin association is part of muscarinic receptor regulation and is supported by conserved M2 receptor evidence, including phosphorylation-site-dependent M2–arrestin interaction in PMID:10952973. Reason: Retain the specific partner-class binding function rather than treating it as generic protein binding. |
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