CHRNA2

Summary: Refine the broad receptor/channel activity to the independently represented acetylcholine-gated cation-channel activity.

Reason: The subunit contributes to the assembled pentamer rather than enabling a complete channel alone. Original source: GO_REF:0000002. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Refine the broad receptor/channel activity to the independently represented acetylcholine-gated cation-channel activity.

Reason: The subunit contributes to the assembled pentamer rather than enabling a complete channel alone. Original source: GO_REF:0000002. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Refine the broad receptor/channel activity to the independently represented acetylcholine-gated cation-channel activity.

Reason: The subunit contributes to the assembled pentamer rather than enabling a complete channel alone. Original source: GO_REF:0000002. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Retain functional receptor surface localization.

Reason: Original source: GO_REF:0000033. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain functional receptor surface localization.

Reason: Original source: GO_REF:0000052. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain functional receptor surface localization.

Reason: Original source: GO_REF:0000044. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain functional receptor surface localization.

Reason: Original source: PMID:18723036. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain functional receptor surface localization.

Reason: Original source: Reactome:R-HSA-622326. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain functional receptor surface localization.

Reason: Original source: Reactome:R-HSA-629595. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain functional receptor surface localization.

Reason: Original source: Reactome:R-HSA-629596. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain functional receptor surface localization.

Reason: Original source: Reactome:R-HSA-629599. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain membership in an acetylcholine-gated pentamer.

Reason: Original source: GO_REF:0000033. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain membership in an acetylcholine-gated pentamer.

Reason: Original source: PMID:24467848. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain membership in an acetylcholine-gated pentamer.

Reason: Original source: PMID:8906617. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain membership in an acetylcholine-gated pentamer.

Reason: Original source: GO_REF:0000117. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Functional human receptor currents support cation transmembrane transport.

Reason: This refines the broad ion-transport assertion without implying cation selectivity of an isolated subunit or identical permeability in every assembly. Original source: GO_REF:0000002. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Functional human receptor currents support cation transmembrane transport.

Reason: This refines the broad ion-transport assertion without implying cation selectivity of an isolated subunit or identical permeability in every assembly. Original source: PMID:8906617. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Retain the PAINT-supported calcium-transport contribution of a cation-permeable neuronal receptor.

Reason: Calcium permeability depends on subunit combination; human alpha5 and alpha6 complex measurements provide specific examples, not an assertion that this isolated subunit is a calcium-selective channel. For alpha2, the target current assay establishes receptor function while the conserved permeability inference is retained without inventing an alpha2-specific calcium-flux experiment.

Summary: The specific signaling mechanism is acetylcholine-dependent pore gating.

Reason: Refine the generic signaling term to the existing acetylcholine receptor signaling pathway, at complex level. Original source: PMID:8906617. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: acetylcholine receptor signaling pathway

Summary: Retain the receptor-mediated receiver step of cholinergic transmission.

Reason: Original source: GO_REF:0000033. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: The PAINT assertion traces to PTN000436077.

Reason: Human functional assembly supports a neuronal cholinergic receptor, but does not establish participation at a neuron-to-muscle synapse. Autonomic ganglion transmission upstream of muscle contraction is not itself that synapse. The historical IBD evidence and any target-specific neuromuscular pool remain unresolved; neither a short donor list nor lack of a muscle assay establishes evolutionary loss.

Summary: Refine the broad receptor/channel activity to the independently represented acetylcholine-gated cation-channel activity.

Reason: The subunit contributes to the assembled pentamer rather than enabling a complete channel alone. Original source: PMID:8906617. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Refine the broad receptor/channel activity to the independently represented acetylcholine-gated cation-channel activity.

Reason: The subunit contributes to the assembled pentamer rather than enabling a complete channel alone. Original source: GO_REF:0000117. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity

Summary: Functional surface expression of human receptors resolves the broad membrane/periphery assertion to plasma membrane.

Reason: This does not deny intracellular assembly or trafficking pools. Original source: GO_REF:0000002. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: plasma membrane

Summary: Functional surface expression of human receptors resolves the broad membrane/periphery assertion to plasma membrane.

Reason: This does not deny intracellular assembly or trafficking pools. Original source: PMID:8906617. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: plasma membrane

Summary: Retain contribution to acetylcholine-gated cation conductance.

Reason: Original source: GO_REF:0000033. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain contribution to acetylcholine-gated cation conductance.

Reason: Original source: PMID:24467848. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain contribution to acetylcholine-gated cation conductance.

Reason: Original source: PMID:8906617. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain contribution to acetylcholine-gated cation conductance.

Reason: Original source: GO_REF:0000120. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: The experimentally established assembly is an acetylcholine-gated channel complex, already independently represented; refine the unspecified protein complex..

Reason: The experimentally established assembly is an acetylcholine-gated channel complex, already independently represented; refine the unspecified protein complex.

Proposed replacements: acetylcholine-gated channel complex

Summary: Functional human receptor currents support cation transmembrane transport.

Reason: This refines the broad ion-transport assertion without implying cation selectivity of an isolated subunit or identical permeability in every assembly. Original source: GO_REF:0000033. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Functional human receptor currents support cation transmembrane transport.

Reason: This refines the broad ion-transport assertion without implying cation selectivity of an isolated subunit or identical permeability in every assembly. Original source: GO_REF:0000002. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Retain receptor response to nicotine.

Reason: Original source: GO_REF:0000033. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Refine the broad synaptic location to the supported receptor membrane pool(s).

Reason: Retain synaptic receptor localization. Molecular surface currents directly support gating; specialized native synaptic positions are conserved biological inferences, not images from the recombinant expression assay. Original source: PMID:24467848. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel. Refine the broad location to postsynaptic membrane, the specific synaptic pool independently supported here. This is not an inference of a native compartment from an oocyte current alone.

Proposed replacements: postsynaptic membrane

Summary: Retain a conserved postsynaptic receptor pool.

Reason: Molecular surface currents directly support gating; specialized native synaptic positions are conserved biological inferences, not images from the recombinant expression assay. Original source: GO_REF:0000033. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain a conserved postsynaptic receptor pool.

Reason: Molecular surface currents directly support gating; specialized native synaptic positions are conserved biological inferences, not images from the recombinant expression assay. Original source: GO_REF:0000002. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Human alpha2 functional studies identify acetylcholine recognition more specifically than the broad chemical class.

Reason: The isolated ligand-bound ECD and heteromeric receptor studies provide complementary binding/function evidence; refine to acetylcholine binding without inferring a native alpha2 homomer.

Proposed replacements: acetylcholine binding

Summary: Retain depolarization from the inward cation current.

Reason: Original source: GO_REF:0000033. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain depolarization from the inward cation current.

Reason: Original source: PMID:22309577. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain regulation of postsynaptic membrane potential.

Reason: Original source: GO_REF:0000108. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain an excitatory postsynaptic cation current.

Reason: Original source: GO_REF:0000108. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain cellular receptor response to nicotine.

Reason: Original source: GO_REF:0000107. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Functional surface expression of human receptors resolves the broad membrane/periphery assertion to plasma membrane.

Reason: This does not deny intracellular assembly or trafficking pools. Original source: GO_REF:0000107. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Proposed replacements: plasma membrane

Summary: Retain acetylcholine recognition coupled to channel gating.

Reason: Original source: GO_REF:0000033. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain acetylcholine recognition coupled to channel gating.

Reason: Original source: PMID:24467848. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Retain acetylcholine recognition coupled to channel gating.

Reason: Original source: GO_REF:0000117. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Refine the broad synaptic location to the supported receptor membrane pool(s).

Reason: Retain synaptic membrane localization. Molecular surface currents directly support gating; specialized native synaptic positions are conserved biological inferences, not images from the recombinant expression assay. Original source: GO_REF:0000044. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel. Refine the broad location to postsynaptic membrane, the specific synaptic pool independently supported here. This is not an inference of a native compartment from an oocyte current alone.

Proposed replacements: postsynaptic membrane

Summary: Refine the broad synaptic location to the supported receptor membrane pool(s).

Reason: Retain synaptic membrane localization. Molecular surface currents directly support gating; specialized native synaptic positions are conserved biological inferences, not images from the recombinant expression assay. Original source: PMID:18723036. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel. Refine the broad location to postsynaptic membrane, the specific synaptic pool independently supported here. This is not an inference of a native compartment from an oocyte current alone.

Proposed replacements: postsynaptic membrane

Summary: The PAINT presynaptic-modulation assertion is retained as unresolved rather than rejected.

Reason: Rat PMID:19385992 identifies alpha2-driven interneuron firing and altered GABAergic output but does not uniquely place alpha2 protein on the presynaptic terminal; that circuit role can arise through somatodendritic activation. Exact historical node evidence for a terminal receptor is not reconstructed.

Summary: Rat PMID:19385992 combines alpha2-positive interneuron identification with recordings showing nicotine-induced changes in inhibitory input to pyramidal cells.

Reason: Retain a conserved circuit-level modulation of inhibitory postsynaptic potentials, not an inhibitory chloride conductance through the alpha2 receptor itself.

Summary: The PAINT presynaptic-modulation assertion is retained as unresolved rather than rejected.

Reason: Rat PMID:19385992 identifies alpha2-driven interneuron firing and altered GABAergic output but does not uniquely place alpha2 protein on the presynaptic terminal; that circuit role can arise through somatodendritic activation. Exact historical node evidence for a terminal receptor is not reconstructed.

Summary: Retain postsynaptic reception of acetylcholine.

Reason: Original source: GO_REF:0000108. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.

Summary: Rat donor P12389 traces to PMID:19385992.

Reason: Full text identifies alpha2 mRNA by single-cell analysis and nicotine-responsive interneurons; a filled neuronal projection or sampled cytoplasm is not itself localization of alpha2 receptor protein to neuron-projection cytoplasm. The precise protein pool behind the transfer remains unresolved; membrane-channel identity alone is not a negative cytoplasm experiment.

Summary: Human alpha2 functional studies identify acetylcholine recognition more specifically than the broad chemical class.

Reason: The isolated ligand-bound ECD and heteromeric receptor studies provide complementary binding/function evidence; refine to acetylcholine binding without inferring a native alpha2 homomer.

Proposed replacements: acetylcholine binding

Summary: Retain the receptor response to acetylcholine.

Reason: Original source: GO_REF:0000107. Human alpha2 forms functional heteromeric receptors with beta2 or beta4. Expression ratios produce distinct sensitivity populations; the isolated alpha2 extracellular-domain homopentamer is not evidence for a native alpha2-only channel.