CHRNB2 encodes the neuronal nicotinic acetylcholine receptor Ξ²2 subunit, an integral plasma-membrane component of heteropentameric ligand-gated cation channels. Ξ²2 contributes pore-lining helices and the complementary face of agonist-binding interfaces. In receptors such as alpha4Ξ²2, subunit composition and stoichiometry tune acetylcholine sensitivity, desensitization, conductance and calcium permeability. These receptors mediate neuronal excitation and modulate transmitter release, with circuit-dependent effects on attention, nicotine responses and development of visual connections. Pathogenic variants can alter channel gating and are associated with sleep-related hypermotor epilepsy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001666 response to hypoxia | IDA PMID:12189247 A novel angiogenic pathway mediated by non-neuronal nicotini... | KEEP AS NON CORE | Summary: Hypoxia alters endothelial Ξ²2 expression in the cited experiment. Reason: PMID:12189247 reports a Ξ²2 expression pattern after hypoxia similar to the detailed alpha7 response, with the Ξ²2 measurements stated as data not shown. Retain the measured response as contextual, without assigning the paperβs alpha7-dominant angiogenesis mechanism to Ξ²2. Supporting Evidence: |
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine to acetylcholine-gated cation-channel activity. Reason: Human Ξ²2 participates in the pore and complementary agonist-binding surface of assembled nicotinic receptors. The specific channel term is more informative than the original broad receptor/channel class. This describes the subunit contribution, not an autonomous Ξ²2 channel. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine to acetylcholine-gated cation-channel activity. Reason: Human Ξ²2 participates in the pore and complementary agonist-binding surface of assembled nicotinic receptors. The specific channel term is more informative than the original broad receptor/channel class. This describes the subunit contribution, not an autonomous Ξ²2 channel. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity |
| GO:0005230 extracellular ligand-gated monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine to acetylcholine-gated cation-channel activity. Reason: Human Ξ²2 participates in the pore and complementary agonist-binding surface of assembled nicotinic receptors. The specific channel term is more informative than the original broad receptor/channel class. This describes the subunit contribution, not an autonomous Ξ²2 channel. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity |
| GO:0005515 protein binding | IPI PMID:27344019 Functional interaction between Lypd6 and nicotinic acetylcho... | REMOVE | Summary: Remove the uninformative bare-binding term while retaining exact interaction evidence. Reason: Recombinant human LYPD6 beads recover Ξ²2 from one human temporal-cortex preparation (Fig. 2a); non-coupled beads and corresponding mouse knockout antibody controls support specificity. This is receptor-complex capture, not purified binary Ξ²2βLYPD6 binding. Alpha7 toxin-competition results do not establish a Ξ²2 orthosteric LYPD6 interface. Current protein-binding policy supersedes the earlier non-core retention: remove only GO:0005515. The described positive interaction, product identity and assay limits remain evidence; this action does not assert that the interaction is false or transfer the partner's function onto the receptor subunit. |
| GO:0005515 protein binding | IPI PMID:29720657 Structural principles of distinct assemblies of the human Ξ±4... | REMOVE | Summary: Remove the uninformative bare-binding term while retaining exact interaction evidence. Reason: The exact source partner is P43681-1. Human assembled alpha4Ξ²2 structures establish a physical subunit interface; the engineered loop deletions/tags and receptor stoichiometry remain explicit. Binding is retained as contextual molecular information, with channel contribution as the core. This subunit association overlaps the accepted channel-complex membership and is retained as non-core; it differs from the extrinsic LYPD6 association. Current protein-binding policy supersedes the earlier non-core retention: remove only GO:0005515. The described positive interaction, product identity and assay limits remain evidence; this action does not assert that the interaction is false or transfer the partner's function onto the receptor subunit. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Remove the uninformative bare-binding term while retaining exact interaction evidence. Reason: The exact positive IntAct record EBI-54508035 / IM-29278-803 joins P30532 and P17787 in tagged human HEK293T AP-MS. A spoke-expanded complex association is not a purified pair or a complete native receptor stoichiometry. No partner activity is transferred to Ξ²2. This subunit association overlaps the accepted channel-complex membership and is retained as non-core; it differs from the extrinsic LYPD6 association. Current protein-binding policy supersedes the earlier non-core retention: remove only GO:0005515. The described positive interaction, product identity and assay limits remain evidence; this action does not assert that the interaction is false or transfer the partner's function onto the receptor subunit. |
| GO:0005515 protein binding | IPI PMID:8663494 Assembly of human neuronal nicotinic receptor alpha5 subunit... | REMOVE | Summary: Remove the uninformative bare-binding term while retaining exact interaction evidence. Reason: Three exact positive records distinguish human subunit coexpression in Xenopus oocytes from endogenous human SH-SY5Y receptor co-immunoprecipitation. The authentic abstract explicitly reports alpha5βΞ²2 assembly. Full original Methods remain unavailable; the literal positive records and independent receptor assembly support retention without inventing a binary affinity assay. This subunit association overlaps the accepted channel-complex membership and is retained as non-core; it differs from the extrinsic LYPD6 association. Current protein-binding policy supersedes the earlier non-core retention: remove only GO:0005515. The described positive interaction, product identity and assay limits remain evidence; this action does not assert that the interaction is false or transfer the partner's function onto the receptor subunit. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Functional Ξ²2-containing receptors act at the plasma membrane. Reason: Human receptor surface expression, electrophysiology and transmembrane structures establish this location. The broad electronic/ancestral assertion is supported independently of an uninspected historical PAINT node. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001054635 UNRESOLVED Exact source ancestral node is retained. Current target experiments support the biological judgment; historical PAINT tree placement and its full experimental evidence set were not reconstructed. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Functional Ξ²2-containing receptors act at the plasma membrane. Reason: Human receptor surface expression, electrophysiology and transmembrane structures establish this location. The broad electronic/ancestral assertion is supported independently of an uninspected historical PAINT node. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-622325 | ACCEPT | Summary: Reactome places Ξ²2 in a plasma-membrane receptor complex. Reason: The exact event-to-complex membership chain reaches human CHRNB2 entity R-HSA-507826, annotated to plasma membrane. This is own-source provenance; independent receptor experiments also support surface localization. Supporting Evidence: Reactome:R-HSA-622325 file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-622326 | ACCEPT | Summary: Reactome places Ξ²2 in a plasma-membrane receptor complex. Reason: The exact event-to-complex membership chain reaches human CHRNB2 entity R-HSA-507826, annotated to plasma membrane. This is own-source provenance; independent receptor experiments also support surface localization. Supporting Evidence: Reactome:R-HSA-622326 file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-629588 | ACCEPT | Summary: Reactome places Ξ²2 in a plasma-membrane receptor complex. Reason: The exact event-to-complex membership chain reaches human CHRNB2 entity R-HSA-507826, annotated to plasma membrane. This is own-source provenance; independent receptor experiments also support surface localization. Supporting Evidence: Reactome:R-HSA-629588 file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-629595 | ACCEPT | Summary: Reactome places Ξ²2 in a plasma-membrane receptor complex. Reason: The exact event-to-complex membership chain reaches human CHRNB2 entity R-HSA-507826, annotated to plasma membrane. This is own-source provenance; independent receptor experiments also support surface localization. Supporting Evidence: Reactome:R-HSA-629595 file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-629596 | ACCEPT | Summary: Reactome places Ξ²2 in a plasma-membrane receptor complex. Reason: The exact event-to-complex membership chain reaches human CHRNB2 entity R-HSA-507826, annotated to plasma membrane. This is own-source provenance; independent receptor experiments also support surface localization. Supporting Evidence: Reactome:R-HSA-629596 file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-629599 | ACCEPT | Summary: Reactome places Ξ²2 in a plasma-membrane receptor complex. Reason: The exact event-to-complex membership chain reaches human CHRNB2 entity R-HSA-507826, annotated to plasma membrane. This is own-source provenance; independent receptor experiments also support surface localization. Supporting Evidence: Reactome:R-HSA-629599 file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0005892 acetylcholine-gated channel complex | IBA GO_REF:0000033 | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. The conserved complex assignment is independently supported by human structures and reconstitution; it is not a claim that every alpha/beta combination or native stoichiometry occurs. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000435923 UNRESOLVED Exact source ancestral node is retained. Current target experiments support the biological judgment; historical PAINT tree placement and its full experimental evidence set were not reconstructed. |
| GO:0005892 acetylcholine-gated channel complex | IDA PMID:16835356 Beta3 subunits promote expression and nicotine-induced up-re... | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. Full current assay protocol not independently accessed; beta3 assembly effects are not assigned as a beta2-specific chaperone function. Supporting Evidence: |
| GO:0005892 acetylcholine-gated channel complex | IDA PMID:17132685 Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry gre... | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. Full Methods not recovered here; use the full text of PMID:20881005 for inspected calcium-current methodology. Supporting Evidence: |
| GO:0005892 acetylcholine-gated channel complex | IDA PMID:20881005 Acetylcholine receptor (AChR) Ξ±5 subunit variant associated ... | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. Full primary resides in preserved CHRNA4 normal/research variant, not the CHRNB2 abstract archive. Alpha5 D398N effect is not transferred to beta2. The reported calcium-only normalization method is retained without claiming an independently calculated permeability coefficient. Supporting Evidence: |
| GO:0005892 acetylcholine-gated channel complex | IDA PMID:24467848 A signal peptide missense mutation associated with nicotine ... | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. Expression ratios bias putative stoichiometries; exact assembly was not directly counted here. The tested disease-associated variant is alpha2 T22I, not a beta2 mutation. Supporting Evidence: |
| GO:0005892 acetylcholine-gated channel complex | IDA PMID:27698419 X-ray structure of the human Ξ±4Ξ²2 nicotinic receptor. | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. Structure uses intracellular-loop deletions, junction linker and beta2 C-terminal Strep tag; prolonged nicotine produces a desensitized nonconducting structure. Structural state does not negate measured currents. Supporting Evidence: |
| GO:0005892 acetylcholine-gated channel complex | IDA PMID:29720657 Structural principles of distinct assemblies of the human Ξ±4... | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. Same large intracellular-loop deletions and tag; calcium-permeability ratio is cited prior physiology, not a new flux measurement in the inspected structural Results. Supporting Evidence: |
| GO:0005892 acetylcholine-gated channel complex | IDA PMID:38161283 Analogs of Ξ±-conotoxin PnIC selectively inhibit Ξ±7Ξ²2- over Ξ±... | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. Enforced alpha7-beta2-alpha7-beta2-alpha7 stoichiometry plus NACHO; this does not quantify native neuronal stoichiometry/distribution. Alpha6/3 comparator is a chimera. Antagonist allostery does not imply beta2 is an autonomous receptor. Supporting Evidence: |
| GO:0005892 acetylcholine-gated channel complex | IDA PMID:38454578 Structural bases for stoichiometry-selective calcium potenti... | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. Structural full-length construct has Bril insertions and tag, alongside loop-deleted constructs. Calcium-site structural/mutational potentiation is not identical to calcium permeation; some sites arise from simulations alone. Alpha4 site mutations are not beta2 calcium-binding-site measurements. Supporting Evidence: |
| GO:0005892 acetylcholine-gated channel complex | IDA PMID:8906617 Comparative structure of human neuronal alpha 2-alpha 7 and ... | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. Original full Methods unavailable after the documented access attempts; supports assembled-receptor function, not free beta2 binding. Supporting Evidence: |
| GO:0005892 acetylcholine-gated channel complex | IEA GO_REF:0000117 | ACCEPT | Summary: Ξ²2 is a constituent of heteromeric acetylcholine-gated channel complexes. Reason: Human Ξ²2 coassembles with alpha subunits in functional receptor preparations. The conserved complex assignment is independently supported by human structures and reconstitution; it is not a claim that every alpha/beta combination or native stoichiometry occurs. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | MODIFY | Summary: Specify monoatomic cation transport across the membrane. Reason: Ξ²2-containing receptors conduct cations through a transmembrane pore after agonist binding. GO:0098655 captures both cation specificity and membrane crossing; it does not imply an ATP-driven pump or a free-subunit transporter. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0006811 monoatomic ion transport | NAS PMID:8906617 Comparative structure of human neuronal alpha 2-alpha 7 and ... | MODIFY | Summary: Specify monoatomic cation transport across the membrane. Reason: Ξ²2-containing receptors conduct cations through a transmembrane pore after agonist binding. GO:0098655 captures both cation specificity and membrane crossing; it does not imply an ATP-driven pump or a free-subunit transporter. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0006816 calcium ion transport | IBA GO_REF:0000033 | MODIFY | Summary: Refine calcium entry to calcium ion transmembrane transport. Reason: Defined human Ξ²2-containing receptor assemblies carry calcium across the membrane, making GO:0070588 more precise than general calcium transport. PMID:20881005 Methods measure ACh-evoked currents in calcium-only solution using human concatemer-defined receptors in Xenopus oocytes; the varied risk allele is alpha5 D398N. Permeability depends on subunit composition and is distinct from calcium-dependent potentiation. This is a channel-complex contribution, not autonomous Ξ²2 transport or calcium-binding activity. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000434994 UNRESOLVED Exact source ancestral node is retained. Current target experiments support the biological judgment; historical PAINT tree placement and its full experimental evidence set were not reconstructed. Proposed replacements: calcium ion transmembrane transport Supporting Evidence: PMID:20881005 reflect only Ca 2+ flow through AChR channels file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0006816 calcium ion transport | ISS GO_REF:0000024 | MODIFY | Summary: Refine calcium entry to calcium ion transmembrane transport. Reason: Defined human Ξ²2-containing receptor assemblies carry calcium across the membrane, making GO:0070588 more precise than general calcium transport. PMID:20881005 Methods measure ACh-evoked currents in calcium-only solution using human concatemer-defined receptors in Xenopus oocytes; the varied risk allele is alpha5 D398N. Permeability depends on subunit composition and is distinct from calcium-dependent potentiation. This is a channel-complex contribution, not autonomous Ξ²2 transport or calcium-binding activity. Proposed replacements: calcium ion transmembrane transport Supporting Evidence: PMID:20881005 reflect only Ca 2+ flow through AChR channels file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0006939 smooth muscle contraction | ISS GO_REF:0000024 | MODIFY | Summary: Refine to regulation of smooth muscle contraction. Reason: The full mouse study locates the nicotinic step in autonomic ganglion neurons. Direct muscarinic contraction remains intact, and electrical stimulation bypasses deficient nicotinic signaling. Beta2/beta4 redundancy supports a regulatory contribution, not absence of beta2 function; the receptor does not perform force generation within smooth muscle. Proposed replacements: regulation of smooth muscle contraction |
| GO:0007165 signal transduction | IDA PMID:8906617 Comparative structure of human neuronal alpha 2-alpha 7 and ... | MODIFY | Summary: Specify acetylcholine receptor signaling. Reason: The original human receptor reconstitution establishes agonist-triggered channel signaling. The specific acetylcholine receptor pathway captures this performed transduction step more precisely than generic signal transduction. Proposed replacements: acetylcholine receptor signaling pathway Supporting Evidence: |
| GO:0007271 synaptic transmission, cholinergic | IBA GO_REF:0000033 | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Human reconstitution and rat receptor experiments support the conserved capability; historical ancestral-node placement has not been reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001054960 UNRESOLVED Exact source ancestral node is retained. Current target experiments support the biological judgment; historical PAINT tree placement and its full experimental evidence set were not reconstructed. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0007271 synaptic transmission, cholinergic | IDA PMID:17132685 Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry gre... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Full Methods not recovered here; use the full text of PMID:20881005 for inspected calcium-current methodology. Supporting Evidence: |
| GO:0007271 synaptic transmission, cholinergic | IDA PMID:27698419 X-ray structure of the human Ξ±4Ξ²2 nicotinic receptor. | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Structure uses intracellular-loop deletions, junction linker and beta2 C-terminal Strep tag; prolonged nicotine produces a desensitized nonconducting structure. Structural state does not negate measured currents. Supporting Evidence: |
| GO:0007271 synaptic transmission, cholinergic | IDA PMID:29720657 Structural principles of distinct assemblies of the human Ξ±4... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Same large intracellular-loop deletions and tag; calcium-permeability ratio is cited prior physiology, not a new flux measurement in the inspected structural Results. Supporting Evidence: |
| GO:0007271 synaptic transmission, cholinergic | IDA PMID:38161283 Analogs of Ξ±-conotoxin PnIC selectively inhibit Ξ±7Ξ²2- over Ξ±... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Enforced alpha7-beta2-alpha7-beta2-alpha7 stoichiometry plus NACHO; this does not quantify native neuronal stoichiometry/distribution. Alpha6/3 comparator is a chimera. Antagonist allostery does not imply beta2 is an autonomous receptor. Supporting Evidence: |
| GO:0007271 synaptic transmission, cholinergic | IDA PMID:38454578 Structural bases for stoichiometry-selective calcium potenti... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Structural full-length construct has Bril insertions and tag, alongside loop-deleted constructs. Calcium-site structural/mutational potentiation is not identical to calcium permeation; some sites arise from simulations alone. Alpha4 site mutations are not beta2 calcium-binding-site measurements. Supporting Evidence: |
| GO:0007271 synaptic transmission, cholinergic | ISS GO_REF:0000024 | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Human reconstitution and rat receptor experiments support the conserved capability; historical ancestral-node placement has not been reconstructed. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0007601 visual perception | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Visual-system function is retained as a contextual circuit role. Reason: Mouse Ξ²2 loss disrupts retinofugal mapping and cortical acuity. Other visual response properties can remain normal; the receptor is not a phototransduction pigment. |
| GO:0007605 sensory perception of sound | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the auditory phenotype at maintenance scope. Reason: The actual donor study finds normal hearing at two months but hearing loss and spiral-ganglion neuron depletion at eight months. This supports a contextual contribution to hearing maintenance, not an autonomous sound-transduction mechanism. |
| GO:0007612 learning | IMP PMID:15964197 The CHRNB2 mutation I312M is associated with epilepsy and di... | KEEP AS NON CORE | Summary: Retain the clinical learning/memory association as contextual. Reason: The authentic PMID:15964197 abstract reports human I312M twins with memory deficits, especially verbal tasks, alongside receptor hypersensitivity. Full neuropsychological Methods were not recovered. The broad clinical association is retained without claiming a direct molecular learning mechanism or assigning the phenotype to ligand affinity. Supporting Evidence: |
| GO:0007613 memory | IMP PMID:15964197 The CHRNB2 mutation I312M is associated with epilepsy and di... | KEEP AS NON CORE | Summary: Retain the clinical learning/memory association as contextual. Reason: The authentic PMID:15964197 abstract reports human I312M twins with memory deficits, especially verbal tasks, alongside receptor hypersensitivity. Full neuropsychological Methods were not recovered. The broad clinical association is retained without claiming a direct molecular learning mechanism or assigning the phenotype to ligand affinity. Supporting Evidence: |
| GO:0007626 locomotory behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain locomotor behavior as a circuit-level contribution. Reason: The current mouse donor includes nicotine/dopamine experiments, and independent Ξ²2-null behavior work resolves altered exploratory organization rather than loss of elementary locomotion. |
| GO:0008306 associative learning | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain associative learning as contextual. Reason: The current donor experiment uses alpha7/beta2 double-mutant mice and passive avoidance. This is a genotype-level contribution with unresolved subunit-specific partition, not an additional molecular learning activity. |
| GO:0008542 visual learning | IMP PMID:15964197 The CHRNB2 mutation I312M is associated with epilepsy and di... | UNDECIDED | Summary: The specific visual-learning claim remains unresolved. Reason: PMID:15964197 reports memory deficits in the accessible abstract, especially verbal tasks; it does not resolve the visual-learning assay underlying this more specific IMP assertion. Full neuropsychological Results were not recovered after bounded access attempts. This uncertainty does not establish a mistaken annotation. |
| GO:0009897 external side of plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The extracellular receptor domain is exposed at the outer plasma-membrane surface. Reason: The definition includes embedded proteins. Mouse donor surface evidence and human extracellular-domain structures support the location, without implying that Ξ²2 is only a peripheral surface protein. |
| GO:0014059 regulation of dopamine secretion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ξ²2-containing neuronal receptors regulate dopamine release. Reason: Mouse striatal synaptosome release and dopaminergic-neuron recordings identify Ξ²2-containing receptor populations. Somatic and terminal subunit combinations differ; Ξ²2 is neither dopamine synthesis machinery nor a dopamine receptor. |
| GO:0015276 ligand-gated monoatomic ion channel activity | TAS PMID:20438829 Low ethanol concentration alters CHRNA5 RNA levels during ea... | MODIFY | Summary: Refine to acetylcholine-gated cation-channel activity. Reason: Human Ξ²2 participates in the pore and complementary agonist-binding surface of assembled nicotinic receptors. The specific channel term is more informative than the original broad receptor/channel class. This describes the subunit contribution, not an autonomous Ξ²2 channel. The original PMID:20438829 TAS linkage is unresolved in its CHRNA5-centered abstract; independent Ξ²2 receptor experiments supply the refinement, without alleging miscitation. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity |
| GO:0015464 acetylcholine receptor activity | IDA PMID:8906617 Comparative structure of human neuronal alpha 2-alpha 7 and ... | MODIFY | Summary: Refine to acetylcholine-gated cation-channel activity. Reason: Human Ξ²2 participates in the pore and complementary agonist-binding surface of assembled nicotinic receptors. The specific channel term is more informative than the original broad receptor/channel class. This describes the subunit contribution, not an autonomous Ξ²2 channel. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity |
| GO:0015464 acetylcholine receptor activity | IEA GO_REF:0000117 | MODIFY | Summary: Refine to acetylcholine-gated cation-channel activity. Reason: Human Ξ²2 participates in the pore and complementary agonist-binding surface of assembled nicotinic receptors. The specific channel term is more informative than the original broad receptor/channel class. This describes the subunit contribution, not an autonomous Ξ²2 channel. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Refine membrane location to plasma membrane. Reason: Ξ²2 is an integral membrane receptor subunit with functional surface expression in the original human receptor reconstitution. Plasma membrane is an informative supported specialization of the broad membrane assertion. Proposed replacements: plasma membrane |
| GO:0016020 membrane | NAS PMID:8906617 Comparative structure of human neuronal alpha 2-alpha 7 and ... | MODIFY | Summary: Refine membrane location to plasma membrane. Reason: Ξ²2 is an integral membrane receptor subunit with functional surface expression in the original human receptor reconstitution. Plasma membrane is an informative supported specialization of the broad membrane assertion. Proposed replacements: plasma membrane Supporting Evidence: |
| GO:0019233 sensory perception of pain | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain nicotine-sensitive nociceptive circuitry as contextual. Reason: Mouse beta2 knockout reduces nicotine antinociception and associated neuronal responses. These pharmacological circuit effects do not define Ξ²2 as a primary noxious-stimulus receptor. |
| GO:0021562 vestibulocochlear nerve development | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Aging-related auditory neuron maintenance does not establish nerve development. Reason: The exact current mouse donor points to PMID:15788760. Its full Results report normal hearing at two months and later hearing impairment/spiral-ganglion loss at eight months; the Discussion explicitly concerns maintenance during aging. These positive findings support auditory maintenance, but do not establish the source termβs developmental progression of the vestibulocochlear nerve. The literal anchor is from Results, Fig. 2, paragraph 18 of the externally accessed PMC2280031 text; the selected cache remains unchanged. |
| GO:0021631 optic nerve morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain retinofugal axon development as contextual. Reason: Mouse receptor loss disrupts early wave-dependent organization of retinal projections. Later glutamatergic activity supports patchy segregation without normal layers; this is not direct axon structural work. |
| GO:0021771 lateral geniculate nucleus development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain lateral geniculate development as contextual. Reason: Actual Ξ²2-null mouse axon tracing shows persistent absence of normal eye-specific layers despite later local segregation. Cholinergic activity contributes to organization; no autonomous morphogen activity is asserted. |
| GO:0021952 central nervous system projection neuron axonogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain activity-dependent CNS projection development as contextual. Reason: Mouse retinal-wave perturbations alter topographic/eye-specific organization. Combined beta2/connexin36 studies retain later local segregation; the receptor supplies neuronal activity rather than an axon-building enzyme. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. The electronic or ortholog assertion agrees with direct human receptor evidence; no historical PAINT placement is inferred. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008360855 UNRESOLVED Exact source ancestral node is retained. Current target experiments support the biological judgment; historical PAINT tree placement and its full experimental evidence set were not reconstructed. |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IDA PMID:16835356 Beta3 subunits promote expression and nicotine-induced up-re... | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Authentic abstract explicitly includes human alpha6beta2 and alpha6beta2beta3 assemblies, expression/ligand-binding and cell-system differences. Full current assay protocol not independently accessed; beta3 assembly effects are not assigned as a beta2-specific chaperone function. Supporting Evidence: |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IDA PMID:17132685 Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry gre... | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Authentic abstract explicitly reports human concatemer-defined receptor stoichiometries, M2 charge mutations and calcium permeability differences. Full Methods not recovered here; use the full text of PMID:20881005 for inspected calcium-current methodology. Supporting Evidence: |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IDA PMID:18387948 PATE gene clusters code for multiple, secreted TFP/Ly-6/uPAR... | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Human receptor clones expressed in Xenopus yielded baseline ACh responses; mouse Pate-P inhibited human alpha4beta2 net charge. Mixed species of modulator and receptor are explicit. PATE modulation is not proof that CHRNB2 itself is a secreted modulator. Supporting Evidence: |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IDA PMID:20881005 Acetylcholine receptor (AChR) Ξ±5 subunit variant associated ... | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Actual human beta2-alpha4-beta2-alpha4 concatemer plus free alpha5 was tested by voltage clamp and calcium-only currents; the study also tested alpha3beta2alpha5. Full primary resides in preserved CHRNA4 normal/research variant, not the CHRNB2 abstract archive. Alpha5 D398N effect is not transferred to beta2. The reported calcium-only normalization method is retained without claiming an independently calculated permeability coefficient. Supporting Evidence: |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IDA PMID:24467848 A signal peptide missense mutation associated with nicotine ... | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Human alpha2 with beta2 produces agonist currents; codon-optimized beta2 improves expression and was used for subsequent assays. Single-subunit negative controls lack functional receptor. Expression ratios bias putative stoichiometries; exact assembly was not directly counted here. The tested disease-associated variant is alpha2 T22I, not a beta2 mutation. Supporting Evidence: |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IDA PMID:27698419 X-ray structure of the human Ξ±4Ξ²2 nicotinic receptor. | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Human alpha4/beta2 form a heteropentameric pore. Nicotine occupies alpha4(+)/beta2(-) interfaces, with beta2 loopD/E residues contributing. Direct ACh patch-clamp comparison supports both full-length and engineered crystallization constructs. Structure uses intracellular-loop deletions, junction linker and beta2 C-terminal Strep tag; prolonged nicotine produces a desensitized nonconducting structure. Structural state does not negate measured currents. The functional comparison is in Results, Fig. 3a; the nicotine-bound structure captures a separate desensitized state. Supporting Evidence: PMID:27698419 receptor constructs to acetylcholine and found them to behave similarly |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IDA PMID:29720657 Structural principles of distinct assemblies of the human Ξ±4... | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Both human alpha4beta2 stoichiometries were structurally resolved. The 3alpha:2beta form has an additional alpha-alpha nicotine site; beta2 complementary face and M2 charge composition explain receptor differences. Same large intracellular-loop deletions and tag; calcium-permeability ratio is cited prior physiology, not a new flux measurement in the inspected structural Results. Supporting Evidence: |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IDA PMID:38161283 Analogs of Ξ±-conotoxin PnIC selectively inhibit Ξ±7Ξ²2- over Ξ±... | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Human alpha7-beta2 concatemer in Xenopus oocytes supports ACh-evoked currents and conotoxin selectivity. Enforced alpha7-beta2-alpha7-beta2-alpha7 stoichiometry plus NACHO; this does not quantify native neuronal stoichiometry/distribution. Alpha6/3 comparator is a chimera. Antagonist allostery does not imply beta2 is an autonomous receptor. Supporting Evidence: |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IDA PMID:38454578 Structural bases for stoichiometry-selective calcium potenti... | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Human full-length subunit recordings establish ACh-elicited single channels and stoichiometry-selective divalent potentiation. Cryo-EM resolves actual ACh density at alpha4-beta2 and alpha4-alpha interfaces. Structural full-length construct has Bril insertions and tag, alongside loop-deleted constructs. Calcium-site structural/mutational potentiation is not identical to calcium permeation; some sites arise from simulations alone. Alpha4 site mutations are not beta2 calcium-binding-site measurements. Supporting Evidence: |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IDA PMID:8906617 Comparative structure of human neuronal alpha 2-alpha 7 and ... | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Authentic abstract explicitly describes human alpha2/alpha3/alpha4 paired with beta2 or beta4 in oocytes and ACh currents blocked by d-tubocurare. Original full Methods unavailable after the documented access attempts; supports assembled-receptor function, not free beta2 binding. Supporting Evidence: |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IEA GO_REF:0000120 | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. The electronic or ortholog assertion agrees with direct human receptor evidence; no historical PAINT placement is inferred. |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | ISS GO_REF:0000024 | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. The electronic or ortholog assertion agrees with direct human receptor evidence; no historical PAINT placement is inferred. |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | TAS PMID:20438829 Low ethanol concentration alters CHRNA5 RNA levels during ea... | ACCEPT | Summary: Ξ²2 contributes to the assembled acetylcholine-gated channel. Reason: Human-subunit reconstitution and structural pore participation establish this activity. Selected abstract centers on CHRNA5 ethanol-responsive expression; it does not resolve the background sentence behind beta2 TAS. Actual beta2 channel capability is independently secure; exact TAS linkage remains unverified. Supporting Evidence: |
| GO:0030890 positive regulation of B cell proliferation | ISS GO_REF:0000024 | UNDECIDED | Summary: The positive B-cell proliferation interpretation remains unresolved. Reason: The current mouse donor has two distinct branches: IGI PMID:15963492 directly studies B cells, whereas IC PMID:11222635 concerns neuronal receptor/channel properties and is not direct B-cell proliferation evidence. The B-cell abstract reports context-dependent activation and nicotine responses; its full body was not recovered, leaving the sign and exact assay scope unsettled. The neural IC branch does not invalidate the separate B-cell IGI evidence. |
| GO:0032225 regulation of synaptic transmission, dopaminergic | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain modulation of dopaminergic transmission. Reason: Mouse Ξ²2 deletion and VTA reexpression change dopamine-neuron firing. The performed receptor step is cholinergic excitation within a dopaminergic circuit, not direct dopamine binding. |
| GO:0033603 positive regulation of dopamine secretion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain nicotine-evoked dopamine release regulation. Reason: The mouse study reports loss of nicotine-stimulated ventral-striatal dopamine release and nicotine currents after Ξ²2 deletion. This is a receptor-mediated regulatory role, not dopamine secretion machinery itself. |
| GO:0034220 monoatomic ion transmembrane transport | IBA GO_REF:0000033 | MODIFY | Summary: Specify monoatomic cation transport across the membrane. Reason: Ξ²2-containing receptors conduct cations through a transmembrane pore after agonist binding. GO:0098655 captures both cation specificity and membrane crossing; it does not imply an ATP-driven pump or a free-subunit transporter. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000434994 UNRESOLVED Exact source ancestral node is retained. Current target experiments support the biological judgment; historical PAINT tree placement and its full experimental evidence set were not reconstructed. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0034220 monoatomic ion transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: Specify monoatomic cation transport across the membrane. Reason: Ξ²2-containing receptors conduct cations through a transmembrane pore after agonist binding. GO:0098655 captures both cation specificity and membrane crossing; it does not imply an ATP-driven pump or a free-subunit transporter. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0035094 response to nicotine | IDA PMID:12189247 A novel angiogenic pathway mediated by non-neuronal nicotini... | KEEP AS NON CORE | Summary: Nicotine-associated endothelial receptor expression is contextual. Reason: The source reports altered Ξ²2 expression after nicotine alongside other nAChR subunits; the Ξ²2-specific pattern is not plotted. Its angiogenesis pharmacology principally implicates alpha7, not a Ξ²2-specific vascular mechanism. Supporting Evidence: |
| GO:0035094 response to nicotine | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Ξ²2-containing receptors respond to nicotine. Reason: Direct agonist currents and desensitization establish a receptor response to nicotine. This pharmacological response is retained outside the endogenous acetylcholine-centered core. |
| GO:0035095 behavioral response to nicotine | IMP PMID:17559419 Why do young women smoke? V. Role of direct and interactive ... | UNDECIDED | Summary: The source-specific behavioral nicotine response needs the full association analysis. Reason: The accessible PMID:17559419 abstract reports genotype associations with cognition in current/past smokers and nonsmokers. It does not resolve a CHRNB2-specific change of behavior after nicotine exposure. Preserve the original IMP assertion while leaving this exact interpretation open; independent nicotine reinforcement biology does not recreate the cited analysis. |
| GO:0035095 behavioral response to nicotine | IMP PMID:20881005 Acetylcholine receptor (AChR) Ξ±5 subunit variant associated ... | UNDECIDED | Summary: The specific human behavioral claim remains unresolved across its sources. Reason: Actual PMID:20881005 Methods/Results test human receptor currents and activation/desensitization in oocytes and cell lines, not organism behavior. The studied risk variant is alpha5 D398N, not Ξ²2. GO:0035094 retains the direct Ξ²2-containing receptor response while separating the paperβs behavioral-risk interpretation. The anchor is from Results, Fig. 3, in the genuine full PMID:20881005 variant now selected in the published cache. The same-term association row remains unresolved, so the judgment of the biological claim is consistently UNDECIDED across both rows. The direct cellular nicotine response is independently represented; the source mismatch does not establish that the human behavioral role is false. Supporting Evidence: PMID:20881005 sensitive to activation by nicotine file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0035176 social behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain social behavior as contextual. Reason: Mouse Ξ²2 deletion alters social interaction and flexible exploration. Actual adult behavioral assays do not establish a separate social-behavior molecular activity in human Ξ²2. |
| GO:0042053 regulation of dopamine metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain contextual regulation of dopamine turnover after cocaine challenge. Reason: GO:0042053 concerns modulation of dopamine metabolism and does not require dopamine-metabolizing catalysis by the regulator. PMID:11282258 Fig. 8 and Results measure tissue DOPAC/DA after cocaine: the wild-type striatal/telencephalic ratio decreases significantly, whereas the knockout response is not significant. Baseline differences are nonsignificant; these comparisons alone do not establish a genotype-by-treatment interaction. This supports a bounded, non-core regulatory interpretation. Unlike the auditory development assertion, the measured endpoint matches the regulatory term. Current mouse IMP uses acts_upstream_of_or_within; the fetched human involved_in qualifier is preserved without claiming a direct human mechanism. |
| GO:0042113 B cell activation | ISS GO_REF:0000024 | UNDECIDED | Summary: B-cell activation versus survival and population effects remains unresolved. Reason: Both current donor IMP sources genuinely concern mouse lymphocytes. Their full bodies were not recovered; the accessible abstracts do not resolve beta2-dependent activation separately from precursor survival and changes in cell abundance. This is not grounds to reject the curated experimental evidence or manufacture a replacement process. |
| GO:0042166 acetylcholine binding | IC PMID:8906617 Comparative structure of human neuronal alpha 2-alpha 7 and ... | ACCEPT | Summary: Ξ²2 contributes a complementary acetylcholine-binding surface. Reason: Actual human ACh-bound structures resolve ligand at alpha4βΞ²2 interfaces, with Ξ²2 forming the complementary pocket face. The original IC/IMP assertion remains intact. I312M sensitivity changes alone do not separate affinity from gating, and no isolated Ξ²2 binding assay is claimed. |
| GO:0042166 acetylcholine binding | IMP PMID:15964197 The CHRNB2 mutation I312M is associated with epilepsy and di... | ACCEPT | Summary: Ξ²2 contributes a complementary acetylcholine-binding surface. Reason: Actual human ACh-bound structures resolve ligand at alpha4βΞ²2 interfaces, with Ξ²2 forming the complementary pocket face. The original IC/IMP assertion remains intact. I312M sensitivity changes alone do not separate affinity from gating, and no isolated Ξ²2 binding assay is claimed. |
| GO:0042220 response to cocaine | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain cocaine response as contextual. Reason: Beta2-null mice show diminished place preference at a low cocaine dose, with higher doses still effective. This is indirect nicotinic/dopaminergic coupling rather than evidence that cocaine is a Ξ²2 agonist. |
| GO:0042320 regulation of circadian sleep/wake cycle, REM sleep | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain regulation of REM sleep organization. Reason: Actual mouse polysomnography shows longer REM episodes and a changed stress-induced REM rebound despite similar baseline amounts of wake, NREM and REM sleep. This is a contextual circuit phenotype, not universal loss of sleep. |
| GO:0042734 presynaptic membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Ξ²2-containing receptors occur in synaptic membranes. Reason: Presynaptic Ξ²2-containing receptor function is supported by rodent bouton/synaptosome experiments and postsynaptic receptor currents by neuronal and human-subunit studies. The exact broader or sided source location is retained; heterologous structural preparations do not themselves establish native synaptic abundance. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0042734 presynaptic membrane | TAS PMID:20881005 Acetylcholine receptor (AChR) Ξ±5 subunit variant associated ... | ACCEPT | Summary: Ξ²2-containing receptors occur in synaptic membranes. Reason: Presynaptic Ξ²2-containing receptor function is supported by rodent bouton/synaptosome experiments and postsynaptic receptor currents by neuronal and human-subunit studies. The exact broader or sided source location is retained; heterologous structural preparations do not themselves establish native synaptic abundance. |
| GO:0044853 plasma membrane raft | ISS GO_REF:0000024 | UNDECIDED | Summary: Physical plasma-membrane raft localization remains unresolved. Reason: The exact rat donor points to PMID:21540349. Its full study expresses rat alpha3/beta2 in hippocampal neurons and measures altered currents after cholesterol/sphingomyelin manipulation. The authors cannot separate receptor localization changes from altered molecular interactions. This establishes lipid-environment sensitivity but does not resolve Ξ²2 residency in a raft; it is not negative localization evidence. |
| GO:0045202 synapse | IDA PMID:24467848 A signal peptide missense mutation associated with nicotine ... | ACCEPT | Summary: Retain the established synaptic receptor location with source limits. Reason: The cited reconstitution papers chiefly establish human receptor composition/function, not direct localization in intact human synapses. Independent neuronal recordings and synaptic-membrane evidence support the location; this is curator deference for the exact original compartment linkage, not an invented imaging assay. |
| GO:0045202 synapse | TAS PMID:16835356 Beta3 subunits promote expression and nicotine-induced up-re... | ACCEPT | Summary: Retain the established synaptic receptor location with source limits. Reason: The cited reconstitution papers chiefly establish human receptor composition/function, not direct localization in intact human synapses. Independent neuronal recordings and synaptic-membrane evidence support the location; this is curator deference for the exact original compartment linkage, not an invented imaging assay. |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Ξ²2-containing receptors can operate postsynaptically. Reason: Postsynaptic somatic currents and the established neuronal receptor role support this membrane compartment. Ξ²2 also occurs presynaptically in other receptor/circuit contexts; the two locations are not exclusive. |
| GO:0045471 response to ethanol | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the contextual nicotineβethanol learning interaction. Reason: Mouse beta2-null animals fail to show nicotine-mediated cognitive enhancement after ethanol. The paper also identifies a distinct alpha7 contribution to ethanol sensitivity, which is not transferred to Ξ²2. |
| GO:0045759 negative regulation of action potential | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the circuit-level negative influence on firing. Reason: Adult beta2-null mouse dLGN neurons have increased spontaneous and visually evoked firing. GO:0045759 includes reducing action-potential frequency through a regulatory process; it does not require the receptor itself to carry a hyperpolarizing current. The observed firing endpoint matches this broad term, whereas age-related auditory loss does not establish nerve development. Retain the contextual inference as non-core: lifelong knockout leaves developmental, retinal, thalamic-inhibitory and cortical explanations unresolved. The current mouse IMP qualifier is acts_upstream_of_or_within; preserve the fetched human involved_in without asserting cell-autonomous inhibition or a direct human experiment. Supporting Evidence: PMID:15456819 spontaneous activity is higher in Ξ²2-/- than in WT dLGN cells file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0048814 regulation of dendrite morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain transient regulation of retinal dendrite refinement. Reason: Mouse Ξ²2 deletion delays individual retinal ganglion dendrite stratification at P7βP8, with near-normal restriction by P14. Initial coarse ON/OFF segregation is not abolished; the effect is activity-dependent and developmental. |
| GO:0050877 nervous system process | IMP PMID:17900292 Autosomal dominant nocturnal frontal lobe epilepsy with a mu... | KEEP AS NON CORE | Summary: Retain the broad nervous-system contribution. Reason: The original abstract reports segregation of beta2 V287M with epilepsy in a family. Independent receptor physiology establishes the neuronal function, but the clinical pedigree alone does not specify a new biochemical activity. |
| GO:0050890 cognition | IMP PMID:17559419 Why do young women smoke? V. Role of direct and interactive ... | KEEP AS NON CORE | Summary: Retain cognition as a contextual human association. Reason: The original study associates CHRNB2 variants with response inhibition/selective attention in a female college-student cohort. This is association evidence, not a controlled protein perturbation; the fetched IMP code is retained as source provenance rather than silently corrected. Supporting Evidence: |
| GO:0051899 membrane depolarization | IBA GO_REF:0000033 | ACCEPT | Summary: Receptor cation current depolarizes the membrane. Reason: Ξ²2 participates in the conducting pore of ligand-gated receptors; neuronal ACh currents and reconstituted human channels support membrane depolarization. This does not imply that every circuit-level firing effect is excitatory. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001450431 UNRESOLVED Exact source ancestral node is retained. Current target experiments support the biological judgment; historical PAINT tree placement and its full experimental evidence set were not reconstructed. |
| GO:0051899 membrane depolarization | ISS GO_REF:0000024 | ACCEPT | Summary: Receptor cation current depolarizes the membrane. Reason: Ξ²2 participates in the conducting pore of ligand-gated receptors; neuronal ACh currents and reconstituted human channels support membrane depolarization. This does not imply that every circuit-level firing effect is excitatory. |
| GO:0051963 regulation of synapse assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain activity-dependent synaptic refinement as contextual. Reason: Mouse Ξ²2-null superior-colliculus neurons have more weaker retinal inputs at P6βP7, whereas input number/strength are similar by P21βP25. The source supports developmental regulation, not direct physical synapse assembly by Ξ²2. |
| GO:0060078 regulation of postsynaptic membrane potential | IEA GO_REF:0000108 | ACCEPT | Summary: Retain the receptor contribution to postsynaptic electrical signaling. Reason: The ligand-gated cation current directly contributes to postsynaptic membrane-potential changes. Presynaptic Ξ²2 receptors can instead modulate release of other transmitters, including GABA; those downstream inhibitory currents are not an anion-conducting Ξ²2 pore. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0060079 excitatory postsynaptic potential | IEA GO_REF:0000108 | ACCEPT | Summary: Retain the receptor contribution to postsynaptic electrical signaling. Reason: The ligand-gated cation current directly contributes to postsynaptic membrane-potential changes. Presynaptic Ξ²2 receptors can instead modulate release of other transmitters, including GABA; those downstream inhibitory currents are not an anion-conducting Ξ²2 pore. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0060084 synaptic transmission involved in micturition | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the autonomic circuit contribution to micturition. Reason: The full mouse IGI study supports beta2/beta4 compensation in autonomic neuronal transmission that sustains bladder contraction. This is circuit-level involvement; it does not place beta2 on the final smooth-muscle postsynaptic receptor or directly establish pelvic receptor stoichiometry. |
| GO:0095500 acetylcholine receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Human reconstitution and rat receptor experiments support the conserved capability; historical ancestral-node placement has not been reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001450431 UNRESOLVED Exact source ancestral node is retained. Current target experiments support the biological judgment; historical PAINT tree placement and its full experimental evidence set were not reconstructed. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0095500 acetylcholine receptor signaling pathway | IDA PMID:16835356 Beta3 subunits promote expression and nicotine-induced up-re... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Full current assay protocol not independently accessed; beta3 assembly effects are not assigned as a beta2-specific chaperone function. Supporting Evidence: |
| GO:0095500 acetylcholine receptor signaling pathway | IDA PMID:17132685 Ca2+ permeability of the (alpha4)3(beta2)2 stoichiometry gre... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Full Methods not recovered here; use the full text of PMID:20881005 for inspected calcium-current methodology. Supporting Evidence: |
| GO:0095500 acetylcholine receptor signaling pathway | IDA PMID:20881005 Acetylcholine receptor (AChR) Ξ±5 subunit variant associated ... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Full primary resides in preserved CHRNA4 normal/research variant, not the CHRNB2 abstract archive. Alpha5 D398N effect is not transferred to beta2. The reported calcium-only normalization method is retained without claiming an independently calculated permeability coefficient. Supporting Evidence: |
| GO:0095500 acetylcholine receptor signaling pathway | IDA PMID:24467848 A signal peptide missense mutation associated with nicotine ... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Expression ratios bias putative stoichiometries; exact assembly was not directly counted here. The tested disease-associated variant is alpha2 T22I, not a beta2 mutation. Supporting Evidence: |
| GO:0095500 acetylcholine receptor signaling pathway | IDA PMID:27698419 X-ray structure of the human Ξ±4Ξ²2 nicotinic receptor. | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Structure uses intracellular-loop deletions, junction linker and beta2 C-terminal Strep tag; prolonged nicotine produces a desensitized nonconducting structure. Structural state does not negate measured currents. Supporting Evidence: |
| GO:0095500 acetylcholine receptor signaling pathway | IDA PMID:29720657 Structural principles of distinct assemblies of the human Ξ±4... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Same large intracellular-loop deletions and tag; calcium-permeability ratio is cited prior physiology, not a new flux measurement in the inspected structural Results. Supporting Evidence: |
| GO:0095500 acetylcholine receptor signaling pathway | IDA PMID:38161283 Analogs of Ξ±-conotoxin PnIC selectively inhibit Ξ±7Ξ²2- over Ξ±... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Enforced alpha7-beta2-alpha7-beta2-alpha7 stoichiometry plus NACHO; this does not quantify native neuronal stoichiometry/distribution. Alpha6/3 comparator is a chimera. Antagonist allostery does not imply beta2 is an autonomous receptor. Supporting Evidence: |
| GO:0095500 acetylcholine receptor signaling pathway | IDA PMID:38454578 Structural bases for stoichiometry-selective calcium potenti... | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Structural full-length construct has Bril insertions and tag, alongside loop-deleted constructs. Calcium-site structural/mutational potentiation is not identical to calcium permeation; some sites arise from simulations alone. Alpha4 site mutations are not beta2 calcium-binding-site measurements. Supporting Evidence: |
| GO:0095500 acetylcholine receptor signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Human reconstitution and rat receptor experiments support the conserved capability; historical ancestral-node placement has not been reconstructed. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0095500 acetylcholine receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Ξ²2 performs the receptor step of cholinergic signaling. Reason: Assembled Ξ²2-containing receptors convert acetylcholine binding into cation current. This is a performed postsynaptic or modulatory receptor step, not acetylcholine synthesis or vesicular release by Ξ²2. Human reconstitution and rat receptor experiments support the conserved capability; historical ancestral-node placement has not been reconstructed. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0097060 synaptic membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Ξ²2-containing receptors occur in synaptic membranes. Reason: Presynaptic Ξ²2-containing receptor function is supported by rodent bouton/synaptosome experiments and postsynaptic receptor currents by neuronal and human-subunit studies. The exact broader or sided source location is retained; heterologous structural preparations do not themselves establish native synaptic abundance. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0097060 synaptic membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Ξ²2-containing receptors occur in synaptic membranes. Reason: Presynaptic Ξ²2-containing receptor function is supported by rodent bouton/synaptosome experiments and postsynaptic receptor currents by neuronal and human-subunit studies. The exact broader or sided source location is retained; heterologous structural preparations do not themselves establish native synaptic abundance. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0099565 chemical synaptic transmission, postsynaptic | IEA GO_REF:0000108 | ACCEPT | Summary: Retain the receptor contribution to postsynaptic electrical signaling. Reason: The ligand-gated cation current directly contributes to postsynaptic membrane-potential changes. Presynaptic Ξ²2 receptors can instead modulate release of other transmitters, including GABA; those downstream inhibitory currents are not an anion-conducting Ξ²2 pore. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:0099634 postsynaptic specialization membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Ξ²2-containing receptors occur in synaptic membranes. Reason: Presynaptic Ξ²2-containing receptor function is supported by rodent bouton/synaptosome experiments and postsynaptic receptor currents by neuronal and human-subunit studies. The exact broader or sided source location is retained; heterologous structural preparations do not themselves establish native synaptic abundance. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008360855 UNRESOLVED Exact source ancestral node is retained. Current target experiments support the biological judgment; historical PAINT tree placement and its full experimental evidence set were not reconstructed. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
| GO:1905144 response to acetylcholine | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the experimentally supported acetylcholine response. Reason: Rat alpha/beta receptor reconstitution and human Ξ²2-containing channels respond to acetylcholine. This broad stimulus-response assertion is retained outside the more specific channel/signaling core. Supporting Evidence: file:human/CHRNB2/CHRNB2-source-evidence.json |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Which native human neuronal receptor populations contain Ξ²2 in each stoichiometry, and how do their calcium permeability and presynaptic versus postsynaptic roles differ?
Q: Does Ξ²2 itself reside in plasma-membrane rafts, or do lipid perturbations primarily alter receptor conformation, trafficking or associated proteins?
Q: Which human cognitive phenotypes reflect altered Ξ²2 gating, developmental circuit organization or clinical seizure burden?
Q: Should the fetched enables qualifiers on the obligate Ξ²2-subunit channel assertions be curated to contributes_to? The integrated core already represents a contributed activity; all original annotation qualifiers remain unchanged.
Q: Can the GO:0007271 cholinergic-transmission definition be corrected to name acetylcholine receptors? The current fetched definition says dopamine receptors; no dopaminergic receptor activity is inferred for Ξ²2.
Q: Should the human ISS regulatory assertions retain involved_in or be qualified to match the mouse acts_upstream_of_or_within evidence, pending cell- and time-specific tests?
Experiment: Measure acetylcholine currents and calcium permeability in native human neuronal preparations while independently quantifying receptor subunit composition and stoichiometry.
Experiment: Combine endogenous Ξ²2 localization with membrane-domain markers and acute lipid perturbation, separating physical redistribution from changes in channel gating.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)