CHRNA1 encodes the alpha1 subunit of the skeletal-muscle nicotinic acetylcholine receptor. Two alpha1 chains join beta1, delta and either fetal gamma or adult epsilon to form a ligand-gated cation channel at the postsynaptic neuromuscular junction. Alpha1 contributes acetylcholine-recognition interfaces and pore-gating elements that convert motor-neuron transmitter release into endplate depolarization and muscle contraction. The assembled receptor also conducts calcium, with permeability influenced strongly by the complementary subunits. Pathogenic variants can impair receptor expression or alter gating and agonist affinity, causing congenital myasthenic syndromes; severe biallelic defects can cause fetal akinesia. Human splice products differ: the P3A-containing alpha+ product was not incorporated into functional receptors in the tested heterologous system.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003009 skeletal muscle contraction | IBA GO_REF:0000033 | ACCEPT | Summary: Retain participation in skeletal muscle contraction. Reason: This PAINT assertion concerns the receptor-mediated excitatory step that triggers skeletal-muscle contraction. Human endplate recordings and receptor reconstitution in PMID:9221765 independently substantiate that role for CHRNA1. The retained PTN002707610 denotes the curated ancestral assertion; its historical tree/MSA/IBD placement was not independently reconstructed. The target appearing among descendant evidence is not circular. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002707610 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0003009 skeletal muscle contraction | IEA GO_REF:0000107 | ACCEPT | Summary: Retain participation in skeletal muscle contraction. Reason: The Ensembl transfer names rat Chrna1/P25108. Human endplate recordings and alpha/beta/delta/epsilon receptor reconstitution in PMID:9221765 independently show the excitatory postsynaptic conductance through which the receptor supports muscle contraction. The donor identifier and inference method remain unchanged. |
| GO:0003009 skeletal muscle contraction | IMP PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | ACCEPT | Summary: Retain participation in skeletal muscle contraction. Reason: PMID:8872460 links human alpha N217K to prolonged endplate currents and postsynaptic myopathy, and tests the corresponding mutation in mouse receptors expressed in HEK cells. The receptor supplies the excitatory transmission step for muscle contraction. This IMP assertion retains the distinction between patient physiology and mouse recombinant constructs. |
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: Specify the acetylcholine-gated cation-channel function. Reason: InterPro IPR006201 describes the neurotransmitter-gated ion-channel family. For CHRNA1, human receptor experiments in PMID:9221765 establish acetylcholine-evoked cation conductance, permitting the ligand-specific GO:0022848 refinement of this broad receptor activity. Alpha1 contributes to a heteropentamer; the original enables relation remains source provenance. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity Supporting Evidence: GO_REF:0000002 https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR006201/ |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: Specify the acetylcholine-gated cation-channel function. Reason: The IPR002394 nicotinic-receptor family and IPR006201 neurotransmitter-gated-channel family underlie this InterPro2GO inference. Human acetylcholine-evoked receptor currents support GO:0022848, which specifies the ligand and cation-selective channel function. This is subunit participation in an assembled receptor, not an alpha1 homomer. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity Supporting Evidence: GO_REF:0000002 https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR002394/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR006201/ |
| GO:0005230 extracellular ligand-gated monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: Specify the acetylcholine-gated cation-channel function. Reason: IPR006202 and IPR036734 identify the neurotransmitter-gated-channel ligand-binding domain and its superfamily. Their broad extracellular-ligand channel inference is refined to GO:0022848 using the demonstrated acetylcholine specificity of human alpha1-containing receptors. Domain membership alone is not treated as the ligand-specific experiment. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity Supporting Evidence: GO_REF:0000002 https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR006202/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR036734/ |
| GO:0005886 plasma membrane | EXP PMID:27375219 Mutations Causing Slow-Channel Myasthenia Reveal That a Vali... | ACCEPT | Summary: Retain experimentally measured plasma-membrane localization. Reason: PMID:27375219 Methods explicitly coexpress human CHRNA1/CHRNB1/CHRND/CHRNE in HEK293 cells. Intact-cell alpha-bungarotoxin binding and surface agonist-competition measurements establish surface receptor expression; alpha-subunit pore mutants are also tested. Neither the title emphasis on beta/epsilon variants nor the heteropentamer context invalidates the alpha localization. Supporting Evidence: |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the active plasma-membrane receptor pool. Reason: The PAINT plasma-membrane assertion is independently corroborated by human receptor currents and intact-cell surface assays in PMID:9221765 and PMID:27375219. PTN001054635 and its descendant evidence are retained; current target evidence supports applicability without reconstructing the historical ancestral placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001054635 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Retain the HPA plasma-membrane localization. Reason: Authentic HPA ENSG00000138435 XML reports supported CHRNA1 immunofluorescence at the plasma membrane in Rh30 and LHCN-M2 cells. The corresponding images were inspected and show peripheral green staining. This is localization in those human cell lines, not proof of functional pentamers or identical localization of both splice products. Supporting Evidence: GO_REF:0000052 https://www.proteinatlas.org/ENSG00000138435.xml |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the conserved plasma-membrane location. Reason: The original mouse P04756/Ensembl and UniProt subcellular mapping are preserved. Independent human receptor reconstitution and intact-cell surface measurements substantiate the target localization, without transferring all mouse tissue contexts or both human splice-product behaviors. |
| GO:0005886 plasma membrane | ISS PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | ACCEPT | Summary: Retain the mouse-supported membrane localization. Reason: Actual original PMID:8872460 Results and Methods distinguish human patient muscle/endplate measurements from recombinant mouse alpha/beta/delta/epsilon receptors expressed in HEK cells. The alpha N217K patient has prolonged endplate currents and postsynaptic myopathy; the engineered mouse alpha mutant changes channel kinetics relative to wild type. Human host cells do not make these mouse constructs human. Mouse receptor surface expression and intact-cell ligand binding support this explicitly ISS annotation; independent human receptor surface measurements corroborate the target. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-622326 | ACCEPT | Summary: Retain the explicitly represented membrane location. Reason: The original Reactome event was followed through its catalyst or receptor input/output sets to physical entity480553, explicitly human CHRNA1/P02708 in the plasma membrane. The exact source path passes through complex532595, labeled homomeric and containing five copies of480553; that modeled composition is not the established muscle heteropentamer and is not silently adopted as target biology. Independent human surface assays corroborate the compartment. This TAS assertion concerns location; it is not inferred solely from a pathway title or taken as proof that alpha1 alone determines high calcium permeability. Supporting Evidence: Reactome:R-HSA-622326 https://reactome.org/ContentService/data/query/480553 https://reactome.org/ContentService/data/query/532595 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-629595 | ACCEPT | Summary: Retain the explicitly represented membrane location. Reason: The original Reactome event was followed through its catalyst or receptor input/output sets to physical entity480553, explicitly human CHRNA1/P02708 in the plasma membrane. The exact source path passes through complex532595, labeled homomeric and containing five copies of480553; that modeled composition is not the established muscle heteropentamer and is not silently adopted as target biology. Independent human surface assays corroborate the compartment. This TAS assertion concerns location; it is not inferred solely from a pathway title or taken as proof that alpha1 alone determines high calcium permeability. Supporting Evidence: Reactome:R-HSA-629595 https://reactome.org/ContentService/data/query/480553 https://reactome.org/ContentService/data/query/532595 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-629596 | ACCEPT | Summary: Retain the explicitly represented membrane location. Reason: The original Reactome event was followed through its catalyst or receptor input/output sets to physical entity480553, explicitly human CHRNA1/P02708 in the plasma membrane. The exact source path passes through complex532595, labeled homomeric and containing five copies of480553; that modeled composition is not the established muscle heteropentamer and is not silently adopted as target biology. Independent human surface assays corroborate the compartment. This TAS assertion concerns location; it is not inferred solely from a pathway title or taken as proof that alpha1 alone determines high calcium permeability. Supporting Evidence: Reactome:R-HSA-629596 https://reactome.org/ContentService/data/query/480553 https://reactome.org/ContentService/data/query/532595 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-629599 | ACCEPT | Summary: Retain the explicitly represented membrane location. Reason: The original Reactome event was followed through its catalyst or receptor input/output sets to physical entity480553, explicitly human CHRNA1/P02708 in the plasma membrane. The exact source path passes through complex532595, labeled homomeric and containing five copies of480553; that modeled composition is not the established muscle heteropentamer and is not silently adopted as target biology. Independent human surface assays corroborate the compartment. This TAS assertion concerns location; it is not inferred solely from a pathway title or taken as proof that alpha1 alone determines high calcium permeability. Supporting Evidence: Reactome:R-HSA-629599 https://reactome.org/ContentService/data/query/480553 https://reactome.org/ContentService/data/query/532595 |
| GO:0005892 acetylcholine-gated channel complex | IBA GO_REF:0000033 | ACCEPT | Summary: Retain membership in the muscle acetylcholine receptor complex. Reason: PAINT assigns membership in the acetylcholine-gated channel complex. Human alpha/beta/delta/epsilon receptor reconstitution in PMID:9221765 and the human splice-product study PMID:8788941 independently support alpha1 participation in that assembly. The historical PTN000435923 placement was not reconstructed; target experimental evidence in the donor set is legitimate descendant support. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000435923 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0005892 acetylcholine-gated channel complex | IEA GO_REF:0000120 | ACCEPT | Summary: Retain membership in the muscle acetylcholine receptor complex. Reason: The combined inference retains ARBA00033574 and mouse P04756/rat P25108 orthology sources. Human receptor reconstitution independently establishes alpha1 complex membership. It does not establish equivalent incorporation of the P3A-containing alternative product. |
| GO:0005892 acetylcholine-gated channel complex | IPI PMID:15701510 Refined structure of the nicotinic acetylcholine receptor at... | ACCEPT | Summary: Retain the conserved receptor-complex membership. Reason: The actual PMID:15701510 original Methods/structure concerns Torpedo marmorata postsynaptic membranes and models two alpha1 chains with beta/gamma/delta chains from an approximately4-Angstrom map. It is not a direct human structure. Independent human alpha/beta/delta/epsilon reconstitution in PMID:9221765 and product experiments in PMID:8788941 establish the same target complex membership. Preserve the original IPI/source object while making its organism boundary explicit; the positive target biology is not rejected from the source title. |
| GO:0005892 acetylcholine-gated channel complex | ISS PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | ACCEPT | Summary: Retain the explicit ortholog-supported receptor assembly. Reason: Actual original PMID:8872460 Results and Methods distinguish human patient muscle/endplate measurements from recombinant mouse alpha/beta/delta/epsilon receptors expressed in HEK cells. The alpha N217K patient has prolonged endplate currents and postsynaptic myopathy; the engineered mouse alpha mutant changes channel kinetics relative to wild type. Human host cells do not make these mouse constructs human. The original P04756 ISS support is faithful to the mouse receptor constructs, and human receptor reconstitution independently corroborates the complex. |
| GO:0005892 acetylcholine-gated channel complex | TAS PMID:7619526 Mutation of the acetylcholine receptor alpha subunit causes ... | ACCEPT | Summary: Retain alpha-subunit membership in functional muscle receptors. Reason: The authentic PMID:7619526 abstract reports alpha G153S in a slow-channel patient and functional expression with the other receptor subunits. Its full original body was not recovered, so exact construct-origin details are not inferred. Independent full human receptor reconstitution in PMID:9221765 establishes the retained complex membership. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | MODIFY | Summary: Specify transmembrane cation transport. Reason: The listed InterPro family, ligand-binding and transmembrane-domain records support a ligand-gated channel rather than an ATP-driven pump. Human receptor current measurements show cations crossing the membrane, making GO:0098655 more precise than ion transport. This refines an existing source assertion without proposing a new process. Proposed replacements: monoatomic cation transmembrane transport Supporting Evidence: GO_REF:0000002 https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR002394/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR006029/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR006202/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR036719/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR036734/ |
| GO:0006812 monoatomic cation transport | IEA GO_REF:0000107 | MODIFY | Summary: Specify transmembrane cation transport. Reason: The source transfers cation transport from rat Chrna1/P25108 through Ensembl orthology. Human alpha1-containing receptor currents establish the membrane-crossing step, supporting refinement to GO:0098655. The inference does not assign exclusive calcium selectivity to alpha1. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0006816 calcium ion transport | IBA GO_REF:0000033 | ACCEPT | Summary: Retain calcium transport by alpha1-containing receptors. Reason: Direct PMID:16527851 full Methods/Results reconstitute human alpha/beta/delta/epsilon receptors in rat GH4C1 cells and measure calcium as about7% of total current; human fetal receptors yield about2–3%, corroborated in cultured human myotubes. Nicotine activates the channels while intracellular-store controls isolate calcium entry. The epsilon subunit strongly determines the adult species difference, and alpha disease variants do not increase the calcium fraction. This establishes target participation in calcium transport, not alpha1-alone selectivity. The original PAINT identifier is preserved as a curated ancestral assertion, not a pairwise similarity vote. Current target biology corroborates applicability, but historical tree placement, MSA and IBD evidence were not independently reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000434994 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0007154 cell communication | IEA GO_REF:0000117 | MODIFY | Summary: Refine broad communication/signaling to neuromuscular transmission. Reason: ARBA00028945 supplies the broad cell-communication inference. Human endplate physiology in PMID:9221765 identifies its target-specific scope: the muscle receptor converts motor-neuron acetylcholine into postsynaptic conductance. GO:0007274 captures this neuromuscular transmission step. Historical rule execution was not reconstructed. Proposed replacements: neuromuscular synaptic transmission |
| GO:0007271 synaptic transmission, cholinergic | IBA GO_REF:0000033 | ACCEPT | Summary: Retain cholinergic neuromuscular transmission. Reason: The PAINT cholinergic-transmission assertion is independently supported by human endplate responses to acetylcholine and receptor reconstitution in PMID:9221765. This supports the postsynaptic contribution of alpha1 without assigning a presynaptic role. Historical PTN001054960 placement remains uninspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001054960 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0007274 neuromuscular synaptic transmission | IBA GO_REF:0000033 | ACCEPT | Summary: Retain cholinergic neuromuscular transmission. Reason: The PAINT neuromuscular-transmission assertion agrees with human patient/control endplate physiology and alpha1-containing receptor reconstitution in PMID:9221765. The receptor performs the postsynaptic conductance step. PTN000436077 and its evidence are retained; the target as a descendant source is not circular, and historical placement was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000436077 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0007274 neuromuscular synaptic transmission | IMP PMID:9221765 Slow-channel myasthenic syndrome caused by enhanced activati... | ACCEPT | Summary: Retain cholinergic neuromuscular transmission. Reason: PMID:9221765 measures human muscle endplate potentials/currents and reconstitutes human wild-type or alpha V249F receptors in HEK cells. Altered channel gating and postsynaptic injury explain impaired neuromuscular transmission. The original acts_upstream_of_or_within relation is preserved. Supporting Evidence: |
| GO:0007528 neuromuscular junction development | IMP PMID:9221765 Slow-channel myasthenic syndrome caused by enhanced activati... | KEEP AS NON CORE | Summary: Retain junctional organization at the tested maintenance scope. Reason: GO:0007528 includes assembly, arrangement and disassembly of the neuromuscular junction. PMID:9221765 human endplate microscopy documents degeneration and loss of junctional folds, reduced receptor numbers and postsynaptic injury under prolonged channel activation. This supports the original broad acts_upstream_of_or_within organization assertion, but does not demonstrate normal initiation of synaptogenesis. It is retained as a non-core maintenance/disease consequence alongside the defining receptor activity. Supporting Evidence: |
| GO:0009986 cell surface | IDA PMID:12928480 Allele-specific silencing of a pathogenic mutant acetylcholi... | ACCEPT | Summary: Retain receptor expression on the cell surface. Reason: Recovered original PMID:12928480 Results/Fig.1 and Methods coexpress alpha with beta/delta/epsilon in HEK cells, quantify intact-cell alpha-bungarotoxin binding and visualize surface receptor using an extracellular delta-subunit antibody. These assays place the assembled receptor containing alpha at the cell surface; they are not isolated alpha imaging or an all-isoform localization test. Supporting Evidence: |
| GO:0009986 cell surface | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the conserved cell-surface receptor location. Reason: The original mouse P04756/Ensembl transfer is consistent with explicit mouse receptor surface expression in PMID:8872460 and independent human intact-cell measurements. The surface claim applies to functional assembled receptors rather than unassembled intracellular chains. |
| GO:0015464 acetylcholine receptor activity | IBA GO_REF:0000033 | MODIFY | Summary: Use the ionotropic acetylcholine-channel term. Reason: This PAINT receptor-activity assertion is refined according to the GO:0015464 comment, which directs nicotinic ion channels to GO:0022848. Human alpha1-containing receptor currents independently substantiate the more specific activity. PTN000436077 remains the original ancestral source; no historical-node reconstruction or alpha-only channel is claimed. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000436077 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity Supporting Evidence: GO_REF:0000033 https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO:0015464 |
| GO:0015464 acetylcholine receptor activity | IEA GO_REF:0000107 | MODIFY | Summary: Use the ionotropic acetylcholine-channel term. Reason: The Ensembl inference transfers receptor activity from mouse Chrna1/P04756. GO:0015464 directs nicotinic channel receptors to GO:0022848, and human alpha1-containing receptor experiments corroborate that ligand-gated cation conductance. The original inference and relation are retained. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity Supporting Evidence: GO_REF:0000107 https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO:0015464 |
| GO:0015464 acetylcholine receptor activity | ISS PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | MODIFY | Summary: Use the ionotropic acetylcholine-channel term. Reason: PMID:8872460 tests recombinant mouse alpha/beta/delta/epsilon receptors alongside human patient endplates. The preserved P04756 ISS source supports the conserved nicotinic channel role. GO:0015464 explicitly directs such receptors to GO:0022848; independent human receptor experiments corroborate the refinement. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity Supporting Evidence: https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO:0015464 |
| GO:0015464 acetylcholine receptor activity | TAS PMID:7619526 Mutation of the acetylcholine receptor alpha subunit causes ... | MODIFY | Summary: Use the ionotropic acetylcholine-channel term. Reason: The PMID:7619526 abstract reports human alpha G153S and functional expression with other receptor subunits; the original full body was not recovered. Independent full human receptor experiments in PMID:9221765 support GO:0022848, the nicotinic-channel term specified by the GO:0015464 comment. The TAS source is preserved without inventing its uninspected construct details. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity Supporting Evidence: https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO:0015464 |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: Specify the plasma membrane for the receptor pool. Reason: The combined mouse orthology/domain evidence correctly identifies a membrane protein. Human receptor surface measurements and endplate localization justify plasma membrane as the better-supported compartment, without claiming that every nascent or alternative-product molecule reaches the cell surface. Proposed replacements: plasma membrane Supporting Evidence: GO_REF:0000120 https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR002394/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR006029/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR006201/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR006202/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR036719/ https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR036734/ |
| GO:0019228 neuronal action potential | IMP PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | MODIFY | Summary: Refine the source endpoint to neuromuscular transmission. Reason: PMID:8872460 measures human compound muscle responses, endplate potentials/currents and postsynaptic injury, with mouse receptor reconstitution in HEK cells. Those endpoints support GO:0007274 neuromuscular synaptic transmission rather than a CHRNA1-dependent neuronal action potential. This is a source-specific refinement, not exclusion of every possible neuronal role. Proposed replacements: neuromuscular synaptic transmission Supporting Evidence: PMID:8872460 prolonged end plate currents |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the defining acetylcholine-gated cation-channel activity. Reason: The combined InterPro IPR002394 and mouse P04756/rat P25108 orthology inference agrees with human alpha1-containing receptor currents. Alpha1 supplies ligand-interface and gating contributions to the assembled channel; original relations remain exact and the core represents contributes_to. Supporting Evidence: GO_REF:0000120 https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR002394/ |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | IMP PMID:9221765 Slow-channel myasthenic syndrome caused by enhanced activati... | ACCEPT | Summary: Retain the defining acetylcholine-gated cation-channel activity. Reason: PMID:9221765 directly compares human wild-type and alpha V249F receptors reconstituted with beta/delta/epsilon subunits in HEK cells. Acetylcholine-activated currents and altered mutant kinetics support alpha1 contribution to the channel activity. The evidence does not describe a functional alpha1 homomer. |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the defining acetylcholine-gated cation-channel activity. Reason: The original curated ISS transfer names P02709, whose captured UniProt identity is bovine CHRNA1, not Torpedo. Independent human receptor reconstitution in PMID:9221765 corroborates the same assembled-channel function. The original donor and evidence fields are preserved; no pairwise experiment or all-product equivalence is invented. Supporting Evidence: GO_REF:0000024 https://rest.uniprot.org/uniprotkb/P02709.json |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | ISS PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | ACCEPT | Summary: Retain the defining acetylcholine-gated cation-channel activity. Reason: PMID:8872460 explicitly uses mouse alpha/beta/delta/epsilon constructs and compares wild-type with alpha N217K receptor kinetics. This supports the preserved mouse P04756 ISS contribution to acetylcholine-gated cation conductance, independently corroborated in human receptors. |
| GO:0022848 acetylcholine-gated monoatomic cation-selective channel activity | TAS PMID:7619526 Mutation of the acetylcholine receptor alpha subunit causes ... | ACCEPT | Summary: Retain the defining acetylcholine-gated cation-channel activity. Reason: The PMID:7619526 abstract positively reports an alpha-subunit mutation affecting agonist affinity and channel activation; the full original body remains inaccessible. Independent human receptor experiments in PMID:9221765 support this channel function. The retained TAS does not imply that uninspected expression details or all splice products were verified. |
| GO:0023052 signaling | IEA GO_REF:0000117 | MODIFY | Summary: Refine broad communication/signaling to neuromuscular transmission. Reason: ARBA00026303 supplies the broad signaling inference. The performed target step is acetylcholine-triggered conductance at the muscle endplate, documented in PMID:9221765; GO:0007274 specifies that neuromuscular transmission role. The historical rule execution was not reconstructed. Proposed replacements: neuromuscular synaptic transmission |
| GO:0031594 neuromuscular junction | IDA PMID:9221765 Slow-channel myasthenic syndrome caused by enhanced activati... | ACCEPT | Summary: Retain localization and activity at the neuromuscular junction. Reason: PMID:9221765 localizes acetylcholine receptors to human junctional folds and records channel activity at patient/control endplates. Those direct observations support the neuromuscular-junction compartment; this source retains the is_active_in relation. Supporting Evidence: |
| GO:0031594 neuromuscular junction | IDA PMID:9221765 Slow-channel myasthenic syndrome caused by enhanced activati... | ACCEPT | Summary: Retain localization and activity at the neuromuscular junction. Reason: PMID:9221765 uses alpha-bungarotoxin electron-microscopy localization and human endplate measurements to establish receptor presence at the neuromuscular junction. This separately preserved IDA assertion uses located_in. Supporting Evidence: |
| GO:0031594 neuromuscular junction | IEA GO_REF:0000107 | ACCEPT | Summary: Retain localization and activity at the neuromuscular junction. Reason: The Ensembl source transfers the junctional location from mouse Chrna1/P04756. Human junctional-fold receptor localization and endplate recordings in PMID:9221765 independently corroborate the target compartment. |
| GO:0031594 neuromuscular junction | IMP PMID:9221765 Slow-channel myasthenic syndrome caused by enhanced activati... | ACCEPT | Summary: Retain localization and activity at the neuromuscular junction. Reason: PMID:9221765 shows altered receptor currents and postsynaptic injury at the human alpha V249F endplate. The original IMP is_active_in assertion remains distinct from the direct localization assertions for the same source. Supporting Evidence: |
| GO:0031594 neuromuscular junction | ISS PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | ACCEPT | Summary: Retain localization and activity at the neuromuscular junction. Reason: PMID:8872460 combines human endplate pathology/physiology with mouse alpha/beta/delta/epsilon receptor constructs. The original mouse ISS source is preserved separately from the observed human endplate evidence, with independent human CHRNA1 localization corroboration in PMID:9221765. |
| GO:0034220 monoatomic ion transmembrane transport | IBA GO_REF:0000033 | MODIFY | Summary: Specify performed transmembrane cation transport. Reason: This PAINT transmembrane-transport assertion is refined to cation transport because alpha1-containing receptors carry acetylcholine-evoked cation currents, with calcium entry independently measured in PMID:16527851. PTN000434994 and its sources remain unchanged; this is a target-supported term refinement, not a claim to reconstruct the historical node. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000434994 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0034220 monoatomic ion transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: Specify performed transmembrane cation transport. Reason: IPR006201 supplies the broad neurotransmitter-gated-channel inference. Human receptor current and calcium-entry measurements establish cation passage across the membrane, supporting GO:0098655 as the target-specific refinement of ion transmembrane transport. The original InterPro source is retained. Proposed replacements: monoatomic cation transmembrane transport Supporting Evidence: GO_REF:0000002 https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR006201/ |
| GO:0035094 response to nicotine | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the pharmacological response to nicotine. Reason: PMID:16527851 directly activates reconstituted human alpha1-containing adult/fetal receptors with nicotine and measures currents; nontransfected GH4C1 controls do not respond. This supplies target-specific support for the existing response term. Nicotine is an experimental agonist rather than the defining endogenous transmitter, so the response is non-core. The original PAINT identifier is preserved as a curated ancestral assertion, not a pairwise similarity vote. Current target biology corroborates applicability, but historical tree placement, MSA and IBD evidence were not independently reconstructed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000436077 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0042166 acetylcholine binding | IEA GO_REF:0000107 | ACCEPT | Summary: Retain alpha-subunit contribution to acetylcholine recognition. Reason: The Ensembl inference names mouse Chrna1/P04756. Mouse receptor agonist-competition assays in PMID:8872460 and independent human receptor binding measurements in PMID:9221765 support the conserved alpha1 contribution to ligand recognition. The binding interfaces contain alpha and neighboring subunits; the original contributes_to relation is preserved. |
| GO:0042166 acetylcholine binding | ISS PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | ACCEPT | Summary: Retain alpha-subunit contribution to acetylcholine recognition. Reason: PMID:8872460 measures agonist competition and altered affinity for mouse receptors containing alpha N217K. These assays support the preserved P04756 ISS contribution to acetylcholine binding, corroborated by human receptor measurements. They do not establish isolated-alpha autonomous binding. |
| GO:0042391 regulation of membrane potential | IEA GO_REF:0000117 | MODIFY | Summary: Refine to regulation of postsynaptic membrane potential. Reason: ARBA00028934 supplies a broad membrane-potential inference. Independent human endplate measurements in PMID:9221765 and PMID:8872460 locate the demonstrated electrical effect on the postsynaptic muscle membrane, supporting the existing child term GO:0060078. This target-supported refinement does not reconstruct the historical rule execution or change its source fields. Proposed replacements: regulation of postsynaptic membrane potential Supporting Evidence: GO_REF:0000117 https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO:0060078 |
| GO:0042391 regulation of membrane potential | IMP PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | MODIFY | Summary: Refine to regulation of postsynaptic membrane potential. Reason: PMID:8872460 records prolonged human endplate potentials and currents, including the alpha N217K patient, and tests mouse receptor kinetics separately. Its Results report temporal summation of endplate potentials; Discussion predicts resulting depolarization block. GO:0060078 matches the measured postsynaptic membrane scope more precisely than the original broad term. Proposed replacements: regulation of postsynaptic membrane potential Supporting Evidence: https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO:0060078 |
| GO:0042391 regulation of membrane potential | IMP PMID:9221765 Slow-channel myasthenic syndrome caused by enhanced activati... | MODIFY | Summary: Refine to regulation of postsynaptic membrane potential. Reason: PMID:9221765 measures altered human endplate-potential/current amplitudes and decay, with human alpha V249F receptor reconstitution linking these changes to channel behavior. GO:0060078 specifies the postsynaptic membrane endpoint. Depolarization block is a mechanistic prediction in Discussion, and the original acts_upstream_of_or_within relation remains unchanged. Proposed replacements: regulation of postsynaptic membrane potential Supporting Evidence: PMID:9221765 MEPPs and MEPCs had a reduced amplitude https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO:0060078 |
| GO:0045211 postsynaptic membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the postsynaptic membrane compartment. Reason: The PAINT postsynaptic-membrane assertion is corroborated by human muscle endplate localization in PMID:9221765. The target evidence supports the muscle side of the junction without resolving all tissues or reconstructing historical PTN008360807 placement. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008360807 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the postsynaptic membrane compartment. Reason: The combined IPR002394 and UniProt SL-0219 mappings identify the nicotinic receptor and postsynaptic membrane. Human junctional-fold receptor localization in PMID:9221765 independently supports that compartment for functional alpha1-containing receptors. Supporting Evidence: GO_REF:0000120 https://www.ebi.ac.uk/interpro/api/entry/interpro/IPR002394/ |
| GO:0045211 postsynaptic membrane | NAS PMID:18252226 Acetylcholine receptor pathway mutations explain various fet... | ACCEPT | Summary: Retain the postsynaptic membrane compartment. Reason: PMID:18252226 describes the skeletal-muscle receptor at the postsynaptic neuromuscular junction. Independent human endplate localization in PMID:9221765 corroborates this NAS assertion; the developmental source is not treated as a presynaptic localization experiment. |
| GO:0046716 muscle cell cellular homeostasis | IMP PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | KEEP AS NON CORE | Summary: Retain muscle-cell maintenance at the disease endpoint scope. Reason: PMID:8872460 describes injury to the postsynaptic muscle region, including damaged junctional folds and receptor loss in slow-channel disease. This supports a contextual muscle-cell homeostasis role, retained as non-core alongside the defining receptor activity. Human pathology and mouse receptor assays remain distinguished. Supporting Evidence: |
| GO:0048630 skeletal muscle tissue growth | IMP PMID:18252226 Acetylcholine receptor pathway mutations explain various fet... | MARK AS OVER ANNOTATED | Summary: Do not equate fetal akinesia with direct skeletal-muscle growth. Reason: The full PMID:18252226 study finds recessive human CHRNA1 variants, fetal hypokinesia/contractures and developmental abnormalities, with mouse somite expression. Results explicitly report reduced muscle mass in all affected individuals; this is a genuine positive phenotype. GO:0048630 specifies increased muscle size/mass through fiber number or size. The observed mass reduction does not distinguish a CHRNA1-performed growth step from a consequence of fetal immobility, and the paper explicitly calls an early mesodermal role speculative. Retain the positive movement/receptor evidence separately; this overannotation judgment is source-specific and does not deny that altered neuromuscular activity can affect muscle growth. Supporting Evidence: PMID:18252226 the evidence is speculative |
| GO:0050881 musculoskeletal movement | IMP PMID:18252226 Acetylcholine receptor pathway mutations explain various fet... | ACCEPT | Summary: Retain participation in musculoskeletal movement. Reason: PMID:18252226 directly links human biallelic CHRNA1 variants to fetal hypokinesia and contractures. Independent receptor physiology identifies the performed excitatory transmission step that enables skeletal-muscle contraction, so this is more than an unassigned necessity phenotype. The early somite observations and RAPSN-specific treatment response are not presented as CHRNA1 growth or rescue experiments. |
| GO:0050905 neuromuscular process | IMP PMID:9546329 Quinidine sulfate therapy for the slow-channel congenital my... | ACCEPT | Summary: Retain the broad neuromuscular role with clinical-source limits. Reason: The authentic PMID:9546329 abstract reports an open-label quinidine trial in six slow-channel syndrome patients, with improved strength and compound muscle action potential measurements in those completing treatment. Its full original body and patient-specific gene assignments were not recovered; this is not treated as a CHRNA1-only cohort or a drug-metabolism assay. Independent full CHRNA1 endplate/channel studies directly establish the retained neuromuscular function. |
| GO:0051899 membrane depolarization | IBA GO_REF:0000033 | ACCEPT | Summary: Retain generation and regulation of postsynaptic depolarization. Reason: Human acetylcholine-evoked endplate currents in PMID:9221765 corroborate the depolarizing conductance represented by this PAINT assertion. PTN000436077 is retained as the curated ancestral source, with its historical placement uninspected. This does not assign alpha1 a presynaptic mechanism. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000436077 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0060078 regulation of postsynaptic membrane potential | IEA GO_REF:0000120 | ACCEPT | Summary: Retain generation and regulation of postsynaptic depolarization. Reason: This combined logical inference comes from GO:0022848 and GO:1904315. Human endplate-potential/current measurements in PMID:9221765 independently establish modulation of the postsynaptic muscle membrane potential, supporting the term at its literal scope. |
| GO:0060079 excitatory postsynaptic potential | IEA GO_REF:0000108 | ACCEPT | Summary: Retain generation and regulation of postsynaptic depolarization. Reason: This logical inference from GO:0022848 describes the excitatory postsynaptic electrical response. Human muscle endplate measurements in PMID:9221765 corroborate the response mediated by the assembled alpha1-containing receptor. |
| GO:0070050 neuron cellular homeostasis | IMP PMID:8872460 New mutations in acetylcholine receptor subunit genes reveal... | MODIFY | Summary: Refine the measured homeostatic endpoint to the muscle cell. Reason: PMID:8872460 describes injury to postsynaptic muscle junctional folds, not a corresponding CHRNA1-dependent neuronal-maintenance assay. GO:0046716 matches the demonstrated muscle-cell homeostasis context and converges with the retained non-core source assertion. The refined function is likewise contextual, not a separate core activity; no general absence of neuronal expression is asserted. Proposed replacements: muscle cell cellular homeostasis Supporting Evidence: PMID:8872460 cationic overloading of the postsynaptic |
| GO:0095500 acetylcholine receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Retain acetylcholine receptor signaling. Reason: Human receptor activation and endplate experiments in PMID:9221765 show conversion of acetylcholine binding into postsynaptic conductance, supporting this PAINT signaling assertion. The PTN000436077 ancestral placement was not independently reconstructed; current target support does not substitute for a historical phylogeny audit. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000436077 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0095500 acetylcholine receptor signaling pathway | NAS PMID:21480901 Multiple inhibitory actions of lidocaine on Torpedo nicotini... | ACCEPT | Summary: Retain receptor signaling with the original species scope. Reason: The authentic PMID:21480901 abstract explicitly studies Torpedo receptors transplanted into Xenopus oocytes and reports acetylcholine-evoked currents affected by lidocaine. Full original Methods were not recovered, and this is not labeled a direct human assay. Independent human receptor experiments substantiate the conserved acetylcholine signaling claim; the source remains NAS rather than being rewritten. |
| GO:0098793 presynapse | IEA GO_REF:0000108 | UNDECIDED | Summary: Leave the specific presynaptic location unresolved. Reason: This is a logical inference from GO:0099171, not a direct alpha1 localization assay. The performed postsynaptic muscle receptor role is established, but alpha1-specific presynaptic localization was not verified. The premise and historical ancestral inference remain unresolved; lack of such verification does not establish absence or justify a NOT/REMOVE assertion. Its decision follows the unresolved GO:0099171 premise; this is not an independent localization result. Supporting Evidence: GO_REF:0000108 GO_REF:0000033 |
| GO:0099171 presynaptic modulation of chemical synaptic transmission | IBA GO_REF:0000033 | UNDECIDED | Summary: Leave the alpha1 presynaptic-modulation assertion unresolved. Reason: Current source identities and experiments for other nicotinic subunits can support a genuine ancestral receptor-family function, and a short donor list is not weak evidence. However, neither the historical PTN000436077 placement nor an alpha1-specific presynaptic regulatory step was independently established. Human endplate papers measure predominantly postsynaptic dysfunction and do not settle every possible alpha1 presynaptic role. Preserve the original IBA pending source-node/target clarification. Alpha1 expression outside skeletal muscle also prevents using a muscle-only premise to reject the inference. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000436077 UNRESOLVED The original curated PAINT node is preserved. Live descendant records and target experiments are current corroboration where available, not a reconstruction of historical IBD placement or MSA. No donor-count/self-source challenge is made. |
| GO:0099565 chemical synaptic transmission, postsynaptic | IEA GO_REF:0000108 | ACCEPT | Summary: Retain the performed postsynaptic transmission step. Reason: The logical source is GO:0022848 channel activity. Human endplate measurements show that the assembled alpha1-containing receptor carries the transmitter-triggered postsynaptic conductance, corroborating the resulting biological-process inference without assigning a presynaptic function. |
| GO:0099634 postsynaptic specialization membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the postsynaptic specialization membrane. Reason: The original mouse P04756 orthology transfer is consistent with human junctional-fold receptor localization and endplate channel activity. This is the specialized postsynaptic muscle membrane, not a claim that the protein is a neuronal presynaptic component. |
| GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential | IDA PMID:9221765 Slow-channel myasthenic syndrome caused by enhanced activati... | MODIFY | Summary: Specify the acetylcholine-gated channel underlying the endplate potential. Reason: PMID:9221765 directly measures acetylcholine-activated human receptor currents. GO:0022848 is an is_a child of the original transmitter-gated postsynaptic-channel term and specifies its ligand/cation selectivity. The IDA/enables source is preserved; the core represents alpha1 subunit contribution rather than an autonomous channel. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity Supporting Evidence: https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO:1904315 |
| GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential | IMP PMID:9221765 Slow-channel myasthenic syndrome caused by enhanced activati... | MODIFY | Summary: Specify the acetylcholine-gated channel underlying the endplate potential. Reason: Human alpha V249F receptor perturbation in PMID:9221765 changes acetylcholine-activated channel kinetics. GO:0022848 refines the original transmitter-gated postsynaptic-channel term by specifying the measured ligand and ion class. The IMP/enables source remains exact and does not imply an alpha1 homomer. Proposed replacements: acetylcholine-gated monoatomic cation-selective channel activity Supporting Evidence: https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO:1904315 |
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Download this section (compressed HTML)Q: How should the Reactome homomeric CHRNA1 complex532595 representation be reconciled with the established muscle heteropentamer, while preserving the supported plasma-membrane location?
Q: What direct alpha1-specific evidence and historical PAINT node placement support presynaptic modulation and the derived presynapse annotation?
Q: What is the endogenous cellular fate of the P3A-containing human alpha+ product, and does any defined context permit assembly or a separate biological function?
Q: How do alpha1 gating changes and complementary-subunit-dependent calcium permeability jointly determine endplate injury without conflating calcium fraction with prolonged total current?
Experiment: At matched endogenous expression in human myotubes, resolve both sequence-verified splice products and measure pentamer assembly, surface abundance and ligand-evoked currents separately; use product-specific rescue and unassembled-chain controls.
Hypothesis: P3A-containing alpha+ has trafficking or assembly behavior distinct from the functional alpha product.
Experiment: Use isoform-aware alpha1 genetic tagging and loss/rescue in a defined human motor-neuron–myotube system, measuring presynaptic transmitter release and postsynaptic current separately with cell-type-specific perturbations and validated paralog controls.
Hypothesis: An alpha1-specific presynaptic pool, if present, must be distinguished from muscle endplate receptors and neuronal nicotinic paralogs.
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