CHRNG

Summary: Retain skeletal-muscle excitation that initiates contraction.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. The assembled receptor performs the acetylcholine-triggered electrical step of neuromuscular excitation. Human CHRNG loss-of-function families in PMID:16826520 and PMID:16826531 have reduced prenatal movement. This does not assign actomyosin chemistry or an autonomous contractile motor to gamma. The rat RGD:2354 identity is authenticated as Chrng/P18916.

Summary: Specify acetylcholine-gated cation channel activity.

Reason: The original InterPro inference and enables qualifier are preserved. Human gamma-containing receptor measurements in PMID:16527851 establish ligand-gated cation-channel function. GO:0022848 is not an is_a descendant of GO:0004888 in the retrieved ontology: this is a lateral, mechanism-based replacement of a broad receptor assertion, not a claimed typed narrowing. The GO:0015464 usage comment directs ionotropic nicotinic receptors to GO:0022848. Gamma contributes to the assembled receptor; the core expresses that relation without altering the historical qualifier.

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

Summary: Specify acetylcholine-gated cation channel activity.

Reason: Official InterPro/rule source identity is retained, with direct target-containing receptor experiments providing specificity. PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. GO:0022848 states the ligand and cation-selective channel mechanism; the official GO:0015464 usage comment directs ionotropic nicotinic receptors to this term. Historical enables/contributes_to qualifiers are preserved exactly; the core uses contributes_to for the subunit.

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

Summary: Specify acetylcholine-gated cation channel activity.

Reason: Official InterPro/rule source identity is retained, with direct target-containing receptor experiments providing specificity. PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. GO:0022848 states the ligand and cation-selective channel mechanism; the official GO:0015464 usage comment directs ionotropic nicotinic receptors to this term. Historical enables/contributes_to qualifiers are preserved exactly; the core uses contributes_to for the subunit.

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

Summary: Remove uninformative bare protein binding while preserving the measured interaction.

Reason: 3 literal positive IntAct records join human CHRNG/P07510 and KRTAP10-7/P60409 to PMID:25416956. The pooling, array and validated two-hybrid records are consistent with the actual primary repeated pairwise verification and sequence-confirmation procedure. Dataset-level orthogonal tests are not claimed for this particular pair. The assay supports this pair at the same evidential strength as the KRT31 pair in this study. Current KRTAP10-7/-8/-9 annotations include GO:0045095 keratin filament, explicitly located_in by InterPro IEA; their documented function is a cysteine-rich interfilamentous matrix associated with hair keratins. That location is acknowledged, not rejected. Whether this accessory matrix role satisfies the protein-component class required by GO:0008092 is unresolved here, whereas KRT31 itself is an established filament-forming keratin. Retain the positive binding as non-core without categorically excluding KRTAPs from cytoskeletal association. Neither native muscle colocalization nor binding to an assembled filament is demonstrated. Current project protein-binding policy supersedes the historical non-core retention: remove only the uninformative GO:0005515 assertion. The positive assay and exact partner provenance remain accepted as observations; neither lack of a specific replacement nor lack of native colocalization makes the interaction false.

Summary: Remove uninformative bare protein binding while preserving the measured interaction.

Reason: 3 literal positive IntAct records join human CHRNG/P07510 and KRTAP10-8/P60410 to PMID:25416956. The pooling, array and validated two-hybrid records are consistent with the actual primary repeated pairwise verification and sequence-confirmation procedure. Dataset-level orthogonal tests are not claimed for this particular pair. The assay supports this pair at the same evidential strength as the KRT31 pair in this study. Current KRTAP10-7/-8/-9 annotations include GO:0045095 keratin filament, explicitly located_in by InterPro IEA; their documented function is a cysteine-rich interfilamentous matrix associated with hair keratins. That location is acknowledged, not rejected. Whether this accessory matrix role satisfies the protein-component class required by GO:0008092 is unresolved here, whereas KRT31 itself is an established filament-forming keratin. Retain the positive binding as non-core without categorically excluding KRTAPs from cytoskeletal association. Neither native muscle colocalization nor binding to an assembled filament is demonstrated. Current project protein-binding policy supersedes the historical non-core retention: remove only the uninformative GO:0005515 assertion. The positive assay and exact partner provenance remain accepted as observations; neither lack of a specific replacement nor lack of native colocalization makes the interaction false.

Summary: Remove uninformative bare protein binding while preserving the measured interaction.

Reason: 3 literal positive IntAct records join human CHRNG/P07510 and KRTAP10-9/P60411 to PMID:25416956. The pooling, array and validated two-hybrid records are consistent with the actual primary repeated pairwise verification and sequence-confirmation procedure. Dataset-level orthogonal tests are not claimed for this particular pair. The assay supports this pair at the same evidential strength as the KRT31 pair in this study. Current KRTAP10-7/-8/-9 annotations include GO:0045095 keratin filament, explicitly located_in by InterPro IEA; their documented function is a cysteine-rich interfilamentous matrix associated with hair keratins. That location is acknowledged, not rejected. Whether this accessory matrix role satisfies the protein-component class required by GO:0008092 is unresolved here, whereas KRT31 itself is an established filament-forming keratin. Retain the positive binding as non-core without categorically excluding KRTAPs from cytoskeletal association. Neither native muscle colocalization nor binding to an assembled filament is demonstrated. Current project protein-binding policy supersedes the historical non-core retention: remove only the uninformative GO:0005515 assertion. The positive assay and exact partner provenance remain accepted as observations; neither lack of a specific replacement nor lack of native colocalization makes the interaction false.

Summary: Specify the experimentally supported keratin-protein binding class.

Reason: 3 literal positive IntAct records join human CHRNG/P07510 and KRT31/Q15323 to PMID:25416956. The pooling, array and validated two-hybrid records are consistent with the actual primary repeated pairwise verification and sequence-confirmation procedure. Dataset-level orthogonal tests are not claimed for this particular pair. KRT31/Q15323 is an authenticated type-I keratin with an intermediate-filament rod domain and structural-constituent annotation. It therefore satisfies the protein-component class in GO:0008092. The positive Y2H evidence has the same strength as that for the KRTAP partners; the different refinement rests on established partner class, not stronger interaction evidence. KRTAP filament-location annotations are acknowledged separately, but do not alone settle their accessory matrix classification. This is assay-only, non-core binding specificity: no native muscle encounter, assembled-filament binding or CHRNG cytoskeletal activity is inferred.

Proposed replacements: cytoskeletal protein binding

Summary: Remove uninformative bare protein binding while preserving the measured interaction.

Reason: 3 literal positive IntAct records join human CHRNG/P07510 and NOTCH2NLA/Q7Z3S9 to PMID:25416956. The pooling, array and validated two-hybrid records are consistent with the actual primary repeated pairwise verification and sequence-confirmation procedure. Dataset-level orthogonal tests are not claimed for this particular pair. NOTCH2NLA is a secreted Notch-pathway modulator, not the transmembrane NOTCH2 receptor itself; the pair does not establish receptor binding or a CHRNG Notch-signaling role. Retain the supported generic interaction as non-core under the campaign convention, without a native physiological encounter or new mechanism claim. Current project protein-binding policy supersedes the historical non-core retention: remove only the uninformative GO:0005515 assertion. The positive assay and exact partner provenance remain accepted as observations; neither lack of a specific replacement nor lack of native colocalization makes the interaction false.

Summary: Remove uninformative bare protein binding while preserving the measured interaction.

Reason: One literal positive IntAct record joins human CHRNG/P07510 and KRTAP10-7/P60409 to PMID:29892012. The actual Methods test WT and variant ORFs using GAL4 fusions in yeast, with empty-vector autoactivation controls. The exact record includes a CHRNG position-448 mutation with no effect on the interaction; retain this tested variant context rather than describing a native membrane complex. The assay supports this pair at the same evidential strength as the KRT31 pair in this study. Current KRTAP10-7/-8/-9 annotations include GO:0045095 keratin filament, explicitly located_in by InterPro IEA; their documented function is a cysteine-rich interfilamentous matrix associated with hair keratins. That location is acknowledged, not rejected. Whether this accessory matrix role satisfies the protein-component class required by GO:0008092 is unresolved here, whereas KRT31 itself is an established filament-forming keratin. Retain the positive binding as non-core without categorically excluding KRTAPs from cytoskeletal association. Neither native muscle colocalization nor binding to an assembled filament is demonstrated. Current project protein-binding policy supersedes the historical non-core retention: remove only the uninformative GO:0005515 assertion. The positive assay and exact partner provenance remain accepted as observations; neither lack of a specific replacement nor lack of native colocalization makes the interaction false.

Summary: Remove uninformative bare protein binding while preserving the measured interaction.

Reason: One literal positive IntAct record joins human CHRNG/P07510 and KRTAP10-8/P60410 to PMID:29892012. The actual Methods test WT and variant ORFs using GAL4 fusions in yeast, with empty-vector autoactivation controls. The exact record includes a CHRNG position-448 mutation with no effect on the interaction; retain this tested variant context rather than describing a native membrane complex. The assay supports this pair at the same evidential strength as the KRT31 pair in this study. Current KRTAP10-7/-8/-9 annotations include GO:0045095 keratin filament, explicitly located_in by InterPro IEA; their documented function is a cysteine-rich interfilamentous matrix associated with hair keratins. That location is acknowledged, not rejected. Whether this accessory matrix role satisfies the protein-component class required by GO:0008092 is unresolved here, whereas KRT31 itself is an established filament-forming keratin. Retain the positive binding as non-core without categorically excluding KRTAPs from cytoskeletal association. Neither native muscle colocalization nor binding to an assembled filament is demonstrated. Current project protein-binding policy supersedes the historical non-core retention: remove only the uninformative GO:0005515 assertion. The positive assay and exact partner provenance remain accepted as observations; neither lack of a specific replacement nor lack of native colocalization makes the interaction false.

Summary: Remove uninformative bare protein binding while preserving the measured interaction.

Reason: One literal positive IntAct record joins human CHRNG/P07510 and KRTAP10-9/P60411 to PMID:29892012. The actual Methods test WT and variant ORFs using GAL4 fusions in yeast, with empty-vector autoactivation controls. The exact record includes a CHRNG position-448 mutation with no effect on the interaction; retain this tested variant context rather than describing a native membrane complex. The assay supports this pair at the same evidential strength as the KRT31 pair in this study. Current KRTAP10-7/-8/-9 annotations include GO:0045095 keratin filament, explicitly located_in by InterPro IEA; their documented function is a cysteine-rich interfilamentous matrix associated with hair keratins. That location is acknowledged, not rejected. Whether this accessory matrix role satisfies the protein-component class required by GO:0008092 is unresolved here, whereas KRT31 itself is an established filament-forming keratin. Retain the positive binding as non-core without categorically excluding KRTAPs from cytoskeletal association. Neither native muscle colocalization nor binding to an assembled filament is demonstrated. Current project protein-binding policy supersedes the historical non-core retention: remove only the uninformative GO:0005515 assertion. The positive assay and exact partner provenance remain accepted as observations; neither lack of a specific replacement nor lack of native colocalization makes the interaction false.

Summary: Specify the experimentally supported keratin-protein binding class.

Reason: One literal positive IntAct record joins human CHRNG/P07510 and KRT31/Q15323 to PMID:29892012. The actual Methods test WT and variant ORFs using GAL4 fusions in yeast, with empty-vector autoactivation controls. The exact record includes a CHRNG position-448 mutation with no effect on the interaction; retain this tested variant context rather than describing a native membrane complex. KRT31/Q15323 is an authenticated type-I keratin with an intermediate-filament rod domain and structural-constituent annotation. It therefore satisfies the protein-component class in GO:0008092. The positive Y2H evidence has the same strength as that for the KRTAP partners; the different refinement rests on established partner class, not stronger interaction evidence. KRTAP filament-location annotations are acknowledged separately, but do not alone settle their accessory matrix classification. This is assay-only, non-core binding specificity: no native muscle encounter, assembled-filament binding or CHRNG cytoskeletal activity is inferred.

Proposed replacements: cytoskeletal protein binding

Summary: Remove uninformative bare protein binding while preserving the measured interaction.

Reason: 1 literal positive IntAct record join human CHRNG/P07510 and NOTCH2NLA/Q7Z3S9 to PMID:29892012. The actual Methods test WT and variant ORFs using GAL4 fusions in yeast, with empty-vector autoactivation controls. The exact record includes a CHRNG position-448 mutation with no effect on the interaction; retain this tested variant context rather than describing a native membrane complex. NOTCH2NLA is a secreted Notch-pathway modulator, not the transmembrane NOTCH2 receptor itself; the pair does not establish receptor binding or a CHRNG Notch-signaling role. Retain the supported generic interaction as non-core under the campaign convention, without a native physiological encounter or new mechanism claim. Current project protein-binding policy supersedes the historical non-core retention: remove only the uninformative GO:0005515 assertion. The positive assay and exact partner provenance remain accepted as observations; neither lack of a specific replacement nor lack of native colocalization makes the interaction false.

Summary: Remove uninformative bare protein binding while preserving the measured interaction.

Reason: 1 literal positive IntAct record join human CHRNG/P07510 and NOTCH2NLA/Q7Z3S9 to PMID:31515488. The actual Methods compare WT/variant GAL4 fusions with autoactivation controls and repeated growth phenotypes. The exact NOTCH2NLA participant carries position-74 and position-115 mutation-with-no-effect features; these are partner variants, not CHRNG changes. NOTCH2NLA is a secreted Notch-pathway modulator, not the transmembrane NOTCH2 receptor itself; the pair does not establish receptor binding or a CHRNG Notch-signaling role. Retain the supported generic interaction as non-core under the campaign convention, without a native physiological encounter or new mechanism claim. Current project protein-binding policy supersedes the historical non-core retention: remove only the uninformative GO:0005515 assertion. The positive assay and exact partner provenance remain accepted as observations; neither lack of a specific replacement nor lack of native colocalization makes the interaction false.

Summary: Retain plasma-membrane localization and activity.

Reason: Human gamma-containing receptor currents measured in rat GH4C1 expression cells and primary human myotubes support the plasma-membrane compartment (PMID:16527851). Mouse-subunit reconstitution in human HEK cells independently demonstrates assembled receptor surface delivery (PMID:16826520); those constructs are not human merely because of the host. The original localization or active-in relation is retained.

Summary: Retain plasma-membrane localization and activity.

Reason: Human gamma-containing receptor currents measured in rat GH4C1 expression cells and primary human myotubes support the plasma-membrane compartment (PMID:16527851). Mouse-subunit reconstitution in human HEK cells independently demonstrates assembled receptor surface delivery (PMID:16826520); those constructs are not human merely because of the host. The original localization or active-in relation is retained.

Summary: Retain plasma-membrane localization and activity.

Reason: The original PMID:3967651 abstract establishes human genomic sequence and predicted four-pass topology; its full body remains unrecovered. Independent human receptor currents in PMID:16527851 support plasma-membrane activity, and mouse-subunit surface-delivery experiments in human HEK cells provide corroboration (PMID:16826520). These later assays are not attributed to the cloning paper.

Summary: Retain the explicit target plasma-membrane compartment.

Reason: The exact Reactome event reaches physical entity 507843, CHRNG/P07510 residues 23–517, annotated to plasma membrane. Its source chain passes through the delta/epsilon/gamma set 532618 inside modeled alpha3-beta4 complex 532621 and highly sodium-permeable receptor set 629576. That source composition is not the established fetal muscle alpha1/beta1/gamma/delta stoichiometry and is not silently reinterpreted. The compartment is independently corroborated by human fetal receptor reconstitution; no neuronal alpha3-beta4 membership is inferred for CHRNG.

Summary: Retain the explicit target plasma-membrane compartment.

Reason: The exact Reactome event reaches physical entity 507843, CHRNG/P07510 residues 23–517, annotated to plasma membrane. Its source chain passes through the delta/epsilon/gamma set 532618 inside modeled alpha3-beta4 complex 532621 and highly sodium-permeable receptor set 629576. That source composition is not the established fetal muscle alpha1/beta1/gamma/delta stoichiometry and is not silently reinterpreted. The compartment is independently corroborated by human fetal receptor reconstitution; no neuronal alpha3-beta4 membership is inferred for CHRNG.

Summary: Retain fetal acetylcholine-gated channel complex membership.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. The fetal receptor contains two alpha1 subunits and one beta1, gamma and delta. PMID:39085615 resolves native bovine fetal receptors, including gamma pore and complementary ligand-site contributions; this is ortholog structural evidence, not a human structure or a test of both human products. The PAINT assertion concerns complex membership, not a gamma-only channel or every product.

Summary: Specify monoatomic cation transmembrane transport.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. The measured inward current and native ortholog pore establish cation passage across the membrane. GO:0098655 preserves both ion charge and the membrane step more precisely than the original broad term. PMID:39085615 resolves native bovine fetal receptors, including gamma pore and complementary ligand-site contributions; this is ortholog structural evidence, not a human structure or a test of both human products.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Retain calcium transport by the gamma-containing fetal receptor.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Simultaneous current/fura-2 measurements give about 3% fractional calcium current for WT gamma receptors and 2.7 ± 0.6% in human myotubes; controls exclude intracellular-store release and responses in untransfected cells. Adult epsilon-containing receptors have higher fractional calcium permeability, so this is not gamma-specific calcium selectivity. These target-containing experiments corroborate the IBA despite its neuronal descendant premises.

Summary: Specify the skeletal-muscle contraction context.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. The performed role is receptor excitation that triggers skeletal-muscle contraction. The ARBA source is preserved, while independently measured target-containing receptor activity supplies the biological precision.

Proposed replacements: skeletal muscle contraction

Summary: Specify the skeletal-muscle contraction context.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. The performed role is receptor excitation that triggers skeletal-muscle contraction. The actual PMID:8040310 full paper compares antibody recognition of human fetal and adult muscle receptor preparations with neonatal myasthenia; it does not isolate gamma-specific antibody epitopes or directly measure contractile force. This TAS context is strengthened by independent receptor physiology and human CHRNG loss-of-function evidence.

Proposed replacements: skeletal muscle contraction

Summary: Specify acetylcholine receptor signaling.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Acetylcholine-triggered gating and postsynaptic cation flow define GO:0095500 more precisely than unrestricted communication/signaling; this is the receptor's own performed signaling step.

Proposed replacements: acetylcholine receptor signaling pathway

Summary: Specify acetylcholine receptor signaling.

Reason: The original PMID:3967651 abstract establishes cloned human genomic sequence and predicted four-pass topology, but its complete body was not recovered after a bounded publisher attempt. Independent human functional reconstitution supplies the positive activity evidence without attributing that assay to the cloning paper. PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Acetylcholine-triggered gating and postsynaptic cation flow define GO:0095500 more precisely than unrestricted communication/signaling; this is the receptor's own performed signaling step.

Proposed replacements: acetylcholine receptor signaling pathway

Summary: Retain cholinergic synaptic transmission.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Gamma helps convert the cholinergic signal to postsynaptic electrical excitation during fetal neuromuscular transmission. This is a direct receptor role, not neurotransmitter synthesis, vesicle release or a neuron-specific claim.

Summary: Specify acetylcholine-gated cation channel activity.

Reason: Official InterPro/rule source identity is retained, with direct target-containing receptor experiments providing specificity. PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. GO:0022848 states the ligand and cation-selective channel mechanism; the official GO:0015464 usage comment directs ionotropic nicotinic receptors to this term. Historical enables/contributes_to qualifiers are preserved exactly; the core uses contributes_to for the subunit.

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

Summary: Specify acetylcholine-gated cation channel activity.

Reason: The original PMID:3967651 abstract establishes cloned human genomic sequence and predicted four-pass topology, but its complete body was not recovered after a bounded publisher attempt. Independent human functional reconstitution supplies the positive activity evidence without attributing that assay to the cloning paper. PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. GO:0022848 states the ligand and cation-selective channel mechanism; the official GO:0015464 usage comment directs ionotropic nicotinic receptors to this term. Historical enables/contributes_to qualifiers are preserved exactly; the core uses contributes_to for the subunit.

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

Summary: Specify acetylcholine-gated cation channel activity.

Reason: The original PMID:3967651 abstract establishes cloned human genomic sequence and predicted four-pass topology, but its complete body was not recovered after a bounded publisher attempt. Independent human functional reconstitution supplies the positive activity evidence without attributing that assay to the cloning paper. PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. GO:0022848 states the ligand and cation-selective channel mechanism; the official GO:0015464 usage comment directs ionotropic nicotinic receptors to this term. Historical enables/contributes_to qualifiers are preserved exactly; the core uses contributes_to for the subunit.

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

Summary: Specify the postsynaptic membrane compartment.

Reason: The domain-based membrane inference is sound but broad. Human fetal receptor physiology and native bovine fetal receptor structure support the muscle postsynaptic membrane as the functional compartment (PMID:16527851; PMID:39085615). This refinement does not restrict every biosynthetic intermediate or developmental extrasynaptic receptor to a mature synapse.

Proposed replacements: postsynaptic membrane

Summary: Retain the specific acetylcholine-gated cation-channel function.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. PMID:39085615 resolves native bovine fetal receptors, including gamma pore and complementary ligand-site contributions; this is ortholog structural evidence, not a human structure or a test of both human products. Original qualifiers remain exact; contributes_to in the core explicitly represents the contribution of gamma to the assembled heteropentamer.

Summary: Retain the specific acetylcholine-gated cation-channel function.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. PMID:39085615 resolves native bovine fetal receptors, including gamma pore and complementary ligand-site contributions; this is ortholog structural evidence, not a human structure or a test of both human products. Original qualifiers remain exact; contributes_to in the core explicitly represents the contribution of gamma to the assembled heteropentamer.

Summary: Specify acetylcholine receptor signaling.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Acetylcholine-triggered gating and postsynaptic cation flow define GO:0095500 more precisely than unrestricted communication/signaling; this is the receptor's own performed signaling step.

Proposed replacements: acetylcholine receptor signaling pathway

Summary: Specify monoatomic cation transmembrane transport.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. The measured inward current and native ortholog pore establish cation passage across the membrane. GO:0098655 preserves both ion charge and the membrane step more precisely than the original broad term. PMID:39085615 resolves native bovine fetal receptors, including gamma pore and complementary ligand-site contributions; this is ortholog structural evidence, not a human structure or a test of both human products.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Specify monoatomic cation transmembrane transport.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. The measured inward current and native ortholog pore establish cation passage across the membrane. GO:0098655 preserves both ion charge and the membrane step more precisely than the original broad term. PMID:39085615 resolves native bovine fetal receptors, including gamma pore and complementary ligand-site contributions; this is ortholog structural evidence, not a human structure or a test of both human products.

Proposed replacements: monoatomic cation transmembrane transport

Summary: Retain the postsynaptic membrane location.

Reason: Gamma-containing fetal receptors mediate excitation on the muscle side of the neuromuscular junction, consistent with human receptor physiology and native bovine receptor structure (PMID:16527851; PMID:39085615). Retain the original postsynaptic location or active-in relation; developmental extrasynaptic expression is not excluded.

Summary: Retain postsynaptic electrical excitation by the receptor.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Opening the cation pore supplies depolarizing inward current and the excitatory postsynaptic potential. This is actual ion-channel work rather than an inference solely from disease or fetal immobility. The gamma-containing assembly, not gamma alone, performs the conductance.

Summary: Retain postsynaptic electrical excitation by the receptor.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Opening the cation pore supplies depolarizing inward current and the excitatory postsynaptic potential. This is actual ion-channel work rather than an inference solely from disease or fetal immobility. The gamma-containing assembly, not gamma alone, performs the conductance.

Summary: Retain postsynaptic electrical excitation by the receptor.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Opening the cation pore supplies depolarizing inward current and the excitatory postsynaptic potential. This is actual ion-channel work rather than an inference solely from disease or fetal immobility. The gamma-containing assembly, not gamma alone, performs the conductance.

Summary: Retain acetylcholine receptor signaling.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. Ligand-dependent current is the receptor-signaling step; the curated PAINT premise is not reduced to a neuronal donor count.

Summary: Retain the postsynaptic part of chemical synaptic transmission.

Reason: PMID:16527851 reconstitutes wild-type human alpha1/beta1/gamma/delta receptors in rat GH4C1 cells and independently measures fetal receptor current in primary human myotubes. Gamma is a component of the conducting heteropentamer, not an autonomous channel. The molecular role is on the receiving muscle membrane. The logical inference from specific transmitter-gated channel activity is consistent with this directly performed postsynaptic step.

Summary: Retain the postsynaptic membrane location.

Reason: Gamma-containing fetal receptors mediate excitation on the muscle side of the neuromuscular junction, consistent with human receptor physiology and native bovine receptor structure (PMID:16527851; PMID:39085615). Retain the original postsynaptic location or active-in relation; developmental extrasynaptic expression is not excluded.

Summary: Specify acetylcholine-gated cation channel activity.

Reason: The original bovine P13536 ortholog, PMID:2423878 donor premises and enables qualifier are preserved. GO:0022848 is an explicit is_a child of GO:1904315 in the retrieved ontology, so the replacement preserves the postsynaptic channel context while specifying acetylcholine and cation selectivity. Human gamma-containing receptor measurements in PMID:16527851 independently support this mechanism. The subunit contributes to the conducting heteropentamer; no autonomous gamma channel or new historical qualifier is asserted.

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

Summary: Add the conserved complementary ligand-binding contribution.

Reason: Native bovine fetal receptor cryo-EM in PMID:39085615 resolves gamma at the complementary alpha1/gamma acetylcholine pocket: W77 contributes the aromatic enclosure, N129/L141 coordinate the ligand-associated water, and Y139 covers the ligand. Official 9AVU entity 4 chain B exactly matches bovine P13536 residues 23–519. Human canonical P07510 retains the eight checked contact/stabilizing positions 75/77/79/83/129/137/139/141; adjacent bovine V138 versus human I138 is explicitly different. This is an ISS inference for gamma contribution within the assembled receptor, not human structural IDA, an isolated-gamma affinity assay or autonomous binding. P07510-2 replaces canonical residues 117–169 with lysine and is untested; this assertion does not establish equivalent activity of that product. Current same-role CHRND contributes_to binding shows that complementary-subunit participation is representable. Typed is_a/part_of checks find no overlap with existing terms; binding adds ligand-contact coverage without a NEW process or separate core mechanism.