CNGB1 encodes beta subunits of sensory cyclic-nucleotide-gated cation channels and the soluble glutamic acid-rich product GARP2. In rod photoreceptors, CNGB1 assembles with three CNGA1 subunits at the outer-segment plasma membrane, contributing to the pore, cGMP recognition, gating and channel targeting. Olfactory beta-containing channels assemble with CNGA2 and CNGA4 and couple cAMP signals to depolarizing cation currents under calcium/calmodulin feedback. Human CNGB1 variants cause recessive retinitis pigmentosa. The separate GARP2 product is inferred to restrain basal rod PDE6 activity from biochemical studies of its bovine ortholog.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001750 photoreceptor outer segment | IBA GO_REF:0000033 | ACCEPT | Summary: Accept conserved photoreceptor outer-segment localization. Reason: The mouse Cngb1 ortholog E1AZ71 and bovine beta-subunit evidence support the rod outer-segment location. Actual mouse retinal localization and human CNGB1 targeting experiments independently corroborate it. The PAINT source also includes mouse Cnga3, which is not relabeled a beta ortholog; no historical ancestral placement is reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000025740 SUPPORTS TRANSFER Independent target/ortholog evidence supports this photoreceptor outer segment assertion as detailed in the row. Current donor identities and literal records were checked where available; the historical PTN tree, alignment and IBD placement were not reconstructed. Donor count and target self-inclusion are not failure criteria. |
| GO:0001750 photoreceptor outer segment | IEA GO_REF:0000107 | ACCEPT | Summary: Accept conserved photoreceptor outer-segment localization. Reason: The mouse Cngb1 ortholog E1AZ71 and bovine beta-subunit evidence support the rod outer-segment location. Actual mouse retinal localization and human CNGB1 targeting experiments independently corroborate it. The PAINT source also includes mouse Cnga3, which is not relabeled a beta ortholog; no historical ancestral placement is reconstructed. |
| GO:0001895 retina homeostasis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain inherited retinal maintenance outside the molecular core. Reason: Direct target clinical evidence and mouse Cngb1 channel-loss experiments support maintenance of the retina. The target appearing in the PAINT evidence is legitimate grounding, not circularity. Progressive degeneration establishes this contextual biological role without identifying a second independent molecular activity or reconstructing the historical node. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002900695 SUPPORTS TRANSFER Independent target/ortholog evidence supports this retina homeostasis assertion as detailed in the row. Current donor identities and literal records were checked where available; the historical PTN tree, alignment and IBD placement were not reconstructed. Donor count and target self-inclusion are not failure criteria. |
| GO:0001895 retina homeostasis | IMP PMID:15557452 A homozygosity-based search for mutations in patients with a... | KEEP AS NON CORE | Summary: Retain the source-specific retinal maintenance phenotype. Reason: The original human study identifies a homozygous CNGB1 splice-donor variant in a patient with retinitis pigmentosa and nonrecordable electroretinograms. CNGB1 family DNA was unavailable, so this paper does not show segregation or directly assay the predicted splice effect. Independent mouse channel disruption supports retinal maintenance; the clinical phenotype is not itself a separate molecular core. |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine the broad channel mapping to cyclic-nucleotide-gated cation-channel activity. Reason: The pore and cyclic-nucleotide-binding domains contribute to assembled channels rather than an autonomous beta-subunit channel. Human rod and olfactory complexes directly support the more informative cyclic-nucleotide-gated cation activity. Proposed replacements: intracellularly cyclic nucleotide-activated monoatomic cation channel activity |
| GO:0005221 intracellularly cyclic nucleotide-activated monoatomic cation channel activity | IEA GO_REF:0000002 | ACCEPT | Summary: Accept the channel-family activity at assembled-complex scope. Reason: Human CNGB1 contributes pore and ligand-gating machinery in rod CNGA1/CNGB1 and olfactory CNGA2/CNGA4/CNGB1 preparations. The existing enables qualifier is preserved, while the synthesis uses contributes_to to express the demonstrated requirement for partner subunits. |
| GO:0005222 intracellularly cAMP-activated cation channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: Accept inherited cAMP-responsive channel capability. Reason: Direct human target evidence includes partial rod-channel activation by high cAMP and cAMP-gated engineered olfactory complexes. The target self-donor is legitimate experimental grounding. The rat beta and human cone beta sources are distinguished, and the historical PAINT node is not independently reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000025739 SUPPORTS TRANSFER Independent target/ortholog evidence supports this intracellularly cAMP-activated cation channel activity assertion as detailed in the row. Current donor identities and literal records were checked where available; the historical PTN tree, alignment and IBD placement were not reconstructed. Donor count and target self-inclusion are not failure criteria. |
| GO:0005222 intracellularly cAMP-activated cation channel activity | IDA PMID:34699778 Structural mechanisms of assembly, permeation, gating, and p... | ACCEPT | Summary: Retain directly measured secondary cAMP activation of the rod channel. Reason: Human rod CNGA1/CNGB1 channels carry cAMP-activated currents at high cAMP concentrations (PMID:34699778), although cAMP is a partial agonist and the captured cAMP-bound structure is closed. This positive capability belongs to the gene-level cyclic-nucleotide channel function, whose physiological cAMP role is independently demonstrated in human olfactory CNGA2/CNGA4/CNGB1 complexes (PMID:41131016). The rod experiment does not establish cAMP as the physiological rod agonist. |
| GO:0005222 intracellularly cAMP-activated cation channel activity | IEA GO_REF:0000120 | ACCEPT | Summary: Accept the rat-supported cAMP-gated channel contribution. Reason: The exact rat Cngb1 source supports olfactory beta-subunit function. Actual rat cloned B1b increases native-like cAMP sensitivity in assembled channels, and an engineered human CNGB1 456β1251 olfactory complex independently conducts cAMP-activated currents. Rat B1b and human RCNC2A are not equated by name. |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: Accept inherited cGMP-gated channel activity. Reason: Direct human rod heteromer structures and currents establish the target contribution. Current descendant sources include the target itself, which is legitimate grounding; alpha and cone subunits elsewhere in the supplied list are not beta orthologs. The original node and alignment remain uninspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000811708 SUPPORTS TRANSFER Independent target/ortholog evidence supports this intracellularly cGMP-activated cation channel activity assertion as detailed in the row. Current donor identities and literal records were checked where available; the historical PTN tree, alignment and IBD placement were not reconstructed. Donor count and target self-inclusion are not failure criteria. |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IDA PMID:24164424 Cyclic nucleotide-gated channel subunit glycosylation regula... | ACCEPT | Summary: Accept the human beta contribution to cGMP-dependent currents. Reason: The original experiment uses HA-tagged human CNGB1 with bovine CNGA1 in Xenopus oocytes and measures cGMP-dependent currents under defined ionic conditions. This is a mixed-species assembled channel, not an isolated beta channel or a comparison of every human product. Supporting Evidence: |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IDA PMID:34699778 Structural mechanisms of assembly, permeation, gating, and p... | ACCEPT | Summary: Accept direct human rod-channel contribution. Reason: Human CNGB1 supplies part of the pore and its own cyclic-nucleotide-binding domain in the resolved 3:1 CNGA1:CNGB1 assembly. The structural beta construct is NP_001288.3 residues 456β1251; full-length functional comparisons are also reported. Neither construct is assigned to all four alternative products. Supporting Evidence: PMID:34699778 cGMP can fully activate both CNGA1 and CNGA1/B1 |
| GO:0005223 intracellularly cGMP-activated cation channel activity | IEA GO_REF:0000120 | ACCEPT | Summary: Accept the combined electronic cGMP-channel assertion. Reason: The rat-source and ARBA mapping agree with direct human rod-channel currents and structures. The exact automated-rule history is not reconstructed, and the original source objects remain unchanged. |
| GO:0005223 intracellularly cGMP-activated cation channel activity | ISS GO_REF:0000024 | ACCEPT | Summary: Accept the complex-level contribution with the alpha-donor identity explicit. Reason: Q00194 is bovine CNGA1, not a CNGB1 ortholog. Its recombinant alpha/beta channel assays support the shared channel activity, while independent human CNGB1 evidence establishes the target contribution. The original contributes_to relation is retained without recasting an alpha donor as beta. |
| GO:0005223 intracellularly cGMP-activated cation channel activity | ISS GO_REF:0000024 | ACCEPT | Summary: Accept the bovine beta-supported channel contribution. Reason: Q28181 is bovine CNGB1. Recombinant bovine alpha/beta currents and permeability measurements support the conserved assembled activity; independent human rod experiments confirm the target. Soluble GARP products are excluded from channel activity. |
| GO:0005515 protein binding | IPI PMID:19299621 Ankyrin-G promotes cyclic nucleotide-gated channel transport... | MODIFY | Summary: Specify the experimentally mapped ankyrin interaction. Reason: Human CNGB1 C-terminal constructs recruit ankyrin-G and co-immunoprecipitate with it; deletion and IL1237/1238 substitutions map the interaction. Native bovine outer-segment association and human-beta targeting experiments provide additional context. The partner is authenticated ANK3/Q12955, supporting ankyrin binding without assigning ankyrin enzymatic activity to CNGB1. Proposed replacements: ankyrin binding Supporting Evidence: PMID:19299621 Ankyrin-G interacted only with the C-terminal domain of CNG-Ξ²1 |
| GO:0005515 protein binding | IPI PMID:20890309 Growth factor receptor-bound protein 14: a new modulator of ... | KEEP AS NON CORE | Summary: Retain positive GRB14 association with construct limits. Reason: Exact MINT records map human Q14028 and bovine GRB14/Q5ICW4 to positive co-immunoprecipitation and two-hybrid records. The actual primary text and supplement establish beta-subunit co-immunoprecipitation and bovine rod-complex association, but do not identify the donated beta plasmid species or independently document beta-specific two-hybrid testing. No concrete beta-sequence contradiction was found, so the curated pair is retained without claiming sequence-verified human binary binding or a mapped regulatory interface. Supporting Evidence: |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Accept inherited plasma-membrane localization. Reason: Actual human CNGB1 channel currents and mapped targeting constructs support plasma-membrane activity. Mouse and rat ortholog localization and current target records corroborate it. The varied CNG-family donors are not all CNGB1 orthologs, and no historical PAINT-node reconstruction is claimed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000811708 SUPPORTS TRANSFER Independent target/ortholog evidence supports this plasma membrane assertion as detailed in the row. Current donor identities and literal records were checked where available; the historical PTN tree, alignment and IBD placement were not reconstructed. Donor count and target self-inclusion are not failure criteria. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Accept rat-supported plasma-membrane activity. Reason: The rat beta product participates in channels recorded from native olfactory neuronal membranes and recombinant cells. Direct human CNGB1 targeting and channel recordings independently support this broad compartment. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2514865 | ACCEPT | Summary: Accept the modeled plasma-membrane channel component. Reason: The actual Reactome cGMP dissociation event resolves through the CNG complex to human CNGB1/Q14028 at the plasma membrane. Direct human rod-channel data corroborate that location. This location assertion does not convert the event into an independent CNGB1 catalytic activity. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2514867 | ACCEPT | Summary: Accept the modeled plasma-membrane channel component. Reason: The actual Reactome cGMP-dependent sodium and calcium transport event resolves through the CNG complex to human CNGB1/Q14028 at the plasma membrane. Direct human rod-channel data corroborate that location. This location assertion does not convert the event into an independent CNGB1 catalytic activity. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-3229181 | ACCEPT | Summary: Accept the modeled plasma-membrane channel component. Reason: The actual Reactome calmodulin association event resolves through the CNG complex to human CNGB1/Q14028 at the plasma membrane. Direct human rod-channel data corroborate that location. This location assertion does not convert the event into an independent CNGB1 catalytic activity. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-74031 | ACCEPT | Summary: Accept the modeled plasma-membrane channel component. Reason: The actual Reactome cGMP binding event resolves through the CNG complex to human CNGB1/Q14028 at the plasma membrane. Direct human rod-channel data corroborate that location. This location assertion does not convert the event into an independent CNGB1 catalytic activity. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000002 | MODIFY | Summary: Specify cation movement across the membrane. Reason: The channel carries cations across a lipid bilayer. Defined-solution patch-clamp currents and permeability measurements support cation transmembrane transport, a more precise performed step than broad ion or cation transport. The beta subunit contributes within the assembled pore. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0006812 monoatomic cation transport | IDA PMID:24164424 Cyclic nucleotide-gated channel subunit glycosylation regula... | MODIFY | Summary: Specify cation movement across the membrane. Reason: The channel carries cations across a lipid bilayer. Defined-solution patch-clamp currents and permeability measurements support cation transmembrane transport, a more precise performed step than broad ion or cation transport. The beta subunit contributes within the assembled pore. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0006813 potassium ion transport | ISS GO_REF:0000024 | MODIFY | Summary: Specify potassium transmembrane transport. Reason: The rat donor product is preserved as A0A8I5ZN27-2. Actual cloned rat olfactory beta-containing channels were tested under biionic sodium/potassium conditions and carry potassium current. This supports the membrane-crossing refinement at assembled-channel scope without assigning an exact human physiological splice-product name. Proposed replacements: potassium ion transmembrane transport Supporting Evidence: GO_REF:0000024 PMID:10377344 The Ξ±3Ξ²1b channel, like the Ξ±3 channel described above, conducts K + just as well as Na + |
| GO:0006814 sodium ion transport | ISS GO_REF:0000024 | MODIFY | Summary: Specify sodium transmembrane transport. Reason: Original defined-solution recordings establish sodium conduction through rat olfactory beta-containing channels. Direct human channel studies corroborate the conserved cation pore. The refinement identifies the membrane-crossing step and preserves the original donor/product assertion. Proposed replacements: sodium ion transmembrane transport |
| GO:0006814 sodium ion transport | ISS GO_REF:0000024 | MODIFY | Summary: Specify sodium transmembrane transport. Reason: Original defined-solution recordings establish sodium conduction through bovine rod alpha/beta channels. Direct human channel studies corroborate the conserved cation pore. The refinement identifies the membrane-crossing step and preserves the original donor/product assertion. Proposed replacements: sodium ion transmembrane transport |
| GO:0006816 calcium ion transport | ISS GO_REF:0000024 | MODIFY | Summary: Specify calcium ion transmembrane transport. Reason: The bovine CNGB1 donor participates in recombinant alpha/beta channels whose calcium-to-sodium permeability was directly measured using reversal potentials. This is genuine ion permeation evidence, distinct from calcium block, CaM regulation or density in a structural pore. The human claim remains an ortholog-supported assembled-channel contribution. Proposed replacements: calcium ion transmembrane transport |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the downstream GPCR-signaling context. Reason: Mouse Cngb1-containing channels perform the electrical output step downstream of olfactory receptor signaling: cAMP-dependent currents, odor-evoked responses and response kinetics are measured. CNGB1 is not itself a GPCR or heterotrimeric G-protein activator. This broad pathway context is retained alongside the more specific visual and olfactory channel roles. |
| GO:0007186 G protein-coupled receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the downstream GPCR-signaling context. Reason: Mouse Cngb1-containing channels perform the electrical output step downstream of olfactory receptor signaling: cAMP-dependent currents, odor-evoked responses and response kinetics are measured. CNGB1 is not itself a GPCR or heterotrimeric G-protein activator. This broad pathway context is retained alongside the more specific visual and olfactory channel roles. |
| GO:0007601 visual perception | IEA GO_REF:0000120 | ACCEPT | Summary: Accept conserved visual perception. Reason: Mouse Cngb1 loss disrupts rod currents and electroretinograms before progressive degeneration. Human CNGB1 disease genetics and direct human rod-channel activity independently establish a performed phototransduction role. The channel converts the intracellular cGMP signal into membrane current; this is more than a disease association. |
| GO:0007601 visual perception | IMP PMID:11379879 Segregation of a mutation in CNGB1 encoding the beta-subunit... | ACCEPT | Summary: Accept the human visual-function evidence. Reason: The original human family study maps recessive retinitis pigmentosa to CNGB1 and shows cosegregation of G993V, absent from the tested controls. It does not directly assay mutant channel currents; independent human electrophysiology and mouse rod recordings establish the mechanistic visual contribution. |
| GO:0007601 visual perception | IMP PMID:7479749 Mutations in the gene encoding the alpha subunit of the rod ... | ACCEPT | Summary: Retain visual function with independent CNGB1 support. Reason: The ACCEPT action concerns the supported CNGB1 visual function, not validation of this row's citation. The inspected original PMID:7479749 mutation and functional assays concern CNGA1, so that source-specific CNGB1 relationship remains miscited. Independent human CNGB1 genetic and channel evidence supports the visual annotation. The original machine reference is preserved while claim support cites the appropriate target evidence. |
| GO:0007601 visual perception | ISS GO_REF:0000024 | ACCEPT | Summary: Accept conserved visual perception. Reason: Mouse Cngb1 loss disrupts rod currents and electroretinograms before progressive degeneration. Human CNGB1 disease genetics and direct human rod-channel activity independently establish a performed phototransduction role. The channel converts the intracellular cGMP signal into membrane current; this is more than a disease association. |
| GO:0007601 visual perception | TAS PMID:7682292 A new subunit of the cyclic nucleotide-gated cation channel ... | ACCEPT | Summary: Accept the rod-channel contribution to vision. Reason: The authentic original abstract describes cloned human CNGB1, rod outer-segment immunolabeling and coexpression with human alpha yielding native-like channel features. Full text was not recovered; later human structural and functional work independently supports the visual role. |
| GO:0007608 sensory perception of smell | ISS GO_REF:0000024 | ACCEPT | Summary: Accept the conserved olfactory signaling role. Reason: Actual mouse Cngb1 deficiency reduces ciliary cAMP currents, odor responses and food-finding performance. Rat beta-containing channels and an engineered human 2:1:1 CNGA2/CNGA4/CNGB1 complex directly perform cyclic-nucleotide-to-current conversion. This is conserved channel participation rather than odorant binding by CNGB1. Supporting Evidence: GO_REF:0000024 PMID:41131016 CNGB1b in the construct is a shorter variant of CNGB1, comprising amino acids 456-1251. |
| GO:0015276 ligand-gated monoatomic ion channel activity | TAS PMID:7682292 A new subunit of the cyclic nucleotide-gated cation channel ... | MODIFY | Summary: Specify intracellular cyclic-nucleotide-gated cation-channel activity. Reason: The original human cloning abstract reports native-like channel behavior only with the alpha subunit. Later human rod and olfactory preparations identify intracellular cyclic nucleotides as the gating ligands and cations as the permeants, supporting this informative refinement. Proposed replacements: intracellularly cyclic nucleotide-activated monoatomic cation channel activity |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: Specify the sensory ciliary membrane for channel-bearing CNGB1. Reason: Human CNG-beta1 expressed in Xenopus rods localizes to the outer-segment plasma membrane; the actual construct and transgenic host are explicit in PMID:19299621. Rat olfactory ciliary-membrane enrichment and mouse olfactory immunolocalization independently support the ciliary destination. GO:0060170 encompasses both sensory membrane contexts and is more specific than a generic plasma-membrane replacement. This refinement applies to channel-bearing products, not soluble GARP2, and does not claim native human olfactory-cilium imaging. Proposed replacements: ciliary membrane |
| GO:0017071 intracellular cyclic nucleotide activated cation channel complex | IBA GO_REF:0000033 | ACCEPT | Summary: Accept assembled cyclic-nucleotide-gated channel membership. Reason: Direct human rod structures resolve three CNGA1 and one CNGB1 subunits; engineered human olfactory structures resolve two CNGA2, one CNGA4 and one CNGB1. Rat and bovine donor assays corroborate complex membership. These assemblies do not establish an autonomous beta channel or a historical PAINT-node reconstruction. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000811708 SUPPORTS TRANSFER Independent target/ortholog evidence supports this intracellular cyclic nucleotide activated cation channel complex assertion as detailed in the row. Current donor identities and literal records were checked where available; the historical PTN tree, alignment and IBD placement were not reconstructed. Donor count and target self-inclusion are not failure criteria. |
| GO:0017071 intracellular cyclic nucleotide activated cation channel complex | IEA GO_REF:0000107 | ACCEPT | Summary: Accept assembled cyclic-nucleotide-gated channel membership. Reason: Direct human rod structures resolve three CNGA1 and one CNGB1 subunits; engineered human olfactory structures resolve two CNGA2, one CNGA4 and one CNGB1. Rat and bovine donor assays corroborate complex membership. These assemblies do not establish an autonomous beta channel or a historical PAINT-node reconstruction. |
| GO:0017071 intracellular cyclic nucleotide activated cation channel complex | ISS GO_REF:0000024 | ACCEPT | Summary: Accept assembled cyclic-nucleotide-gated channel membership. Reason: Direct human rod structures resolve three CNGA1 and one CNGB1 subunits; engineered human olfactory structures resolve two CNGA2, one CNGA4 and one CNGB1. Rat and bovine donor assays corroborate complex membership. These assemblies do not establish an autonomous beta channel or a historical PAINT-node reconstruction. |
| GO:0021630 olfactory nerve maturation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Treat olfactory-nerve maturation as overextended from the inspected donor study. Reason: The original acts_upstream_of relation and mouse E1AZ71 source are preserved. Its current experimental premise studies adult CNGB1 CaM-site/NCKX4 mutants and olfactory responses, not developmental attainment of a mature nerve. OMP protein per tissue falls in the double mutant, but the OMP-positive neuron fraction and GAP43 signal do not show reduced neuronal maturation. Positive signaling and marker effects remain; they do not substantiate this specific developmental allocation. |
| GO:0030552 cAMP binding | IDA PMID:34699778 Structural mechanisms of assembly, permeation, gating, and p... | ACCEPT | Summary: Accept direct cAMP binding within the human rod channel. Reason: The cAMP-bound human heteromer resolves ligand in the CNGB1 cyclic-nucleotide-binding domain. Partial activation by high cAMP is separately measured; ligand occupancy is not confused with full opening. Olfactory cAMP gating is an independent assembled context. |
| GO:0030553 cGMP binding | IBA GO_REF:0000033 | ACCEPT | Summary: Accept inherited cGMP recognition. Reason: Direct target cGMP-bound structural evidence supports CNGB1 ligand recognition within the rod channel. Target inclusion in the descendant evidence is legitimate. The historical PAINT placement and the behavior of every alternative product are not inferred. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000025739 SUPPORTS TRANSFER Independent target/ortholog evidence supports this cGMP binding assertion as detailed in the row. Current donor identities and literal records were checked where available; the historical PTN tree, alignment and IBD placement were not reconstructed. Donor count and target self-inclusion are not failure criteria. |
| GO:0030553 cGMP binding | IDA PMID:24164424 Cyclic nucleotide-gated channel subunit glycosylation regula... | ACCEPT | Summary: Retain cGMP recognition with the assay-to-subunit limit explicit. Reason: The cited mixed human-beta/bovine-alpha preparation measures cGMP-dependent gating but does not isolate beta-subunit binding. Independent human rod structures resolve cGMP in CNGB1 itself, supporting the existing capability without misdescribing the older assay. |
| GO:0030553 cGMP binding | IDA PMID:34699778 Structural mechanisms of assembly, permeation, gating, and p... | ACCEPT | Summary: Accept direct cGMP recognition by human CNGB1. Reason: The human rod heteromer structure resolves cGMP in the beta-subunit binding domain, coupled to asymmetric channel opening. The experimental sequence boundary is preserved and the ligand-binding role remains part of the integrated channel mechanism. Supporting Evidence: |
| GO:0030553 cGMP binding | IEA GO_REF:0000117 | ACCEPT | Summary: Accept the electronic cGMP-binding assertion. Reason: Direct human rod structural evidence independently supports the capability. The ARBA identifier is preserved, without claiming that the historical rule logic or all human splice products were experimentally tested. |
| GO:0030660 Golgi-associated vesicle membrane | TAS Reactome:R-HSA-5623524 | KEEP AS NON CORE | Summary: Retain the modeled Golgi-vesicle transit compartment. Reason: The actual Reactome event/entity chain reaches Q14028 as a member of the ciliary-cargo set in a Golgi-associated vesicle membrane. This is an explicit curated transit location, not a claim that CNGB1 is an exocyst component or catalyzes vesicle budding. The principal channel locations remain sensory plasma membranes. Supporting Evidence: Reactome:R-HSA-5623524 |
| GO:0030660 Golgi-associated vesicle membrane | TAS Reactome:R-HSA-5623525 | KEEP AS NON CORE | Summary: Retain the modeled Golgi-vesicle transit compartment. Reason: The actual Reactome event/entity chain reaches Q14028 as a member of the ciliary-cargo set in a Golgi-associated vesicle membrane. This is an explicit curated transit location, not a claim that CNGB1 is an exocyst component or catalyzes vesicle budding. The principal channel locations remain sensory plasma membranes. Supporting Evidence: Reactome:R-HSA-5623525 |
| GO:0030660 Golgi-associated vesicle membrane | TAS Reactome:R-HSA-5623527 | KEEP AS NON CORE | Summary: Retain the modeled Golgi-vesicle transit compartment. Reason: The actual Reactome event/entity chain reaches Q14028 as a member of the ciliary-cargo set in a Golgi-associated vesicle membrane. This is an explicit curated transit location, not a claim that CNGB1 is an exocyst component or catalyzes vesicle budding. The principal channel locations remain sensory plasma membranes. Supporting Evidence: Reactome:R-HSA-5623527 |
| GO:0042622 photoreceptor outer segment membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Accept conserved photoreceptor outer-segment membrane localization. Reason: Mouse Cngb1 retinal immunolabeling and channel disruption support the donor location. Human CNGB1 targeting experiments and rod-channel currents corroborate membrane activity. Soluble GARP2 is kept separate from the membrane-channel interpretation. |
| GO:0042622 photoreceptor outer segment membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Accept conserved photoreceptor outer-segment membrane localization. Reason: Mouse Cngb1 retinal immunolabeling and channel disruption support the donor location. Human CNGB1 targeting experiments and rod-channel currents corroborate membrane activity. Soluble GARP2 is kept separate from the membrane-channel interpretation. |
| GO:0043195 terminal bouton | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the source-specific presynaptic localization context. Reason: The rat study explicitly reports CNGB1/CNGA1 expression and colocalization with synapsin I in cultured cerebellar granule cells. Its complete abstract was inspected; full Results were not recovered. This positive donor evidence is retained without generalizing a cultured rat bouton observation to a demonstrated native human location or assigning the presumed rat B1b to a human product. Retention follows the source's positive CNGB1-containing channel observations; predominantly rod/olfactory expression elsewhere is not evidence that invalidates the assayed rat culture context. |
| GO:0043855 cyclic nucleotide-activated monoatomic ion channel activity | IEA GO_REF:0000107 | MODIFY | Summary: Specify the established cyclic-nucleotide-gated cation activity. Reason: The inherited term captures true cyclic-nucleotide-dependent channel function but leaves the ionic class broader than the directly measured cation conductance. Human rod and olfactory complexes support the specific cation-channel refinement at contributed activity scope. Proposed replacements: intracellularly cyclic nucleotide-activated monoatomic cation channel activity |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain complex association without a speculative interface refinement. Reason: The exact rat donor carries this term by IDA from PMID:22786723. Its rat CNGB1b/AF068572 combinations with CNGA2 and CNGA4 in Xenopus oocytes support functional heteromeric channel assembly and cyclic-nucleotide coupling. Retain this broad complex-binding context as non-core. Calmodulin binding is independently mapped to the human 456β1251 construct in PMID:41131016; GO:0005516 is not a child of GO:0044877, so that distinct interaction does not replace the positive channel-complex premise. |
| GO:0050908 detection of light stimulus involved in visual perception | IMP PMID:15557452 A homozygosity-based search for mutations in patients with a... | ACCEPT | Summary: Retain the visual detection-series context with the performed step explicit. Reason: Retain the curated human clinical assertion from PMID:15557452, interpreted with independent channel experiments. GO:0050908 covers the series converting light stimulation to a molecular signal. CNGB1 performs the cyclic-nucleotide-to-cation-current step in that series as part of the rod channel; it need not absorb photons. This detection-stage function is more precise for the channel core than the broader visual-perception context, without claiming that the clinical study alone isolated the molecular step. |
| GO:0050911 detection of chemical stimulus involved in sensory perception of smell | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the olfactory detection-series context. Reason: Retain the source-scoped orthology assertion. GO:0050911 covers the olfactory stimulus-to-molecular-signal series, including the cyclic-nucleotide-to-current step performed by the assembled channel. Native rat CNGB1b-containing channels (PMID:10377344) and engineered human CNGA2/CNGA4/CNGB1 channels (PMID:41131016) support this role. CNGB1 is not asserted to bind odorants directly, and the human engineered construct is not equated with a complete named physiological isoform. |
| GO:0050911 detection of chemical stimulus involved in sensory perception of smell | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the olfactory detection-series context. Reason: Retain the source-scoped orthology assertion. GO:0050911 covers the olfactory stimulus-to-molecular-signal series, including the cyclic-nucleotide-to-current step performed by the assembled channel. Native rat CNGB1b-containing channels (PMID:10377344) and engineered human CNGA2/CNGA4/CNGB1 channels (PMID:41131016) support this role. CNGB1 is not asserted to bind odorants directly, and the human engineered construct is not equated with a complete named physiological isoform. |
| GO:0051480 regulation of cytosolic calcium ion concentration | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain contextual control of cytosolic calcium through channel activity. Reason: The rat-source study explicitly links functional CNG channels to cytosolic calcium responses, while mouse olfactory recordings show channel-dependent CaM feedback and calcium transients. These observations support a channel-mediated contribution, not calcium-pump catalysis, buffering, or a universal direction of calcium regulation. The rat original remains abstract-limited. Retention follows the source's positive CNGB1-containing channel observations; predominantly rod/olfactory expression elsewhere is not evidence that invalidates the assayed rat culture context. |
| GO:0051899 membrane depolarization | IEA GO_REF:0000107 | ACCEPT | Summary: Accept depolarizing cation-current contribution. Reason: The mouse olfactory donor exhibits channel-dependent cAMP and odor-evoked currents. Recombinant human olfactory channels directly conduct inward cation current; this is the performed electrical step underlying depolarization, with ligand gating and CaM feedback distinguished. |
| GO:0051899 membrane depolarization | ISS GO_REF:0000024 | ACCEPT | Summary: Accept depolarizing cation-current contribution. Reason: The mouse olfactory donor exhibits channel-dependent cAMP and odor-evoked currents. Recombinant human olfactory channels directly conduct inward cation current; this is the performed electrical step underlying depolarization, with ligand gating and CaM feedback distinguished. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: Specify cation transmembrane transport. Reason: The channel-family mapping is supported by direct currents and ionic selectivity measurements. Cation passage through an assembled pore is the specific performed transport step. Proposed replacements: monoatomic cation transmembrane transport |
| GO:0060170 ciliary membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Accept ciliary-membrane localization. Reason: The UniProt subcellular mapping agrees with directly inspected rat ciliary fractionation/immunolabeling and mouse olfactory channel localization. Human engineered channel work supports the conserved complex function, without claiming direct human native-cilium imaging. |
| GO:0060170 ciliary membrane | TAS Reactome:R-HSA-5623527 | ACCEPT | Summary: Accept the modeled ciliary destination. Reason: The actual Reactome delivery event resolves to Q14028 in the ciliary-membrane cargo set. Independent rodent olfactory localization corroborates that destination. This is a cargo location assertion, not a claim that CNGB1 performs vesicle transport. |
| GO:0098655 monoatomic cation transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: Accept inherited cation transmembrane transport. Reason: Direct human beta-containing channels and rat/bovine permeability experiments establish the target contribution to cation passage. Fly and worm evidence and the historical PAINT node are not reconstructed into an ancestral claim; unresolved donor mappings do not negate independently supported target chemistry. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000811708 SUPPORTS TRANSFER Independent target/ortholog evidence supports this monoatomic cation transmembrane transport assertion as detailed in the row. Current donor identities and literal records were checked where available; the historical PTN tree, alignment and IBD placement were not reconstructed. Donor count and target self-inclusion are not failure criteria. |
| GO:0098804 non-motile cilium membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Accept activity at non-motile sensory-cilium membranes. Reason: Actual mouse and rat olfactory beta localization supports the original ortholog assertion, and the rod outer segment is a specialized non-motile sensory cilium. This location is compatible with the channel core without assigning membrane topology to soluble GARP2. |
| GO:0098804 non-motile cilium membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Accept activity at non-motile sensory-cilium membranes. Reason: Actual mouse and rat olfactory beta localization supports the original ortholog assertion, and the rod outer segment is a specialized non-motile sensory cilium. This location is compatible with the channel core without assigning membrane topology to soluble GARP2. |
| GO:0120200 rod photoreceptor outer segment | IEA GO_REF:0000107 | ACCEPT | Summary: Accept rod-specific outer-segment localization. Reason: The mouse Cngb1 source has direct rod outer-segment localization and rod-current phenotypes. Human rod beta targeting and channel experiments independently support the conserved compartment. The claim remains distinct from cone beta-subunit localization. |
| GO:0120200 rod photoreceptor outer segment | ISS GO_REF:0000024 | ACCEPT | Summary: Accept rod-specific outer-segment localization. Reason: The mouse Cngb1 source has direct rod outer-segment localization and rod-current phenotypes. Human rod beta targeting and channel experiments independently support the conserved compartment. The claim remains distinct from cone beta-subunit localization. |
| GO:1902495 transmembrane transporter complex | IDA PMID:24164424 Cyclic nucleotide-gated channel subunit glycosylation regula... | MODIFY | Summary: Specify the cyclic-nucleotide-gated channel complex. Reason: The original preparation coexpresses human CNGB1 and bovine CNGA1 to form a conducting complex. Later human structures resolve its specific CNG assembly, which is more informative than the general transmembrane-transporter complex. Proposed replacements: intracellular cyclic nucleotide activated cation channel complex |
| GO:1990834 response to odorant | IEA GO_REF:0000107 | ACCEPT | Summary: Accept performed odor-response signaling. Reason: Mouse Cngb1 perturbation changes odor-evoked currents and kinetics, with direct cAMP-channel recordings identifying the performed electrical step. Rat and engineered human olfactory assemblies corroborate the molecular contribution. CNGB1 is not assigned direct odorant binding. |
| GO:1990834 response to odorant | ISS GO_REF:0000024 | ACCEPT | Summary: Accept performed odor-response signaling. Reason: Mouse Cngb1 perturbation changes odor-evoked currents and kinetics, with direct cAMP-channel recordings identifying the performed electrical step. Rat and engineered human olfactory assemblies corroborate the molecular contribution. CNGB1 is not assigned direct odorant binding. |
| GO:0004857 enzyme inhibitor activity | ISS Q14028-3 PMID:16407240 The glutamic acid-rich protein-2 (GARP2) is a high affinity ... | NEW | Summary: The soluble GARP2 product is an ortholog-inferred inhibitor of basal rod PDE6 activity. Reason: Native bovine GARP2 binds PDE6 and suppresses the basal catalytic activity of the nonactivated holoenzyme. The authenticated human GARP2 splice product supports an explicitly product-specific ortholog inference. This is not direct human IDA, does not establish inhibition of activated PDE6, and does not assign the activity to the membrane-channel products. Supporting Evidence: PMID:16407240 GARP2 suppresses nonactivated PDE6 activity but is ineffective with activated PDE6. |
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Download this section (compressed HTML)Q: Which full-length human olfactory transcript corresponds to physiological B1b, and how does it relate to the four current UniProt products and the engineered 456β1251 construct?
Suggested experts: CNG-channel transcript and structural investigators
Q: Does sequence-verified human GARP2 inhibit basal PDE6 under the same conditions as native bovine GARP2, and does this alter physiological rod noise?
Suggested experts: Photoreceptor biochemists and electrophysiologists
Q: Which beta-subunit plasmid species and sequence were used in the original GRB14 interaction assays?
Suggested experts: GRB14 and rod-channel investigators
Q: How should GO:0005516 be represented when direct CaM binding is established for the human olfactory CNGB1 456β1251 construct but an independent positive GRB14 assertion retains GO:0005515? The current strict ancestor/descendant NEW rule prevents a duplicate descendant assertion; neither partner-specific prose nor a different evidence strength removes that retained ancestor. Source-model refinement would need to preserve both interactions and their construct limits.
Suggested experts: GO curators and CNG-channel structural investigators
Experiment: Compare purified sequence-verified human Q14028-3 and native or recombinant bovine GARP2 in matched PDE6 binding and basal, transducin-activated and trypsin-activated activity assays. Control PDE6 gamma-subunit contamination and assess the human R100H variant separately.
Hypothesis: Human GARP2 conserves basal-selective PDE6 inhibition.
Type: Product-resolved binding and enzyme inhibition
Experiment: Sequence full-length human olfactory transcripts and compare their channel assembly, ciliary targeting and cAMP/CaM responses with the defined 456β1251 construct. Do not infer physiological identity solely from a legacy product name.
Hypothesis: Human olfactory beta splice architecture affects CaM feedback and trafficking.
Type: Transcript mapping and assembled-channel electrophysiology
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