CNGA3 supplies ligand-binding and pore-forming elements of the cone cyclic nucleotide-gated channel. Human recombinant CNGA3 homomers conduct current, while the physiological cone channel combines CNGA3 with CNGB3. Two independent purified human structural studies resolve three alpha subunits and one beta subunit. Full-length detergent structures and engineered truncated nanodisc constructs are distinct preparations, and expression-plasmid ratios are not measurements of subunit stoichiometry (PMID:34969976(https://pubmed.ncbi.nlm.nih.gov/34969976/), PMID:37463923(https://pubmed.ncbi.nlm.nih.gov/37463923/)).
The integrated core is contributed cGMP-gated channel activity, cation transmembrane transport and cone vision. Human homomer and heteromer responses to cAMP are real but less effective than cGMP; they are retained as non-core secondary agonism. The original source qualifiers remain unchanged. Structural cGMP density establishes ligand contact, whereas electrophysiological half-activation concentrations combine binding and gating and are not purified binding constants (PMID:12815043(https://pubmed.ncbi.nlm.nih.gov/12815043/), PMID:24164424(https://pubmed.ncbi.nlm.nih.gov/24164424/)). No new annotation is proposed.
The displayed human product has 694 residues. Official variant reconstruction independently matches the 676- and 698-residue alternative FASTAs. The accession named for full-length human structural expression maps to the displayed product. Neither engineered N-terminal truncations nor historical rat and mouse constructs establish functional equivalence of every human alternative. All three fetched product identities and sequence notes are preserved.
Mouse retinal antibody controls and pre-embedding EM support localization to cone outer-segment membrane folds. The paper explicitly distinguishes these cone infoldings from rod-disc organization, so plasma-membrane and cone-disc membrane assertions can coexist. These remain mouse-to-human ISS inferences, not direct human EM claims (PMID:10813773(https://pubmed.ncbi.nlm.nih.gov/10813773/)).
Rat CNGA3 N-terminal fragments bind a myosin VIIa tail and the exon-68-containing cadherin 23 fragment in controlled two-hybrid, pulldown and SPR assays. The rat constructs and calcium dependence are retained; a direct human hair-cell mechanotransduction role is not inferred (PMID:23329832(https://pubmed.ncbi.nlm.nih.gov/23329832/)). Three exact positive human HuRI records support CNGA3βMIS18A association. The array and prey-pooling records assign CNGA3 as prey, while the validated two-hybrid record has neutral roles. Supported generic binding is retained as non-core under campaign policy. No endogenous centromeric function or molecular-adaptor activity is assigned from this pair (PMID:32296183(https://pubmed.ncbi.nlm.nih.gov/32296183/)).
The rat olfactory-bulb abstract positively reports neuronal and ensheathing-glial expression. Current experimental donor annotations are genuine; however, full original controls for dendrite, axon-initial-segment and glial-projection localization were not recovered. Those precise transfers remain undecided, while the broader positive cell-body context is retained. A second source uses historical CNG2/CNG4.3/CNG5 nomenclature; unavailable probe and antibody details prevent resolving its exact CNGA3 perikaryon premise. Neither access gap establishes wrong-paralog attribution or biological absence (PMID:18434027(https://pubmed.ncbi.nlm.nih.gov/18434027/), PMID:12021210(https://pubmed.ncbi.nlm.nih.gov/12021210/)).
Official MGI data resolves real Cnga3 retinal-development IGI premises in addition to the current UniProt donor view. The original triple-mutant experiment examines adult physiology and cone-transducin redistribution; the resource article's actual XML table identifies the cpfl5 Cnga3 model as cone-function loss. These support retention of curated retinal context as non-core, without demonstrating a separate channel-directed patterning mechanism. Historical PAINT node placement remains unresolved independently of target-function confidence; donor number and target self-inclusion are not reasons to reject an IBA (PMID:21124780(https://pubmed.ncbi.nlm.nih.gov/21124780/), PMID:21052544(https://pubmed.ncbi.nlm.nih.gov/21052544/)).
Human mutation cohorts directly support cone-vision involvement. The source-specific CNGA3 IMP linkage to PMID:10958649 remains undecided: inspected original passages focus on CNGB3 families after excluding CNGA3 mutations or linkage, but that does not establish a whole-paper miscitation. Independent CNGA3 cohorts retain the positive visual biology (PMID:11536077(https://pubmed.ncbi.nlm.nih.gov/11536077/)).
Genuine normal intake produced 45 assertions, three products and 14 original reference identities. All source objects are preserved. Exact main caches and PANTHER files remain unchanged; fresh variants are archived separately. The default Falcon attempt timed out after 90 seconds and its configured Perplexity fallback returned a quota-related HTTP 401. Manual primary-source research supplied the review; no provider-named content was invented. The compact source index records database identifiers, hashes, access limits and selected read ranges. Raw tool responses remain in the temporary audit packet.
The final draft contains 22 ACCEPT, nine KEEP_AS_NON_CORE, nine MODIFY and five UNDECIDED decisions. The broad membrane assertion was refined to plasma membrane using the same positive human surface-imaging and current evidence. The single contributed channel core retains the physiological heteromer while preserving experimentally conductive homomers. Independent bounded review confirmed the channel, ligand and product distinctions. Publication and history creation are handled separately after final review and normal checks.
The core-driving experimental assertions now carry bounded primary anchors. Four short 12815043 excerpts come from the unchanged selected abstract, whose mutant comparisons are not represented as wild-type-only measurements. Independent original full-text Results establish the wild-type controls, functional homomers/heteromers and surface assays. Public access is available through the author-uploaded original. In the authenticated indexed responses, Experimental Procedures were reinspected at open2 lines 326β405, and actual Results at results1 lines 640β780 and 1152β1265. These response versions have different line coordinates. The source index records their hashes and locators; it does not substitute for the primary paper. The selected cache remains abstract-only. Because original full text was actually accessed, the review does not mark it unavailable. PMID:12815043
Selected full 24164424 Methods/Results retain the human construct, sodium-current and MMP context; functional activation half-concentrations are not isolated binding constants. Full-length human A3/B3 purification and lipid reconstitution in 34969976 directly support functional assembled-channel current and the three-alpha/one-beta composition. The new anchors are drawn from those actual source passages. Primary quoted text is not repeated in this appendix. [PMID:24164424; PMID:34969976]
The broad signal-transduction assertion is refined to phototransduction: CNGA3 performs the cGMP-dependent conductance step downstream of photon reception. The core now uses that specific process instead of repeating the broader visual-perception context; existing visual-perception assertions remain unchanged. This is a refinement of a supported existing process, not a NEW annotation or a claim that CNGA3 is the photopigment. [PMID:9517456; PMID:34969976; PMID:37463923]
The core's contributed channel activity describes the assembled physiological heteromer. Conductive CNGA3 homomers remain explicit, and no original enables qualifier is rewritten. The human plasma-membrane refinement is retained at its direct assay scope; convergence of an existing broad row with a specific existing term is allowed for MODIFY. The independently supported mouse outer-segment assertions remain intact. [PMID:12815043; PMID:10813773]
The magnesium-response assertion remains non-core after an independent source and definition check. The exact rat RGD IDA and available abstract describe magnesium-dependent modulation of the sodium current conducted by the channel in Xenopus oocytes. This is the measured work of the channel, not an unrelated downstream phenotype. The definition does not demand adaptation or homeostasis, but the full original Methods and figures remain uninspected. No physiological human response, magnesium transport, or general rule for inhibited proteins is inferred. PMID:11387380
All authored-source-index support pointers are removed from annotation support lists. The compact JSON index and its original reference identity remain as provenance, with public primary locators added. A format change would add no scientific evidence. Existing history and the complete previous notes remain unchanged; ROOT will append genuine new history. The tracker remains pending until an actual qualifying merge, rather than counting an open gene PR.
The current official pure is_a closure places phototransduction under signal transduction. It does not place phototransduction under visual perception, even when part_of is included. The reviewer's suggested direct part_of relationship is therefore not adopted as an ontology fact; the core synthesis chooses the performed cellular signaling step on the actual evidence.
Normal validation, status dry-run and rendering pass. The two advisories retain the campaign-supported non-core protein-binding assertion and the source-specific visual-perception uncertainty for 10958649 alongside independently supported visual-perception assertions. Neither advisory warrants erasing the assay or source distinction. The calculated DRAFT status is unchanged. The complete original notes remain an exact prefix; no prior history is rewritten.
The preceding follow-up's replacement of visual perception in the core list is superseded. Fresh official QuickGO ancestor and descendant queries using both is_a and part_of establish that GO:0007601 and GO:0007602 are not in either subsumption direction. CNGA3 performs the cGMP-controlled channel step and contributes directly to cone vision; the clinical mutation cohorts and cone-response measurements support the retained visual-perception assertions. Both supported processes now appear in the core, alongside cation transport. No new annotation or change to the three accepted visual-perception rows is needed. [PMID:11536077; PMID:15712225; PMID:9662398; PMID:34969976]
The complex-membership anchor now uses the abstract's positive functional-heteromer result instead of a short fragment from the mutant's negative assembly-disruption comparison. The S435F mutant context remains explicit, with wild-type assembly supported by the original Results already inspected. The DOI https://doi.org/10.1074/jbc.M305102200 provides a stable identifier alongside the documented author-uploaded access route. PMID:12815043
The core description now states the biological heteromer/homomer distinction without qualifier-preservation bookkeeping. Original source qualifiers and products remain unchanged. Completion will be recorded only after a qualifying merge.