2026-09-29. Human ATP8A2/Q9NTI2/HGNC:13533. The review retains all 39 seeded annotation source objects and all three alternative products. All rows were manually assessed: 19 ACCEPT, 7 KEEP_AS_NON_CORE, 11 MODIFY and 2 MARK_AS_OVER_ANNOTATED. No NEW assertion is proposed.
The biological synthesis is one ATP-dependent inward aminophospholipid flippase in a CDC50A-containing complex. ATP binding, magnesium dependence and ATP hydrolysis describe parts of this mechanism. Neuronal, auditory, visual and historical growth-control phenotypes remain contextual rather than additional catalytic cores.
The electronic outward-PS mapping conflicts with the actual inward transport function. Its source tuple is preserved and the review proposes the existing PS flippase term. Retinal-layer formation and embryonic inner-ear morphogenesis are flagged for excessive developmental specificity because the inspected donor experiments principally describe degeneration. Direct flipping replaces a regulatory interpretation of the mouse lipid-uptake experiment. Experimental annotations and ancestral PAINT judgments are retained with their actual evidence scope.
Root read every proposed decision and the complete consultant source ledger, independently checked the direction and developmental/regulatory term definitions, and read selected primary human-construct transport Results and Methods. The source ledger below attributes the remaining original-section readings to the annotation consultant. Neither a complete-paper read nor a reconstructed PAINT phylogeny is implied.
The one Falcon command with perplexity-lite fallback returned an error and produced no provider report. The retained diagnostic does not establish its precise failure cause. This is manual research; no provider-named report was authored.
Direct PMC opens sometimes returned challenge pages, while official indexed originals exposed the specifically listed sections. A combined web display was truncated; only the visible sections and subsequent bounded rereads are included in these scopes. No secondary AI gene summary was used as primary evidence.
The official historical MGI Atp8a2 GO graph identifies P98200-related experimental routes: 24413176 for localization and sensory/retinal terms; 22641037 for neurite outgrowth; 22912588 for neurofilament organization and positive translocation; and 1634998 for neuron development. Its dated graph is a route to sources, not proof of the current complete annotation set or PAINT history.
GO:0090556 specifies outward PS movement, whereas GO:0140346 specifies inward movement. The existing Rhea-derived row should be refined to inward flippase. The immutable record's PS/PE Rhea directions are inconsistent with one another; they are preserved and do not establish bidirectionality. GO:0015247 is the aminophospholipid flippase umbrella. GO:0090555 describes inward PE flipping, although its displayed parent chain runs through glycerophospholipid flippase rather than a direct aminophospholipid child relation.
GO:0061092 is a regulator term, with regulation/positive-regulation parents and a regulates relationship to translocation. It is not an ancestor refinement of GO:0140331. The proposed replacement for row 31 corrects the role from regulating transport to carrying out transport; the original electronic tuple stays intact. No redundant NEW assertion is proposed.
GO:0010842 means retinal lamination, and GO:0042472 has an embryonic-morphogenesis parent. The focused original degeneration endpoints support over-annotation flags for these developmental specificities, not denial of sensory physiology. GO:0048666 includes neuronal progression/maturation and has neuron-projection development as a part; the considered IBA can be retained as non-core with separate neurite corroboration, without pretending that its exact ancestral node was revalidated.
Preserve Q9NTI2-4, Q9NTI2-1 and Q9NTI2-3 exactly. The displayed sequence is isoform 3; isoform 1 lacks the initial 40 residues, and the alternative named 2 has additional extensive sequence changes/truncation. The UniProt frameshift caution prevents an assertion that every listed product has the same established transport activity. No observed experiment is assigned to a particular seeded isoform without a sequence-level match.
One catalytic PS/PE flippase core in a CDC50A-containing complex is sufficient. ATP binding, magnesium dependence and ATP hydrolysis are mechanism facets, not separate biological cores. Sensory, growth and neurite consequences remain separate contexts. AMER's independent core proposal supplies the final core object and sole 31397519 quote; no core is authored here.
The displayed product Q9NTI2-4 (name 3) has 1188 residues. The listed Q9NTI2-1 (name 1) lacks the initial 40 residues. Q9NTI2-3 (name 2) additionally loses the C-terminal region and has a sequence-derived length of 528 residues; UniProt flags the underlying AAF40215.2 sequence with a frameshift caution. These sequence observations do not establish equivalent activity for every product or prove that the truncated product is expressed and inactive. All three machine-sourced product objects are preserved, and no historical experiment is assigned a splice-isoform field without sequence matching.
The independent core consultation selects GO:0015247 with direct aminophospholipid translocation, plasma/Golgi membranes and the phospholipid-translocating ATPase complex. Golgi localization from PMID:20947505 is retained as curated heterologous ATP8A2 evidence; the inspected construct paragraph did not establish its species. Human plasma-membrane transport is separately supported by PMID:26567335 and the ATP8A2 experiments within PMID:34403372. The latter explicitly uses human NM_016529.4, fluorescent lipid uptake, BSA extraction and dead-cell exclusion; its simulation comparator is ATP8A1.
Root independently verified the official definitions and displayed parents of retina layer formation, inner ear morphogenesis and positive regulation of phospholipid translocation. The direct transport process is related to the regulatory term by positively_regulates, not by is_a. These checks support the specific electronic-row decisions without creating redundant NEW functions.
The four original and six additional normal publication records are used with their cached availability flags. External selected-section reading is described separately. Focused validation, rendering and history checks follow canonical application; this draft does not assert their results or an external reviewer approval.
After Source72 exact import, root read all six newly available abstracts and the selected ATP8A2 Results, construct and uptake Methods in PMID:34403372. Five references now contain short verbatim findings; the core also cites the direct human ATP8A2 PS-uptake result. The historical PMID:1634998 remains background for the donor route without a new ATP8A2-specific finding. Every excerpt matches the canonical cache, and total quoted words per source remain at most 25. No annotation decision, source tuple, product or proposed core term changed.
2026-09-29. just validate human ATP8A2 passed schema, authored-term and reference checks; just render human ATP8A2 passed. Four advisories remain: the supported CDC50A association is retained as non-core under the supplied action definitions; the two IBA substrate refinements do not claim an inspected PAINT placement and therefore do not manufacture propagation metadata; and the broad experimental Golgi assignment is retained while its electronic counterpart is refined to membrane. The latter preserves experimental curation at its demonstrated resolution. These warnings are disclosed, not a claim that they disappeared. The generated history is checked separately. No new global validation pass or external PR approval is claimed.
Refined the generic CDC50A interaction to protein heterodimerization activity
(GO:0046982). The original IPI row and Q9NV96 partner are preserved. The normal
PMID:21454556 source establishes the ATP8A2–CDC50A alpha/beta transport complex;
its dual-purification and reconstitution constructs are bovine. Endogenous human
CDC50A also associates with expressed bovine ATP8A2. This supports conserved
assembly, without claiming a human 1:1 stoichiometry measurement in the original
PMID:31397519 abstract. GO:0046982 remains a molecular-function refinement; the
existing complex-location assertion describes a separate aspect of the protein.
Added a short literal evidence anchor for preserved organ-of-Corti morphology at
the adult mouse endpoint. This supports the existing caution about inner-ear
morphogenesis, alongside the distinct spiral-ganglion degeneration phenotype.
Clarified the experimentally curated Golgi resolution and the two target-specific
refinements of broader PAINT assertions. These refinements do not reject the
ancestral node placement or imply a newly inspected PAINT tree.
The current normal caches for PMID:21454556 and PMID:24413176 contain full text;
the review retains the recorded limits of the selected sections actually read.
Newer papers PMID:38436085 and PMID:39662833 were considered as corroborating
leads, but were not added as cached or principal evidence for this correction.
The earlier journal entries remain as the record of the initial assessment.
Current scope: 39 preserved source assertions, three unchanged alternative
products and one unchanged transport core; 19 ACCEPT, 12 MODIFY,
6 KEEP_AS_NON_CORE and 2 MARK_AS_OVER_ANNOTATED. No new annotation or process
assertion was added. Review status remains DRAFT.
Focused follow-up checks passed: gene validation reports three advisories (the
two PAINT rows lack a claimed inspected-node propagation record, and Golgi IDA
versus IEA decisions remain source-specific). Rendering and the new history
record also passed. No repository-wide validation pass is claimed.