The genuine fetch created 150 stored rows for 151 TSV rows and 152 original QuickGO contexts. All source fields, order and three natural products are preserved. The two deterministic projection collapses and structured extension limits are recorded in the source guide. The completed review has 25 ACCEPT, 111 KEEP_AS_NON_CORE, 7 UNDECIDED, 2 MARK_AS_OVER_ANNOTATED and 5 TOO_GENERAL stored decisions; original-context counts are 26 ACCEPT and 112 KEEP_AS_NON_CORE with the other counts unchanged.
Annotation-reviewer and core-function-synthesizer criteria were applied with independent source consultations. One core captures FLNA's actual F-actin binding and structural crosslinking. Nuclear, neuronal, extracellular, platelet and signaling contexts are retained where supported without making them universal core functions. Forty-eight supported generic-binding rows remain non-core under the explicit campaign instruction; one source-specific cyclin partner assertion remains unresolved. No NEW annotation or supporting-text quotation is added. Three natural products are conserved without assigning proteolytic fragments or experimental deletions as extra isoforms.
The intrinsic-coagulation and nuclear Myb-complex mappings exceed the supported source role, although platelet scaffolding and the cytosolic Myb-Clafi association are real. Seven source-specific assertions remain UNDECIDED: cyclin B2 association, cadherin binding, NF-kappaB regulation, megakaryocyte development, directed protein-localization establishment, calcium-store release and positive neural-precursor proliferation. The review does not use inaccessible full text as proof that an experiment did not occur. The evidence synthesis distinguishes actual primary reading, abstract access, ortholog transfer, assay constructs and curated target evidence retained on trust.
Thirty-eight exact-main normal sources were hydrated and verified before genuine fetch. Only the 35 qualified absent sources were acquired. Existing owner-held publication blobs were reused unchanged. One authentic family IBD assertion lies on a plant branch outside FLNA ancestry; no human function is transferred from it. No new environment, clone, worktree or bulk PAINT archive was created. Existing scratch and branches remain preserved. Known provider credential/quota failures were not retried; this document records manual research honestly.
Earlier private research could not access three Reactome summaries because their API calls returned403. The genuine normal fetch subsequently recovered R-HSA-5669240, R-HSA-5669250 and R-HSA-8985123. Their PAK1/FLNA and RNase L/FLNA summaries were read and current rationale access language updated without changing any action. The earlier receipts remain preserved as dated history. Complete event entity graphs and cited primary assays were not newly replayed. Original PMID:12393796 primary text also resolves earlier human-construct/NT2/cytoplasmic-colocalization uncertainty without adding a migration-compensation or product-specific claim.
The candidate remains DRAFT with seven unresolved assertions and expected generic-binding advisories. Schema, strict GOA, reference/term, status, history and private-render checks are recorded in the candidate handoff; no claim is made that the pathway-PMID helper validates these notes when no pathway files match. Independent review of the completed candidate and exact source/object closure precedes publication. Tracker credit follows actual merge and executed merge-group checks.
FLNA binds and crosslinks F-actin into networks through its dimeric structure. Human recombinant and cellular evidence anchors that activity, with reagent and species limits preserved (PMID:25358863(https://pubmed.ncbi.nlm.nih.gov/25358863/), PMID:10051605(https://pubmed.ncbi.nlm.nih.gov/10051605/)). A second core now distinguishes coupling of those networks to integrin cytoplasmic tails. Reconstituted F-actin–FLNA–beta7-tail experiments directly measure strain-dependent association, and human FLNA-repeat experiments establish the ligand-binding interface (PMID:21926999(https://pubmed.ncbi.nlm.nih.gov/21926999/), PMID:17690686(https://pubmed.ncbi.nlm.nih.gov/17690686/)). This adaptor role is bounded to the demonstrated connection, without assigning all partner functions to FLNA.
The two questioned process decisions remain contextual. In the rat mesangial system, FLNA recruits Smad factors into a nuclear promoter-associated complex and supports laminin-gene induction; the scaffold/shuttle is a positive contribution to transcription (PMID:20167606(https://pubmed.ncbi.nlm.nih.gov/20167606/)). In injured mouse sensory axons, disrupting the FLNA–HDAC5 interaction reduces local HDAC5 and tubulin deacetylation. Human M2/A7 experiments distinguish this FLNA-dependent response from HDAC5 nuclear export (PMID:26157139(https://pmc.ncbi.nlm.nih.gov/articles/PMC4566247/)). The former does not establish direct FLNA-DNA binding or a specific Pol II catalytic step, and the latter assigns the chemistry to HDAC5. Species, construct and natural-product limits remain explicit in the evidence synthesis.
The stored counts remain 25 ACCEPT, 111 KEEP_AS_NON_CORE, 7 UNDECIDED, 2 MARK_AS_OVER_ANNOTATED and 5 TOO_GENERAL, covering all 152 original contexts. There are now two complementary cores, with the original actin core unchanged, and three unchanged natural products. The campaign's supported-generic-binding NC and no-new-quotes instructions remain in force. No source cache or original annotation field changed. This appended journal records the follow-up without rewriting the earlier one-core review history.
Nine generic-binding decisions now use MODIFY with source-supported specific classes: four small-GTPase interactions (PMID:10051605(https://pubmed.ncbi.nlm.nih.gov/10051605/)); D2, D3 and mu-opioid receptor interactions (PMID:10692483(https://pubmed.ncbi.nlm.nih.gov/10692483/), independently corroborating PMID:17536008(https://pubmed.ncbi.nlm.nih.gov/17536008/), and PMID:14573758(https://pubmed.ncbi.nlm.nih.gov/14573758/)); FOXC1 association (PMID:15684392(https://pmc.ncbi.nlm.nih.gov/articles/PMC548007/)); and Fc-gamma receptor I association (PMID:18322202(https://pubmed.ncbi.nlm.nih.gov/18322202/)). These refinements identify the observed binding class, not the partner's catalytic or regulatory function.
The original mixed-filamin purity caveat remains for CDC42/RHOA/RAC1, distinct from recombinant FLNA/RalA and its GTP dependence. D3 support from PMID:17536008 does not retroactively establish which D3 assay PMID:10692483 performed. FOXC1 cellular co-complex evidence is distinct from purified binary kinetics, and Fc-receptor alpha-tail/U937 evidence does not establish gamma-chain binding or intact-complex affinity. No natural-product-specific function is inferred.
The current stored counts are 25 ACCEPT, 102 KEEP_AS_NON_CORE, 9 MODIFY, 7 UNDECIDED, 2 MARK_AS_OVER_ANNOTATED and 5 TOO_GENERAL; the 152 original contexts give 26 ACCEPT and 103 KEEP_AS_NON_CORE, with the other counts identical. The prior journal entries and both prior history records remain as written. Two cores, three products, all 150 immutable source objects/order, 73 normal sources and zero quotations remain unchanged. Supported generic binding stays non-core for 39 assertions under the campaign exception; the specificity refinements follow its conditional MODIFY instruction. No NEW annotation is introduced.
A bounded comparison with the same-paper FLNB/FLNC reviews identified two supported partner classes left generic in FLNA. The original PMID:16076904 abstract explicitly includes FLNA binding to FATZ-1/MYOZ1 and myotilin. Stored17/raw16 now uses MODIFY GO:0051373 FATZ binding; stored18/raw17 uses MODIFY GO:0008092 cytoskeletal protein binding. Official partner identities and cytoskeletal-component evidence support those classes. Unavailable individual assay/construct details, FLNC-specific interface mapping and natural-product limits remain explicit in the evidence synthesis.
The updated stored counts are 25 ACCEPT, 100 KEEP_AS_NON_CORE, 11 MODIFY, 7 UNDECIDED, 2 MARK_AS_OVER_ANNOTATED and 5 TOO_GENERAL. Across 152 original contexts the counts are 26 ACCEPT, 101 KEEP_AS_NON_CORE, 11 MODIFY, 7 UNDECIDED, 2 MARK_AS_OVER_ANNOTATED and 5 TOO_GENERAL. All 150 machine objects/order, the other 148 review objects, three natural products, two cores, 78 reference entries, original extension/projection records and 73 exact-main normal sources are unchanged. The review remains DRAFT; 37 supported generic-binding NC assertions and the unmirrored-adaptor-core advisory remain. No NEW annotation, supporting-text quotation or new gene-completion credit is introduced. Earlier journal and history entries are preserved.
Scoped schema/reference/ontology validation, strict GOA comparison, deterministic DRAFT status, the new Codex history and private rendering passed. The 38 retained advisories comprise 37 generic-binding NC assertions and the unmirrored adaptor core; the dependency deprecation warning is also disclosed. Independent focused peer review found no issue and replayed the exact two-review change plus conserved context/product/core/reference objects. The pathway-PMID helper found no pathway files, so it is not claimed to validate these notes.
The MYOT rationale now accepts that GO:0008092 is subsumed in FLNA's deduplicated GO term set by the retained actin-filament-binding terms. The separately supported FLNA–MYOT interaction, including Q9UBF9 and PMID:16076904, is not entailed by the actin-binding evidence; the existing source row retains that evidential distinction without claiming new gene-level function coverage. Both MODIFY actions and replacement terms are unchanged. The FATZ1 reason now identifies Q9NP98 directly as MYOZ1/FATZ-1.
The source guide records the existing UniProt isoform-2/MYOZ1 pair without claiming independent publication evidence or isoform restriction. It also distinguishes the dedicated interaction table from the CC:SUBUNIT and PMID:16076904 reference annotations that already name MYOT. All 150 source objects/order, 152 original contexts, actions/counts, three natural products, two cores, 78 references, 73 normal sources and zero quotations remain unchanged. A new Codex EDIT history links PR5715; prior committed histories, including the provenance link to PR5708, are preserved.
The affected schema/reference/ontology, new-history, private-render and diff checks passed, with the same 38 disclosed advisories. Independent focused peer review found no issue and verified the exact two-reason delta, unchanged source/action/product/core/reference objects and all four prior history records. Earlier passing strict-GOA and status checks remain applicable because those fields and the DRAFT status are unchanged; they were not rerun merely for the prose clarification.