This manual evidence synthesis accompanies the review and source/context guide. Annotation-reviewer and core-function-synthesizer criteria were applied to every seeded assertion. Original evidence codes, partners, qualifiers, order and natural products are preserved. Supported generic associations remain non-core where an evidence-backed specific replacement has not been established. Eleven binding assertions are refined below using source-supported partner classes; no partner catalytic or regulatory activity is assigned to FLNA. No new annotation or supporting-text quotation is added. References below support paraphrased assessments, with actual source access distinguished from curated evidence retained on trust.
The actin-binding core describes F-actin binding and structural crosslinking. Human FLNA recombinants, full-length human FLNA purified from HEK293 cells, actin co-sedimentation and gelation support the gene-level activity in PMID:25358863(https://www.nature.com/articles/ncomms6325). The related human recombinant and M2/A7 experiments in PMID:10051605(https://pubmed.ncbi.nlm.nih.gov/10051605/) anchor target identity even though the original bulk platelet/leiomyoma filamin preparation does not independently establish isotype purity. FLNA itself supplies the crosslinks. C-terminal deletion can impair dimerization as well as partner binding, so it is not a selective RalA- or CRMP1-binding experiment. Rat CRMP1 and mouse neuronal assays are distinguished from human FLNA reagents. The older PMID:2391361(https://pubmed.ncbi.nlm.nih.gov/2391361/) and PMID:3138234(https://pubmed.ncbi.nlm.nih.gov/3138234/) evidence was verified at abstract level; their full Methods and modern residue coordinates are not claimed. The independent human assays support retaining those core assertions.
Human HFF1 focal-adhesion proteomics names filamin-1 separately from filamin-B/C in PMID:21423176(https://pubmed.ncbi.nlm.nih.gov/21423176/). Location does not make FLNA a motor or show that every recovered protein executes adhesion assembly. The core uses cytosol, cortical cytoskeleton and focal adhesion, without adding redundant NEW annotations. Official definitions are actin filament binding, actin crosslink formation, cytosol, cortical cytoskeleton and focal adhesion. No additional kinase, phosphatase, GAP, GEF, transcription-enzyme or actin-depolymerase core is asserted.
A second core captures a distinct structural activity: bringing receptor tails and the actin network into functional contact. GO:0030674 protein-macromolecule adaptor activity covers this coordinated connection. It is not an ancestor or descendant of the retained actin-filament-binding molecular function under the official is_a/part_of paths.
Actual PMID:21926999(https://pubmed.ncbi.nlm.nih.gov/21926999/) Results reconstitute F-actin–FLNA networks containing beta7-integrin cytoplasmic tails. Applied shear or myosin-generated stress changes integrin-tail association with the network. Human FLNA-repeat/integrin-tail structural and biochemical experiments in PMID:17690686(https://pubmed.ncbi.nlm.nih.gov/17690686/) independently establish the human ligand-binding side; the cellular host in that study includes CHO cells. This is positive evidence for connecting the cytoskeleton to receptor tails, rather than an inference from two unrelated binding lists. The first core describes actin crosslinks; the second describes the receptor-tail connection.
The 21926999 supplementary protein-production/species protocols were not replayed. The core does not declare every reconstituted component human, map experimental deletions onto natural products, or generalize the same linkage to all GPCR, SK2 or GPIb contexts. The four ligand alternatives in PMID:19828450 do not establish simultaneous occupancy on intact FLNA. No additional biological-process term or GOA annotation is introduced. Source-specific generic binding decisions remain unchanged under the campaign instruction.
Source-specific binding methods remain explicit in each reason. Exact IntAct pairs can establish curated association, co-complex membership or proximity without demonstrating purified binary affinity. Peptide/repeat NMR, calorimetry and binding experiments are distinguished from intact endogenous receptor occupancy. Spoke expansion, crosslinking and proximity ligation are not silently described as direct binary contact. Species and processed viral-chain identifiers remain unchanged.
PMID:24951510(https://pmc.ncbi.nlm.nih.gov/articles/PMC4103345/) supplies actual human SK2/FLNA fragment and cell experiments plus mouse cardiomyocyte knockdown, channel-surface measurements and apamin-sensitive currents. These support channel regulation through trafficking; altered gating is not required. Delivery versus removal is not fully separated. The calcium-sensitive alpha-actinin2/CaM effect is not assigned to FLNA. Cardiac repolarization remains downstream inference, and Z-line imaging is directly mouse; human atrial Western blot is expression evidence, not human Z-disc imaging. Separate supplementary Methods and figure pixels were not inspected.
PMID:17536008(https://academic.oup.com/mend/article/21/9/2242/2738634) supports PMA-induced D3 receptor sequestration in restored A7 but not FLNA-deficient M2 cells, although receptors reach the surface in both. This establishes a contextual sequestering role without FLNA kinase activity or universal delivery dependence. PMID:18322202(https://pubmed.ncbi.nlm.nih.gov/18322202/) supports Fc gamma RI surface retention and lysosomal protection in human systems. Bafilomycin rescue supports stabilization, whereas initial delivery occurs without FLNA and recycling remains a qualified model. The GO:0045184 directed-movement assertion is therefore UNDECIDED; GO:0034394 is not a formal descendant that could justify TOO_GENERAL. The older PMID:1833070(https://pubmed.ncbi.nlm.nih.gov/1833070/) abstract directly describes ligand-sensitive receptor/actin-binding-protein association in U937 and receptor-transfected COS cells.
PMID:12393796(https://pubmed.ncbi.nlm.nih.gov/12393796/) was subsequently recovered as original primary text: human FLNA/FLNB fragment two-hybrid, human NT2 co-IP and cytoplasmic colocalization resolve earlier species/access uncertainty. No migration-compensation mechanism, purified affinity or natural-product-specific heterodimer function follows.
Human FLNA/GPIb attachment, recombinant and native platelet complex evidence in PMID:16293600(https://pmc.ncbi.nlm.nih.gov/articles/PMC1895705/) supports contextual receptor-complex and activation roles. Human platelet Syk association and separate mouse FlnA-loss experiments in PMID:20713593(https://pubmed.ncbi.nlm.nih.gov/20713593/) corroborate receptor/scaffold organization. FLNA binds the kinase; it does not acquire kinase activity. Intrinsic coagulation GO:0007597 describes the coagulation-factor cascade, which these receptor-cytoskeleton experiments do not establish FLNA performing. That mapping is over-annotated without denying haemostatic function. Specific megakaryocyte-development and calcium-store-release contexts remain UNDECIDED rather than treating missing inspected experiments as proof of absence. The MDS proteomics in PMID:23382103(https://pubmed.ncbi.nlm.nih.gov/23382103/) includes FLNA immunoblot validation but no FLNA-specific causal perturbation.
Rat-fragment and human M2/A7 experiments in PMID:16291724(https://pubmed.ncbi.nlm.nih.gov/16291724/) support receptor/GTPase scaffolding and cellular migration/spreading; scratch assays are not organismal wound-repair demonstrations. PMID:22121117(https://pubmed.ncbi.nlm.nih.gov/22121117/) reports impaired, not absent, ciliation in human mosaic patient cells. PMID:25358863(https://pubmed.ncbi.nlm.nih.gov/25358863/) semaphorin evidence includes mouse knockdown with human FLNA rescue and human receptor-reconstituted cells, not only worm biology.
PMID:15684392(https://pmc.ncbi.nlm.nih.gov/articles/PMC548007/) supports FOXC1 association, nuclear FLNA and PBX1a distribution in distinct human and mouse experiments. PBX1a import is contextual; FOXC1 remains nuclear in both M2 and A7. Antibody/fractionation evidence is not replaced by a claim that all nuclear FLNA is a cleavage fragment. PMID:22307607(https://pmc.ncbi.nlm.nih.gov/articles/PMC3277164/) supports cellular negative Pol I regulation and nucleolar retention. Its isolated in-vitro immunodepletion Results versus Fig2F-caption sign discrepancy remains unresolved; it is not silently corrected or used to erase independent cellular evidence.
The cytosolic Myb/clathrin/FLNA association in PMID:18548008(https://pmc.ncbi.nlm.nih.gov/articles/PMC2486420/) is real, but is distinct from the replication/transcription-regulatory nuclear Myb complex represented by GO:0031523. This term mapping is over-annotated while the contextual spindle process is retained with B-Myb-perturbation limits. PMID:26157139(https://pmc.ncbi.nlm.nih.gov/articles/PMC4566247/) supports FLNA organizing HDAC5 localization and tubulin deacetylation; HDAC5 is the enzyme. Engineered fragments are not natural FLNA products.
The rat donor A0A8I5ZV49 and ENSRNOP00000082035 identify the same protein. PMID:22948144(https://pmc.ncbi.nlm.nih.gov/articles/PMC3488041/) rat-brain FLNA co-IP supports complex association, not the HCN1/protocadherin purified SPR result as a FLNA assay. PMID:20167606(https://pubmed.ncbi.nlm.nih.gov/20167606/) rat mesangial experiments distinguish endogenous protein from an expressed human C-terminal construct. Recruitment into a Smad-containing promoter-associated scaffold/shuttle supports contextual transcription involvement beyond necessity alone; direct Smad3 contact, DNA binding and the exact post-arrival Pol II step remain unresolved.
PMID:22076441(https://pubmed.ncbi.nlm.nih.gov/22076441/) abstract evidence supports rat radial scaffolds/cortical migration, but not an independently resolved positive proliferation direction. PMID:22872576(https://pmc.ncbi.nlm.nih.gov/articles/PMC3512009/) selected primary sections support actin organization and developmental Sertoli-barrier/junction maintenance; GO:1902396 includes maintenance and does not require a motor. Rat synaptic and mature dendritic pools in PMID:26972007(https://pubmed.ncbi.nlm.nih.gov/26972007/) and PMID:22434607(https://pmc.ncbi.nlm.nih.gov/articles/PMC3393847/) differ in developmental/imaging context, not a universal exclusion. Mouse PMID:23525008(https://pmc.ncbi.nlm.nih.gov/articles/PMC3672938/) supports podosome localization; Amotl2 perturbation is not attributed to FLNA. Donor transfers remain transfers rather than relabeled human experiments.
Urinary exosome target inclusion in the original-author table for PMID:19056867(https://pubmed.ncbi.nlm.nih.gov/19056867/) and Table1 of PMID:21362503(https://pmc.ncbi.nlm.nih.gov/articles/PMC3085584/) was independently checked. For PMID:20458337(https://pubmed.ncbi.nlm.nih.gov/20458337/) and PMID:23533145(https://pubmed.ncbi.nlm.nih.gov/23533145/), exact FLNA supplement rows were not recovered; retention explicitly combines curated HDA support and independent target-vesicle evidence. Whole-exosome proteomics is distinct from a small MHC-II co-IP subset. Vesicle detection does not establish conventional secretion, a cancer-specific change or a universal extracellular core function.
The GO:0005642 annulate-lamella extension on the genuine FLNA-FilGAP association differs from the peripheral lamellae described in selected actual PMID:16862148(https://pubmed.ncbi.nlm.nih.gov/16862148/) Results. The CL:0000639 extension on one PMID:20458337(https://pubmed.ncbi.nlm.nih.gov/20458337/) context officially names a basophil cell of the anterior pituitary, not a B cell. Both source fields are preserved and flagged as questions. The binding or exosome term is not rejected solely because its extension is unresolved. The PMID:28297718 DND1 nuclear extension likewise remains source-specific uncertainty despite independently supported nuclear crosslink association in PMID:30021884.
The PMID:17408621 exact MINT fragment/assay record points to the original Figure3A cyclin-B1 experiment, while the retained source partner O95067 is officially CCNB2. This concrete accession/assay discrepancy remains UNDECIDED; it is stronger than a title mismatch but does not prove all B2 experiments absent. No source partner is silently replaced.
Earlier private research recorded API403 limitations for Reactome R-HSA-5669240, R-HSA-5669250 and R-HSA-8985123. The normal fetch subsequently recovered all three summaries. They now explicitly support PAK1-FLNA binding, PAK1 phosphorylation of FLNA and RNase L-FLNA association/dissociation context, respectively. The earlier access receipts are preserved as history; the current reasons use the recovered summaries. Full event entity graphs and underlying experiments were not newly replayed. No annotation action changed because of this access update.
The genuine PTHR38537 entries/metadata and complete official 297-node tree were acquired. Repository parsing of a pinned original IBD file yielded one family assertion, GO:0048235 at PTN002213724, on a plant branch outside the human FLNA ancestry. The normal one-row PAINT slice is genuine; no human annotation is inferred from it. FLNA has no incoming IBA context. Source release provenance remains separate rather than asserting whole-release equivalence. The official tree endpoint and normal source hashes are recorded in the guide.
The genuine seed preserves P21333-1, P21333-2 and P21333-3/VAR-1 exactly. Independently fetched sequences correspond to 2647, 2639 and 2606 residues, with the official VSP_035454 and VSP_062479 deletions. No assay is assigned universally to all three. Proteolytic fragments, GFP fusions, repeat deletions and point mutants are not extra natural products.
Primary reading was source-specific: some complete original texts were available, some selected indexed Methods/Results/captions were read, and other papers remained abstract-only or curator-supported target contexts. No figure-pixel audit, universal supplement replay or independent experimental replication is claimed. Cache metadata marked full text does not establish that every section or target table is present. No provider research text was fabricated; current credential/quota failures were not repeatedly retried.
For PMID:20167606(https://pubmed.ncbi.nlm.nih.gov/20167606/), the positive contribution is recruitment of Smad factors into a nuclear, promoter-associated FLNA complex. The existing rat-to-human transcription assertion is retained contextually because this scaffold/shuttle supplies part of the process. ChIP does not establish direct FLNA-DNA contact, and the experiment does not separate initiation, elongation or mRNA stability after promoter arrival. Those limits do not convert the process assertion into a claim of FLNA polymerase activity. The experimentally generated C-terminal fragment is distinct from a natural splice product.
For PMID:26157139(https://pmc.ncbi.nlm.nih.gov/articles/PMC4566247/), HDAC5 C-terminal interaction interference reduces both enzyme accumulation at injured mouse axon tips and local tubulin deacetylation. Human M2/A7 experiments distinguish the FLNA-dependent deacetylation response from HDAC5 nuclear export. FLNA therefore has a measured local scaffold/positioning role, while HDAC5 performs the chemistry. This is stronger than a requirement inferred only from an injury phenotype and does not create a universal axon-growth function.
The two retained process assertions differ from the rejected nuclear Myb-complex mapping: the latter names a compartment-specific complex that the actual cytosolic Myb-Clafi association does not establish. No action changed in this follow-up; the positive structural rationale is now explicit.
Nine original protein-binding assertions are refined to existing specific molecular-function classes. The source assertions are conserved rather than collapsed with the separate specific GOA records. These are contextual partner interactions; both structural cores remain unchanged.
All four specific terms have protein binding in their official is_a ancestry. This refinement applies the campaign's evidence-sensitive specificity instruction while retaining, at that stage, 39 supported generic-binding assertions as non-core and the unresolved cyclin source context as UNDECIDED. No source, natural product, process annotation, core function or publication quotation is added or changed by these nine refinements.
The original PMID:16076904 abstract explicitly reports binding of both FATZ-1 and myotilin to filamin-A, as well as other filamins. It identifies FATZ-1 as myozenin-1/calsarcin-2, matching the retained human Q9NP98/MYOZ1 partner and the family definition of FATZ binding. The same abstract identifies myotilin as a sarcomeric Z-disc protein; reviewed Q9UBF9/MYOT metadata independently records experimentally supported cytoskeletal and Z-line localization. These component data establish the partner class in cytoskeletal protein binding, rather than inferring it merely from the MYOT name or its actin-binding activity.
The original abstract describes transfection, biochemical and/or yeast two-hybrid assays collectively. Individual FLNA assay allocation, constructs and natural products were not recovered. Its FLNC Ig19–24 and interface mapping is not assigned to FLNA, and no universal sarcomeric bridge or binding by every FLNA product is asserted. The original experimental interaction assertions and demonstrated partner classes justify these two MODIFY refinements despite those mechanistic limits.
FATZ binding descends from cytoskeletal protein binding, which is also an ancestor of retained actin-binding terms. At the level of the gene's deduplicated GO term set, the MYOT replacement GO:0008092 is subsumed by the retained actin-filament-binding annotations. That subsumption is accepted. The separately evidenced FLNA–MYOT interaction (UniProtKB:Q9UBF9, PMID:16076904) is not entailed by evidence that FLNA binds actin; retaining the refinement preserves this source/partner assertion under the supported existing binding class. It adds no separate core function or NEW annotation. The other 148 review objects and both cores remain unchanged, with 37 supported generic-binding assertions retained as non-core and the unresolved cyclin context still UNDECIDED. No source or quotation was added.