Filamin C supplies actin-associated structure in striated muscle. The review retains one connected structural core: actin filament binding supporting sarcomere organization at Z-discs, the sarcolemma and costameres. Human target evidence, ortholog transfers, peptide/fragment binding and natural products are kept distinct.
Human FLNC-null induced pluripotent stem-cell cardiomyocytes have disordered actin bundles and reduced sarcomere organization even on patterned matrices. This is positive evidence for the structural organization role; the tested heterozygous variants did not produce the same structural deficit. Selected original Methods/Results and caption text were read, without inspecting figure pixels, videos or separate supplements. The downstream expression and lysosomal changes do not make FLNC a transcription factor or lysosomal enzyme. PMID:34405687(https://pubmed.ncbi.nlm.nih.gov/34405687/)
Human muscle tissue and differentiating human cultures support endogenous FLNC at Z-discs, sarcoplasm and sarcolemma. The source distinguishes an antibody recognizing alpha/gamma filamin from an alpha-specific antibody: its historical isoform terminology often names paralogs, not modern splice products. Human FLNC fragments tested in rat cardiomyocytes or mouse C2C12 hosts are separate from endogenous human localization. Purified human FLNC/myotilin fragment assays support binding, whereas the proposed alpha-actinin bridge runs through myotilin. Myotilin-fragment perturbation is not a FLNC knockout, and FLNC repeat-20 overexpression did not visibly disrupt assembly. PMID:11038172(https://pmc.ncbi.nlm.nih.gov/articles/PMC2192634/)
The original FLNC/FATZ/myotilin study explicitly reports FLNC C-terminal contacts with beta1A integrin, FATZ1 and myotilin. These support structural connections between muscle Z-disc and membrane-associated partners. They do not establish a particular simultaneous ternary assembly or every natural product's affinity. Xin's other ligand interfaces and ankyrin's membrane-associated properties are not transferred to FLNC. This supports the single structural core without inventing a separate adaptor mechanism. PMID:16076904(https://pubmed.ncbi.nlm.nih.gov/16076904/), PMID:16631741(https://pubmed.ncbi.nlm.nih.gov/16631741/), PMID:21223964(https://pubmed.ncbi.nlm.nih.gov/21223964/)
Nine original protein-binding assertions receive evidence-backed replacements: three cytoskeletal-protein-binding contexts (myotilin twice and Xin), FATZ binding, integrin binding, three SH3-domain-binding contexts and ankyrin binding. Exact pair/context identity is preserved. The two remaining generic associations are retained as non-core under the explicit campaign instruction: FBXL22-associated FLNC degradation and RTF2-containing affinity-purified complexes do not establish a more specific FLNC molecular activity.
Six positive IntAct peptide-array records distinguish ABL1 residues 61–121, GRB2 residues 156–215 and CRK residues 132–192/256–296. Official UniProt domain coordinates identify the corresponding SH3 regions; CRK 256–296 is only part of its second annotated SH3 domain. The ABL1 and GRB2 records test FLNC peptides 260–273 and 1749–1762; the CRK records test 260–273. Exact target/construct claims come from the curated experimental records, not an independently recovered primary target table. The original abstract establishes the domain-peptide screen; its PLCgamma1 validation rate is not assigned to FLNC pairs. PMID:17474147(https://pubmed.ncbi.nlm.nih.gov/17474147/), IntAct Q14315, ABL1, CRK, GRB2
Official UniProt declares Q14315-1 (2725 residues) and Q14315-2 (2692 residues). Both official FASTAs were checked: product 2 exactly equals product 1 after deletion of residues 1734–1766 (VSP_007579). This deletion contains the tested 1749–1762 peptide, while peptide 260–273 is retained. This is a sequence boundary, not proof that product 2 loses all full-length partner binding. The 33-residue splice deletion differs from the 78-residue muscle-filamin insertion discussed in the older localization study. Neither tags, experimental deletions, disease substitutions nor historical paralog names create an additional natural product. UniProt Q14315
Human FLNC expressed in rat cardiac cells is cytoplasmic and associated with actin fibers; mutant aggregates do not redefine the normal location. Human HFF1 fraction proteomics independently identifies FLNC in focal adhesions. These studies preserve human construct versus host-species distinctions and do not establish equal localization of both natural products. PMID:25351925(https://pubmed.ncbi.nlm.nih.gov/25351925/), PMID:21423176(https://pmc.ncbi.nlm.nih.gov/articles/PMC3279191/)
Rat D3ZHA0 retains experimental ankyrin-binding, sarcoplasm and sarcolemma evidence from PMID:21223964. Its original abstract supports the ankyrin-G interaction and adult muscle costamere localization, while independent PMID:11038172 supports human muscle compartments. The O70511-7 partner remains a rat Ank3 product; exact construct correspondence to that splice product was not recovered. Mouse Q8VHX6 carries muscle-cell-development evidence from PMID:16914736, whose abstract describes C2C12 differentiation/fusion and defective mouse myogenesis. These are explicit ortholog transfers, not relabeled human experiments. Rat FLNC, Mouse FLNC, PMID:16914736(https://pubmed.ncbi.nlm.nih.gov/16914736/)
The cytoplasm assertions are true but covered by retained cytosol; sarcolemma entails membrane. Official is_a/part_of paths support these four TOO_GENERAL decisions. Z-disc/costamere ancestry does not itself entail the cytoskeleton term. The broad cytoskeleton assertion is instead refined to actin cytoskeleton using actual actin-associated localization and the official definition; no missing edge or disjointness is invented. HPA cytosol is retained on curator evidence without a new antibody/image audit. The Reactome summary supports cytosolic association; the detailed entity graph and FLNC stoichiometry were not independently replayed. Cytosol, Sarcolemma, Reactome R-HSA-430347
The normal cache's full-text flag is recorded separately from what was actually read. Identifier/title verification does not claim full reproduction of a paper. No new publication quotations were authored.
The source guide records all normal source hashes and the original context mapping.
Both original extensions are represented in the review YAML and in the context guide: the Xin binding context occurs_in GO:0014704 (intercalated disc), and the HFF1 focal-adhesion context part_of CL:0000057 (fibroblast). The predicates map to BFO:0000066 and BFO:0000050 respectively; this recovers original source context omitted by the seed projection.
The actual wild-type localization experiment in PMID:25351925 Results, Functional analysis of FLNC mutations (author-copy text lines 301–306), places tagged human FLNC mainly with actin fibres in rat neonatal cardiomyocytes. This supports GO:0015629 actin cytoskeleton, which includes actin-associated proteins. The inference uses localization rather than binding alone and makes no all-product assignment. PMID:25351925(https://pubmed.ncbi.nlm.nih.gov/25351925/), GO:0015629
The core retains the specific sarcomere-organization process. Official ancestry is GO:0045214 is_a GO:0031032 is_a GO:0030036, so the accepted actin-cytoskeleton-organization assertion is already represented without duplicating its ancestor in the core. GO:0045214, GO:0031032
The PMID:34405687 Results distinguish structural defects in FLNC-null human cardiomyocytes from protein accumulation, lysosome changes and altered autophagic flux in the tested heterozygous variants. Its Discussion places ubiquitinated FLNC among proteins disposed of by BAG3 and p62. This turnover context does not establish FLNC as a chaperone or as an executor of selective autophagy, and no NEW process is proposed. The current sources do not establish an HSPB8-specific assay in these experiments. Likewise, cellular actin-bundle disruption and the paper's background crosslinking description are not a purified FLNC crosslinking measurement. These limits support retaining the current binding core while asking what direct biochemical evidence is available. The relevant source locators are PMID:34405687 Results on lysosome accumulation/autophagic flux and Discussion on Z-disc protein turnover and BAG3/p62 disposal. PMID:34405687(https://pmc.ncbi.nlm.nih.gov/articles/PMC9053646/)