FLNA

UniProt ID: P21333
Organism: Homo sapiens
Review Status: DRAFT
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Gene Description

Filamin A is a large dimeric actin-binding scaffold that connects actin filaments into networks and couples the cortical cytoskeleton to membrane-associated proteins. Its N-terminal actin-binding region and repeated immunoglobulin-like domains support filament crosslinking and interactions with receptors, adhesion proteins and signaling partners. Filamin A organizes actin at the cell cortex and adhesion sites, contributing to cell shape, mechanical stability and context-dependent migration and signaling. Additional nuclear and neuronal pools participate in specialized cellular responses.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001664 G protein-coupled receptor binding
IPI
PMID:26460884
G protein-coupled receptors directly bind filamin A with hig...
KEEP AS NON CORE
Summary: G protein-coupled receptor binding: retained in its supported cellular or assay context.
Reason: PMID:26460884 reports NMR/calorimetric binding of GPCR intracellular peptides to FLNA Ig fragments and receptor-dependent cellular recruitment. This supports contextual receptor binding, not all motif-predicted interactions or FLNA kinase activity. The second source context retains rat Agtr1 P25095; the exact rat insert allocation was not independently recovered. Selected original primary text was read, with no supplementary replay or natural-product assignment.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0001664 G protein-coupled receptor binding
IPI
PMID:26460884
G protein-coupled receptors directly bind filamin A with hig...
KEEP AS NON CORE
Summary: G protein-coupled receptor binding: retained in its supported cellular or assay context.
Reason: PMID:26460884 reports NMR/calorimetric binding of GPCR intracellular peptides to FLNA Ig fragments and receptor-dependent cellular recruitment. This supports contextual receptor binding, not all motif-predicted interactions or FLNA kinase activity. The second source context retains rat Agtr1 P25095; the exact rat insert allocation was not independently recovered. Selected original primary text was read, with no supplementary replay or natural-product assignment.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0002102 podosome
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: podosome: retained in its supported cellular or assay context.
Reason: The mouse donor Q8BTM8 is supported by PMID:23525008 FLNA immunostaining in laminin-grown C2C12 myotube podosome cores, with other cell-model observations. Retain the contextual human similarity/location mappings as distinct source assertions. Amotl2-depletion phenotypes and purified Amotl2-LL5beta binding do not establish FLNA catalysis or a new assembly process.
Supporting Evidence:
GO_REF:0000044
file:human/FLNA/FLNA-source-evidence.md
GO:0002102 podosome
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: podosome: retained in its supported cellular or assay context.
Reason: The mouse donor Q8BTM8 is supported by PMID:23525008 FLNA immunostaining in laminin-grown C2C12 myotube podosome cores, with other cell-model observations. Retain the contextual human similarity/location mappings as distinct source assertions. Amotl2-depletion phenotypes and purified Amotl2-LL5beta binding do not establish FLNA catalysis or a new assembly process.
Supporting Evidence:
GO_REF:0000024
file:human/FLNA/FLNA-source-evidence.md
GO:0003723 RNA binding
HDA
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-bi...
KEEP AS NON CORE
Summary: RNA binding: retained in its supported cellular or assay context.
Reason: Retain the existing human HDA RNA-association assertion as non-core, supported by the independent mRNA-interactome studies PMID:22658674 and PMID:22681889. Their UV-crosslink/capture approaches support contextual RNA association. Exact FLNA supplemental rows were not independently replayed; an indexed original-author dissertation table corroborates FLNA inclusion in the latter study. This explicitly retains curator-supported target inclusion without claiming sequence-specific RNA recognition or an RNA-processing core.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0003723 RNA binding
HDA
PMID:22681889
The mRNA-bound proteome and its global occupancy profile on ...
KEEP AS NON CORE
Summary: RNA binding: retained in its supported cellular or assay context.
Reason: Retain the existing human HDA RNA-association assertion as non-core, supported by the independent mRNA-interactome studies PMID:22658674 and PMID:22681889. Their UV-crosslink/capture approaches support contextual RNA association. Exact FLNA supplemental rows were not independently replayed; an indexed original-author dissertation table corroborates FLNA inclusion in the latter study. This explicitly retains curator-supported target inclusion without claiming sequence-specific RNA recognition or an RNA-processing core.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:10051605
The small GTPase RalA targets filamin to induce filopodia.
MODIFY
Summary: FLNA binds the small GTPase RalA in the tested recombinant and cellular systems.
Reason: PMID:10051605 demonstrates binding of recombinant FLNA C-terminal fragments to RalA and association with activated RalA in transfected cells. GO:0031267 specifies the observed small-GTPase partner class and is already retained from this source. The RalA interaction is GTP-selective; the reported purified-filamin affinity uses a bulk preparation whose FLNA exclusivity was not established. This refinement does not assign GTPase catalysis, a natural FLNA product, or the same nucleotide dependence to other partners.
Proposed replacements: small GTPase binding
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:10051605
The small GTPase RalA targets filamin to induce filopodia.
MODIFY
Summary: The curated CDC42 association supports the more informative small-GTPase-binding class.
Reason: PMID:10051605 shows binding of purified human platelet/leiomyoma filamin to GST-CDC42. CDC42 is a small monomeric GTPase, so GO:0031267 describes the retained interaction more specifically than protein binding and is already retained from this paper. The experiment uses bulk filamin of unresolved isotype purity and the binding is nucleotide-independent; the refinement preserves that FLNA assignment limit and does not convert it into an FLNA-exclusive purified affinity or a GTP-selective interaction.
Proposed replacements: small GTPase binding
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:10051605
The small GTPase RalA targets filamin to induce filopodia.
MODIFY
Summary: The curated RHOA association supports the more informative small-GTPase-binding class.
Reason: PMID:10051605 shows binding of purified human platelet/leiomyoma filamin to GST-RHOA. RHOA is a small monomeric GTPase, so GO:0031267 describes the retained interaction more specifically than protein binding and is already retained from this paper. The experiment uses bulk filamin of unresolved isotype purity and the binding is nucleotide-independent; the refinement preserves that FLNA assignment limit and does not convert it into an FLNA-exclusive purified affinity or a GTP-selective interaction.
Proposed replacements: small GTPase binding
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:10051605
The small GTPase RalA targets filamin to induce filopodia.
MODIFY
Summary: The curated RAC1 association supports the more informative small-GTPase-binding class.
Reason: PMID:10051605 shows binding of purified human platelet/leiomyoma filamin to GST-RAC1. RAC1 is a small monomeric GTPase, so GO:0031267 describes the retained interaction more specifically than protein binding and is already retained from this paper. The experiment uses bulk filamin of unresolved isotype purity and the binding is nucleotide-independent; the refinement preserves that FLNA assignment limit and does not convert it into an FLNA-exclusive purified affinity or a GTP-selective interaction.
Proposed replacements: small GTPase binding
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:10604475
Binding of paxillin to alpha4 integrins modifies integrin-de...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the curated beta1-integrin association as non-core, corroborated independently by the direct filamin–beta1 experiments in PMID:9722563 and PMID:17690686. The accessible PMID:10604475 abstract foregrounds paxillin/alpha4 signaling and does not independently establish the exact FLNA pair; that is an access limitation, not evidence of misattribution. Preserve the source reference and partner isoform without inventing a source-specific assay. Access scope: Exact-main original abstract and current official PubMed identity; independently read beta1 source and primary structural/biochemical corroboration.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:10692483
Modulation of dopamine D(2) receptor signaling by actin-bind...
MODIFY
Summary: FLNA associates with the intracellular loop of the dopamine D2 receptor.
Reason: The authentic PMID:10692483 abstract reports a dopamine D2 third-cytoplasmic-loop yeast two-hybrid interaction confirmed by protein binding, with receptor signaling effects in FLNA-deficient and replete human melanoma cells. GO:0001664 specifies this experimentally supported receptor-binding class; it does not require extracellular agonism and is already retained for FLNA. Full original Methods and exact construct boundaries remain unrecovered. The S358D mutation concerns the receptor, not a natural FLNA product or an observed phosphorylation event.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:10692483
Modulation of dopamine D(2) receptor signaling by actin-bind...
MODIFY
Summary: The retained dopamine D3 association can be specified as GPCR binding, with the original source limit preserved.
Reason: GO:0001664 is supported by the retained D3 interaction and actual independent PMID:17536008 human D3 receptor co-immunoprecipitation in HEK293 cells, alongside M2/A7 sequestration experiments. The original PMID:10692483 abstract foregrounds D2 and its D3 assay was not independently recovered; no matching current IntAct record was found, which is not evidence against the original curation. The original source and partner remain unchanged, and the independent corroboration is identified separately. This refinement does not transfer D2 mutant effects to D3, establish purified binary kinetics, or assign a natural FLNA product.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:12393796
Filamin A and Filamin B are co-expressed within neurons duri...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Human FLNA-FLNB association is supported by original human-fragment yeast two-hybrid experiments, human NT2 co-IP, and cytoplasmic colocalization. Retain as contextual binding; no migration compensation, purified affinity, or natural-product-specific mechanism is established. Access scope: Selected original human-fragment Methods/Results and human NT2 co-IP/cytoplasmic colocalization read; earlier species/access uncertainty is resolved.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:12577067
A proteomics strategy to elucidate functional protein-protei...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Official IntAct exact publication/FLNA/partner records support the existing generic association. Retain as non-core under campaign policy without inferring a functional subtype. Method and interaction-type limits are retained explicitly; this does not claim all records demonstrate purified binary binding. Exact-source curated methods: pull down. Interaction types: association. Official IntAct MITAB2.7 curation; original full text not independently replayed in this checkpoint. Spoke expansion represents a complex-associated pair rather than establishing purified binary contact.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:14573758
Interaction between the mu opioid receptor and filamin A is ...
MODIFY
Summary: FLNA binds the cytoplasmic tail of the human mu-opioid receptor.
Reason: The authentic PMID:14573758 abstract explicitly reports human mu-opioid-receptor-tail interaction with human FLNA, yeast two-hybrid evidence confirmed by direct protein binding and cellular co-immunoprecipitation. This supports GO:0001664, an informative receptor-binding class already retained for FLNA; it does not imply extracellular ligand agonism or FLNA G-protein signaling activity. Detailed original Methods and construct boundaries were not recovered, and no natural FLNA product is assigned.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:15684392
FOXC1 transcriptional regulatory activity is impaired by PBX...
MODIFY
Summary: FLNA associates with the DNA-binding transcription factor FOXC1.
Reason: Actual PMID:15684392 Results identify FLNA in FOXC1 affinity purification from human NPCE cells and confirm association by tagged human HeLa co-immunoprecipitation; mouse C2C12 endogenous nuclear co-immunoprecipitation is a separate corroborating experiment. FOXC1 is a DNA-binding transcription factor, including source-demonstrated DNA binding and reporter activity. GO:0140297 is therefore a supported refinement and is already retained with the same PMID and Q12948 partner. The experiments do not establish purified binary kinetics, a natural FLNA product, or a universal FLNA transcriptional role.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:16076904
The Z-disc proteins myotilin and FATZ-1 interact with each o...
MODIFY
Summary: The cited study explicitly reports FLNA binding to FATZ-1/MYOZ1.
Reason: PMID:16076904 explicitly includes filamin-A among the filamins bound by FATZ-1, which the original abstract identifies as myozenin-1/calsarcin-2. The retained human partner Q9NP98 is MYOZ1/FATZ-1, directly matching GO:0051373 FATZ binding. This supports refining the existing interaction to FATZ binding. The available original abstract describes a combined transfection, biochemical and/or yeast two-hybrid assay panel but does not allocate each assay or construct to the FLNA pair. It therefore does not establish an FLNA-specific binding interface, an endogenous Z-disc bridge, or binding by every FLNA natural product; the reported FLNC Ig-repeat and interface mapping is not transferred to FLNA. Access scope remains the original abstract, with official partner identity and GO definition corroboration.
Proposed replacements: FATZ binding
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:16076904
The Z-disc proteins myotilin and FATZ-1 interact with each o...
MODIFY
Summary: The cited study supports FLNA binding to the cytoskeletal Z-disc protein myotilin.
Reason: PMID:16076904 explicitly reports myotilin binding to filamin-A and describes myotilin as a sarcomeric protein involved in Z-disc assembly and stability. The retained human partner Q9UBF9 is MYOT; its reviewed identity and experimentally supported cytoskeletal/Z-line component annotations corroborate the partner class required by GO:0008092. This refines the existing MYOT interaction without inferring that FLNA performs MYOT's biological roles. At the level of the gene's deduplicated GO term set, GO:0008092 is subsumed by the retained actin-filament-binding annotations. Retaining this replacement preserves the separately evidenced FLNA–MYOT interaction (UniProtKB:Q9UBF9, PMID:16076904); that partner-specific assertion is not entailed by evidence that FLNA binds actin. This is a refinement of the existing source row and adds no separate core function or NEW annotation. The original abstract does not resolve the individual FLNA assay, binding interface, construct or natural product; FLNC-specific mapping and a universal sarcomeric bridge are not inferred. Access scope remains the original abstract plus official partner/component and GO metadata.
Proposed replacements: cytoskeletal protein binding
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:16291724
CEACAM1 functionally interacts with filamin A and exerts a d...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain CEACAM1 association as non-core. The actual primary study separates rat FLNA/CEACAM1-L fragment binding by affinity/SPR from human M2/A7 cellular reconstitution with CEACAM1-4L. Do not describe the rat fragment result as purified human binary affinity, equate scratch migration with organismal wound repair, or give FLNA a GTPase catalytic role. Access scope: actual indexed original16291724 Methods/Results/captions
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:16862148
FilGAP, a Rho- and ROCK-regulated GAP for Rac binds filamin ...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Keep the genuine human FLNA–FilGAP association as non-core, supported by actual primary recombinant, cellular and endogenous experiments. The original occurs_in GO:0005642 extension names annulate lamellae, ER membrane stacks containing nuclear pores. Actual selected Results/Figure3 instead describe EGF-induced peripheral lamellae in human A7 cells. This does not establish annulate-lamellae localization and does not invalidate binding. Preserve the extension and raise a specific curator question; do not silently replace it or create a new location annotation. Access scope: verified original-format Ohta2006 PDF from a public Stossel-papers mirror, selected Results/Methods/captions, official term and partner identities and exact IntAct records.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:17408621
Cyclin B1/Cdk1 binds and phosphorylates Filamin A and regula...
UNDECIDED
Summary: protein binding: source-specific evidence remains unresolved.
Reason: UNDECIDED for the exact O95067/PMID:17408621 source assertion. Official UniProt identifies O95067 as CCNB2, but the exact MINT-4653303/EBI-7364703 record describes a positive GST1–40/Figure3A cyclin fragment, while indexed original Methods and Results3.3 assign that experiment to cyclin B1. This specific assay/accession discrepancy is stronger than a title mismatch, but does not establish that all B2 experiments are absent. Preserve O95067 and seek curator resolution; no silent replacement with CCNB1, REMOVE or kinase-function inference. Access scope: selected indexed original Wiley Methods/Results plus exact original MINT record and official O95067/P14635 identities.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:17474147
Systematic identification of SH3 domain-mediated human prote...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Official IntAct exact publication/FLNA/partner records support the existing generic association. Retain as non-core under campaign policy without inferring a functional subtype. Method and interaction-type limits are retained explicitly; this does not claim all records demonstrate purified binary binding. Exact-source curated methods: peptide array. Interaction types: physical association. Official IntAct MITAB2.7 curation; original full text not independently replayed in this checkpoint.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:17474147
Systematic identification of SH3 domain-mediated human prote...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Official IntAct exact publication/FLNA/partner records support the existing generic association. Retain as non-core under campaign policy without inferring a functional subtype. Method and interaction-type limits are retained explicitly; this does not claim all records demonstrate purified binary binding. Exact-source curated methods: peptide array. Interaction types: physical association. Official IntAct MITAB2.7 curation; original full text not independently replayed in this checkpoint.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:17690686
Structure of three tandem filamin domains reveals auto-inhib...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain beta1/beta7-integrin binding as non-core. The actual human FLNA domain study combines structural/NMR analysis with integrin-tail binding, showing partial autoinhibition by adjacent repeats and relief in engineered deletion/point mutants. Fragment and peptide affinities are distinct from endogenous full-length receptor occupancy. Experimental var-1 boundaries are not automatically assigned to a natural product without sequence reconciliation. Access scope: Selected actual Results and protein-production/NMR Methods in unchanged exact-main17690686 full text, with official PubMed identity.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:17690686
Structure of three tandem filamin domains reveals auto-inhib...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain beta1/beta7-integrin binding as non-core. The actual human FLNA domain study combines structural/NMR analysis with integrin-tail binding, showing partial autoinhibition by adjacent repeats and relief in engineered deletion/point mutants. Fragment and peptide affinities are distinct from endogenous full-length receptor occupancy. Experimental var-1 boundaries are not automatically assigned to a natural product without sequence reconciliation. Access scope: Selected actual Results and protein-production/NMR Methods in unchanged exact-main17690686 full text, with official PubMed identity.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:18177638
Filamin A regulates cell spreading and survival via beta1 in...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain curated beta1-integrin association as non-core with positive human-cell functional support. Full Results/Methods and the exact interaction assay were not independently recovered; no purified binding, rescue design or specific molecular subtype is asserted. Access scope: original-abstract consultation and exact-main abstract.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:18322202
Filamin A stabilizes Fc gamma RI surface expression and prev...
MODIFY
Summary: FLNA associates with the Fc-gamma receptor I cytoplasmic region and endogenous receptor-containing complexes.
Reason: PMID:18322202 identifies an Fc-gamma RI cytoplasmic-region interaction by human-bone-marrow yeast two-hybrid screening and confirms endogenous receptor association by U937 co-immunoprecipitation. GO:0034988 describes binding to a site on the Fc-gamma receptor I complex and is already retained with independent PMID:1833070 corroboration. The refinement names the supported receptor context without requiring FLNA to bind every subunit. It does not establish a purified intact-complex affinity, a direct interaction with the signaling gamma chain, or a universal natural-product interaction.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:19828450
Identification and characterization of multiple similar liga...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the four original partner alternatives: integrin beta2, GPIb alpha, integrin beta7 and migfilin. Actual indexed Results identify these four ligands, and original calorimetry/NMR evidence supports their binding to a related subgroup of human FLNA repeats. The repeat-level promiscuity does not demonstrate simultaneous occupancy of all four ligands on intact FLNA or universal receptor clustering. Access scope: Official19828450 abstract and indexed original Results; full downloaded article XML was unavailable by publisher policy, and an associated correction exists at PMC2878575.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:20236936
LL5beta directs the translocation of filamin A and SHIP2 to ...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain LL5beta/PHLDB2 association as non-core. The original abstract directly describes LL5beta recruitment of FLNA to PIP3-rich membrane with SHIP2 and contextual perturbation results in COS-7 cells. FLNA crosslinks actin; LL5beta senses phosphoinositide and SHIP2 dephosphorylates it. Do not assign either partner activity to FLNA or claim a purified binary affinity from this abstract. Access scope: Official20236936 original abstract; full XML was unavailable by publisher policy, actual detailed Methods not recovered.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:21228480
Identification of novel nuclear protein interactions with th...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the original contextual association with mouse TAF1B or Mis18bp1, with a prominent species limit. The actual original three-page study uses mouse FLNA fragments and a mouse embryonic cDNA library, followed by reticulocyte-lysate translation/pull-down and two-hybrid assays. It does not independently establish a purified human FLNA complex or a human transcription/centromere mechanism. Keep the existing human annotation and mouse partner identifiers without silently converting them into direct human assays. Access scope: Original J-STAGE advance-view PDF text, pages1–3; Methods/Results and figure2 caption read. Official partner identities confirm both mouse accessions.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:21228480
Identification of novel nuclear protein interactions with th...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the original contextual association with mouse TAF1B or Mis18bp1, with a prominent species limit. The actual original three-page study uses mouse FLNA fragments and a mouse embryonic cDNA library, followed by reticulocyte-lysate translation/pull-down and two-hybrid assays. It does not independently establish a purified human FLNA complex or a human transcription/centromere mechanism. Keep the existing human annotation and mouse partner identifiers without silently converting them into direct human assays. Access scope: Original J-STAGE advance-view PDF text, pages1–3; Methods/Results and figure2 caption read. Official partner identities confirm both mouse accessions.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:21524097
Evidence for multisite ligand binding and stretching of fila...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain beta7-integrin and migfilin association as non-core. Actual primary Methods use recombinant human FLNA Ig19–21 and receptor/migfilin peptides; NMR and calorimetry support ligand engagement and release of autoinhibition. This is repeat/peptide biochemistry, not a demonstrated endogenous whole-protein stoichiometry or a natural isoform-wide phenotype. Access scope: Downloaded actual21524097 primary HTML: selected Methods, Results and figure1–3 captions, including human construct origin.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:21653829
Protein interactome reveals converging molecular pathways am...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the curated FXR1 association as non-core, with original high-throughput scope. The study performed stringent yeast two-hybrid screening and sampled 52 interactions for mammalian validation; that global validation fraction cannot be assigned to this pair. The official FLNA UniProt record independently retains FXR1 as an interaction partner. The exact supplemental edge and its validation status were not independently replayed. Access scope: Actual21653829 Methods/Results in unchanged main cache; official FLNA interaction record identifies FXR1. Exact targeted IntAct query did not return this pair, which is not negative evidence.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:21653829
Protein interactome reveals converging molecular pathways am...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain SHANK3 association as non-core. The actual primary text explicitly reports the FLNA–SHANK3 two-hybrid interaction and independent co-immunoprecipitation in mouse brain extracts. Distinguish the heterologous screen from the native mouse experiment; neither alone establishes a direct human neuronal binary affinity or a synapse-specific causal mechanism. Access scope: Actual21653829 Results in unchanged exact-main cache; original supplemental figure itself was not inspected.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:21914078
Association of filamin A and vimentin with hepatitis C virus...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the two HCV-protein associations as non-core. The original abstract reports FLNA co-immunoprecipitation with NS3 and NS5A in infected human hepatoma cells. The original WITH/FROM entries refer to processed viral polyprotein chains, not human paralogs. Association and interferon-sensitive abundance do not establish a FLNA catalytic role in viral replication or therapeutic efficacy. Access scope: Official21914078 original abstract and current officialQ9WMX2 processed-chain identities.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:21914078
Association of filamin A and vimentin with hepatitis C virus...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the two HCV-protein associations as non-core. The original abstract reports FLNA co-immunoprecipitation with NS3 and NS5A in infected human hepatoma cells. The original WITH/FROM entries refer to processed viral polyprotein chains, not human paralogs. Association and interferon-sensitive abundance do not establish a FLNA catalytic role in viral replication or therapeutic efficacy. Access scope: Official21914078 original abstract and current officialQ9WMX2 processed-chain identities.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:21926999
Mechanical strain in actin networks regulates FilGAP and int...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain beta7-integrin association as non-core. Actual primary results use reconstituted actin–FLNA networks and labeled receptor tails: externally imposed shear and myosin-generated forces increase integrin binding while decreasing FilGAP association. FLNA is the crosslinking mechanosensitive scaffold, not the motor or GTPase. Do not equate recombinant deletion constructs with natural isoform effects or use differing text/caption time constants as exact kinetic estimates. Access scope: Actual21926999 primary body XML and indexed Results/captions; supplementary protein-production protocols were not replayed.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:22121117
A meckelin-filamin A interaction mediates ciliogenesis.
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain meckelin/TMEM67 association as non-core. Human fetal-brain two-hybrid FLNA fragment, human HEK293 endogenous co-IP and lysate pull-down support association; the latter is not a purified binary assay. Separate these from patient fibroblast, mouse knockdown and embryonic phenotypes. Engineered fragments and discrepant source endpoint notation do not define natural FLNA products. Access scope: actual22121117 primary Methods/Results/captions
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:24021649
The cytoplasmic domain of neuropilin-1 regulates focal adhes...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain NRP1 association as non-core. Actual original Results report receptor co-immunoprecipitation in primary mouse heart endothelial cells and independent SPR/ITC binding of recombinant FLNA repeats23–24 to the NRP1 cytoplasmic region. Cellular VEGF-dependent colocalization is distinct from the fragment assay. The recovered main text does not identify every recombinant insert species; do not call the whole experiment human or infer that FLNA catalyzes receptor recycling. Access scope: Actual24021649 body XML, selected Results and Discussion; detailed Methods are delegated to uninspected supplements.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:25241761
Using an in situ proximity ligation assay to systematically ...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Official IntAct exact publication/FLNA/partner records support the existing generic association. Retain as non-core under campaign policy without inferring a functional subtype. Method and interaction-type limits are retained explicitly; this does not claim all records demonstrate purified binary binding. Exact-source curated methods: proximity ligation assay. Interaction types: proximity. Official IntAct MITAB2.7 curation; original full text not independently replayed in this checkpoint.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:25358863
Amino- and carboxyl-terminal domains of Filamin-A interact w...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain CRMP3/CRMP1/CRMP4 association as non-core. Original Figure3 and Methods explicitly report co-immunoprecipitation of human FLNA with those CRMP constructs in HEK293T cells. Detailed subsequent binding, actin and Sema3A experiments focus on CRMP1 and must not be transferred to CRMP3/4. Rat brain endogenous association is a separate corroborating experiment. CRMP5 low expression was inconclusive, not negative evidence about the retained partners. Access scope: downloaded actual25358863 primary, paragraphs19/20/52, plus earlier CRMP1 Methods/Results consultation.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:25358863
Amino- and carboxyl-terminal domains of Filamin-A interact w...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain CRMP3/CRMP1/CRMP4 association as non-core. Original Figure3 and Methods explicitly report co-immunoprecipitation of human FLNA with those CRMP constructs in HEK293T cells. Detailed subsequent binding, actin and Sema3A experiments focus on CRMP1 and must not be transferred to CRMP3/4. Rat brain endogenous association is a separate corroborating experiment. CRMP5 low expression was inconclusive, not negative evidence about the retained partners. Access scope: downloaded actual25358863 primary, paragraphs19/20/52, plus earlier CRMP1 Methods/Results consultation.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:25358863
Amino- and carboxyl-terminal domains of Filamin-A interact w...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain CRMP3/CRMP1/CRMP4 association as non-core. Original Figure3 and Methods explicitly report co-immunoprecipitation of human FLNA with those CRMP constructs in HEK293T cells. Detailed subsequent binding, actin and Sema3A experiments focus on CRMP1 and must not be transferred to CRMP3/4. Rat brain endogenous association is a separate corroborating experiment. CRMP5 low expression was inconclusive, not negative evidence about the retained partners. Access scope: downloaded actual25358863 primary, paragraphs19/20/52, plus earlier CRMP1 Methods/Results consultation.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:25666618
A mechanism of global shape-dependent recognition and phosph...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain GPIb-alpha association as non-core. Actual indexed Figure2/Results distinguish the wild-type GPIb-alpha peptide from an engineered FW-to-AA peptide; both bind FLNA Ig21, with different reported affinities. Ligand-induced FLNA phosphorylation is performed by PKA, not FLNA. Do not equate the engineered peptide or Ig fragments with a natural protein product. Access scope: Official25666618 original abstract and indexed original Figure2/3 captions and Results; full XML unavailable by publisher policy.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:25849143
Structural mechanism of integrin inactivation by filamin.
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain beta3 and alphaIIb integrin associations as non-core. Actual human FLNA-Ig21 recombinant Methods and NMR/SPR/pull-down Results establish interaction with both cytoplasmic tails and stabilization of their clasp. Engineered linkers and beta3 solubility mutations are assay tools. CHO receptor-activation experiments support the contextual model but do not establish identical in-vivo affinities or a physiological natural-isoform assignment. Access scope: Actual25849143 body XML, selected Results and Methods14/19/21; supplementary spectra and raw structures not reanalyzed.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:25849143
Structural mechanism of integrin inactivation by filamin.
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain beta3 and alphaIIb integrin associations as non-core. Actual human FLNA-Ig21 recombinant Methods and NMR/SPR/pull-down Results establish interaction with both cytoplasmic tails and stabilization of their clasp. Engineered linkers and beta3 solubility mutations are assay tools. CHO receptor-activation experiments support the contextual model but do not establish identical in-vivo affinities or a physiological natural-isoform assignment. Access scope: Actual25849143 body XML, selected Results and Methods14/19/21; supplementary spectra and raw structures not reanalyzed.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Official IntAct exact publication/FLNA/partner records support the existing generic association. Retain as non-core under campaign policy without inferring a functional subtype. Method and interaction-type limits are retained explicitly; this does not claim all records demonstrate purified binary binding. Exact-source curated methods: anti tag coimmunoprecipitation. Interaction types: association. Official IntAct MITAB2.7 curation; original full text not independently replayed in this checkpoint. Spoke expansion represents a complex-associated pair rather than establishing purified binary contact.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:28297718
DND1 maintains germline stem cells via recruitment of the CC...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the curated DND1 association as non-core, independently corroborated by the exact positive DND1–FLNA cross-linking record for PMID:30021884 and the official UniProt interaction list. The earlier PMID:28297718 paper centers on DND1 RNA/CCR4–NOT biology; its exact FLNA protein-association edge was not independently recovered. Do not mistake FLNA mRNA targeting for FLNA protein binding or infer germline/CCR4 function for FLNA. The source-specific nuclear extension remains unverified; separate raw48 nuclear crosslink evidence is not a substitute for this assay context. Access scope: Actual28297718 selected original body XML/Methods now read: RNase-treated FH-DND1 HEK293 immunoprecipitates underwent mass spectrometry, with Table2 listing proteins. Exact FLNA edge remains unverified because targeted supplement acquisition returned404/challenge. Independent30021884 exact positive crosslink pair and official UniProt corroborate association.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:30021884
Histone Interaction Landscapes Visualized by Crosslinking Ma...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the DND1 association and original nucleus extension as non-core in the experiment context. Official IntAct records the exact positive human DND1–FLNA crosslink pair in U2OS, and the original study explicitly crosslinked isolated intact human nuclei. This supports proximity/physical association in that preparation; it does not establish purified binary affinity, a stable functional complex, universal nuclear residence or DND1-mediated RNA regulation by FLNA. Access scope: Exact IntActIM-26653-2143 record, official original30021884 abstract, and indexed original sample-context text.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:36577757
LPA receptor 1 (LPAR1) is a novel interaction partner of Fil...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Official IntAct exact publication/FLNA/partner records support the existing generic association. Retain as non-core under campaign policy without inferring a functional subtype. Method and interaction-type limits are retained explicitly; this does not claim all records demonstrate purified binary binding. Exact-source curated methods: anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, proximity ligation assay. Interaction types: association, physical association, proximity. Official IntAct MITAB2.7 curation; original full text not independently replayed in this checkpoint. Spoke expansion represents a complex-associated pair rather than establishing purified binary contact.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:36577757
LPA receptor 1 (LPAR1) is a novel interaction partner of Fil...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Official IntAct exact publication/FLNA/partner records support the existing generic association. Retain as non-core under campaign policy without inferring a functional subtype. Method and interaction-type limits are retained explicitly; this does not claim all records demonstrate purified binary binding. Exact-source curated methods: anti tag coimmunoprecipitation, fluorescent resonance energy transfer, proximity ligation assay. Interaction types: association, physical association, proximity. Official IntAct MITAB2.7 curation; original full text not independently replayed in this checkpoint. Spoke expansion represents a complex-associated pair rather than establishing purified binary contact.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:4044584
Identification of actin-binding protein as the protein linki...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain GPIb-beta-associated platelet membrane-skeleton context as non-core. The original abstract reports immunoprecipitation of membrane glycoproteins with actin-binding-protein antibodies after actin depolymerization and proteolysis-dependent dissociation. This is complex association; it does not identify a purified direct GPIb-beta binding interface. Later alpha-chain-specific FLNA binding must not be silently reassigned to beta. Access scope: Official4044584 original abstract and verified humanGP1BB identity.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:9722563
Filamin binds to the cytoplasmic domain of the beta1-integri...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the original beta1-integrin associations as non-core. The original abstract reports a two-hybrid screen, mammalian co-immunoprecipitation and recombinant fragment binding to the beta1 cytoplasmic domain. The original partners distinguish human P05556 and chicken P07228; no species correction or inferred natural FLNA isoform is made. Full construct-species allocation was not independently recovered. Access scope: Exact-main original9722563 abstract, verified current PubMed identity and official partner species; publisher PDF access failed.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005515 protein binding
IPI
PMID:9722563
Filamin binds to the cytoplasmic domain of the beta1-integri...
KEEP AS NON CORE
Summary: protein binding: retained in its supported cellular or assay context.
Reason: Retain the original beta1-integrin associations as non-core. The original abstract reports a two-hybrid screen, mammalian co-immunoprecipitation and recombinant fragment binding to the beta1 cytoplasmic domain. The original partners distinguish human P05556 and chicken P07228; no species correction or inferred natural FLNA isoform is made. Full construct-species allocation was not independently recovered. Access scope: Exact-main original9722563 abstract, verified current PubMed identity and official partner species; publisher PDF access failed.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005576 extracellular region
TAS
Reactome:R-HSA-482772
KEEP AS NON CORE
Summary: extracellular region: retained in its supported cellular or assay context.
Reason: Reactome R-HSA-482772 includes extracellular release of platelet cytosolic components and explicitly allows lysis as a contribution. Retain this contextual extracellular pool rather than rejecting it because FLNA is mainly intracellular. The assertion does not establish conventional secretion, a signal peptide or an extracellular core function.
Supporting Evidence:
Reactome:R-HSA-482772
file:human/FLNA/FLNA-source-evidence.md
GO:0005634 nucleus
IDA
PMID:15684392
FOXC1 transcriptional regulatory activity is impaired by PBX...
KEEP AS NON CORE
Summary: nucleus: retained in its supported cellular or assay context.
Reason: PMID:15684392 provides nuclear antibody/fractionation and cellular evidence, including human FLNA contexts. Retain contextual nuclear FLNA without assigning all signal to a proteolytic fragment or all natural products to the same pool. Elevated nuclear FLNA in A7 and differing HeLa behavior constrain a universal nuclear regulatory model.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005730 nucleolus
IMP
PMID:22307607
Cytoskeletal protein filamin A is a nucleolar protein that s...
KEEP AS NON CORE
Summary: nucleolus: retained in its supported cellular or assay context.
Reason: PMID:22307607 supports endogenous nucleolar FLNA and cellular negative regulation of pre-rRNA/promoter activity through depletion and re-expression, with actin-binding-domain and promoter-occupancy evidence. Retain the contextual nucleolar/regulatory assertion. An internal Results versus Fig2F-caption discrepancy prevents resolving the isolated in-vitro immunodepletion sign; that discrepancy is not silently corrected and does not erase the independent cellular evidence. The AARA retention mutant is engineered, not a natural isoform.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005737 cytoplasm
IDA
PMID:15684392
FOXC1 transcriptional regulatory activity is impaired by PBX...
TOO GENERAL
Summary: cytoplasm: covered by retained, more specific locations.
Reason: The original cytoplasmic localization remains biologically plausible. TOO_GENERAL reflects retained, independently supported cytosol and cortical locations, which official is_a/part_of paths place within cytoplasm. It does not claim that this particular source resolved every specific compartment. Original source and experimental context are preserved, including partial-access limits for PMID:25468996 and PMID:21914078.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005737 cytoplasm
IDA
PMID:21914078
Association of filamin A and vimentin with hepatitis C virus...
TOO GENERAL
Summary: cytoplasm: covered by retained, more specific locations.
Reason: The original cytoplasmic localization remains biologically plausible. TOO_GENERAL reflects retained, independently supported cytosol and cortical locations, which official is_a/part_of paths place within cytoplasm. It does not claim that this particular source resolved every specific compartment. Original source and experimental context are preserved, including partial-access limits for PMID:25468996 and PMID:21914078.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005737 cytoplasm
IDA
PMID:25468996
E-cadherin interactome complexity and robustness resolved by...
TOO GENERAL
Summary: cytoplasm: covered by retained, more specific locations.
Reason: The original cytoplasmic localization remains biologically plausible. TOO_GENERAL reflects retained, independently supported cytosol and cortical locations, which official is_a/part_of paths place within cytoplasm. It does not claim that this particular source resolved every specific compartment. Original source and experimental context are preserved, including partial-access limits for PMID:25468996 and PMID:21914078.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005829 cytosol
IDA
GO_REF:0000052
ACCEPT
Summary: cytosol: retained as a core structural function or location.
Reason: Cytosol is a defining location consistent with the HPA-curated assertion and independent human FLNA cellular/biochemical evidence. Retain the core location while explicitly noting that the original HPA image was not independently replayed; no product-specific localization follows from this source.
Supporting Evidence:
GO_REF:0000052
file:human/FLNA/FLNA-source-evidence.md
GO:0005829 cytosol
TAS
Reactome:R-HSA-430096
ACCEPT
Summary: cytosol: retained as a core structural function or location.
Reason: Retain this distinct Reactome cytosol context, consistent with human FLNA acting as an intracellular actin scaffold. The cached event describes GPIb-filamin association. The original event entity graph was not independently replayed; the summary and independent target evidence support location without assigning partner catalysis to FLNA.
Supporting Evidence:
Reactome:R-HSA-430096
file:human/FLNA/FLNA-source-evidence.md
GO:0005829 cytosol
TAS
Reactome:R-HSA-430347
ACCEPT
Summary: cytosol: retained as a core structural function or location.
Reason: Retain this distinct Reactome cytosol context, consistent with human FLNA acting as an intracellular actin scaffold. The cached event describes migfilin-filamin/F-actin association. The original event entity graph was not independently replayed; the summary and independent target evidence support location without assigning partner catalysis to FLNA.
Supporting Evidence:
Reactome:R-HSA-430347
file:human/FLNA/FLNA-source-evidence.md
GO:0005829 cytosol
TAS
Reactome:R-HSA-482772
ACCEPT
Summary: cytosol: retained as a core structural function or location.
Reason: Retain this distinct Reactome cytosol context, consistent with human FLNA acting as an intracellular actin scaffold. The cached event describes release from a platelet cytosolic pool. The original event entity graph was not independently replayed; the summary and independent target evidence support location without assigning partner catalysis to FLNA.
Supporting Evidence:
Reactome:R-HSA-482772
file:human/FLNA/FLNA-source-evidence.md
GO:0005829 cytosol
TAS
Reactome:R-HSA-5669240
ACCEPT
Summary: cytosol: retained as a core structural function or location.
Reason: Retain this distinct Reactome cytosol context, consistent with human FLNA acting as an intracellular actin scaffold. The genuinely fetched summary describes PAK1 binding to FLNA repeat 23. The original event entity graph was not independently replayed; the summary and independent target evidence support location without assigning partner catalysis to FLNA.
Supporting Evidence:
Reactome:R-HSA-5669240
file:human/FLNA/FLNA-source-evidence.md
GO:0005829 cytosol
TAS
Reactome:R-HSA-5669250
ACCEPT
Summary: cytosol: retained as a core structural function or location.
Reason: Retain this distinct Reactome cytosol context, consistent with human FLNA acting as an intracellular actin scaffold. The genuinely fetched summary describes PAK1 phosphorylation of FLNA S2152; FLNA is the substrate, not the kinase. The original event entity graph was not independently replayed; the summary and independent target evidence support location without assigning partner catalysis to FLNA.
Supporting Evidence:
Reactome:R-HSA-5669250
file:human/FLNA/FLNA-source-evidence.md
GO:0005829 cytosol
TAS
Reactome:R-HSA-8985123
ACCEPT
Summary: cytosol: retained as a core structural function or location.
Reason: Retain this distinct Reactome cytosol context, consistent with human FLNA acting as an intracellular actin scaffold. The genuinely fetched summary explicitly describes RNase L-FLNA association in uninfected cells and dissociation on RNase L activation; nuclease catalysis belongs to RNase L. The original event entity graph was not independently replayed; the summary and independent target evidence support location without assigning partner catalysis to FLNA.
Supporting Evidence:
Reactome:R-HSA-8985123
file:human/FLNA/FLNA-source-evidence.md
GO:0005856 cytoskeleton
IEA
GO_REF:0000044
TOO GENERAL
Summary: cytoskeleton: covered by retained, more specific locations.
Reason: Cytoskeleton is a true but broader location already entailed by retained actin cytoskeleton through the verified is_a path. TOO_GENERAL is a resolution judgment, not rejection of the original location or donor. Core actin-network evidence supports the more informative location.
Supporting Evidence:
GO_REF:0000044
file:human/FLNA/FLNA-source-evidence.md
GO:0005884 actin filament
IEA
GO_REF:0000107
ACCEPT
Summary: actin filament: retained as a core structural function or location.
Reason: Verified rat donor PMID:22872576 reports FLNA RNAi in Sertoli cultures and immature testes, disorganized F-actin, barrier defects and redistribution of occludin/ZO1/JAM-A. FLNA supplies the actin scaffold; bundle organization and actin/cortical location are core, while developmental barrier assembly and junction-protein localization are contextual. GO:1902396 includes maintenance at junctions and does not require a transport motor. The human rows remain transferred evidence, and later developmental recovery limits a universal barrier requirement.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0005886 plasma membrane
IDA
PMID:18322202
Filamin A stabilizes Fc gamma RI surface expression and prev...
ACCEPT
Summary: plasma membrane: retained as a core structural function or location.
Reason: PMID:18322202 reports FLNA/Fc gamma RI cellular localization in human monocytes/U937 and M2/A7 models, supporting plasma-membrane-associated FLNA. Retain the core membrane-cytoskeleton interface location without treating FLNA as an integral membrane receptor or assigning every natural product to the same pool.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005911 cell-cell junction
IDA
PMID:16291724
CEACAM1 functionally interacts with filamin A and exerts a d...
KEEP AS NON CORE
Summary: cell-cell junction: retained in its supported cellular or assay context.
Reason: PMID:16291724 supports contextual migration/spreading and junction-associated FLNA in human M2/A7 cells reconstituted with CEACAM1-4L. Rat recombinant-fragment binding is a separate part of the study. Retain the existing cellular scaffold role without equating a scratch/spreading assay with organismal wound repair, assigning partner GTPase catalysis to FLNA or claiming every natural product has been tested.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005925 focal adhesion
HDA
PMID:21423176
Analysis of the myosin-II-responsive focal adhesion proteome...
ACCEPT
Summary: focal adhesion: retained as a core structural function or location.
Reason: PMID:21423176 identifies filamin-1 in isolated human HFF1 fibroblast focal adhesions, separately from filamin-B/C, with fractionation controls and myosin-II-sensitive abundance. Retain this core adhesion-associated cytoskeletal location and the fibroblast context. Target spectra were not independently replayed, and localization does not imply FLNA motor activity or that every detected protein independently performs adhesion assembly.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0005938 cell cortex
IEA
GO_REF:0000120
ACCEPT
Summary: cell cortex: retained as a core structural function or location.
Reason: Verified rat donor PMID:22872576 reports FLNA RNAi in Sertoli cultures and immature testes, disorganized F-actin, barrier defects and redistribution of occludin/ZO1/JAM-A. FLNA supplies the actin scaffold; bundle organization and actin/cortical location are core, while developmental barrier assembly and junction-protein localization are contextual. GO:1902396 includes maintenance at junctions and does not require a transport motor. The human rows remain transferred evidence, and later developmental recovery limits a universal barrier requirement.
Supporting Evidence:
GO_REF:0000120
file:human/FLNA/FLNA-source-evidence.md
GO:0007195 adenylate cyclase-inhibiting dopamine receptor signaling pathway
IMP
PMID:10692483
Modulation of dopamine D(2) receptor signaling by actin-bind...
KEEP AS NON CORE
Summary: adenylate cyclase-inhibiting dopamine receptor signaling pathway: retained in its supported cellular or assay context.
Reason: The verified PMID:10692483 abstract reports dopamine D2 receptor-FLNA binding, membrane clustering and coupling to adenylate-cyclase inhibition in FLNA-deficient versus replete human melanoma cells. Retain the existing receptor-specific signaling/clustering context as non-core. Full source Methods were not independently recovered; receptor S358D is an engineered receptor construct, not a natural FLNA product or a direct measurement of receptor phosphorylation.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0007597 blood coagulation, intrinsic pathway
NAS
PMID:16293600
The structure of the GPIb-filamin A complex.
MARK AS OVER ANNOTATED
Summary: blood coagulation, intrinsic pathway: the term mapping exceeds the supported role.
Reason: GO:0007597 specifies the intrinsic coagulation-factor cascade, whereas the inspected PMID:16293600 experiments establish FLNA-mediated GPIb-cytoskeleton attachment. That real platelet structural role does not identify FLNA performing a step of the XII/prekallikrein/kininogen-to-factor-X cascade. Mark this process mapping as over-annotated without denying platelet haemostatic function; the narrower platelet-activation and receptor-complex contexts are retained.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0010572 positive regulation of platelet activation
NAS
PMID:16293600
The structure of the GPIb-filamin A complex.
KEEP AS NON CORE
Summary: positive regulation of platelet activation: retained in its supported cellular or assay context.
Reason: PMID:16293600 establishes human FLNA coupling of GPIb to the platelet cytoskeleton. PMID:20713593 adds native human Syk association and mouse loss-of-FlnA receptor-response experiments, supporting contextual positive regulation of platelet activation. Retain non-core participation through receptor/scaffold organization, preserving the human versus mouse and construct limits rather than treating FLNA as a kinase.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0015459 potassium channel regulator activity
IDA
PMID:24951510
Functional interaction with filamin A and intracellular Ca2+...
KEEP AS NON CORE
Summary: potassium channel regulator activity: retained in its supported cellular or assay context.
Reason: PMID:24951510 supports regulation of SK2 through FLNA interaction, increased surface abundance and apamin-sensitive whole-cell current. Human constructs/cell experiments and mouse cardiomyocyte knockdown are distinct. Regulation through trafficking satisfies channel regulation without requiring altered single-channel gating. The calcium-sensitive alpha-actinin2/CaM effect is not transferred to FLNA; this remains a contextual function.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0015629 actin cytoskeleton
IC
PMID:2391361
Human endothelial actin-binding protein (ABP-280, nonmuscle ...
ACCEPT
Summary: actin cytoskeleton: retained as a core structural function or location.
Reason: The verified PMID:2391361 abstract supports human filamin dimeric architecture and F-actin association. These are defining structural properties of FLNA, independently corroborated by human FLNA recombinant/cellular work in PMID:10051605 and PMID:25358863. Retain the core assertion, while explicitly limiting this older source to abstract access rather than claiming its full Methods or assigning all constructs to every natural product.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0015629 actin cytoskeleton
IDA
PMID:25358863
Amino- and carboxyl-terminal domains of Filamin-A interact w...
ACCEPT
Summary: actin cytoskeleton: retained as a core structural function or location.
Reason: PMID:25358863 reports human FLNA recombinant fragments and human full-length FLNA purified from HEK293 cells, with direct F-actin co-sedimentation and gelation experiments. These support core filament binding and actin-network association. Rat CRMP1 and neuronal models are distinguished from the human FLNA preparation. CRMP1 S522D is a phosphomimetic, and FLNA Ig24 deletion also alters dimerization; neither defines a natural-product-specific effect.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0015629 actin cytoskeleton
IEA
GO_REF:0000107
ACCEPT
Summary: actin cytoskeleton: retained as a core structural function or location.
Reason: Rat donor PMID:20167606 fractionation/imaging is consistent with the defining FLNA actin-cytoskeleton location and independently established human actin-binding/crosslinking activity. Retain the core structural location while distinguishing endogenous rat protein from a human C-terminal construct and avoiding natural-product claims.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0016020 membrane
HDA
PMID:19946888
Defining the membrane proteome of NK cells.
TOO GENERAL
Summary: membrane: covered by retained, more specific locations.
Reason: The original PMID:19946888 HDA membrane assertion is retained as true but TOO_GENERAL because accepted plasma membrane GO:0005886 is_a membrane GO:0016020. The source concerns a human YTS membrane-proteomics preparation; its exact FLNA supplemental row was not recovered. The resolution judgment uses independent plasma-membrane evidence, not a claim that this source alone specifies that membrane.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0016479 negative regulation of transcription by RNA polymerase I
IDA
PMID:22307607
Cytoskeletal protein filamin A is a nucleolar protein that s...
KEEP AS NON CORE
Summary: negative regulation of transcription by RNA polymerase I: retained in its supported cellular or assay context.
Reason: PMID:22307607 supports endogenous nucleolar FLNA and cellular negative regulation of pre-rRNA/promoter activity through depletion and re-expression, with actin-binding-domain and promoter-occupancy evidence. Retain the contextual nucleolar/regulatory assertion. An internal Results versus Fig2F-caption discrepancy prevents resolving the isolated in-vitro immunodepletion sign; that discrepancy is not silently corrected and does not erase the independent cellular evidence. The AARA retention mutant is engineered, not a natural isoform.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0019900 kinase binding
IPI
PMID:20713593
A novel interaction between FlnA and Syk regulates platelet ...
KEEP AS NON CORE
Summary: kinase binding: retained in its supported cellular or assay context.
Reason: PMID:20713593 reports native human platelet Syk-FLNA co-immunoprecipitation and recombinant binding/Ig5 mapping, supporting actual kinase binding. The insect expression host does not independently establish every insert species. Mouse FlnA-loss phenotypes support a receptor-context scaffold role but are separate from the human association. Retain non-core binding without assigning Syk kinase activity to FLNA.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0021943 formation of radial glial scaffolds
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: formation of radial glial scaffolds: retained in its supported cellular or assay context.
Reason: The verified rat donor PMID:22076441 reports in-utero Flna knockdown, disrupted polarized radial-glial scaffolds and impaired cortical migration, with a separate developmental-expression context. This supports contextual scaffold/cortex/migration involvement transferred to human. Human pathological observations are not human knockdown experiments. Only the original abstract was recovered; detailed rescue and cell-cycle direction are not asserted.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0021987 cerebral cortex development
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: cerebral cortex development: retained in its supported cellular or assay context.
Reason: The verified rat donor PMID:22076441 reports in-utero Flna knockdown, disrupted polarized radial-glial scaffolds and impaired cortical migration, with a separate developmental-expression context. This supports contextual scaffold/cortex/migration involvement transferred to human. Human pathological observations are not human knockdown experiments. Only the original abstract was recovered; detailed rescue and cell-cycle direction are not asserted.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
ISS
PMID:24951510
Functional interaction with filamin A and intracellular Ca2+...
KEEP AS NON CORE
Summary: Z disc: retained in its supported cellular or assay context.
Reason: PMID:24951510 directly images FLNA/SK2 at Z lines in adult mouse atrial cells. Retain the existing human ISS location through the verified mouse donor. Human atrial Western blot confirms expression but is not direct human Z-disc imaging; antibody controls and inaccessible supplementary detail remain distinct. This contextual cardiac pool is not a universal core FLNA location.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0030036 actin cytoskeleton organization
IDA
PMID:10051605
The small GTPase RalA targets filamin to induce filopodia.
ACCEPT
Summary: actin cytoskeleton organization: retained as a core structural function or location.
Reason: PMID:10051605 combines filamin biochemistry with explicit human FLNA recombinant and M2/A7 cellular experiments, supporting FLNA-driven actin crosslinks and network organization. Bulk platelet/leiomyoma filamin isotype purity is not independently established, so that preparation alone is not treated as target-exclusive. FLNA supplies the structural crosslinks; C-terminal deletion affects dimerization as well as partner binding. This is a core structural activity, corroborated by human FLNA assays in PMID:25358863.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0030036 actin cytoskeleton organization
IEA
GO_REF:0000120
ACCEPT
Summary: actin cytoskeleton organization: retained as a core structural function or location.
Reason: The official Filamin-family InterPro IPR044801 mapping agrees with defining human FLNA F-actin binding and cytoskeletal organization established by recombinant protein and human-cell studies. Retain this core function. This is target-supported family inference, not a claim to have audited every ARBA rule or experimentally tested every family member.
Supporting Evidence:
GO_REF:0000120
file:human/FLNA/FLNA-source-evidence.md
GO:0030334 regulation of cell migration
IDA
PMID:16291724
CEACAM1 functionally interacts with filamin A and exerts a d...
KEEP AS NON CORE
Summary: regulation of cell migration: retained in its supported cellular or assay context.
Reason: PMID:16291724 supports contextual migration/spreading and junction-associated FLNA in human M2/A7 cells reconstituted with CEACAM1-4L. Rat recombinant-fragment binding is a separate part of the study. Retain the existing cellular scaffold role without equating a scratch/spreading assay with organismal wound repair, assigning partner GTPase catalysis to FLNA or claiming every natural product has been tested.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0030426 growth cone
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: growth cone: retained in its supported cellular or assay context.
Reason: The verified mouse Q8BTM8 donor maps the neuronal growth-cone/perikaryon location to PMID:25358863, whose actual neuronal FLNA/CRMP1 experiments support contextual localization. Retain the original mouse-to-human inference without describing it as direct human neuronal imaging or assigning all engineered fragments to natural products.
Supporting Evidence:
GO_REF:0000044
file:human/FLNA/FLNA-source-evidence.md
GO:0030863 cortical cytoskeleton
IEA
GO_REF:0000107
ACCEPT
Summary: cortical cytoskeleton: retained as a core structural function or location.
Reason: Verified rat PMID:15661894 abstract evidence supports submembrane F-actin/filamin association, coherent with direct human FLNA actin-crosslinking and membrane-scaffold experiments. Retain cortical cytoskeleton as core location. The donor detailed Methods were not independently recovered and are not presented as a human experiment.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0031267 small GTPase binding
IDA
PMID:10051605
The small GTPase RalA targets filamin to induce filopodia.
KEEP AS NON CORE
Summary: small GTPase binding: retained in its supported cellular or assay context.
Reason: PMID:10051605 supports RalA and other small-GTPase association. Human recombinant FLNA anchors RalA binding and GTP selectivity; the RHOA/RAC1/CDC42 experiments use bulk human platelet/leiomyoma filamin of unresolved isotype purity and show nucleotide-independent association. Retain the contextual binding function without giving FLNA GTPase activity or extending the RalA nucleotide dependence to all partners.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0031523 Myb complex
IDA
PMID:18548008
A B-Myb complex containing clathrin and filamin is required ...
MARK AS OVER ANNOTATED
Summary: Myb complex: the term mapping exceeds the supported role.
Reason: PMID:18548008 establishes a real cytosolic B-Myb/clathrin/FLNA association, explicitly distinct from nuclear dREAM/Myb-MuvB. Official GO:0031523 describes a replication/transcription-regulatory Myb complex with nuclear ancestry. Mark this term mapping as over-annotated while preserving the true cytosolic interaction and contextual mitotic role; this is not a claim that the source lacks FLNA or that association is false.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0032233 positive regulation of actin filament bundle assembly
IEA
GO_REF:0000107
ACCEPT
Summary: positive regulation of actin filament bundle assembly: retained as a core structural function or location.
Reason: Verified rat donor PMID:22872576 reports FLNA RNAi in Sertoli cultures and immature testes, disorganized F-actin, barrier defects and redistribution of occludin/ZO1/JAM-A. FLNA supplies the actin scaffold; bundle organization and actin/cortical location are core, while developmental barrier assembly and junction-protein localization are contextual. GO:1902396 includes maintenance at junctions and does not require a transport motor. The human rows remain transferred evidence, and later developmental recovery limits a universal barrier requirement.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0034394 protein localization to cell surface
IDA
PMID:18322202
Filamin A stabilizes Fc gamma RI surface expression and prev...
KEEP AS NON CORE
Summary: protein localization to cell surface: retained in its supported cellular or assay context.
Reason: PMID:18322202 uses primary human monocytes/U937 and FLNA-deficient/reconstituted M2/A7 cells to link FLNA to Fc gamma RI surface retention and protection from lysosomal loss. Bafilomycin rescue of total receptor supports the catabolic/stabilization interpretation. Retain these contextual localization/protection functions; normal initial surface delivery and a qualified recycling model are distinguished from demonstrated directed transport.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0034988 Fc-gamma receptor I complex binding
IDA
PMID:1833070
Ligand-sensitive binding of actin-binding protein to immunog...
KEEP AS NON CORE
Summary: Fc-gamma receptor I complex binding: retained in its supported cellular or assay context.
Reason: The verified PMID:1833070 abstract directly reports Fc gamma RI association with actin-binding protein in human U937 cells and receptor-transfected COS cells, with ligand-sensitive avidity. This supports the specialized receptor-complex-binding context, corroborated by target evidence in PMID:18322202. Retain it as non-core while limiting the older source to abstract access rather than claiming its full Methods or an isoform-specific interface.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0035855 megakaryocyte development
NAS
PMID:16293600
The structure of the GPIb-filamin A complex.
UNDECIDED
Summary: megakaryocyte development: source-specific evidence remains unresolved.
Reason: PMID:16293600 establishes platelet receptor-cytoskeleton attachment, but the specific megakaryocyte-development evidence was not recovered in the inspected primary sections. Platelet number/morphology observations in PMID:20713593 do not independently resolve this developmental assertion. Keep UNDECIDED without claiming the whole paper lacks evidence or treating a missing inspected experiment as a negative result.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0042177 negative regulation of protein catabolic process
IMP
PMID:18322202
Filamin A stabilizes Fc gamma RI surface expression and prev...
KEEP AS NON CORE
Summary: negative regulation of protein catabolic process: retained in its supported cellular or assay context.
Reason: PMID:18322202 uses primary human monocytes/U937 and FLNA-deficient/reconstituted M2/A7 cells to link FLNA to Fc gamma RI surface retention and protection from lysosomal loss. Bafilomycin rescue of total receptor supports the catabolic/stabilization interpretation. Retain these contextual localization/protection functions; normal initial surface delivery and a qualified recycling model are distinguished from demonstrated directed transport.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0042307 positive regulation of protein import into nucleus
IMP
PMID:15684392
FOXC1 transcriptional regulatory activity is impaired by PBX...
KEEP AS NON CORE
Summary: positive regulation of protein import into nucleus: retained in its supported cellular or assay context.
Reason: PMID:15684392 reports reduced PBX1a nuclear distribution in FLNA-deficient M2 compared with restored A7 cells, whereas FOXC1 remains nuclear in both. Preserve the original PBX1a partner context. This supports contextual positive regulation of import/localization without establishing direct FLNA-PBX1 binding, a transport mechanism or universal transcriptional repression.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0042789 mRNA transcription by RNA polymerase II
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: FLNA recruits a promoter-associated Smad complex during stimulated laminin-gene transcription.
Reason: In rat mesangial cells, PMID:20167606 shows stimulus-dependent recruitment of Smad3/4 to a C-terminal FLNA complex, nuclear accumulation of that complex and FLNA association with the lamc1 promoter. FLNA depletion reduces nuclear Smad accumulation and lamc1 induction. These experiments support a structural shuttle/scaffold contribution to the transcription process beyond necessity alone, so retain the transferred involvement as non-core. The endogenous rat protein and expressed human C-terminal construct are distinct; the exact contribution after promoter arrival remains unresolved.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0042803 protein homodimerization activity
IDA
PMID:2391361
Human endothelial actin-binding protein (ABP-280, nonmuscle ...
ACCEPT
Summary: protein homodimerization activity: retained as a core structural function or location.
Reason: The verified PMID:2391361 abstract supports human filamin dimeric architecture and F-actin association. These are defining structural properties of FLNA, independently corroborated by human FLNA recombinant/cellular work in PMID:10051605 and PMID:25358863. Retain the core assertion, while explicitly limiting this older source to abstract access rather than claiming its full Methods or assigning all constructs to every natural product.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0043025 neuronal cell body
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: neuronal cell body: retained in its supported cellular or assay context.
Reason: PMID:22434607 reports mature rat tissue and three-to-four-week hippocampal cultures, two N/C-terminal FLNA antibodies, expected-size bands and corroborating in-situ hybridization. Soma/apical dendritic-shaft puncta support this contextual neuronal location transferred to human. Minimal mature-spine signal in that experiment does not negate later higher-resolution remodeling-spine evidence or define a natural human isoform.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0043066 negative regulation of apoptotic process
IMP
PMID:18177638
Filamin A regulates cell spreading and survival via beta1 in...
KEEP AS NON CORE
Summary: negative regulation of apoptotic process: retained in its supported cellular or assay context.
Reason: The verified PMID:18177638 abstract reports human gingival-fibroblast and HEK293 FLNA knockdown with reduced collagen-associated spreading, integrin association and increased TUNEL-positive spreading cells. These support contextual adhesion/integrin signaling and survival functions. Full Methods, rescue design and a specific apoptotic mechanism were not independently recovered; calcium-chelation results do not establish that FLNA is a calcium sensor.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0043113 receptor clustering
IDA
PMID:10692483
Modulation of dopamine D(2) receptor signaling by actin-bind...
KEEP AS NON CORE
Summary: receptor clustering: retained in its supported cellular or assay context.
Reason: The verified PMID:10692483 abstract reports dopamine D2 receptor-FLNA binding, membrane clustering and coupling to adenylate-cyclase inhibition in FLNA-deficient versus replete human melanoma cells. Retain the existing receptor-specific signaling/clustering context as non-core. Full source Methods were not independently recovered; receptor S358D is an engineered receptor construct, not a natural FLNA product or a direct measurement of receptor phosphorylation.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0043123 positive regulation of canonical NF-kappaB signal transduction
HMP
PMID:12761501
Large-scale identification and characterization of human gen...
UNDECIDED
Summary: positive regulation of canonical NF-kappaB signal transduction: source-specific evidence remains unresolved.
Reason: PMID:12761501 describes a human HEK293 cDNA-overexpression/luciferase screen, but the FLNA-specific result, direction and controls could not be recovered from the available abstract. Keep the existing positive NF-kappaB assertion UNDECIDED pending the target table. Neither the high-throughput design nor incomplete access justifies a wrong-gene or negative-function conclusion.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0043198 dendritic shaft
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: dendritic shaft: retained in its supported cellular or assay context.
Reason: PMID:22434607 reports mature rat tissue and three-to-four-week hippocampal cultures, two N/C-terminal FLNA antibodies, expected-size bands and corroborating in-situ hybridization. Soma/apical dendritic-shaft puncta support this contextual neuronal location transferred to human. Minimal mature-spine signal in that experiment does not negate later higher-resolution remodeling-spine evidence or define a natural human isoform.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0043204 perikaryon
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: perikaryon: retained in its supported cellular or assay context.
Reason: The verified mouse Q8BTM8 donor maps the neuronal growth-cone/perikaryon location to PMID:25358863, whose actual neuronal FLNA/CRMP1 experiments support contextual localization. Retain the original mouse-to-human inference without describing it as direct human neuronal imaging or assigning all engineered fragments to natural products.
Supporting Evidence:
GO_REF:0000044
file:human/FLNA/FLNA-source-evidence.md
GO:0043204 perikaryon
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: perikaryon: retained in its supported cellular or assay context.
Reason: The verified mouse Q8BTM8 donor maps the neuronal growth-cone/perikaryon location to PMID:25358863, whose actual neuronal FLNA/CRMP1 experiments support contextual localization. Retain the original mouse-to-human inference without describing it as direct human neuronal imaging or assigning all engineered fragments to natural products.
Supporting Evidence:
GO_REF:0000024
file:human/FLNA/FLNA-source-evidence.md
GO:0044319 wound healing, spreading of cells
IDA
PMID:16291724
CEACAM1 functionally interacts with filamin A and exerts a d...
KEEP AS NON CORE
Summary: wound healing, spreading of cells: retained in its supported cellular or assay context.
Reason: PMID:16291724 supports contextual migration/spreading and junction-associated FLNA in human M2/A7 cells reconstituted with CEACAM1-4L. Rat recombinant-fragment binding is a separate part of the study. Retain the existing cellular scaffold role without equating a scratch/spreading assay with organismal wound repair, assigning partner GTPase catalysis to FLNA or claiming every natural product has been tested.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0044325 transmembrane transporter binding
IPI
PMID:24951510
Functional interaction with filamin A and intracellular Ca2+...
KEEP AS NON CORE
Summary: transmembrane transporter binding: retained in its supported cellular or assay context.
Reason: PMID:24951510 demonstrates human SK2 N-terminal fragment interaction with a human FLNA C-terminal fragment by reciprocal yeast two-hybrid tests and mutations, with cellular corroboration. Retain contextual transporter binding; the assay is not a purified affinity determination, and the heart extension does not by itself demonstrate native purified human cardiac binding.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0044877 protein-containing complex binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: protein-containing complex binding: retained in its supported cellular or assay context.
Reason: The Ensembl donor accessions A0A8I5ZV49 and ENSRNOP00000082035 identify the same rat Flna protein. PMID:22948144 reports controlled rat-brain FLNA co-immunoprecipitation with HCN1 and protocadherin15 CD3, supporting complex association transferred to human. HCN1-protocadherin SPR and rat cochlear localization are separate experiments; neither proves a purified FLNA binary interaction. Retain this contextual association without inventing a specific human complex subtype.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0045184 establishment of protein localization
IDA
PMID:18322202
Filamin A stabilizes Fc gamma RI surface expression and prev...
UNDECIDED
Summary: establishment of protein localization: source-specific evidence remains unresolved.
Reason: Actual PMID:18322202 experiments support Fc gamma RI retention and lysosomal protection, while initial surface delivery apparently proceeds without FLNA. GO:0045184 concerns establishment through directed movement; a possible recycling contribution remains a qualified model. This leaves the exact term unresolved despite valid retained surface-localization/stabilization annotations. GO:0034394 is not a formal descendant, so neither a false TOO_GENERAL argument nor a curator-error claim is used.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0045296 cadherin binding
HDA
PMID:25468996
E-cadherin interactome complexity and robustness resolved by...
UNDECIDED
Summary: cadherin binding: source-specific evidence remains unresolved.
Reason: PMID:25468996 uses E-cadherin proximity biotinylation/MS. The available cached extraction lacks the Results, Methods and FLNA target table despite its full-text metadata flag. Vicinity alone does not resolve the specific cadherin-binding assertion, and the original FLNA validation could not be recovered. Keep UNDECIDED rather than declaring a curation error or excluding a real interaction from the partial article.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0046332 SMAD binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: SMAD binding: retained in its supported cellular or assay context.
Reason: Verified rat donor PMID:20167606 shows endogenous FLNA and an expressed human C-terminal FLNA construct associating with Smad3/Smad4-containing complexes in rat mesangial cells. Reciprocal immunoprecipitation and nuclear fractionation support contextual SMAD association; direct Smad3 contact versus recruitment through Smad4 remains unresolved. Retain the human orthology-based binding context without asserting purified binary binding, DNA binding, or a natural C-terminal isoform.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0048471 perinuclear region of cytoplasm
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: perinuclear region of cytoplasm: retained in its supported cellular or assay context.
Reason: Rat donor PMID:20167606 reports stimulus-dependent perinuclear C-terminal FLNA staining. Retain the contextual location with antibody-domain and cleavage limits; this does not establish universal full-length localization or a distinct natural FLNA product.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0050821 protein stabilization
IMP
PMID:18322202
Filamin A stabilizes Fc gamma RI surface expression and prev...
KEEP AS NON CORE
Summary: protein stabilization: retained in its supported cellular or assay context.
Reason: PMID:18322202 uses primary human monocytes/U937 and FLNA-deficient/reconstituted M2/A7 cells to link FLNA to Fc gamma RI surface retention and protection from lysosomal loss. Bafilomycin rescue of total receptor supports the catabolic/stabilization interpretation. Retain these contextual localization/protection functions; normal initial surface delivery and a qualified recycling model are distinguished from demonstrated directed transport.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0051015 actin filament binding
IDA
PMID:2391361
Human endothelial actin-binding protein (ABP-280, nonmuscle ...
ACCEPT
Summary: actin filament binding: retained as a core structural function or location.
Reason: The verified PMID:2391361 abstract supports human filamin dimeric architecture and F-actin association. These are defining structural properties of FLNA, independently corroborated by human FLNA recombinant/cellular work in PMID:10051605 and PMID:25358863. Retain the core assertion, while explicitly limiting this older source to abstract access rather than claiming its full Methods or assigning all constructs to every natural product.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0051015 actin filament binding
IDA
PMID:25358863
Amino- and carboxyl-terminal domains of Filamin-A interact w...
ACCEPT
Summary: actin filament binding: retained as a core structural function or location.
Reason: PMID:25358863 reports human FLNA recombinant fragments and human full-length FLNA purified from HEK293 cells, with direct F-actin co-sedimentation and gelation experiments. These support core filament binding and actin-network association. Rat CRMP1 and neuronal models are distinguished from the human FLNA preparation. CRMP1 S522D is a phosphomimetic, and FLNA Ig24 deletion also alters dimerization; neither defines a natural-product-specific effect.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0051015 actin filament binding
IDA
PMID:3138234
Localization of the domain of actin-binding protein that bin...
ACCEPT
Summary: actin filament binding: retained as a core structural function or location.
Reason: The verified original abstract directly supports filamin-actin association. Detailed original Methods and modern domain coordinates were not independently recovered. Retain the defining FLNA actin-filament-binding function, independently corroborated by actual human recombinant/purified FLNA assays in PMID:25358863 and the human FLNA experiments in PMID:10051605; do not claim a full-text replay of this older source.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0051015 actin filament binding
IDA
PMID:4044584
Identification of actin-binding protein as the protein linki...
ACCEPT
Summary: actin filament binding: retained as a core structural function or location.
Reason: The verified original abstract directly supports filamin-actin association. Detailed original Methods and modern domain coordinates were not independently recovered. Retain the defining FLNA actin-filament-binding function, independently corroborated by actual human recombinant/purified FLNA assays in PMID:25358863 and the human FLNA experiments in PMID:10051605; do not claim a full-text replay of this older source.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0051015 actin filament binding
IEA
GO_REF:0000002
ACCEPT
Summary: actin filament binding: retained as a core structural function or location.
Reason: The official Filamin-family InterPro IPR044801 mapping agrees with defining human FLNA F-actin binding and cytoskeletal organization established by recombinant protein and human-cell studies. Retain this core function. This is target-supported family inference, not a claim to have audited every ARBA rule or experimentally tested every family member.
Supporting Evidence:
GO_REF:0000002
file:human/FLNA/FLNA-source-evidence.md
GO:0051020 GTPase binding
IPI
PMID:16291724
CEACAM1 functionally interacts with filamin A and exerts a d...
KEEP AS NON CORE
Summary: GTPase binding: retained in its supported cellular or assay context.
Reason: PMID:16291724 supports a CEACAM1-FLNA scaffold linking receptor context to small-GTPase associations and signaling. Purified rat fragments and human M2/A7 reconstitution are distinct experiments. Retain contextual GTPase binding; the association does not make FLNA a GTPase, GAP or GEF.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0051209 release of sequestered calcium ion into cytosol
NAS
PMID:16293600
The structure of the GPIb-filamin A complex.
UNDECIDED
Summary: release of sequestered calcium ion into cytosol: source-specific evidence remains unresolved.
Reason: The specific FLNA contribution to calcium release from intracellular stores was not recovered in the inspected PMID:16293600 sections. Later PMID:20713593 receptor-dependent calcium discussion is partly hypothetical and does not isolate this step. Keep UNDECIDED while retaining the real receptor/scaffold evidence; no claim is made that the paper or gene definitively lacks calcium-related function.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0051764 actin crosslink formation
IDA
PMID:10051605
The small GTPase RalA targets filamin to induce filopodia.
ACCEPT
Summary: actin crosslink formation: retained as a core structural function or location.
Reason: PMID:10051605 combines filamin biochemistry with explicit human FLNA recombinant and M2/A7 cellular experiments, supporting FLNA-driven actin crosslinks and network organization. Bulk platelet/leiomyoma filamin isotype purity is not independently established, so that preparation alone is not treated as target-exclusive. FLNA supplies the structural crosslinks; C-terminal deletion affects dimerization as well as partner binding. This is a core structural activity, corroborated by human FLNA assays in PMID:25358863.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0060271 cilium assembly
IMP
PMID:22121117
A meckelin-filamin A interaction mediates ciliogenesis.
KEEP AS NON CORE
Summary: cilium assembly: retained in its supported cellular or assay context.
Reason: PMID:22121117 supports meckelin-FLNA association and impaired ciliation in human mosaic patient cells, with separate mouse knockdown/embryonic observations. Retain contextual cilium-assembly involvement, distinguishing impaired from absent ciliation and association from purified binary binding. These data do not establish FLNA as a universal core ciliogenesis enzyme.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0070062 extracellular exosome
HDA
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exos...
KEEP AS NON CORE
Summary: extracellular exosome: retained in its supported cellular or assay context.
Reason: PMID:19056867 original-author urinary-exosome table independently identifies FLNA NP_001447 with one peptide, separately from FLNB. Retain the contextual extracellular-vesicle detection and original urine extension. Limited peptide depth does not establish abundance, topology or conventional secretion, and no extracellular core function is inferred.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0070062 extracellular exosome
HDA
PMID:20458337
MHC class II-associated proteins in B-cell exosomes and pote...
KEEP AS NON CORE
Summary: extracellular exosome: retained in its supported cellular or assay context.
Reason: PMID:20458337 surveys whole exosomes from human EBV-transformed B cells; that proteome is distinct from the small MHC-II co-IP subset. The exact FLNA supplement row was not independently recovered, so retention explicitly combines the curator-supported HDA assertion with independent target exosome evidence. Preserve both original contexts: one has no extension and the other carries CL:0000639, officially a basophil cell of the anterior pituitary rather than a B cell. This extension discrepancy warrants a curator question without rejecting FLNA detection or silently correcting source fields.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0070062 extracellular exosome
HDA
PMID:21362503
Protein profile of exosomes from trabecular meshwork cells.
KEEP AS NON CORE
Summary: extracellular exosome: retained in its supported cellular or assay context.
Reason: Actual PMID:21362503 Table1 identifies FLNA/P21333 in exosomes from primary human trabecular-meshwork cells and the urinary comparison. Retain the contextual location; the two-donor/three-sample design and normalized spectral measurements do not establish a universal secretory role. Vesicle-marker assays are not FLNA-specific topology tests.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0070062 extracellular exosome
HDA
PMID:23533145
In-depth proteomic analyses of exosomes isolated from expres...
KEEP AS NON CORE
Summary: extracellular exosome: retained in its supported cellular or assay context.
Reason: PMID:23533145 profiles pooled expressed-prostatic-secretion urine from healthy and cancer groups. Retain the curator-supported FLNA exosome context, corroborated independently by target exosome evidence, while noting that its exact supplemental FLNA row was not recovered. Do not infer prostate-exclusive origin, a cancer-specific abundance change or a conventional secretory function.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0070527 platelet aggregation
HMP
PMID:23382103
Platelet proteome analysis reveals integrin-dependent aggreg...
KEEP AS NON CORE
Summary: platelet aggregation: retained in its supported cellular or assay context.
Reason: PMID:23382103 reports myelodysplastic-syndrome platelet proteomics and FLNA immunoblot validation. Retain the existing non-core platelet-aggregation context in light of independent FLNA receptor/scaffold evidence. The source itself does not provide an FLNA-specific causal perturbation, and a disease-associated abundance change is not presented as such.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0071526 semaphorin-plexin signaling pathway
IGI
PMID:25358863
Amino- and carboxyl-terminal domains of Filamin-A interact w...
KEEP AS NON CORE
Summary: semaphorin-plexin signaling pathway: retained in its supported cellular or assay context.
Reason: PMID:25358863 links FLNA-CRMP1 actin organization to Sema3A responses through mouse neuronal knockdown with reported human FLNA rescue and human receptor-reconstituted cells. Retain the contextual semaphorin-plexin pathway assertion; it is not based only on worm data. CRMP1-specific mechanistic assays are not transferred to CRMP3/4, and Ig24 deletion also affects FLNA dimerization.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0072659 protein localization to plasma membrane
IDA
PMID:24951510
Functional interaction with filamin A and intracellular Ca2+...
KEEP AS NON CORE
Summary: protein localization to plasma membrane: retained in its supported cellular or assay context.
Reason: PMID:24951510 combines human SK2/FLNA coexpression and mouse cardiomyocyte knockdown with surface-channel measurements and apamin-sensitive currents. This supports contextual channel localization and positive potassium transport regulation through channel abundance. Increased delivery versus reduced removal is not fully distinguished, and calcium-sensitive alpha-actinin2/CaM trafficking is not assigned to FLNA.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0090042 tubulin deacetylation
IMP
PMID:26157139
Filamin A is required in injured axons for HDAC5 activity an...
KEEP AS NON CORE
Summary: FLNA organizes local HDAC5-dependent tubulin deacetylation at injured axon tips.
Reason: PMID:26157139 supports a structural contribution through FLNA-dependent positioning of HDAC5 at microtubule-containing injury tips. In mouse sensory neurons, either FLNA depletion or an HDAC5 C-terminal interaction competitor reduces local HDAC5 accumulation and injury-induced tubulin deacetylation. Human M2/A7 experiments separately show that FLNA-dependent deacetylation is distinguishable from HDAC5 nuclear export. Retain this contextual process involvement: FLNA organizes the local enzyme-substrate compartment, while HDAC5 supplies deacetylase activity.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0090307 mitotic spindle assembly
IDA
PMID:18548008
A B-Myb complex containing clathrin and filamin is required ...
KEEP AS NON CORE
Summary: mitotic spindle assembly: retained in its supported cellular or assay context.
Reason: PMID:18548008 identifies human FLNA in the cytosolic B-Myb/clathrin complex and separates mitotic effects from B-Myb transcriptional effects. B-Myb M14 perturbs association, and mouse replacement experiments support a mitotic role; these are not an isolated FLNA knockout/rescue. Retain contextual spindle-assembly involvement without asserting stable spindle enrichment or membership in nuclear Myb-MuvB.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0097368 establishment of Sertoli cell barrier
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: establishment of Sertoli cell barrier: retained in its supported cellular or assay context.
Reason: Verified rat donor PMID:22872576 reports FLNA RNAi in Sertoli cultures and immature testes, disorganized F-actin, barrier defects and redistribution of occludin/ZO1/JAM-A. FLNA supplies the actin scaffold; bundle organization and actin/cortical location are core, while developmental barrier assembly and junction-protein localization are contextual. GO:1902396 includes maintenance at junctions and does not require a transport motor. The human rows remain transferred evidence, and later developmental recovery limits a universal barrier requirement.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0097440 apical dendrite
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: apical dendrite: retained in its supported cellular or assay context.
Reason: PMID:22434607 reports mature rat tissue and three-to-four-week hippocampal cultures, two N/C-terminal FLNA antibodies, expected-size bands and corroborating in-situ hybridization. Soma/apical dendritic-shaft puncta support this contextual neuronal location transferred to human. Minimal mature-spine signal in that experiment does not negate later higher-resolution remodeling-spine evidence or define a natural human isoform.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0098794 postsynapse
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: postsynapse: retained in its supported cellular or assay context.
Reason: Rat donor PMID:26972007 reports endogenous hippocampal FLNA puncta in filopodia/spine heads by structured-illumination microscopy, with separate mouse tagged-FLNA/PSD experiments. Retain the contextual synaptic locations transferred to human. Developmental/imaging differences from mature-rat shaft localization do not establish universal absence from either compartment; PHD2/VHL partner activities are not assigned to FLNA.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0098978 glutamatergic synapse
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: glutamatergic synapse: retained in its supported cellular or assay context.
Reason: Rat donor PMID:26972007 reports endogenous hippocampal FLNA puncta in filopodia/spine heads by structured-illumination microscopy, with separate mouse tagged-FLNA/PSD experiments. Retain the contextual synaptic locations transferred to human. Developmental/imaging differences from mature-rat shaft localization do not establish universal absence from either compartment; PHD2/VHL partner activities are not assigned to FLNA.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:0140297 DNA-binding transcription factor binding
IPI
PMID:15684392
FOXC1 transcriptional regulatory activity is impaired by PBX...
KEEP AS NON CORE
Summary: DNA-binding transcription factor binding: retained in its supported cellular or assay context.
Reason: PMID:15684392 supports FLNA association with FOXC1 by human NPCE affinity purification, human HeLa co-IP and mouse C2C12 endogenous nuclear co-IP. These source-specific experiments support non-core transcription-factor binding but do not demonstrate purified binary kinetics or a universal nuclear transcription function.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:0140311 protein sequestering activity
IMP
PMID:17536008
Roles of protein kinase C and actin-binding protein 280 in t...
KEEP AS NON CORE
Summary: protein sequestering activity: retained in its supported cellular or assay context.
Reason: PMID:17536008 reports PMA-induced D3 receptor sequestration in reconstituted A7 but not FLNA-deficient M2 cells, with receptor surface expression in both backgrounds. Ligand-accessibility assays, imaging and co-IP support the existing context-dependent sequestering activity. FLNA is not inferred to be the kinase; purified binary affinity, universal surface-delivery dependence and natural-product specificity were not established.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:1900026 positive regulation of substrate adhesion-dependent cell spreading
IMP
PMID:18177638
Filamin A regulates cell spreading and survival via beta1 in...
KEEP AS NON CORE
Summary: positive regulation of substrate adhesion-dependent cell spreading: retained in its supported cellular or assay context.
Reason: The verified PMID:18177638 abstract reports human gingival-fibroblast and HEK293 FLNA knockdown with reduced collagen-associated spreading, integrin association and increased TUNEL-positive spreading cells. These support contextual adhesion/integrin signaling and survival functions. Full Methods, rescue design and a specific apoptotic mechanism were not independently recovered; calcium-chelation results do not establish that FLNA is a calcium sensor.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:1901381 positive regulation of potassium ion transmembrane transport
IDA
PMID:24951510
Functional interaction with filamin A and intracellular Ca2+...
KEEP AS NON CORE
Summary: positive regulation of potassium ion transmembrane transport: retained in its supported cellular or assay context.
Reason: PMID:24951510 combines human SK2/FLNA coexpression and mouse cardiomyocyte knockdown with surface-channel measurements and apamin-sensitive currents. This supports contextual channel localization and positive potassium transport regulation through channel abundance. Increased delivery versus reduced removal is not fully distinguished, and calcium-sensitive alpha-actinin2/CaM trafficking is not assigned to FLNA.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:1902396 protein localization to bicellular tight junction
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: protein localization to bicellular tight junction: retained in its supported cellular or assay context.
Reason: Verified rat donor PMID:22872576 reports FLNA RNAi in Sertoli cultures and immature testes, disorganized F-actin, barrier defects and redistribution of occludin/ZO1/JAM-A. FLNA supplies the actin scaffold; bundle organization and actin/cortical location are core, while developmental barrier assembly and junction-protein localization are contextual. GO:1902396 includes maintenance at junctions and does not require a transport motor. The human rows remain transferred evidence, and later developmental recovery limits a universal barrier requirement.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:1905000 regulation of membrane repolarization during atrial cardiac muscle cell action potential
IC
GO_REF:0000111
KEEP AS NON CORE
Summary: regulation of membrane repolarization during atrial cardiac muscle cell action potential: retained in its supported cellular or assay context.
Reason: PMID:24951510 supports FLNA-dependent SK2 surface abundance and current in human constructs/cells and mouse cardiomyocytes. Retain the existing contextual cardiac-repolarization inference, with the atrial IC row preserving its asserted GO:1905031 source. Whole-cell currents were measured at fixed potentials, not a direct FLNA action-potential-duration experiment; mouse-to-human transfer and downstream physiology remain explicit.
Supporting Evidence:
GO_REF:0000111
file:human/FLNA/FLNA-source-evidence.md
GO:1905031 regulation of membrane repolarization during cardiac muscle cell action potential
ISS
PMID:24951510
Functional interaction with filamin A and intracellular Ca2+...
KEEP AS NON CORE
Summary: regulation of membrane repolarization during cardiac muscle cell action potential: retained in its supported cellular or assay context.
Reason: PMID:24951510 supports FLNA-dependent SK2 surface abundance and current in human constructs/cells and mouse cardiomyocytes. Retain the existing contextual cardiac-repolarization inference, with the atrial IC row preserving its asserted GO:1905031 source. Whole-cell currents were measured at fixed potentials, not a direct FLNA action-potential-duration experiment; mouse-to-human transfer and downstream physiology remain explicit.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:1990779 glycoprotein Ib-IX-V complex
NAS
PMID:16293600
The structure of the GPIb-filamin A complex.
KEEP AS NON CORE
Summary: glycoprotein Ib-IX-V complex: retained in its supported cellular or assay context.
Reason: PMID:16293600 combines recombinant human FLNA/receptor-tail evidence with native human platelet GPIb-FLNA complex purification, supporting stable association at the receptor-cytoskeleton interface. Retain the contextual complex assertion without making FLNA an integral membrane receptor subunit. Repeat mutations, CHO expression and cross-reactive endogenous hamster filamin detection are separate from human native-complex evidence.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:2000179 positive regulation of neural precursor cell proliferation
IEA
GO_REF:0000107
UNDECIDED
Summary: positive regulation of neural precursor cell proliferation: source-specific evidence remains unresolved.
Reason: Rat donor PMID:22076441 reports altered neural progenitor cell-cycle progression after Flna knockdown, but the precise positive-proliferation direction and assay interpretation could not be established from the recovered abstract. Keep this existing human transfer UNDECIDED rather than infer a sign from disrupted development or reject the curators without the relevant experiment.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md
GO:2001046 positive regulation of integrin-mediated signaling pathway
IMP
PMID:18177638
Filamin A regulates cell spreading and survival via beta1 in...
KEEP AS NON CORE
Summary: positive regulation of integrin-mediated signaling pathway: retained in its supported cellular or assay context.
Reason: The verified PMID:18177638 abstract reports human gingival-fibroblast and HEK293 FLNA knockdown with reduced collagen-associated spreading, integrin association and increased TUNEL-positive spreading cells. These support contextual adhesion/integrin signaling and survival functions. Full Methods, rescue design and a specific apoptotic mechanism were not independently recovered; calcium-chelation results do not establish that FLNA is a calcium sensor.
Supporting Evidence:
file:human/FLNA/FLNA-source-evidence.md
GO:2001224 positive regulation of neuron migration
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: positive regulation of neuron migration: retained in its supported cellular or assay context.
Reason: The verified rat donor PMID:22076441 reports in-utero Flna knockdown, disrupted polarized radial-glial scaffolds and impaired cortical migration, with a separate developmental-expression context. This supports contextual scaffold/cortex/migration involvement transferred to human. Human pathological observations are not human knockdown experiments. Only the original abstract was recovered; detailed rescue and cell-cycle direction are not asserted.
Supporting Evidence:
GO_REF:0000107
file:human/FLNA/FLNA-source-evidence.md

Core Functions

Binds F-actin and crosslinks filaments through dimeric FLNA, organizing cytoskeletal networks at the cell cortex and adhesion sites and connecting these networks to membrane-associated partners.

Supporting Evidence:

Links the cortical actin network to integrin cytoplasmic tails, allowing receptor-tail association to respond to mechanical strain in the network.

Supporting Evidence:

References

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Suggested Questions for Experts

Q: Can the original PMID:17408621 cyclin-fragment assay be reconciled with the curated O95067/CCNB2 partner, given that the exact recorded Figure 3A fragment matches indexed CCNB1 Methods/Results? Preserve the original partner until curator resolution.

Q: Do the original occurrence extensions for PMID:16862148 (GO:0005642 annulate lamellae) and PMID:20458337 (CL:0000639 basophil cell of anterior pituitary) reflect the intended peripheral-lamella/B-cell contexts? The binding and exosome assertions remain separate from these extension questions.

Q: Can the source-specific nuclear extension of the PMID:28297718 DND1 association be verified independently of the later PMID:30021884 nuclear crosslink experiment?

Q: Can the original FLNA target evidence resolve cadherin binding (PMID:25468996), positive NF-kappaB signaling (PMID:12761501), megakaryocyte development and calcium-store release (PMID:16293600), and the positive neural-precursor proliferation direction transferred from PMID:22076441?

Q: Does FLNA perform directed Fc gamma RI transport in addition to surface retention and lysosomal protection, and what explains the isolated in-vitro sign discrepancy in PMID:22307607?

Q: Which endogenous contexts distinguish the three natural FLNA products? Engineered deletions and proteolytic C-terminal fragments should be separated from natural splice products.

πŸ“š Additional Documentation

Notes

(FLNA-notes.md)

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Source Evidence

(FLNA-source-evidence.md)

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Source Guide

(FLNA-source-guide.md)

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πŸ“„ View Raw YAML

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