CORO1A

Summary: Preserve the source-specific NOT annotation for immunological synapse formation.

Reason: Human NK-cell depletion and patient studies distinguish forming a target-cell synapse from remodeling its actin meshwork for granule access. CORO1A deficiency impairs the latter without abolishing synapse formation; this existing negation is not a denial of its positive synaptic localization or degranulation role.

Summary: CORO1A localizes to the lytic immunological synapse.

Reason: The human NK-cell source directly localizes CORO1A in the synaptic actin network. The functional evidence concerns meshwork organization and granule access, not formation of the synapse itself.

Summary: Retain the orthology-supported immunological-synapse location.

Reason: The paired mouse CORO1A identity and current same-term IDA record were checked. Independent human NK-cell localization supports the conclusion; the historical Ensembl Compara alignment/release was not reconstructed.

Summary: The cited study links p57 phosphorylation and coat release to phagosome maturation but does not isolate a CORO1A fusion function.

Reason: GO:0001845 describes phagosome–lysosome fusion. In differentiated human HL60 cells, PKC inhibitors retained p57 and F-actin on phagosomes and reduced LAMP1 recruitment. Purified p57 was phosphorylated by PKC, but the authors explicitly allow effects through other substrates, including MARCKS and pleckstrin. These positive temporal and biochemical observations do not distinguish a CORO1A-specific contribution to fusion from the broader kinase perturbation. This source-specific over-annotation judgment does not deny its phagosomal association. The original Discussion explicitly allows other PKC substrates as the cause of the inhibitor phenotype (DOI:10.1248/bpb.25.837, printed page843, Figure6 and adjacent Discussion; public original https://www.jstage.jst.go.jp/article/bpb/25/7/25_7_837/_pdf). The later mouse-macrophage infection study, PMID:17632055, reports coronin-dependent calcium/calcineurin signaling that inhibits lysosomal delivery of mycobacteria. Its complete abstract is available, but original full text was not recovered here. That infection-specific inhibitory context is not a disproof of all positive CORO1A contributions to phagosome maturation; this overannotation judgment remains specific to the unresolved causal attribution in the human PKC-inhibitor experiment.

Summary: CORO1A accumulates at phagocytic cups in human neutrophils.

Reason: Actual primary imaging supports cup localization during particle uptake. The localization assertion is retained separately from the dominant-negative construct effects, which can interfere with more than one coronin.

Summary: Retain RNA binding detected by the HeLa mRNA-interactome capture study.

Reason: Original Table S1 row 183 explicitly lists CORO1A in the mRNA interactome, with significant ion-count enrichment (adjusted P=0.00245116), despite not meeting the separately displayed identification threshold in the crosslinked or control columns. The study explains this enriched-but-not-identified subset. UV crosslinking, stringent oligo(dT) purification and RNase release support a direct RNA-contact observation, without establishing an RNA-regulatory mechanism or principal CORO1A function.

Summary: Retain actin binding with both filament and isolated-monomer assay support.

Reason: The original phosphorylation study tests human CORO1A and its C-terminal fragment. Full-length protein co-sediments with F-actin, while the immunopurified 372–461 fragment captures added G-actin. The broad term covers these distinct observed interactions; it does not imply identical phosphorylation sensitivity or physiological roles.

Summary: The isolated human C-terminal fragment binds actin monomers.

Reason: The actual Methods and Results use immunopurified EGFP-p57LZ residues 372–461 and added G-actin, with T412A/T412D comparisons. Retain the positive fragment-scoped observation, but do not extrapolate its monomer-binding regulation to intact endogenous protein or claim that Thr412 phosphorylation suppresses full-length F-actin binding.

Summary: Retain association with the NCF1-containing phox complex.

Reason: The original mammalian-cell study reports coronin association with p47phox/NCF1-containing material and separates phox-associated and phox-free coronin pools. NCF1 is a noncatalytic organizer subunit, and the experiment does not establish a distinct catalytic or adaptor molecular activity of CORO1A.

Summary: Refine the positive bacterial LpdC interaction to enzyme binding.

Reason: The original study identifies mycobacterial dihydrolipoyl dehydrogenase and shows cholesterol-dependent capture with GST-coronin and GST controls. LpdC/P9WHH9 is an experimentally characterized enzyme; that participant class supports the replacement. The cellular experiments use mouse J774 cells, and the recovered GST-coronin Methods do not explicitly identify its species, so the original human curator mapping is preserved without inventing a human reagent or a general host physiological role.

Proposed replacements: enzyme binding

Summary: Refine the STAT3 interaction to STAT-family protein binding.

Reason: The exact source has two positive records for canonical human CORO1A and STAT3, from two-hybrid and pull-down assays; both participant sequence checksums match the official products. The current term specifically names STAT-family partners and is more informative than generic protein binding. It does not assign STAT transcriptional activity or a native signaling mechanism to CORO1A.

Proposed replacements: STAT family protein binding

Summary: Retain the source-specific positive FSD2 interaction.

Reason: The exact CORO1A–FSD2/A1L4K1 record is preserved with its assay and product mapping. The current official record does not establish a more precise molecular-activity class for FSD2; its structural motifs or inferred muscle localization alone do not justify a regulatory-partner label. The interaction remains positive at the tested scope.

Summary: Refine the GM130 interaction to cytoskeletal-regulatory protein binding.

Reason: All three source records match canonical human GOLGA2/GM130 and CORO1A products. The official experimentally supported GM130 functional record describes microtubule nucleation/capture and centrosome organization, beyond merely Golgi localization. This supports the partner class under the actual GO definition; it does not show that CORO1A performs GM130 tethering or microtubule functions.

Proposed replacements: cytoskeletal regulatory protein binding

Summary: Retain the source-specific positive FSD2 interaction.

Reason: The exact CORO1A–FSD2/A1L4K1 record is preserved with its assay and product mapping. This variant-interaction record includes the annotated FSD2 substitutions and is not a new test of every allele. The current official record does not establish a more precise molecular-activity class for FSD2; its structural motifs or inferred muscle localization alone do not justify a regulatory-partner label. The interaction remains positive at the tested scope.

Summary: Retain the source-specific positive FSD2 interaction.

Reason: The exact CORO1A–FSD2/A1L4K1 record is preserved with its assay and product mapping. The current official record does not establish a more precise molecular-activity class for FSD2; its structural motifs or inferred muscle localization alone do not justify a regulatory-partner label. The interaction remains positive at the tested scope.

Summary: Refine the MAGEA11 interaction to transcription-coactivator binding.

Reason: The three exact HuRI records specify MAGEA11 residues 111–429. This retains the MAGE region; the original activity study independently tests the corresponding short 112–429 form in androgen-receptor interaction assays, while curated experimental evidence establishes MAGEA11 as an androgen-receptor coactivator. The class refinement describes the bound partner, not a transcriptional role or physiological nuclear contact by CORO1A.

Proposed replacements: transcription coactivator binding

Summary: Retain the positive interaction with IFT20 isoform 3.

Reason: Three exact HuRI records match the reconstructed 148-residue Q8IY31-3 product, including its official alternative-sequence change. IFT20 participation in intraflagellar transport does not by itself establish a more precise binding-activity class, and this screen does not demonstrate ciliary transport by CORO1A.

Summary: Retain the positive APP interaction at the recorded assay scope.

Reason: The three exact interaction records match the APP reference sequence and retain their residue 670–671 mutation feature. APP is a processed precursor with multiple product-dependent functions; the screen does not identify a particular processed ligand activity or establish protease binding. Preserve the positive interaction without assigning a neuronal disease mechanism to CORO1A.

Summary: Retain the directly tested interaction with p40phox/NCF4.

Reason: The original work uses human neutrophil material and recombinant components. Immobilized phox proteins and GST controls identify p40phox and its C-terminal region as coronin-binding material under the tested conditions. NCF4 is a noncatalytic oxidase-complex subunit; association does not make CORO1A an oxidase or prove a distinct adaptor mechanism.

Summary: Preserve the original NOT-nucleus staining result.

Reason: The source explicitly excludes nuclear CORO1A staining in the studied HL60 cells and rat microglia. The original annotation is negated, not a positive nuclear-localization assertion. Retention is confined to this evidence context and does not manufacture a universal absence across cell types or conditions.

Summary: CORO1A has a cytoplasmic pool in the examined cells and tissues.

Reason: Actual human-cell/tissue immunostaining supports cytoplasmic as well as peripheral staining. Cytoplasmic localization is compatible with dynamic association with cortical structures; it is not restricted to an insoluble actin-bound fraction.

Summary: Retain early-endosome localization transferred from mouse CORO1A.

Reason: The exact mouse donor carries IDA from the signaling-endosome study, whose abstract explicitly identifies mouse sympathetic neurons and CORO1A recruitment. This is a scoped ortholog-based neuronal location, not direct human endosome imaging or a claim that every CORO1A pool is endosomal.

Summary: Retain cytosolic participation in the curated LpdC–CORO1A binding event.

Reason: The current Reactome event names human CORO1A and mycobacterial LpdC as cytosolic inputs and their complex as output. This supports the location assertion in an infection-related model; it neither establishes an endogenous host enzyme activity nor resolves every species detail of the underlying experimental reagent.

Summary: Specify the cortical actin cytoskeleton within the broad cytoskeleton mapping.

Reason: The UniProt subcellular-vocabulary mapping is biologically sound but broad. Native and perturbation studies identify cortical actin-associated CORO1A in leukocyte contexts, supporting the more informative location. This does not imply that all cellular CORO1A is continuously F-actin bound.

Proposed replacements: cortical actin cytoskeleton

Summary: Retain inherited actin-filament association.

Reason: The current target and family records include experimental actin-filament evidence, consistent with the direct CORO1A assays. The target appearing among PAINT evidence sources is legitimate experimental grounding, not circularity. Historical node placement and alignment were not independently reconstructed.

Summary: Retain actin-filament association observed in the native-coronin study.

Reason: The original study links leukocyte coronin to actin filaments and membrane-associated structures, with mouse J774 and defined C-terminal peptide contexts distinguished. It supports the location/association while not proving one universal human oligomer stoichiometry.

Summary: Retain the phylogenetically supported plasma-membrane association.

Reason: Current donor and target records, including independent human imaging, support membrane-associated CORO1A. The PAINT node is retained without reconstructing its historical placement or treating self-source evidence as circular. The qualifier is preserved and is not used to infer a molecular activity.

Summary: Human immunostaining supports plasma-membrane-associated CORO1A.

Reason: The actual source detects strong peripheral staining in human tissues together with cytoplasmic signal. This is peripheral association rather than transmembrane topology, and nuclear exclusion is recorded separately.

Summary: CORO1A is recruited to peripheral structures during neutrophil responses.

Reason: The original human-neutrophil localization experiments support plasma-membrane-associated protein at protrusions and phagocytic sites. The assertion does not require permanent membrane residence.

Summary: Retain the mouse-to-human membrane-localization transfer.

Reason: The resolved mouse donor carries experimental plasma-membrane records, and independent human staining supports the same location. This Ensembl Compara inference is distinguished from PAINT ancestral-node propagation.

Summary: Retain the ortholog-supported cell-junction location as a context-specific assertion.

Reason: The current mouse CORO1A donor has a same-term IDA record from the T-cell costimulation study. Its abstract foregrounds Rltpr, which is not evidence that CORO1A was absent from the full experiments; the exact target image was not independently recovered. Independent synaptic/peripheral biology is compatible, without asserting direct human junction imaging from that source.

Summary: Specify the actin component of the cell cortex.

Reason: The source is a subcellular-vocabulary mapping rather than an experimental donor transfer. Cortical actin association is directly supported and provides greater specificity than the undifferentiated cortex location, while the mobile cytoplasmic pool remains recognized.

Proposed replacements: cortical actin cytoskeleton

Summary: Retain a role in phagocytosis within the human-neutrophil experiments.

Reason: The original localization and dominant-negative studies connect coronin-dependent actin remodeling to particle uptake. The dominant-negative WD fragment may inhibit more than one coronin, so its effects are not attributed exclusively to selective CORO1A loss, nor interpreted as a phagocytic receptor activity.

Summary: Retain inherited actin-filament organization.

Reason: The term includes arranging actin filaments into networks, and direct CORO1A biochemical and NK-cell studies support that biological role. Current donor records provide additional context; neither donor counts nor uninspected historical PAINT placement are used to invent a propagation failure.

Summary: Specify actin-filament binding within cytoskeletal-protein binding.

Reason: The exact mouse CORO1A donor carries experimental cytoskeletal-binding evidence. Independent human F-actin assays resolve the more precise ligand class; the change does not transfer a motor or another cytoskeletal enzyme activity. The source is automatic Ensembl Compara transfer.

Proposed replacements: actin filament binding

Summary: Specify actin-filament binding within cytoskeletal-protein binding.

Reason: The exact mouse CORO1A donor carries experimental cytoskeletal-binding evidence. Independent human F-actin assays resolve the more precise ligand class; the change does not transfer a motor or another cytoskeletal enzyme activity. The source is curator-reviewed sequence-similarity transfer.

Proposed replacements: actin filament binding

Summary: Retain actin-cytoskeleton association supported by the mouse ortholog and human evidence.

Reason: The current mouse donor has the same-term IDA record, while the human binding and NK-cell studies independently support CORO1A in actin-associated structures. This does not equate the whole cytoplasmic protein pool with the cytoskeleton.

Summary: Retain the membrane-proteome detection as a non-core location.

Reason: The YTS membrane-proteomics abstract includes stably or transiently associated proteins, not only integral proteins. The exact CORO1A supplementary row was not recovered, but independent membrane-associated imaging supports the location; retain the curator assertion without claiming target peptide verification or transmembrane topology.

Summary: Retain a conserved contribution to cell migration.

Reason: The term concerns controlled cell movement. Mouse CORO1A mutant/complementation and localization studies support migration, together with human-neutrophil coronin perturbation. The PAINT evidence is retained at its phylogenetic scope; current missing donor-term records are not proof of a historical placement error.

Summary: Retain inherited lamellipodial localization with target-specific support.

Reason: The target itself has a direct lamellipodium annotation from the human-neutrophil study, legitimately contributing to the ancestral inference. The current family records support peripheral protrusion localization; historical PAINT placement was not reread.

Summary: Human-neutrophil imaging supports lamellipodial CORO1A.

Reason: The source localizes coronin at actin-rich protrusions during stimulated movement. This cell-state-specific observation is retained despite later evidence that bulk endogenous CORO1A in other tested settings is not predominantly actin associated.

Summary: Retain the ARBA lamellipodium prediction with independent experimental support.

Reason: The current rule matches the target coronin FunFam and primate condition set. The location is independently supported by human-neutrophil imaging, so the prediction is not accepted merely because a rule emitted it.

Summary: Retain CORO1A-associated actin-cytoskeleton organization.

Reason: The original human protein inhibits Arp2/3-dependent nucleation in a purified assay, and cellular experiments connect coronin perturbation to actin-rich structures. The dominant-negative cellular construct can affect multiple coronins; the specific biochemical result and human NK-cell remodeling evidence provide independent grounding.

Summary: Retain the ortholog-supported axonal location.

Reason: The actual mouse donor has IDA from the neuronal signaling-endosome study. Its original abstract explicitly places CORO1A in mouse sympathetic-neuron endosomal biology. This supports a context-specific ortholog transfer, not a universal human axonal location or a conclusion from leukocyte expression alone.

Summary: Retain phagocytic-vesicle membrane association.

Reason: The subcellular-location mapping is consistent with the observed transient coronin coat on nascent phagosomes. Association and coat release are distinct from being an integral membrane protein or directly catalyzing phagosome–lysosome fusion.

Summary: Retain cortical actin association in leukocyte contexts.

Reason: The actual native-coronin and defined-coiled-coil study supports membrane-proximal actin association. The mouse-cell and isolated-peptide scope is distinguished from claiming that every human pool has fixed oligomeric architecture.

Summary: CORO1A participates in the cortical actin network at the NK-cell lytic synapse.

Reason: Human depletion and patient observations link CORO1A to fine meshwork remodeling and granule access. This supports the specified location and functional context without asserting direct severing chemistry.

Summary: Retain leading-edge localization transferred from the mouse ortholog.

Reason: The current mouse donor carries an IDA record from an actual study of migrating T cells; wild-type and E26K localization differ. Independent human-neutrophil protrusion observations are consistent, while the historical Compara alignment itself was not re-created.

Summary: Retain the adhesion phenotype at its experimental scope.

Reason: The human-neutrophil study connects coronin perturbation with cell-substrate attachment. This is a downstream cellular behavior associated with cytoskeletal remodeling, and the dominant-negative construct is not selective for CORO1A. It does not establish a cell-surface adhesion receptor activity.

Summary: Retain association with myosin heavy chain MYH9.

Reason: Actual native HL60 co-immunoprecipitation followed by protein identification supports association. The experiment does not resolve a direct binary interface or demonstrate that CORO1A is a myosin motor, cargo adaptor or contractile enzyme.

Summary: CORO1A regulates actin-network organization at the human lytic synapse.

Reason: The human NK-cell study directly measures local actin-network organization: CORO1A deficiency increases cortical F-actin density while reducing area, volume and granule-permissive clearances. Bulk G/F-actin distribution and total synaptic F-actin are not increased. Jasplakinolide phenocopy supports a requirement for actin dynamics, but the reported deconstruction does not resolve increased filament depolymerization rather than altered branching or meshwork rearrangement. Thus GO:0032956 remains the precise source-supported scope. GO:0030836 would not require CORO1A itself to sever filaments, but does require evidence for increased depolymerization; that particular mechanism is not established by these architecture measurements. This limitation does not negate local depolymerization as a possible contributor.

Summary: Retain membership in experimentally detected coronin-containing complexes.

Reason: The original biochemical fractionation and phox association distinguish heterogeneous coronin pools. This generic complex location remains positive without equating co-elution with a defined stoichiometric complex or with PI3K binding.

Summary: Retain self-association supported by the mouse ortholog.

Reason: The current donor has an IPI identical-protein-binding annotation from the native/peptide oligomerization study. Positive homotypic association is supported; this term appropriately avoids a fixed dimer-versus-trimer claim.

Summary: Preserve human self-association without fixing the oligomer at two subunits.

Reason: The original human full-length, deletion and leucine-mutant experiments establish homotypic interaction. Its dimer stoichiometry estimate depends on hydrodynamic sizing, whereas a subsequent mouse-native/defined-peptide AUC and EM study supports a trimer and explicitly questions the earlier sizing interpretation. Identical-protein binding captures the shared positive result without declaring every human assembly trimeric. The separate mouse-derived GO:0042802 row is retained as a distinct source assertion. This replacement preserves the human experimental self-association evidence without fixing stoichiometry; it is not a NEW annotation or a second formal core.

Proposed replacements: identical protein binding

Summary: Retain a contribution to natural-killer-cell degranulation.

Reason: Human NK-cell depletion and patient evidence support granule access and cytotoxic output through remodeling of the synaptic actin meshwork. The regulated exocytosis phenotype is retained as a specialized consequence of that cellular role, without assigning CORO1A a fusion-pore or granule-cargo activity.

Summary: The cited experiment does not support physical PI3K binding.

Reason: The original Results explicitly report failure of coronin to co-precipitate with anti-p85 immunocomplexes under the tested conditions. PI3K-dependent changes in a coronin pool and phagosomal colocalization establish regulation/context, not the physical association required by GO:0043548. Remove this citation-specific binding assertion while retaining the separate phox-complex positives. A later PI3Kδ survival-pathway paper does not establish binding in its accessible abstract; its unavailable full experiments are not declared negative. The decisive source passage is in Results3.1 (DOI:10.1016/S0014-5793(00)02220-1, publisher https://febs.onlinelibrary.wiley.com/doi/10.1016/S0014-5793(00)02220-1, indexed line149). Its original publisher text was independently checked; the short public excerpt is a quotation aid rather than independent experimental evidence.

Summary: Retain the broad innate-immune context without assigning a new immune effector mechanism.

Reason: The cited paper primarily establishes leukocyte/microglial expression and localization, and discusses coronin biology. Independent neutrophil and NK-cell experiments support innate-cell functions, while the NAS statement is broader than a defined molecular mechanism.

Summary: Retain neuronal synapse localization transferred from mouse CORO1A.

Reason: The exact donor has IDA records from the neuronal study. The original abstract distinguishes excitatory-neuron expression and synaptic physiology from leukocyte experiments; this is a context-specific ortholog inference, not direct human neuronal imaging or proof that the NK-synapse formation NOT annotation applies to neurons.

Summary: Retain localization to phagocytic vesicles in the human-neutrophil source.

Reason: The actual imaging supports transient recruitment during particle uptake. Vesicle localization is retained independently of whether the protein itself performs membrane fusion.

Summary: Retain the positive-chemotaxis phenotype with construct limits.

Reason: The original human-neutrophil experiments test directed movement toward a chemical stimulus. Coronin perturbation impairs the response, but the dominant-negative WD construct may affect several coronins; no direct chemoattractant activity is assigned to CORO1A.

Summary: Retain conserved actin-filament binding.

Reason: Direct human biochemical assays support the molecular function and legitimately contribute to the PAINT evidence alongside other species. Neither a short donor list nor target self-source is a failure. Current records were checked without claiming reconstruction of the historical node or MSA.

Summary: Human recombinant CORO1A binds F-actin.

Reason: The original biochemical work supports F-actin association, independently of its more uncertain hydrodynamic dimer estimate. Binding activity and exact oligomer stoichiometry are adjudicated separately.

Summary: Retain the original p57 F-actin-binding evidence.

Reason: The complete authentic abstract reports a cloned actin-binding human protein, consistent with later direct studies. Full original recovery remained unsuccessful, so no uninspected construct or assay detail is invented; the function is independently established.

Summary: Retain the combined electronic actin-filament-binding inference.

Reason: The current ARBA rule matches the coronin FunFam/primate branch, and the paired mouse donor has experimental F-actin evidence. The historical Ensembl mapping was not re-created. Multiple independent human assays support the conclusion beyond the electronic methods.

Summary: The comparative coronin study directly tests CORO1A F-actin binding.

Reason: Although the title emphasizes CORO1C, the actual primary experiments include human CORO1A wild-type/R29D comparators and F-actin co-sedimentation. Retain this target result; CORO1C-specific second-site cooperativity is not transferred to CORO1A.

Summary: Retain full-length human CORO1A F-actin association.

Reason: The actual study finds similar F-actin co-sedimentation for the tested wild-type and Thr412 mutant full-length proteins. Its phosphorylation-sensitive G-actin result concerns a separate C-terminal fragment, not suppression of intact-protein F-actin binding.

Summary: Specify inhibition of Arp2/3-mediated actin nucleation.

Reason: The purified assay uses human full-length GST-CORO1A with Arp2/3, VCA and pyrene actin; full-length protein inhibits nucleation while GST and the isolated WD fragment do not. The source therefore supports the pathway-specific negative-regulation term, without making CORO1A an actin-nucleating enzyme or general inhibitor of all polymerization conditions.

Proposed replacements: negative regulation of Arp2/3 complex-mediated actin nucleation

Summary: Specify the demonstrated negative regulation of Arp2/3-mediated actin nucleation.

Reason: The current ARBA rule correctly matches the target coronin FunFam/primate branch but emits an extremely broad organization term. The direct purified human-protein assay resolves the biologically supported subtype. This precision change is not a claim that the rule propagated a foreign catalytic function.

Proposed replacements: negative regulation of Arp2/3 complex-mediated actin nucleation

Summary: Retain CORO1A detected in purified human B-cell exosomes.

Reason: The recovered original Figure 2 lists CORO1A among detected exosome proteins. Methods describe human RN B-cell material, differential centrifugation, sucrose-gradient separation and MHCII immunoadsorption; the dataset requires two unique peptides in at least two of three experiments. This supports fraction localization, not a CORO1A-specific exosome-biogenesis mechanism in that paper.

Summary: Retain the EPS-urine exosome detection with its source limits.

Reason: The full main text describes pooled human samples, differential ultracentrifugation, duplicate MS and a below 1% identification FDR. The exact CORO1A supplementary row was not recovered, so no peptide, isoform or patient-group quantitation is claimed. The curator location is consistent with independently verified B-cell exosome detection and remains non-core; fluid detection does not establish prostate-cell origin.

Summary: Retain the mouse-supported glutamatergic-synapse location.

Reason: The current mouse CORO1A donor carries same-term IDA evidence, and the original study explicitly distinguishes excitatory from inhibitory neuronal expression. The transfer remains non-core and species-scoped; human leukocyte expression does not refute an ortholog neuronal location.