{"gene":"CORO1C","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":2002,"finding":"The carboxyl terminus of coronin 3 (CORO1C) forms oligomers (rather than dimers as in other coronins), is sufficient to bind and cross-link F-actin in vitro, and confers membrane association in vivo; removal of the coiled-coil domain abolishes membrane localization but not in vitro F-actin binding. Cytosolic coronin 3 is highly phosphorylated, likely regulating its subcellular localization.","method":"Recombinant protein biochemistry (in vitro F-actin binding/cross-linking assay), GFP-fusion live-cell imaging, subcellular fractionation, deletion mutagenesis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with mutagenesis plus in vivo localization assays, single lab but multiple orthogonal methods","pmids":["12377779"],"is_preprint":false},{"year":2000,"finding":"CORO1C protein co-localizes with F-actin in cells and contains five N-terminal WD repeats and a C-terminal coiled-coil domain conserved among coronin family members; the gene maps to chromosome 12q24.1.","method":"Immunocytochemical staining with F-actin co-localization, FISH chromosomal mapping, cDNA sequence analysis","journal":"Cytogenetics and cell genetics","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct co-localization experiment, single lab, but no functional manipulation","pmids":["10828594"],"is_preprint":false},{"year":2005,"finding":"Full-length coronin 3 localizes to outgrowing neurites in neuro-2a and PC-12 cells, whereas truncated coronin 3 constructs efficiently suppress neurite formation, indicating a role in neuron morphogenesis. PKC activator PMA reduces coronin 3 protein levels.","method":"GFP-tagged coronin 3 overexpression and truncation mutants in differentiating neuronal cell lines, PMA treatment","journal":"The European journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — GFP-fusion localization plus dominant-negative truncation phenotype, single lab","pmids":["15813925"],"is_preprint":false},{"year":2006,"finding":"Coronin 3 interacts with the Arp2/3 complex and cofilin, and has roles in wound healing, protrusion formation, cell proliferation, cytokinesis, endocytosis, axonal growth, and secretion; actin accumulation precedes focal coronin 3 enrichment during protrusion formation, suggesting coronin 3 acts downstream of initial F-actin assembly.","method":"GFP-tagged fusion proteins, RNAi silencing, functional assays (wound healing, endocytosis), co-immunoprecipitation/pulldown for Arp2/3 and cofilin interaction","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi loss-of-function with multiple cellular phenotypes plus direct binding partners identified, single lab","pmids":["17274980"],"is_preprint":false},{"year":2008,"finding":"Coronin 3 (CORO1C) directly binds GDP-Rab27a (but not GTP-Rab27a) through its beta-propeller structure. Knockdown of coronin 3 in MIN6 pancreatic beta-cells inhibits endocytosis of phogrin (an insulin-granule-associated protein) and uptake of FM4-64; dominant-negative coronin 3 disrupting the GDP-Rab27a interaction reproduces this defect, and GDP-Rab27a mutant coexpression rescues it, placing coronin 3 downstream of the GTP-to-GDP switch of Rab27a in stimulus-endocytosis coupling.","method":"Co-immunoprecipitation, RNAi knockdown, dominant-negative constructs, fluorescent endocytosis assay (FM4-64), genetic epistasis with Rab27a mutants","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal interaction validated with dominant-negative and epistasis rescue, multiple orthogonal methods, single lab","pmids":["18768935"],"is_preprint":false},{"year":2008,"finding":"shRNA-mediated knockdown of coronin 3 in U373 and A172 human glioblastoma cells reduces cell proliferation, motility, and invasion into extracellular matrix, establishing a direct functional role for coronin 3 in glioblastoma malignant behavior.","method":"shRNA knockdown, cell proliferation assay, cell motility assay, matrix invasion assay","journal":"The Journal of pathology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean loss-of-function with defined cellular phenotypes, single lab","pmids":["18189330"],"is_preprint":false},{"year":2010,"finding":"Glucose stimulation causes redistribution of coronin 3 to the vicinity of the plasma membrane in pancreatic beta-cells in a Rab27a-dependent manner; this translocation is mimicked by GDP-Rab27a overexpression or Rab27a GAP overexpression and is blocked by Rab27a knockdown, indicating coronin 3 regulates retrograde transport of the secretory membrane downstream of Rab27a GDP loading.","method":"Immunofluorescence, GFP-fusion live-cell imaging, siRNA knockdown of Rab27a, overexpression of Rab27a mutants and GAP","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional genetic epistasis, single lab","pmids":["20362548"],"is_preprint":false},{"year":2012,"finding":"Stable knockdown of coronin 3 in gastric cancer cells inhibits migration, invasion, and liver metastasis in mice; this is associated with reduced expression of MMP-9 and cathepsin K, identified via a Tumor Metastasis PCR Array.","method":"Lentiviral shRNA knockdown, migration/invasion assays, tail-vein metastasis mouse model, PCR array","journal":"Molecular cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with in vitro and in vivo metastasis phenotype plus pathway target identification, single lab","pmids":["22974233"],"is_preprint":false},{"year":2016,"finding":"CORO1C directly binds PLS3 (plastin 3) in a calcium-dependent manner, as shown by biochemical/proteomics analysis. CORO1C overexpression restores fluid-phase endocytosis in SMN-knockdown cells by elevating F-actin amounts, and rescues the axonal truncation and branching phenotype in Smn-depleted zebrafish, placing CORO1C in the endocytosis pathway relevant to SMA pathomechanism.","method":"Proteomics, co-immunoprecipitation, fluid-phase endocytosis assay, F-actin quantification, zebrafish Smn knockdown rescue experiment","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding established by biochemistry, functional rescue in multiple systems (mammalian cells and zebrafish), multiple orthogonal methods","pmids":["27499521"],"is_preprint":false},{"year":2017,"finding":"YBX1 (YB-1) regulates CORO1C expression as an indirect downstream target; CORO1C knockdown in breast cancer cells reduces migration and invasion, and CORO1C overexpression-induced migration/invasion is abrogated by YBX1 knockdown, placing CORO1C downstream of YBX1 in a migration-promoting pathway.","method":"siRNA knockdown of YBX1 and CORO1C, luciferase reporter assay, migration and invasion assays, overexpression experiments","journal":"BMC cancer","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — epistasis established by double manipulation experiments, single lab","pmids":["28302118"],"is_preprint":false},{"year":2021,"finding":"RAD23B interacts and co-localizes with CORO1C in colorectal cancer cells; RAD23B overexpression causes CORO1C to aggregate toward the cell margin, and combined overexpression of RAD23B and/or CORO1C increases invadopodia formation and matrix degradation. RAD23B knockdown suppresses talin1/2-integrin-FAK-RhoA-Rac1-CORO1C signaling.","method":"Co-immunoprecipitation, immunofluorescence co-localization, invadopodia assay, matrix degradation assay, siRNA knockdown, xenograft mouse model","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-localization and interaction with functional gain-of-function and loss-of-function, single lab","pmids":["34062216"],"is_preprint":false},{"year":2022,"finding":"CORO1C is identified as a novel PAK4 binding partner via its C-terminal extension (CE) domain (residues 353–457). PAK4 phosphorylated on serine 99 is required for its release from microtubules (from PAK4/GEF-H1/Tctex-1 complex) and subsequent recruitment by CORO1C to the leading edge, where it regulates a CORO1C/RCC2 complex to promote gastric cancer cell migration.","method":"Co-immunoprecipitation, domain mapping (CE domain constructs), phosphomutant analysis, immunofluorescence localization, migration assays","journal":"Acta biochimica et biophysica Sinica","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding mapped to domain with phosphorylation-dependent mechanism and functional cell migration readout, single lab","pmids":["35593474"],"is_preprint":false},{"year":2022,"finding":"Conditional double knockout of Coro1B and Coro1C in cells results in altered lamellipodial protrusion dynamics due to increased branched actin density and reduced actin turnover within lamellipodia, leading to defective haptotaxis; coronin null cells show excessive cofilin accumulation in lamellipodia and increased cellular contractility. Coro1C localization to branched actin requires Arp2/3 activity.","method":"Conditional knockout cell lines, live-cell imaging of lamellipodia dynamics, F-actin quantification, fluorescence microscopy, haptotaxis assay, Arp2/3 inhibition","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — clean genetic knockout with multiple orthogonal functional readouts, mechanistic dissection of branched actin turnover","pmids":["35657370"],"is_preprint":false},{"year":2026,"finding":"CORO1C interacts with the Arp2/3 (ACTR2/ACTR3) complex, and this interaction is essential for branched actin network assembly, SQSTM1/p62 body formation, and maintaining autophagosome structural integrity. CORO1C possesses a unique second actin-binding site (absent in CORO1A and CORO1B) involved in regulating the branched actin network and autophagic process. coro1c-knockout newborn mice die earlier in starvation than wild-type and show autophagy-deficient phenotypes in multiple tissues; adult coro1c-deficient mice exhibit severe spatial learning memory impairment.","method":"Genome-wide haploid loss-of-function screen, CRISPR/KO mouse model, immunoprecipitation, immunofluorescence, transmission electron microscopy, autophagy flux assays","journal":"Autophagy","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — unbiased genome-wide screen converging on CORO1C, in vivo KO phenotype, mechanistic interaction with Arp2/3, unique second actin-binding site, multiple orthogonal methods","pmids":["41968673"],"is_preprint":false},{"year":2026,"finding":"UBC9 SUMOylates CORO1C at lysine residues K19, K311, and K440; this SUMOylation enhances CORO1C binding to the Arp2 (Arp2/3) complex, promotes actin-based cytoskeletal remodeling, and drives lung adenocarcinoma cell migration, invasion, and tumorigenesis.","method":"Immunoprecipitation-mass spectrometry identification, mutagenesis of SUMOylation sites (K19/K311/K440), functional assays (migration, invasion, proliferation), in vivo tumorigenesis, UBC9 genetic ablation","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — site-specific mutagenesis with functional readouts plus MS identification of substrate, single lab","pmids":["41912501"],"is_preprint":false}],"current_model":"CORO1C (coronin 3) is a ubiquitously expressed F-actin-binding protein that oligomerizes via its coiled-coil C-terminus, localizes to lamellipodia and the submembranous cytoskeleton, and regulates branched actin network dynamics through direct interaction with the Arp2/3 complex; it functions in endocytosis (acting downstream of GDP-Rab27a in secretory membrane recycling), autophagosome formation (via a unique second actin-binding site), cell migration and invasion (by recruiting phospho-PAK4 to the leading edge via its CE domain and coupling to MMP-9/cathepsin K upregulation), and neurite/axon morphogenesis, and is subject to regulatory SUMOylation at K19/K311/K440 by UBC9 that amplifies its Arp2/3 binding and cytoskeletal remodeling activity."},"narrative":{"mechanistic_narrative":"CORO1C (coronin 3) is a ubiquitously expressed F-actin-binding protein that governs branched actin network dynamics and couples the actin cytoskeleton to membrane trafficking, cell migration, and autophagy [PMID:12377779, PMID:35657370]. It comprises five N-terminal WD repeats forming a beta-propeller and a C-terminal coiled-coil that mediates oligomerization, F-actin cross-linking in vitro, and membrane association in vivo [PMID:12377779, PMID:10828594]. CORO1C acts downstream of initial F-actin assembly through direct interaction with the Arp2/3 complex and cofilin, and its recruitment to branched actin requires Arp2/3 activity; loss of CORO1C (together with CORO1B) increases branched actin density, reduces actin turnover, and causes cofilin accumulation and defective lamellipodial protrusion and haptotaxis [PMID:17274980, PMID:35657370]. Through its beta-propeller, CORO1C binds GDP-Rab27a but not GTP-Rab27a, functioning downstream of the Rab27a GTP-to-GDP switch to drive stimulus-coupled endocytosis and retrograde recycling of secretory membrane in pancreatic beta-cells [PMID:18768935, PMID:20362548]. A unique second actin-binding site, absent in CORO1A and CORO1B, supports SQSTM1/p62 body formation and autophagosome structural integrity, and CORO1C-knockout mice show autophagy deficiency, reduced starvation survival, and spatial learning impairment [PMID:41968673]. In cancer, CORO1C promotes migration, invasion, and metastasis: it recruits serine-99-phosphorylated PAK4 to the leading edge via its C-terminal extension domain to regulate a CORO1C/RCC2 complex [PMID:35593474], couples to MMP-9 and cathepsin K upregulation [PMID:22974233], and operates downstream of YBX1 and within RAD23B–talin/integrin–FAK–RhoA/Rac1 signaling [PMID:28302118, PMID:34062216]. CORO1C activity is amplified by UBC9-mediated SUMOylation at K19, K311, and K440, which enhances Arp2/3 binding and cytoskeletal remodeling [PMID:41912501]. It additionally binds plastin 3 (PLS3) in a calcium-dependent manner and restores endocytosis and rescues axonal defects in SMN-depleted models, linking it to spinal muscular atrophy pathomechanisms [PMID:27499521].","teleology":[{"year":2000,"claim":"Establishing CORO1C as a bona fide coronin family actin-associated protein required defining its domain architecture and cellular distribution.","evidence":"Immunocytochemical F-actin co-localization, FISH mapping, and cDNA sequence analysis","pmids":["10828594"],"confidence":"Medium","gaps":["No functional manipulation","F-actin binding inferred from co-localization, not biochemistry"]},{"year":2002,"claim":"Defined the biochemical basis of CORO1C activity: which domains drive oligomerization, F-actin cross-linking, and membrane targeting.","evidence":"In vitro F-actin binding/cross-linking with recombinant protein, GFP live-cell imaging, fractionation, deletion mutagenesis","pmids":["12377779"],"confidence":"High","gaps":["Kinase mediating the regulatory phosphorylation unidentified","Stoichiometry of oligomers not resolved"]},{"year":2005,"claim":"Extended CORO1C function to neuronal morphogenesis by showing full-length protein localizes to outgrowing neurites while truncations block neurite formation.","evidence":"GFP-tagged overexpression and dominant-negative truncation in neuronal cell lines, PMA treatment","pmids":["15813925"],"confidence":"Medium","gaps":["Relies on dominant-negative overexpression rather than loss-of-function","Molecular link to actin machinery in neurites not defined"]},{"year":2006,"claim":"Identified the core actin-regulatory partners and ordered CORO1C downstream of initial F-actin assembly during protrusion formation.","evidence":"GFP fusions, RNAi, wound healing/endocytosis assays, co-IP/pulldown for Arp2/3 and cofilin","pmids":["17274980"],"confidence":"Medium","gaps":["Many phenotypes catalogued without mechanistic dissection","Direct vs. indirect binding to Arp2/3 and cofilin not separated"]},{"year":2008,"claim":"Connected CORO1C to membrane trafficking by demonstrating nucleotide-state-specific binding to GDP-Rab27a and placing it downstream of the Rab27a GTP-to-GDP switch in endocytosis.","evidence":"Co-IP, RNAi, dominant-negative constructs, FM4-64 endocytosis assay, epistasis rescue with Rab27a mutants in beta-cells","pmids":["18768935"],"confidence":"High","gaps":["Structural basis of GDP-state recognition by the beta-propeller unresolved","Link between Rab27a binding and actin remodeling not established"]},{"year":2008,"claim":"Provided early evidence for a pro-tumorigenic role by showing CORO1C knockdown reduces glioblastoma proliferation, motility, and invasion.","evidence":"shRNA knockdown with proliferation, motility, and matrix invasion assays","pmids":["18189330"],"confidence":"Medium","gaps":["No molecular mediators identified","In vitro only"]},{"year":2010,"claim":"Showed CORO1C translocation to the plasma membrane is Rab27a-GDP-dependent, defining its role in retrograde secretory membrane transport.","evidence":"Immunofluorescence, live imaging, Rab27a siRNA and GAP/mutant overexpression in beta-cells","pmids":["20362548"],"confidence":"Medium","gaps":["Cargo specificity of retrograde transport not defined","Role of CORO1C oligomerization in translocation untested"]},{"year":2012,"claim":"Linked CORO1C to metastasis in vivo and identified MMP-9 and cathepsin K as associated downstream effectors.","evidence":"Lentiviral shRNA, migration/invasion assays, tail-vein liver metastasis mouse model, Tumor Metastasis PCR Array","pmids":["22974233"],"confidence":"Medium","gaps":["Mechanism linking CORO1C to protease expression unknown","Direct vs. indirect regulation of MMP-9/cathepsin K unresolved"]},{"year":2016,"claim":"Identified a calcium-dependent PLS3 interaction and demonstrated CORO1C can rescue endocytic and axonal defects in SMN-depleted models, implicating it in SMA pathomechanism.","evidence":"Proteomics, co-IP, fluid-phase endocytosis assay, F-actin quantification, zebrafish Smn rescue","pmids":["27499521"],"confidence":"High","gaps":["Whether CORO1C variation modifies human SMA not established","Mechanism by which CORO1C elevates F-actin in this context unclear"]},{"year":2017,"claim":"Positioned CORO1C downstream of the transcription/translation regulator YBX1 in a breast cancer migration pathway.","evidence":"siRNA of YBX1 and CORO1C, luciferase reporter, migration/invasion and overexpression epistasis assays","pmids":["28302118"],"confidence":"Medium","gaps":["Regulation stated to be indirect; intermediary factors unknown","Single cell-line context"]},{"year":2021,"claim":"Defined a RAD23B–CORO1C axis driving invadopodia and matrix degradation within talin/integrin–FAK–RhoA/Rac1 signaling.","evidence":"Co-IP, immunofluorescence co-localization, invadopodia/matrix degradation assays, siRNA, xenograft model","pmids":["34062216"],"confidence":"Medium","gaps":["Direct vs. signaling-mediated RAD23B–CORO1C coupling not fully separated","Position of CORO1C within the signaling cascade inferred"]},{"year":2022,"claim":"Mapped a direct PAK4 interaction to the CORO1C C-terminal extension domain and showed phospho-S99 PAK4 is recruited by CORO1C to the leading edge to drive migration via a CORO1C/RCC2 complex.","evidence":"Co-IP, CE domain mapping, phosphomutant analysis, immunofluorescence, migration assays","pmids":["35593474"],"confidence":"Medium","gaps":["Functional consequence of the CORO1C/RCC2 complex on actin not defined","Single-lab gastric cancer context"]},{"year":2022,"claim":"Provided clean genetic dissection of CORO1C in branched actin turnover, showing it limits branched actin density and cofilin accumulation to enable lamellipodial dynamics and haptotaxis, with Arp2/3-dependent localization.","evidence":"Conditional Coro1B/Coro1C double knockout, live imaging, F-actin quantification, haptotaxis assays, Arp2/3 inhibition","pmids":["35657370"],"confidence":"High","gaps":["Functional redundancy with CORO1B not fully separated","Molecular trigger for cofilin clearance by coronins unresolved"]},{"year":2026,"claim":"Established a CORO1C-specific second actin-binding site and Arp2/3 interaction as essential for autophagosome integrity and p62 body formation, with in vivo autophagy and learning phenotypes.","evidence":"Genome-wide haploid screen, CRISPR KO mouse, IP, immunofluorescence, TEM, autophagy flux assays","pmids":["41968673"],"confidence":"High","gaps":["Structural definition of the second actin-binding site pending","Mechanistic link from branched actin to autophagosome closure incomplete"]},{"year":2026,"claim":"Identified SUMOylation as a post-translational switch amplifying CORO1C–Arp2/3 binding and pro-tumorigenic cytoskeletal remodeling.","evidence":"IP-MS, site-specific mutagenesis (K19/K311/K440), migration/invasion/proliferation assays, in vivo tumorigenesis, UBC9 ablation","pmids":["41912501"],"confidence":"Medium","gaps":["Signals controlling CORO1C SUMOylation unknown","Whether SUMOylation regulates non-cancer functions untested"]},{"year":null,"claim":"How CORO1C's distinct activities — branched actin turnover, GDP-Rab27a-coupled trafficking, autophagosome formation, and migration — are integrated and selectively engaged by post-translational state remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No high-resolution structure of full-length CORO1C with Arp2/3 or actin","Kinases/signals dictating phosphorylation and SUMOylation context-specificity undefined","Mechanistic unification of trafficking vs. cytoskeletal vs. autophagy roles missing"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1,3,12,13]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,12,14]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1,12]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,6]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[13]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[4,6]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[5,7,9,10,14]}],"complexes":[],"partners":["ARPC (ARP2/3 COMPLEX)","CFL1","RAB27A","PLS3","PAK4","RAD23B","RCC2","UBE2I"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9ULV4","full_name":"Coronin-1C","aliases":["Coronin-3","hCRNN4"],"length_aa":474,"mass_kda":53.2,"function":"Plays a role in directed cell migration by regulating the activation and subcellular location of RAC1 (PubMed:25074804, PubMed:25925950). Increases the presence of activated RAC1 at the leading edge of migrating cells (PubMed:25074804, PubMed:25925950). Required for normal organization of the cytoskeleton, including the actin cytoskeleton, microtubules and the vimentin intermediate filaments (By similarity). Plays a role in endoplasmic reticulum-associated endosome fission: localizes to endosome membrane tubules and promotes recruitment of TMCC1, leading to recruitment of the endoplasmic reticulum to endosome tubules for fission (PubMed:30220460). Endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane (PubMed:30220460). Required for normal cell proliferation, cell migration, and normal formation of lamellipodia (By similarity). Required for normal distribution of mitochondria within cells (By similarity). Interacts with GDP-bound RAB44 in bone marrow macrophages to promote osteoclastogenesis (By similarity). Involved in the migration and chemotaxis of macrophages (By similarity) Involved in myogenic differentiation","subcellular_location":"Cell membrane, sarcolemma; Cytoplasm, myofibril, sarcomere; Synapse; Cell membrane; Cytoplasm, cytoskeleton; Cytoplasm, cell cortex","url":"https://www.uniprot.org/uniprotkb/Q9ULV4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CORO1C","classification":"Not Classified","n_dependent_lines":29,"n_total_lines":1208,"dependency_fraction":0.024006622516556293},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000110880","cell_line_id":"CID000520","localizations":[{"compartment":"membrane","grade":3},{"compartment":"vesicles","grade":3},{"compartment":"cytoplasmic","grade":1}],"interactors":[{"gene":"CAPZB","stoichiometry":0.2},{"gene":"CORO1B","stoichiometry":0.2},{"gene":"PARP1","stoichiometry":0.2},{"gene":"CTTN","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000520","total_profiled":1310},"omim":[{"mim_id":"616242","title":"TRANSMEMBRANE AND COILED-COIL DOMAIN FAMILY, MEMBER 1; TMCC1","url":"https://www.omim.org/entry/616242"},{"mim_id":"605269","title":"CORONIN 1C; CORO1C","url":"https://www.omim.org/entry/605269"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CORO1C"},"hgnc":{"alias_symbol":["coronin-3","HCRNN4"],"prev_symbol":[]},"alphafold":{"accession":"Q9ULV4","domains":[{"cath_id":"2.130.10.10","chopping":"10-171_333-407","consensus_level":"medium","plddt":95.208,"start":10,"end":407},{"cath_id":"1.20.5","chopping":"444-474","consensus_level":"medium","plddt":88.6687,"start":444,"end":474}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9ULV4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9ULV4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9ULV4-F1-predicted_aligned_error_v6.png","plddt_mean":90.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CORO1C","jax_strain_url":"https://www.jax.org/strain/search?query=CORO1C"},"sequence":{"accession":"Q9ULV4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9ULV4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9ULV4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9ULV4"}},"corpus_meta":[{"pmid":"27499521","id":"PMC_27499521","title":"The Power of Human Protective Modifiers: PLS3 and CORO1C Unravel Impaired Endocytosis in Spinal Muscular Atrophy and Rescue SMA Phenotype.","date":"2016","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27499521","citation_count":133,"is_preprint":false},{"pmid":"12377779","id":"PMC_12377779","title":"Oligomerization, F-actin interaction, and membrane association of the ubiquitous mammalian coronin 3 are mediated by its carboxyl terminus.","date":"2002","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12377779","citation_count":77,"is_preprint":false},{"pmid":"28302118","id":"PMC_28302118","title":"YBX1 gene silencing inhibits migratory and invasive potential via CORO1C in breast cancer in vitro.","date":"2017","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/28302118","citation_count":67,"is_preprint":false},{"pmid":"18768935","id":"PMC_18768935","title":"The GDP-dependent Rab27a effector coronin 3 controls endocytosis of secretory membrane in insulin-secreting cell lines.","date":"2008","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/18768935","citation_count":59,"is_preprint":false},{"pmid":"22974233","id":"PMC_22974233","title":"Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K.","date":"2012","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/22974233","citation_count":53,"is_preprint":false},{"pmid":"20690162","id":"PMC_20690162","title":"Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration.","date":"2010","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/20690162","citation_count":52,"is_preprint":false},{"pmid":"32206066","id":"PMC_32206066","title":"MiR-206 may suppress non-small lung cancer metastasis by targeting CORO1C.","date":"2020","source":"Cellular & molecular biology 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biology","url":"https://pubmed.ncbi.nlm.nih.gov/35657370","citation_count":21,"is_preprint":false},{"pmid":"33061567","id":"PMC_33061567","title":"miR-133a-3p Regulates Hepatocellular Carcinoma Progression Through Targeting CORO1C.","date":"2020","source":"Cancer management and research","url":"https://pubmed.ncbi.nlm.nih.gov/33061567","citation_count":20,"is_preprint":false},{"pmid":"35388975","id":"PMC_35388975","title":"Circ_0020123 plays an oncogenic role in non-small cell lung cancer depending on the regulation of miR-512-3p/CORO1C.","date":"2022","source":"Thoracic cancer","url":"https://pubmed.ncbi.nlm.nih.gov/35388975","citation_count":13,"is_preprint":false},{"pmid":"31595425","id":"PMC_31595425","title":"miR-26 suppresses renal cell cancer via down-regulating coronin-3.","date":"2019","source":"Molecular and cellular 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Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/35593474","citation_count":5,"is_preprint":false},{"pmid":"39278098","id":"PMC_39278098","title":"Down-regulation of CORO1C mediated by lncMALAT1/miR-133a-3p axis contributes to trophoblast dysfunction and preeclampsia.","date":"2024","source":"Placenta","url":"https://pubmed.ncbi.nlm.nih.gov/39278098","citation_count":4,"is_preprint":false},{"pmid":"37286017","id":"PMC_37286017","title":"Molecular characterization of the unusual peptide CORO1C-47aa encoded by the circular RNA and docking simulations with its binding partner.","date":"2023","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/37286017","citation_count":4,"is_preprint":false},{"pmid":"28713988","id":"PMC_28713988","title":"Coronin 3 negatively regulates G6PC3 in HepG2 cells, as identified by label‑free mass‑spectrometry.","date":"2017","source":"Molecular medicine reports","url":"https://pubmed.ncbi.nlm.nih.gov/28713988","citation_count":4,"is_preprint":false},{"pmid":"35892027","id":"PMC_35892027","title":"DLEU7-AS1 promotes renal cell cancer by silencing the miR-26a-5p/coronin-3 axis.","date":"2022","source":"Clinical kidney journal","url":"https://pubmed.ncbi.nlm.nih.gov/35892027","citation_count":3,"is_preprint":false},{"pmid":"39702523","id":"PMC_39702523","title":"The neurodevelopmental regulatory role and clinical value of hsa-circ-CORO1C-hsa-miR-708-3p-JARID2 + LNPEP axis in early-onset schizophrenia.","date":"2024","source":"Schizophrenia (Heidelberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/39702523","citation_count":3,"is_preprint":false},{"pmid":"41968673","id":"PMC_41968673","title":"CORO1C (coronin 1C) promotes autophagosome formation by coordinating branched actin network dynamics.","date":"2026","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/41968673","citation_count":0,"is_preprint":false},{"pmid":"41912501","id":"PMC_41912501","title":"UBC9-mediated SUMOylation of CORO1C drives lung adenocarcinoma progression via Arp2/3-dependent cytoskeletal remodeling.","date":"2026","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/41912501","citation_count":0,"is_preprint":false},{"pmid":"38414760","id":"PMC_38414760","title":"Coronin 3 Promotes the Development of Oncogenic Properties in Glioma Through the Wnt/β-Catenin Signaling Pathway [Retraction].","date":"2024","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/38414760","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":19264,"output_tokens":3997,"usd":0.058874,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11717,"output_tokens":4703,"usd":0.08808,"stage2_stop_reason":"end_turn"},"total_usd":0.146954,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"The carboxyl terminus of coronin 3 (CORO1C) forms oligomers (rather than dimers as in other coronins), is sufficient to bind and cross-link F-actin in vitro, and confers membrane association in vivo; removal of the coiled-coil domain abolishes membrane localization but not in vitro F-actin binding. Cytosolic coronin 3 is highly phosphorylated, likely regulating its subcellular localization.\",\n      \"method\": \"Recombinant protein biochemistry (in vitro F-actin binding/cross-linking assay), GFP-fusion live-cell imaging, subcellular fractionation, deletion mutagenesis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with mutagenesis plus in vivo localization assays, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"12377779\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"CORO1C protein co-localizes with F-actin in cells and contains five N-terminal WD repeats and a C-terminal coiled-coil domain conserved among coronin family members; the gene maps to chromosome 12q24.1.\",\n      \"method\": \"Immunocytochemical staining with F-actin co-localization, FISH chromosomal mapping, cDNA sequence analysis\",\n      \"journal\": \"Cytogenetics and cell genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct co-localization experiment, single lab, but no functional manipulation\",\n      \"pmids\": [\"10828594\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Full-length coronin 3 localizes to outgrowing neurites in neuro-2a and PC-12 cells, whereas truncated coronin 3 constructs efficiently suppress neurite formation, indicating a role in neuron morphogenesis. PKC activator PMA reduces coronin 3 protein levels.\",\n      \"method\": \"GFP-tagged coronin 3 overexpression and truncation mutants in differentiating neuronal cell lines, PMA treatment\",\n      \"journal\": \"The European journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — GFP-fusion localization plus dominant-negative truncation phenotype, single lab\",\n      \"pmids\": [\"15813925\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Coronin 3 interacts with the Arp2/3 complex and cofilin, and has roles in wound healing, protrusion formation, cell proliferation, cytokinesis, endocytosis, axonal growth, and secretion; actin accumulation precedes focal coronin 3 enrichment during protrusion formation, suggesting coronin 3 acts downstream of initial F-actin assembly.\",\n      \"method\": \"GFP-tagged fusion proteins, RNAi silencing, functional assays (wound healing, endocytosis), co-immunoprecipitation/pulldown for Arp2/3 and cofilin interaction\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi loss-of-function with multiple cellular phenotypes plus direct binding partners identified, single lab\",\n      \"pmids\": [\"17274980\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Coronin 3 (CORO1C) directly binds GDP-Rab27a (but not GTP-Rab27a) through its beta-propeller structure. Knockdown of coronin 3 in MIN6 pancreatic beta-cells inhibits endocytosis of phogrin (an insulin-granule-associated protein) and uptake of FM4-64; dominant-negative coronin 3 disrupting the GDP-Rab27a interaction reproduces this defect, and GDP-Rab27a mutant coexpression rescues it, placing coronin 3 downstream of the GTP-to-GDP switch of Rab27a in stimulus-endocytosis coupling.\",\n      \"method\": \"Co-immunoprecipitation, RNAi knockdown, dominant-negative constructs, fluorescent endocytosis assay (FM4-64), genetic epistasis with Rab27a mutants\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal interaction validated with dominant-negative and epistasis rescue, multiple orthogonal methods, single lab\",\n      \"pmids\": [\"18768935\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"shRNA-mediated knockdown of coronin 3 in U373 and A172 human glioblastoma cells reduces cell proliferation, motility, and invasion into extracellular matrix, establishing a direct functional role for coronin 3 in glioblastoma malignant behavior.\",\n      \"method\": \"shRNA knockdown, cell proliferation assay, cell motility assay, matrix invasion assay\",\n      \"journal\": \"The Journal of pathology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean loss-of-function with defined cellular phenotypes, single lab\",\n      \"pmids\": [\"18189330\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Glucose stimulation causes redistribution of coronin 3 to the vicinity of the plasma membrane in pancreatic beta-cells in a Rab27a-dependent manner; this translocation is mimicked by GDP-Rab27a overexpression or Rab27a GAP overexpression and is blocked by Rab27a knockdown, indicating coronin 3 regulates retrograde transport of the secretory membrane downstream of Rab27a GDP loading.\",\n      \"method\": \"Immunofluorescence, GFP-fusion live-cell imaging, siRNA knockdown of Rab27a, overexpression of Rab27a mutants and GAP\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional genetic epistasis, single lab\",\n      \"pmids\": [\"20362548\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Stable knockdown of coronin 3 in gastric cancer cells inhibits migration, invasion, and liver metastasis in mice; this is associated with reduced expression of MMP-9 and cathepsin K, identified via a Tumor Metastasis PCR Array.\",\n      \"method\": \"Lentiviral shRNA knockdown, migration/invasion assays, tail-vein metastasis mouse model, PCR array\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with in vitro and in vivo metastasis phenotype plus pathway target identification, single lab\",\n      \"pmids\": [\"22974233\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"CORO1C directly binds PLS3 (plastin 3) in a calcium-dependent manner, as shown by biochemical/proteomics analysis. CORO1C overexpression restores fluid-phase endocytosis in SMN-knockdown cells by elevating F-actin amounts, and rescues the axonal truncation and branching phenotype in Smn-depleted zebrafish, placing CORO1C in the endocytosis pathway relevant to SMA pathomechanism.\",\n      \"method\": \"Proteomics, co-immunoprecipitation, fluid-phase endocytosis assay, F-actin quantification, zebrafish Smn knockdown rescue experiment\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding established by biochemistry, functional rescue in multiple systems (mammalian cells and zebrafish), multiple orthogonal methods\",\n      \"pmids\": [\"27499521\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"YBX1 (YB-1) regulates CORO1C expression as an indirect downstream target; CORO1C knockdown in breast cancer cells reduces migration and invasion, and CORO1C overexpression-induced migration/invasion is abrogated by YBX1 knockdown, placing CORO1C downstream of YBX1 in a migration-promoting pathway.\",\n      \"method\": \"siRNA knockdown of YBX1 and CORO1C, luciferase reporter assay, migration and invasion assays, overexpression experiments\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistasis established by double manipulation experiments, single lab\",\n      \"pmids\": [\"28302118\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RAD23B interacts and co-localizes with CORO1C in colorectal cancer cells; RAD23B overexpression causes CORO1C to aggregate toward the cell margin, and combined overexpression of RAD23B and/or CORO1C increases invadopodia formation and matrix degradation. RAD23B knockdown suppresses talin1/2-integrin-FAK-RhoA-Rac1-CORO1C signaling.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence co-localization, invadopodia assay, matrix degradation assay, siRNA knockdown, xenograft mouse model\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-localization and interaction with functional gain-of-function and loss-of-function, single lab\",\n      \"pmids\": [\"34062216\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CORO1C is identified as a novel PAK4 binding partner via its C-terminal extension (CE) domain (residues 353–457). PAK4 phosphorylated on serine 99 is required for its release from microtubules (from PAK4/GEF-H1/Tctex-1 complex) and subsequent recruitment by CORO1C to the leading edge, where it regulates a CORO1C/RCC2 complex to promote gastric cancer cell migration.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping (CE domain constructs), phosphomutant analysis, immunofluorescence localization, migration assays\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding mapped to domain with phosphorylation-dependent mechanism and functional cell migration readout, single lab\",\n      \"pmids\": [\"35593474\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Conditional double knockout of Coro1B and Coro1C in cells results in altered lamellipodial protrusion dynamics due to increased branched actin density and reduced actin turnover within lamellipodia, leading to defective haptotaxis; coronin null cells show excessive cofilin accumulation in lamellipodia and increased cellular contractility. Coro1C localization to branched actin requires Arp2/3 activity.\",\n      \"method\": \"Conditional knockout cell lines, live-cell imaging of lamellipodia dynamics, F-actin quantification, fluorescence microscopy, haptotaxis assay, Arp2/3 inhibition\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — clean genetic knockout with multiple orthogonal functional readouts, mechanistic dissection of branched actin turnover\",\n      \"pmids\": [\"35657370\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CORO1C interacts with the Arp2/3 (ACTR2/ACTR3) complex, and this interaction is essential for branched actin network assembly, SQSTM1/p62 body formation, and maintaining autophagosome structural integrity. CORO1C possesses a unique second actin-binding site (absent in CORO1A and CORO1B) involved in regulating the branched actin network and autophagic process. coro1c-knockout newborn mice die earlier in starvation than wild-type and show autophagy-deficient phenotypes in multiple tissues; adult coro1c-deficient mice exhibit severe spatial learning memory impairment.\",\n      \"method\": \"Genome-wide haploid loss-of-function screen, CRISPR/KO mouse model, immunoprecipitation, immunofluorescence, transmission electron microscopy, autophagy flux assays\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — unbiased genome-wide screen converging on CORO1C, in vivo KO phenotype, mechanistic interaction with Arp2/3, unique second actin-binding site, multiple orthogonal methods\",\n      \"pmids\": [\"41968673\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"UBC9 SUMOylates CORO1C at lysine residues K19, K311, and K440; this SUMOylation enhances CORO1C binding to the Arp2 (Arp2/3) complex, promotes actin-based cytoskeletal remodeling, and drives lung adenocarcinoma cell migration, invasion, and tumorigenesis.\",\n      \"method\": \"Immunoprecipitation-mass spectrometry identification, mutagenesis of SUMOylation sites (K19/K311/K440), functional assays (migration, invasion, proliferation), in vivo tumorigenesis, UBC9 genetic ablation\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — site-specific mutagenesis with functional readouts plus MS identification of substrate, single lab\",\n      \"pmids\": [\"41912501\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CORO1C (coronin 3) is a ubiquitously expressed F-actin-binding protein that oligomerizes via its coiled-coil C-terminus, localizes to lamellipodia and the submembranous cytoskeleton, and regulates branched actin network dynamics through direct interaction with the Arp2/3 complex; it functions in endocytosis (acting downstream of GDP-Rab27a in secretory membrane recycling), autophagosome formation (via a unique second actin-binding site), cell migration and invasion (by recruiting phospho-PAK4 to the leading edge via its CE domain and coupling to MMP-9/cathepsin K upregulation), and neurite/axon morphogenesis, and is subject to regulatory SUMOylation at K19/K311/K440 by UBC9 that amplifies its Arp2/3 binding and cytoskeletal remodeling activity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CORO1C (coronin 3) is a ubiquitously expressed F-actin-binding protein that governs branched actin network dynamics and couples the actin cytoskeleton to membrane trafficking, cell migration, and autophagy [#0, #12]. It comprises five N-terminal WD repeats forming a beta-propeller and a C-terminal coiled-coil that mediates oligomerization, F-actin cross-linking in vitro, and membrane association in vivo [#0, #1]. CORO1C acts downstream of initial F-actin assembly through direct interaction with the Arp2/3 complex and cofilin, and its recruitment to branched actin requires Arp2/3 activity; loss of CORO1C (together with CORO1B) increases branched actin density, reduces actin turnover, and causes cofilin accumulation and defective lamellipodial protrusion and haptotaxis [#3, #12]. Through its beta-propeller, CORO1C binds GDP-Rab27a but not GTP-Rab27a, functioning downstream of the Rab27a GTP-to-GDP switch to drive stimulus-coupled endocytosis and retrograde recycling of secretory membrane in pancreatic beta-cells [#4, #6]. A unique second actin-binding site, absent in CORO1A and CORO1B, supports SQSTM1/p62 body formation and autophagosome structural integrity, and CORO1C-knockout mice show autophagy deficiency, reduced starvation survival, and spatial learning impairment [#13]. In cancer, CORO1C promotes migration, invasion, and metastasis: it recruits serine-99-phosphorylated PAK4 to the leading edge via its C-terminal extension domain to regulate a CORO1C/RCC2 complex [#11], couples to MMP-9 and cathepsin K upregulation [#7], and operates downstream of YBX1 and within RAD23B–talin/integrin–FAK–RhoA/Rac1 signaling [#9, #10]. CORO1C activity is amplified by UBC9-mediated SUMOylation at K19, K311, and K440, which enhances Arp2/3 binding and cytoskeletal remodeling [#14]. It additionally binds plastin 3 (PLS3) in a calcium-dependent manner and restores endocytosis and rescues axonal defects in SMN-depleted models, linking it to spinal muscular atrophy pathomechanisms [#8].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Establishing CORO1C as a bona fide coronin family actin-associated protein required defining its domain architecture and cellular distribution.\",\n      \"evidence\": \"Immunocytochemical F-actin co-localization, FISH mapping, and cDNA sequence analysis\",\n      \"pmids\": [\"10828594\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional manipulation\", \"F-actin binding inferred from co-localization, not biochemistry\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Defined the biochemical basis of CORO1C activity: which domains drive oligomerization, F-actin cross-linking, and membrane targeting.\",\n      \"evidence\": \"In vitro F-actin binding/cross-linking with recombinant protein, GFP live-cell imaging, fractionation, deletion mutagenesis\",\n      \"pmids\": [\"12377779\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase mediating the regulatory phosphorylation unidentified\", \"Stoichiometry of oligomers not resolved\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Extended CORO1C function to neuronal morphogenesis by showing full-length protein localizes to outgrowing neurites while truncations block neurite formation.\",\n      \"evidence\": \"GFP-tagged overexpression and dominant-negative truncation in neuronal cell lines, PMA treatment\",\n      \"pmids\": [\"15813925\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Relies on dominant-negative overexpression rather than loss-of-function\", \"Molecular link to actin machinery in neurites not defined\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Identified the core actin-regulatory partners and ordered CORO1C downstream of initial F-actin assembly during protrusion formation.\",\n      \"evidence\": \"GFP fusions, RNAi, wound healing/endocytosis assays, co-IP/pulldown for Arp2/3 and cofilin\",\n      \"pmids\": [\"17274980\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Many phenotypes catalogued without mechanistic dissection\", \"Direct vs. indirect binding to Arp2/3 and cofilin not separated\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Connected CORO1C to membrane trafficking by demonstrating nucleotide-state-specific binding to GDP-Rab27a and placing it downstream of the Rab27a GTP-to-GDP switch in endocytosis.\",\n      \"evidence\": \"Co-IP, RNAi, dominant-negative constructs, FM4-64 endocytosis assay, epistasis rescue with Rab27a mutants in beta-cells\",\n      \"pmids\": [\"18768935\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of GDP-state recognition by the beta-propeller unresolved\", \"Link between Rab27a binding and actin remodeling not established\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Provided early evidence for a pro-tumorigenic role by showing CORO1C knockdown reduces glioblastoma proliferation, motility, and invasion.\",\n      \"evidence\": \"shRNA knockdown with proliferation, motility, and matrix invasion assays\",\n      \"pmids\": [\"18189330\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular mediators identified\", \"In vitro only\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Showed CORO1C translocation to the plasma membrane is Rab27a-GDP-dependent, defining its role in retrograde secretory membrane transport.\",\n      \"evidence\": \"Immunofluorescence, live imaging, Rab27a siRNA and GAP/mutant overexpression in beta-cells\",\n      \"pmids\": [\"20362548\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cargo specificity of retrograde transport not defined\", \"Role of CORO1C oligomerization in translocation untested\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Linked CORO1C to metastasis in vivo and identified MMP-9 and cathepsin K as associated downstream effectors.\",\n      \"evidence\": \"Lentiviral shRNA, migration/invasion assays, tail-vein liver metastasis mouse model, Tumor Metastasis PCR Array\",\n      \"pmids\": [\"22974233\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking CORO1C to protease expression unknown\", \"Direct vs. indirect regulation of MMP-9/cathepsin K unresolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified a calcium-dependent PLS3 interaction and demonstrated CORO1C can rescue endocytic and axonal defects in SMN-depleted models, implicating it in SMA pathomechanism.\",\n      \"evidence\": \"Proteomics, co-IP, fluid-phase endocytosis assay, F-actin quantification, zebrafish Smn rescue\",\n      \"pmids\": [\"27499521\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether CORO1C variation modifies human SMA not established\", \"Mechanism by which CORO1C elevates F-actin in this context unclear\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Positioned CORO1C downstream of the transcription/translation regulator YBX1 in a breast cancer migration pathway.\",\n      \"evidence\": \"siRNA of YBX1 and CORO1C, luciferase reporter, migration/invasion and overexpression epistasis assays\",\n      \"pmids\": [\"28302118\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Regulation stated to be indirect; intermediary factors unknown\", \"Single cell-line context\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined a RAD23B–CORO1C axis driving invadopodia and matrix degradation within talin/integrin–FAK–RhoA/Rac1 signaling.\",\n      \"evidence\": \"Co-IP, immunofluorescence co-localization, invadopodia/matrix degradation assays, siRNA, xenograft model\",\n      \"pmids\": [\"34062216\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs. signaling-mediated RAD23B–CORO1C coupling not fully separated\", \"Position of CORO1C within the signaling cascade inferred\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Mapped a direct PAK4 interaction to the CORO1C C-terminal extension domain and showed phospho-S99 PAK4 is recruited by CORO1C to the leading edge to drive migration via a CORO1C/RCC2 complex.\",\n      \"evidence\": \"Co-IP, CE domain mapping, phosphomutant analysis, immunofluorescence, migration assays\",\n      \"pmids\": [\"35593474\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the CORO1C/RCC2 complex on actin not defined\", \"Single-lab gastric cancer context\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Provided clean genetic dissection of CORO1C in branched actin turnover, showing it limits branched actin density and cofilin accumulation to enable lamellipodial dynamics and haptotaxis, with Arp2/3-dependent localization.\",\n      \"evidence\": \"Conditional Coro1B/Coro1C double knockout, live imaging, F-actin quantification, haptotaxis assays, Arp2/3 inhibition\",\n      \"pmids\": [\"35657370\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional redundancy with CORO1B not fully separated\", \"Molecular trigger for cofilin clearance by coronins unresolved\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Established a CORO1C-specific second actin-binding site and Arp2/3 interaction as essential for autophagosome integrity and p62 body formation, with in vivo autophagy and learning phenotypes.\",\n      \"evidence\": \"Genome-wide haploid screen, CRISPR KO mouse, IP, immunofluorescence, TEM, autophagy flux assays\",\n      \"pmids\": [\"41968673\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural definition of the second actin-binding site pending\", \"Mechanistic link from branched actin to autophagosome closure incomplete\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Identified SUMOylation as a post-translational switch amplifying CORO1C–Arp2/3 binding and pro-tumorigenic cytoskeletal remodeling.\",\n      \"evidence\": \"IP-MS, site-specific mutagenesis (K19/K311/K440), migration/invasion/proliferation assays, in vivo tumorigenesis, UBC9 ablation\",\n      \"pmids\": [\"41912501\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signals controlling CORO1C SUMOylation unknown\", \"Whether SUMOylation regulates non-cancer functions untested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CORO1C's distinct activities — branched actin turnover, GDP-Rab27a-coupled trafficking, autophagosome formation, and migration — are integrated and selectively engaged by post-translational state remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No high-resolution structure of full-length CORO1C with Arp2/3 or actin\", \"Kinases/signals dictating phosphorylation and SUMOylation context-specificity undefined\", \"Mechanistic unification of trafficking vs. cytoskeletal vs. autophagy roles missing\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 3, 12, 13]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 12, 14]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1, 12]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [13]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [4, 6]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [5, 7, 9, 10, 14]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ARPC (Arp2/3 complex)\", \"CFL1\", \"RAB27A\", \"PLS3\", \"PAK4\", \"RAD23B\", \"RCC2\", \"UBE2I\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":8,"faith_total":8,"faith_pct":100.0}}