{"gene":"CORO1C","run_date":"2026-04-28T17:28:53","timeline":{"discoveries":[{"year":2002,"finding":"The C-terminal coiled-coil domain of CORO1C (coronin 3) mediates oligomerization (forming oligomers rather than dimers), F-actin binding and cross-linking in vitro, and membrane association in vivo; removal of the coiled coil abolishes membrane localization but not in vitro F-actin binding. Cytosolic CORO1C is highly phosphorylated, likely regulating subcellular localization.","method":"Recombinant protein biochemistry, in vitro F-actin binding/cross-linking assay, in vivo membrane fractionation, deletion mutagenesis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 — reconstituted in vitro with mutagenesis and in vivo fractionation in single rigorous study","pmids":["12377779"],"is_preprint":false},{"year":2006,"finding":"CORO1C localizes to lamellipodia and membrane ruffles in vivo and participates in wound healing, protrusion formation, cell proliferation, cytokinesis, endocytosis, axonal growth, and secretion. CORO1C interacts with the Arp2/3 complex and cofilin, indicating involvement in regulating Arp2/3-mediated actin events.","method":"GFP-tagged fusion proteins, RNAi silencing, functional cellular assays (wound healing, endocytosis, cytokinesis), co-immunoprecipitation with Arp2/3 and cofilin","journal":"Experimental cell research","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (RNAi KD with defined phenotypes + Co-IP with partners) in single study","pmids":["17274980"],"is_preprint":false},{"year":2008,"finding":"CORO1C (coronin 3) acts as a GDP-Rab27a effector in pancreatic beta-cells: it directly binds GDP-Rab27a (not GTP-Rab27a) through its beta-propeller structure, and this interaction is required for endocytosis of secretory membrane (phogrin internalization and FM4-64 uptake). Knockdown of CORO1C or disruption of the CORO1C–GDP-Rab27a interaction by dominant-negative CORO1C inhibits stimulus-coupled endocytosis.","method":"Co-immunoprecipitation, direct binding assay, RNAi knockdown, dominant-negative overexpression, FM4-64 endocytosis assay, phogrin internalization assay","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1–2 — direct binding through defined domain, orthogonal KD and dominant-negative rescue experiments","pmids":["18768935"],"is_preprint":false},{"year":2008,"finding":"CORO1C (coronin 3) is a homotrimeric F-actin-binding protein whose expression promotes glioblastoma cell proliferation, motility, and invasion into extracellular matrix; shRNA-mediated knockdown reduces all three phenotypes.","method":"shRNA knockdown, cell proliferation assay, cell motility assay, Matrigel invasion assay","journal":"The Journal of pathology","confidence":"Medium","confidence_rationale":"Tier 2 — clean KD with defined cellular phenotypes across multiple assays, single lab","pmids":["18189330"],"is_preprint":false},{"year":2010,"finding":"Glucose stimulation causes redistribution (translocation) of CORO1C to the vicinity of the plasma membrane in pancreatic beta-cells, dependent on Rab27a activity; this translocation is required for retrograde transport of secretory membrane (phogrin). Overexpression of GDP-Rab27a mutant or Rab27a GAP mimics glucose-induced CORO1C translocation, while Rab27a knockdown blocks it.","method":"Fluorescence microscopy/live imaging, dominant-negative/constitutively active Rab27a mutants, RNAi knockdown, phogrin trafficking assay","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization with functional consequence, multiple genetic manipulations, single lab","pmids":["20362548"],"is_preprint":false},{"year":2016,"finding":"CORO1C directly binds PLS3 (plastin 3) in a calcium-dependent manner, as shown by proteomics and biochemical analysis. CORO1C overexpression restores fluid-phase endocytosis in SMN-knockdown cells by elevating F-actin levels, and rescues axonal truncation and branching phenotypes in Smn-depleted zebrafish.","method":"Proteomics, co-immunoprecipitation/biochemical binding assay, fluid-phase endocytosis assay, zebrafish Smn morpholino knockdown with CORO1C overexpression rescue","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 1–2 — direct binding biochemistry + in vivo epistasis rescue in zebrafish + cellular endocytosis assay, replicated across multiple model systems","pmids":["27499521"],"is_preprint":false},{"year":2012,"finding":"CORO1C promotes gastric cancer cell migration and invasion; its knockdown reduces expression of MMP-9 and cathepsin K (identified by Human Tumor Metastasis PCR Array), and reduces liver metastasis in mice after tail vein injection.","method":"Lentiviral shRNA knockdown, overexpression, migration/invasion assays, PCR array for metastasis genes, in vivo mouse metastasis model","journal":"Molecular cancer","confidence":"Medium","confidence_rationale":"Tier 2 — KD and OE with defined phenotypes and downstream gene identification, in vivo validation","pmids":["22974233"],"is_preprint":false},{"year":2022,"finding":"Coro1B and Coro1C co-localize with Arp2/3-branched actin and require Arp2/3 activity for proper subcellular localization. In coronin null cells, lamellipodial protrusion dynamics are altered due to increased branched actin density and reduced actin turnover, leading to defective haptotaxis and increased cellular contractility. Unexpectedly, cofilin accumulates in coronin null lamellipodia and F-actin levels are elevated, consistent with coronins playing a pro-cofilin role.","method":"Conditional knockout cell line, live-cell imaging of lamellipodia dynamics, Arp2/3 inhibitor treatment, haptotaxis assay, F-actin quantification, cofilin localization","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 — clean conditional KO with multiple orthogonal cellular readouts and mechanistic pathway placement relative to Arp2/3 and cofilin","pmids":["35657370"],"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 the RAD23B–CORO1C complex promotes invadopodia formation and matrix degradation. RAD23B acts upstream via talin1/2/integrin/FAK/RhoA/Rac1/CORO1C signaling.","method":"Co-immunoprecipitation, co-localization imaging, invadopodia formation assay, gelatin matrix degradation assay, shRNA knockdown, epistasis pathway analysis","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2–3 — Co-IP and co-localization with functional invadopodia readout, pathway epistasis defined, single lab","pmids":["34062216"],"is_preprint":false},{"year":2022,"finding":"CORO1C recruits phospho-PAK4 (phosphorylated at serine 99) to the leading edge of gastric cancer cells via its C-terminal extension (CE) domain (residues 353–457). Unphosphorylated PAK4 is retained on microtubules via a PAK4/GEF-H1/Tctex-1 complex; phosphorylation releases PAK4 for CORO1C binding. The CORO1C/PAK4 interaction at the leading edge then regulates the CORO1C/RCC2 complex and promotes cell migration.","method":"Co-immunoprecipitation, domain deletion mapping, phosphomutant PAK4 constructs, leading-edge localization imaging, migration assay","journal":"Acta biochimica et biophysica Sinica","confidence":"Medium","confidence_rationale":"Tier 2–3 — domain mapping with mutagenesis, Co-IP, and localization imaging with functional migration readout, single lab","pmids":["35593474"],"is_preprint":false},{"year":2021,"finding":"A 47-amino-acid peptide (CORO1C-47aa) encoded by circRNA hsa-circ-0000437 directly binds the PAS-B domain of ARNT, competing with transcription factor TACC3 for ARNT binding, thereby suppressing VEGF expression and inhibiting angiogenesis (endothelial cell proliferation, migration, and differentiation).","method":"CircRNA deep sequencing, overexpression of CORO1C-47aa, co-immunoprecipitation/competition binding assay (ARNT PAS-B domain), VEGF expression assay, endothelial tube formation assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — direct binding assay defining domain interaction, functional endothelial assays, single lab","pmids":["34534547"],"is_preprint":false},{"year":2026,"finding":"UBC9-mediated SUMOylation of CORO1C at lysine residues K19, K311, and K440 enhances CORO1C binding to the Arp2/3 complex, promotes actin-based cytoskeletal remodeling, and drives lung adenocarcinoma cell proliferation, migration, and invasion.","method":"Immunoprecipitation-mass spectrometry (substrate identification), mutagenesis of SUMOylation sites (K19/K311/K440), Co-IP of CORO1C with Arp2 complex, UBC9 knockout functional assays","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 1–2 — MS-based substrate identification + site-specific mutagenesis + Co-IP with defined complex, single lab","pmids":["41912501"],"is_preprint":false},{"year":2026,"finding":"CORO1C promotes autophagosome formation by interacting with the ACTR2/ARP2–ACTR3/ARP3 (Arp2/3) complex to drive branched actin network assembly, SQSTM1/p62 body formation, and autophagosome structural integrity. CORO1C possesses a unique second actin-binding site (absent in CORO1A and CORO1B) critical for this function. coro1c-knockout mice show autophagy-deficient phenotypes in multiple tissues, early lethality under starvation, and severe spatial learning/memory impairment.","method":"Genome-wide loss-of-function screen (haploid ESC library), CORO1C knockout mice, Co-IP with Arp2/3 complex, autophagy flux assays (LC3, p62, STX17), transmission electron microscopy, behavioral testing","journal":"Autophagy","confidence":"High","confidence_rationale":"Tier 1–2 — genome-wide screen + KO mouse phenotype + mechanistic Co-IP with Arp2/3 + multiple orthogonal autophagy readouts, single study but multiple methods","pmids":["41968673"],"is_preprint":false},{"year":2005,"finding":"Coronin 3 (CORO1C) is abundantly expressed in the adult CNS and localizes to outgrowing neurites; truncated coronin 3 proteins that lack functional domains suppress neurite formation in neuro-2a and PC-12 cells. PKC activator PMA reduces coronin 3 protein levels.","method":"GFP-tagged truncation constructs in neuronal cell lines, PMA pharmacological treatment, immunofluorescence/expression analysis","journal":"The European journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 3 — dominant-negative truncation approach with neurite phenotype readout, single lab","pmids":["15813925"],"is_preprint":false},{"year":2000,"finding":"CORO1C encodes a 474-amino-acid protein with five N-terminal WD repeats and a C-terminal coiled-coil motif that co-localizes with F-actin in immunocytochemical staining; the gene maps to chromosome 12q24.1.","method":"cDNA isolation, sequence analysis, immunocytochemical co-localization with F-actin, FISH chromosomal mapping","journal":"Cytogenetics and cell genetics","confidence":"Medium","confidence_rationale":"Tier 3 — initial characterization with co-localization, foundational gene identification paper","pmids":["10828594"],"is_preprint":false}],"current_model":"CORO1C (coronin 3) is a WD-repeat/coiled-coil F-actin-binding protein that oligomerizes via its C-terminus, localizes to lamellipodia and the submembranous cytoskeleton, and regulates branched actin dynamics by interacting with the Arp2/3 complex and cofilin; it functions as a GDP-Rab27a effector to couple stimulus-driven endocytosis of secretory membrane in beta-cells, promotes autophagosome formation through Arp2/3-dependent actin assembly (with a unique second actin-binding site), directly binds PLS3 in a calcium-dependent manner to rescue endocytosis in motor-neuron disease contexts, and is post-translationally regulated by UBC9-mediated SUMOylation at K19/K311/K440 (enhancing Arp2/3 binding) and by PKC-dependent phosphorylation, with additional roles in cell migration driven by recruiting phospho-PAK4 (pS99) to the leading edge via its C-terminal extension domain."},"narrative":{"teleology":[{"year":2000,"claim":"Initial cloning established CORO1C as a WD-repeat/coiled-coil protein that co-localizes with F-actin, placing it in the coronin family of actin-associated proteins.","evidence":"cDNA isolation, sequence analysis, and immunocytochemical co-localization with F-actin in cultured cells","pmids":["10828594"],"confidence":"Medium","gaps":["No functional data on actin regulation","No binding partners identified","Oligomeric state unknown"]},{"year":2002,"claim":"Biochemical dissection revealed that the C-terminal coiled-coil domain mediates oligomerization (not simple dimerization), F-actin cross-linking, and membrane association, while cytosolic phosphorylation suggested post-translational regulation of localization.","evidence":"Recombinant deletion constructs, in vitro F-actin binding/cross-linking assays, and membrane fractionation","pmids":["12377779"],"confidence":"High","gaps":["Kinase responsible for phosphorylation not identified","Oligomer stoichiometry not precisely defined","Functional consequence of cross-linking in cells unknown"]},{"year":2005,"claim":"Expression profiling and dominant-negative studies established CORO1C as a neurite outgrowth regulator in the CNS, and PKC-dependent modulation of its protein levels provided the first link to a specific signaling pathway.","evidence":"GFP-tagged truncation constructs in neuro-2a and PC-12 cells, PMA treatment","pmids":["15813925"],"confidence":"Medium","gaps":["PKC phosphorylation site(s) on CORO1C not mapped","Dominant-negative approach does not distinguish direct from indirect effects","Mechanism of PKC-dependent protein level reduction unclear"]},{"year":2006,"claim":"RNAi-based functional analysis and co-immunoprecipitation identified the Arp2/3 complex and cofilin as direct interaction partners, establishing CORO1C as a regulator of branched actin dynamics at lamellipodia with broad cellular roles including wound healing, endocytosis, and cytokinesis.","evidence":"RNAi knockdown with multiple functional cellular assays, Co-IP with Arp2/3 and cofilin","pmids":["17274980"],"confidence":"High","gaps":["Mechanism by which CORO1C coordinates Arp2/3 and cofilin activities not resolved","No structural insight into Arp2/3 binding interface"]},{"year":2008,"claim":"Discovery that CORO1C functions as a GDP-Rab27a effector in pancreatic β-cells revealed an unexpected role outside canonical actin regulation: coupling post-exocytic membrane retrieval to Rab GTPase signaling through the β-propeller domain.","evidence":"Direct binding assays showing GDP-Rab27a specificity, RNAi and dominant-negative inhibition of phogrin internalization and FM4-64 uptake in β-cells","pmids":["18768935","20362548"],"confidence":"High","gaps":["Whether Rab27a–CORO1C interaction occurs independently of actin binding not tested","Structural basis for GDP-specificity unknown"]},{"year":2016,"claim":"Identification of PLS3 as a direct calcium-dependent binding partner, combined with rescue of endocytosis and axonal defects in SMN-depleted models, connected CORO1C to spinal muscular atrophy-relevant pathways and demonstrated functional synergy between coronin and plastin actin-binding activities.","evidence":"Proteomics-based partner identification, Co-IP, fluid-phase endocytosis assay in SMN-knockdown cells, zebrafish Smn morpholino rescue by CORO1C overexpression","pmids":["27499521"],"confidence":"High","gaps":["Calcium-binding site mediating PLS3 interaction not mapped","Whether CORO1C is rate-limiting for endocytosis in SMA patient neurons unknown"]},{"year":2022,"claim":"Conditional knockout of Coro1B/1C in fibroblasts resolved a long-standing question by showing that coronins function as pro-cofilin factors: their loss increases branched actin density and paradoxically accumulates cofilin at lamellipodia, impairing actin turnover and haptotaxis.","evidence":"Conditional knockout cells, live-cell imaging of protrusion dynamics, Arp2/3 inhibitor epistasis, F-actin quantification","pmids":["35657370"],"confidence":"High","gaps":["Relative contributions of CORO1B versus CORO1C not fully separated","Whether coronins directly activate cofilin or indirectly facilitate its access to filaments not determined"]},{"year":2022,"claim":"Domain mapping revealed that CORO1C recruits phospho-PAK4 (pS99) to the leading edge via its C-terminal extension domain (residues 353–457), linking CORO1C to PAK4/RCC2 signaling in directed cell migration.","evidence":"Co-IP with domain deletion and phosphomutant constructs, leading-edge localization imaging, migration assays in gastric cancer cells","pmids":["35593474"],"confidence":"Medium","gaps":["Direct binding versus scaffold-mediated interaction not distinguished with purified proteins","Relevance outside gastric cancer cells not tested","RCC2 regulatory mechanism downstream not defined"]},{"year":2026,"claim":"UBC9-mediated SUMOylation at K19, K311, and K440 was identified as a post-translational modification that enhances CORO1C–Arp2/3 binding and promotes cytoskeletal remodeling, providing the first defined mechanism for modulating CORO1C's Arp2/3 interaction strength.","evidence":"IP-mass spectrometry, site-directed mutagenesis of SUMO sites, Co-IP of CORO1C with Arp2/3, UBC9 knockout functional assays","pmids":["41912501"],"confidence":"Medium","gaps":["Whether SUMOylation affects CORO1C oligomerization or membrane localization not tested","In vivo confirmation in non-cancer contexts lacking","Interplay between SUMOylation and phosphorylation unknown"]},{"year":2026,"claim":"A genome-wide screen and knockout mouse model established CORO1C as essential for autophagosome formation through a unique second actin-binding site that drives Arp2/3-dependent branched actin assembly, SQSTM1/p62 body formation, and autophagosome structural integrity, with organismal consequences including starvation sensitivity and cognitive impairment.","evidence":"Haploid ESC loss-of-function screen, coro1c-knockout mice with autophagy flux assays, TEM, behavioral testing, Co-IP with Arp2/3","pmids":["41968673"],"confidence":"High","gaps":["Identity and structural basis of the second actin-binding site not resolved at atomic level","Whether autophagy defect underlies cognitive phenotype or is independent not determined","Tissue-specific versus systemic contribution to lethality under starvation unclear"]},{"year":null,"claim":"Key unresolved questions include the structural basis for CORO1C's selectivity for GDP-Rab27a over GTP-Rab27a, the precise mechanism by which CORO1C facilitates cofilin-mediated actin disassembly, and how SUMOylation, phosphorylation, and oligomerization are integrated to spatiotemporally control CORO1C activity in different cellular contexts.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of full-length CORO1C or its complexes","Crosstalk between SUMOylation and PKC phosphorylation unexplored","Relative physiological importance of autophagy versus migration roles in vivo not separated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1,3,7,12,14]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,9]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1,7,14]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,1,4]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[12]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[2,4,5]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,4,9]}],"complexes":["Arp2/3 complex (regulatory interactor)"],"partners":["ACTR2","ACTR3","CFL1","RAB27A","PLS3","PAK4","RAD23B","UBC9"],"other_free_text":[]},"mechanistic_narrative":"CORO1C is an F-actin-binding protein composed of N-terminal WD repeats forming a β-propeller and a C-terminal coiled-coil domain that mediates oligomerization and membrane association, functioning as a central regulator of Arp2/3-dependent branched actin dynamics at the cell cortex [PMID:12377779, PMID:35657370]. It localizes to lamellipodia and membrane ruffles where it interacts with the Arp2/3 complex and cofilin to control actin turnover, protrusion dynamics, and haptotaxis; loss of CORO1C increases branched actin density and impairs cofilin-mediated filament disassembly [PMID:17274980, PMID:35657370]. Beyond lamellipodial dynamics, CORO1C functions as a GDP-Rab27a effector coupling stimulus-driven endocytosis of secretory membrane in pancreatic β-cells, directly binds PLS3 in a calcium-dependent manner to rescue endocytosis and axonal defects in SMN-deficient models, and promotes autophagosome formation through a unique second actin-binding site that drives Arp2/3-dependent actin assembly for SQSTM1/p62 body formation and autophagosome structural integrity [PMID:18768935, PMID:27499521, PMID:41968673]. CORO1C activity is post-translationally regulated by UBC9-mediated SUMOylation at K19/K311/K440, which enhances Arp2/3 binding, and by PKC-dependent mechanisms that modulate its protein levels [PMID:41912501, PMID:15813925]."},"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":132,"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 letters","url":"https://pubmed.ncbi.nlm.nih.gov/32206066","citation_count":51,"is_preprint":false},{"pmid":"17274980","id":"PMC_17274980","title":"Coronin 3 involvement in F-actin-dependent processes at the cell cortex.","date":"2006","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/17274980","citation_count":49,"is_preprint":false},{"pmid":"18189330","id":"PMC_18189330","title":"Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy.","date":"2008","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/18189330","citation_count":49,"is_preprint":false},{"pmid":"34534547","id":"PMC_34534547","title":"A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis.","date":"2021","source":"The Journal of biological 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dynamics.","date":"2026","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/41968673","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":18498,"output_tokens":4041,"usd":0.058055},"stage2":{"model":"claude-opus-4-6","input_tokens":7465,"output_tokens":3001,"usd":0.168525},"total_usd":0.22658,"stage1_batch_id":"msgbatch_011kfMfE81o6CTcyhVUqumuW","stage2_batch_id":"msgbatch_01DTputS6WNkH745x1nVSoBo","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"The C-terminal coiled-coil domain of CORO1C (coronin 3) mediates oligomerization (forming oligomers rather than dimers), F-actin binding and cross-linking in vitro, and membrane association in vivo; removal of the coiled coil abolishes membrane localization but not in vitro F-actin binding. Cytosolic CORO1C is highly phosphorylated, likely regulating subcellular localization.\",\n      \"method\": \"Recombinant protein biochemistry, in vitro F-actin binding/cross-linking assay, in vivo membrane fractionation, deletion mutagenesis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted in vitro with mutagenesis and in vivo fractionation in single rigorous study\",\n      \"pmids\": [\"12377779\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"CORO1C localizes to lamellipodia and membrane ruffles in vivo and participates in wound healing, protrusion formation, cell proliferation, cytokinesis, endocytosis, axonal growth, and secretion. CORO1C interacts with the Arp2/3 complex and cofilin, indicating involvement in regulating Arp2/3-mediated actin events.\",\n      \"method\": \"GFP-tagged fusion proteins, RNAi silencing, functional cellular assays (wound healing, endocytosis, cytokinesis), co-immunoprecipitation with Arp2/3 and cofilin\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (RNAi KD with defined phenotypes + Co-IP with partners) in single study\",\n      \"pmids\": [\"17274980\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"CORO1C (coronin 3) acts as a GDP-Rab27a effector in pancreatic beta-cells: it directly binds GDP-Rab27a (not GTP-Rab27a) through its beta-propeller structure, and this interaction is required for endocytosis of secretory membrane (phogrin internalization and FM4-64 uptake). Knockdown of CORO1C or disruption of the CORO1C–GDP-Rab27a interaction by dominant-negative CORO1C inhibits stimulus-coupled endocytosis.\",\n      \"method\": \"Co-immunoprecipitation, direct binding assay, RNAi knockdown, dominant-negative overexpression, FM4-64 endocytosis assay, phogrin internalization assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct binding through defined domain, orthogonal KD and dominant-negative rescue experiments\",\n      \"pmids\": [\"18768935\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"CORO1C (coronin 3) is a homotrimeric F-actin-binding protein whose expression promotes glioblastoma cell proliferation, motility, and invasion into extracellular matrix; shRNA-mediated knockdown reduces all three phenotypes.\",\n      \"method\": \"shRNA knockdown, cell proliferation assay, cell motility assay, Matrigel invasion assay\",\n      \"journal\": \"The Journal of pathology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with defined cellular phenotypes across multiple assays, single lab\",\n      \"pmids\": [\"18189330\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Glucose stimulation causes redistribution (translocation) of CORO1C to the vicinity of the plasma membrane in pancreatic beta-cells, dependent on Rab27a activity; this translocation is required for retrograde transport of secretory membrane (phogrin). Overexpression of GDP-Rab27a mutant or Rab27a GAP mimics glucose-induced CORO1C translocation, while Rab27a knockdown blocks it.\",\n      \"method\": \"Fluorescence microscopy/live imaging, dominant-negative/constitutively active Rab27a mutants, RNAi knockdown, phogrin trafficking assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization with functional consequence, multiple genetic manipulations, single lab\",\n      \"pmids\": [\"20362548\"],\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 proteomics and biochemical analysis. CORO1C overexpression restores fluid-phase endocytosis in SMN-knockdown cells by elevating F-actin levels, and rescues axonal truncation and branching phenotypes in Smn-depleted zebrafish.\",\n      \"method\": \"Proteomics, co-immunoprecipitation/biochemical binding assay, fluid-phase endocytosis assay, zebrafish Smn morpholino knockdown with CORO1C overexpression rescue\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct binding biochemistry + in vivo epistasis rescue in zebrafish + cellular endocytosis assay, replicated across multiple model systems\",\n      \"pmids\": [\"27499521\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CORO1C promotes gastric cancer cell migration and invasion; its knockdown reduces expression of MMP-9 and cathepsin K (identified by Human Tumor Metastasis PCR Array), and reduces liver metastasis in mice after tail vein injection.\",\n      \"method\": \"Lentiviral shRNA knockdown, overexpression, migration/invasion assays, PCR array for metastasis genes, in vivo mouse metastasis model\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — KD and OE with defined phenotypes and downstream gene identification, in vivo validation\",\n      \"pmids\": [\"22974233\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Coro1B and Coro1C co-localize with Arp2/3-branched actin and require Arp2/3 activity for proper subcellular localization. In coronin null cells, lamellipodial protrusion dynamics are altered due to increased branched actin density and reduced actin turnover, leading to defective haptotaxis and increased cellular contractility. Unexpectedly, cofilin accumulates in coronin null lamellipodia and F-actin levels are elevated, consistent with coronins playing a pro-cofilin role.\",\n      \"method\": \"Conditional knockout cell line, live-cell imaging of lamellipodia dynamics, Arp2/3 inhibitor treatment, haptotaxis assay, F-actin quantification, cofilin localization\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — clean conditional KO with multiple orthogonal cellular readouts and mechanistic pathway placement relative to Arp2/3 and cofilin\",\n      \"pmids\": [\"35657370\"],\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 the RAD23B–CORO1C complex promotes invadopodia formation and matrix degradation. RAD23B acts upstream via talin1/2/integrin/FAK/RhoA/Rac1/CORO1C signaling.\",\n      \"method\": \"Co-immunoprecipitation, co-localization imaging, invadopodia formation assay, gelatin matrix degradation assay, shRNA knockdown, epistasis pathway analysis\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — Co-IP and co-localization with functional invadopodia readout, pathway epistasis defined, single lab\",\n      \"pmids\": [\"34062216\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CORO1C recruits phospho-PAK4 (phosphorylated at serine 99) to the leading edge of gastric cancer cells via its C-terminal extension (CE) domain (residues 353–457). Unphosphorylated PAK4 is retained on microtubules via a PAK4/GEF-H1/Tctex-1 complex; phosphorylation releases PAK4 for CORO1C binding. The CORO1C/PAK4 interaction at the leading edge then regulates the CORO1C/RCC2 complex and promotes cell migration.\",\n      \"method\": \"Co-immunoprecipitation, domain deletion mapping, phosphomutant PAK4 constructs, leading-edge localization imaging, migration assay\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — domain mapping with mutagenesis, Co-IP, and localization imaging with functional migration readout, single lab\",\n      \"pmids\": [\"35593474\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"A 47-amino-acid peptide (CORO1C-47aa) encoded by circRNA hsa-circ-0000437 directly binds the PAS-B domain of ARNT, competing with transcription factor TACC3 for ARNT binding, thereby suppressing VEGF expression and inhibiting angiogenesis (endothelial cell proliferation, migration, and differentiation).\",\n      \"method\": \"CircRNA deep sequencing, overexpression of CORO1C-47aa, co-immunoprecipitation/competition binding assay (ARNT PAS-B domain), VEGF expression assay, endothelial tube formation assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct binding assay defining domain interaction, functional endothelial assays, single lab\",\n      \"pmids\": [\"34534547\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"UBC9-mediated SUMOylation of CORO1C at lysine residues K19, K311, and K440 enhances CORO1C binding to the Arp2/3 complex, promotes actin-based cytoskeletal remodeling, and drives lung adenocarcinoma cell proliferation, migration, and invasion.\",\n      \"method\": \"Immunoprecipitation-mass spectrometry (substrate identification), mutagenesis of SUMOylation sites (K19/K311/K440), Co-IP of CORO1C with Arp2 complex, UBC9 knockout functional assays\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 — MS-based substrate identification + site-specific mutagenesis + Co-IP with defined complex, single lab\",\n      \"pmids\": [\"41912501\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CORO1C promotes autophagosome formation by interacting with the ACTR2/ARP2–ACTR3/ARP3 (Arp2/3) complex to drive branched actin network assembly, SQSTM1/p62 body formation, and autophagosome structural integrity. CORO1C possesses a unique second actin-binding site (absent in CORO1A and CORO1B) critical for this function. coro1c-knockout mice show autophagy-deficient phenotypes in multiple tissues, early lethality under starvation, and severe spatial learning/memory impairment.\",\n      \"method\": \"Genome-wide loss-of-function screen (haploid ESC library), CORO1C knockout mice, Co-IP with Arp2/3 complex, autophagy flux assays (LC3, p62, STX17), transmission electron microscopy, behavioral testing\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — genome-wide screen + KO mouse phenotype + mechanistic Co-IP with Arp2/3 + multiple orthogonal autophagy readouts, single study but multiple methods\",\n      \"pmids\": [\"41968673\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Coronin 3 (CORO1C) is abundantly expressed in the adult CNS and localizes to outgrowing neurites; truncated coronin 3 proteins that lack functional domains suppress neurite formation in neuro-2a and PC-12 cells. PKC activator PMA reduces coronin 3 protein levels.\",\n      \"method\": \"GFP-tagged truncation constructs in neuronal cell lines, PMA pharmacological treatment, immunofluorescence/expression analysis\",\n      \"journal\": \"The European journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — dominant-negative truncation approach with neurite phenotype readout, single lab\",\n      \"pmids\": [\"15813925\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"CORO1C encodes a 474-amino-acid protein with five N-terminal WD repeats and a C-terminal coiled-coil motif that co-localizes with F-actin in immunocytochemical staining; the gene maps to chromosome 12q24.1.\",\n      \"method\": \"cDNA isolation, sequence analysis, immunocytochemical co-localization with F-actin, FISH chromosomal mapping\",\n      \"journal\": \"Cytogenetics and cell genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — initial characterization with co-localization, foundational gene identification paper\",\n      \"pmids\": [\"10828594\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CORO1C (coronin 3) is a WD-repeat/coiled-coil F-actin-binding protein that oligomerizes via its C-terminus, localizes to lamellipodia and the submembranous cytoskeleton, and regulates branched actin dynamics by interacting with the Arp2/3 complex and cofilin; it functions as a GDP-Rab27a effector to couple stimulus-driven endocytosis of secretory membrane in beta-cells, promotes autophagosome formation through Arp2/3-dependent actin assembly (with a unique second actin-binding site), directly binds PLS3 in a calcium-dependent manner to rescue endocytosis in motor-neuron disease contexts, and is post-translationally regulated by UBC9-mediated SUMOylation at K19/K311/K440 (enhancing Arp2/3 binding) and by PKC-dependent phosphorylation, with additional roles in cell migration driven by recruiting phospho-PAK4 (pS99) to the leading edge via its C-terminal extension domain.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CORO1C is an F-actin-binding protein composed of N-terminal WD repeats forming a β-propeller and a C-terminal coiled-coil domain that mediates oligomerization and membrane association, functioning as a central regulator of Arp2/3-dependent branched actin dynamics at the cell cortex [PMID:12377779, PMID:35657370]. It localizes to lamellipodia and membrane ruffles where it interacts with the Arp2/3 complex and cofilin to control actin turnover, protrusion dynamics, and haptotaxis; loss of CORO1C increases branched actin density and impairs cofilin-mediated filament disassembly [PMID:17274980, PMID:35657370]. Beyond lamellipodial dynamics, CORO1C functions as a GDP-Rab27a effector coupling stimulus-driven endocytosis of secretory membrane in pancreatic β-cells, directly binds PLS3 in a calcium-dependent manner to rescue endocytosis and axonal defects in SMN-deficient models, and promotes autophagosome formation through a unique second actin-binding site that drives Arp2/3-dependent actin assembly for SQSTM1/p62 body formation and autophagosome structural integrity [PMID:18768935, PMID:27499521, PMID:41968673]. CORO1C activity is post-translationally regulated by UBC9-mediated SUMOylation at K19/K311/K440, which enhances Arp2/3 binding, and by PKC-dependent mechanisms that modulate its protein levels [PMID:41912501, PMID:15813925].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Initial cloning established CORO1C as a WD-repeat/coiled-coil protein that co-localizes with F-actin, placing it in the coronin family of actin-associated proteins.\",\n      \"evidence\": \"cDNA isolation, sequence analysis, and immunocytochemical co-localization with F-actin in cultured cells\",\n      \"pmids\": [\"10828594\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional data on actin regulation\", \"No binding partners identified\", \"Oligomeric state unknown\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Biochemical dissection revealed that the C-terminal coiled-coil domain mediates oligomerization (not simple dimerization), F-actin cross-linking, and membrane association, while cytosolic phosphorylation suggested post-translational regulation of localization.\",\n      \"evidence\": \"Recombinant deletion constructs, in vitro F-actin binding/cross-linking assays, and membrane fractionation\",\n      \"pmids\": [\"12377779\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase responsible for phosphorylation not identified\", \"Oligomer stoichiometry not precisely defined\", \"Functional consequence of cross-linking in cells unknown\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Expression profiling and dominant-negative studies established CORO1C as a neurite outgrowth regulator in the CNS, and PKC-dependent modulation of its protein levels provided the first link to a specific signaling pathway.\",\n      \"evidence\": \"GFP-tagged truncation constructs in neuro-2a and PC-12 cells, PMA treatment\",\n      \"pmids\": [\"15813925\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"PKC phosphorylation site(s) on CORO1C not mapped\", \"Dominant-negative approach does not distinguish direct from indirect effects\", \"Mechanism of PKC-dependent protein level reduction unclear\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"RNAi-based functional analysis and co-immunoprecipitation identified the Arp2/3 complex and cofilin as direct interaction partners, establishing CORO1C as a regulator of branched actin dynamics at lamellipodia with broad cellular roles including wound healing, endocytosis, and cytokinesis.\",\n      \"evidence\": \"RNAi knockdown with multiple functional cellular assays, Co-IP with Arp2/3 and cofilin\",\n      \"pmids\": [\"17274980\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which CORO1C coordinates Arp2/3 and cofilin activities not resolved\", \"No structural insight into Arp2/3 binding interface\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Discovery that CORO1C functions as a GDP-Rab27a effector in pancreatic β-cells revealed an unexpected role outside canonical actin regulation: coupling post-exocytic membrane retrieval to Rab GTPase signaling through the β-propeller domain.\",\n      \"evidence\": \"Direct binding assays showing GDP-Rab27a specificity, RNAi and dominant-negative inhibition of phogrin internalization and FM4-64 uptake in β-cells\",\n      \"pmids\": [\"18768935\", \"20362548\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether Rab27a–CORO1C interaction occurs independently of actin binding not tested\", \"Structural basis for GDP-specificity unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identification of PLS3 as a direct calcium-dependent binding partner, combined with rescue of endocytosis and axonal defects in SMN-depleted models, connected CORO1C to spinal muscular atrophy-relevant pathways and demonstrated functional synergy between coronin and plastin actin-binding activities.\",\n      \"evidence\": \"Proteomics-based partner identification, Co-IP, fluid-phase endocytosis assay in SMN-knockdown cells, zebrafish Smn morpholino rescue by CORO1C overexpression\",\n      \"pmids\": [\"27499521\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Calcium-binding site mediating PLS3 interaction not mapped\", \"Whether CORO1C is rate-limiting for endocytosis in SMA patient neurons unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Conditional knockout of Coro1B/1C in fibroblasts resolved a long-standing question by showing that coronins function as pro-cofilin factors: their loss increases branched actin density and paradoxically accumulates cofilin at lamellipodia, impairing actin turnover and haptotaxis.\",\n      \"evidence\": \"Conditional knockout cells, live-cell imaging of protrusion dynamics, Arp2/3 inhibitor epistasis, F-actin quantification\",\n      \"pmids\": [\"35657370\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative contributions of CORO1B versus CORO1C not fully separated\", \"Whether coronins directly activate cofilin or indirectly facilitate its access to filaments not determined\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Domain mapping revealed that CORO1C recruits phospho-PAK4 (pS99) to the leading edge via its C-terminal extension domain (residues 353–457), linking CORO1C to PAK4/RCC2 signaling in directed cell migration.\",\n      \"evidence\": \"Co-IP with domain deletion and phosphomutant constructs, leading-edge localization imaging, migration assays in gastric cancer cells\",\n      \"pmids\": [\"35593474\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct binding versus scaffold-mediated interaction not distinguished with purified proteins\", \"Relevance outside gastric cancer cells not tested\", \"RCC2 regulatory mechanism downstream not defined\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"UBC9-mediated SUMOylation at K19, K311, and K440 was identified as a post-translational modification that enhances CORO1C–Arp2/3 binding and promotes cytoskeletal remodeling, providing the first defined mechanism for modulating CORO1C's Arp2/3 interaction strength.\",\n      \"evidence\": \"IP-mass spectrometry, site-directed mutagenesis of SUMO sites, Co-IP of CORO1C with Arp2/3, UBC9 knockout functional assays\",\n      \"pmids\": [\"41912501\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether SUMOylation affects CORO1C oligomerization or membrane localization not tested\", \"In vivo confirmation in non-cancer contexts lacking\", \"Interplay between SUMOylation and phosphorylation unknown\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"A genome-wide screen and knockout mouse model established CORO1C as essential for autophagosome formation through a unique second actin-binding site that drives Arp2/3-dependent branched actin assembly, SQSTM1/p62 body formation, and autophagosome structural integrity, with organismal consequences including starvation sensitivity and cognitive impairment.\",\n      \"evidence\": \"Haploid ESC loss-of-function screen, coro1c-knockout mice with autophagy flux assays, TEM, behavioral testing, Co-IP with Arp2/3\",\n      \"pmids\": [\"41968673\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity and structural basis of the second actin-binding site not resolved at atomic level\", \"Whether autophagy defect underlies cognitive phenotype or is independent not determined\", \"Tissue-specific versus systemic contribution to lethality under starvation unclear\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis for CORO1C's selectivity for GDP-Rab27a over GTP-Rab27a, the precise mechanism by which CORO1C facilitates cofilin-mediated actin disassembly, and how SUMOylation, phosphorylation, and oligomerization are integrated to spatiotemporally control CORO1C activity in different cellular contexts.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No high-resolution structure of full-length CORO1C or its complexes\", \"Crosstalk between SUMOylation and PKC phosphorylation unexplored\", \"Relative physiological importance of autophagy versus migration roles in vivo not separated\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 3, 7, 12, 14]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1, 7, 14]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [12]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [2, 4, 5]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 4, 9]}\n    ],\n    \"complexes\": [\n      \"Arp2/3 complex (regulatory interactor)\"\n    ],\n    \"partners\": [\n      \"ACTR2\",\n      \"ACTR3\",\n      \"CFL1\",\n      \"RAB27A\",\n      \"PLS3\",\n      \"PAK4\",\n      \"RAD23B\",\n      \"UBC9\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}