Affinage

CORO1C

Coronin-1C · UniProt Q9ULV4

Length
474 aa
Mass
53.2 kDa
Annotated
2026-06-09
33 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 Medium

    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

    PMID:10828594

    Open questions at the time
    • No functional manipulation
    • F-actin binding inferred from co-localization, not biochemistry
  2. 2002 High

    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

    PMID:12377779

    Open questions at the time
    • Kinase mediating the regulatory phosphorylation unidentified
    • Stoichiometry of oligomers not resolved
  3. 2005 Medium

    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

    PMID:15813925

    Open questions at the time
    • Relies on dominant-negative overexpression rather than loss-of-function
    • Molecular link to actin machinery in neurites not defined
  4. 2006 Medium

    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

    PMID:17274980

    Open questions at the time
    • Many phenotypes catalogued without mechanistic dissection
    • Direct vs. indirect binding to Arp2/3 and cofilin not separated
  5. 2008 High

    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

    PMID:18768935

    Open questions at the time
    • Structural basis of GDP-state recognition by the beta-propeller unresolved
    • Link between Rab27a binding and actin remodeling not established
  6. 2008 Medium

    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

    PMID:18189330

    Open questions at the time
    • No molecular mediators identified
    • In vitro only
  7. 2010 Medium

    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

    PMID:20362548

    Open questions at the time
    • Cargo specificity of retrograde transport not defined
    • Role of CORO1C oligomerization in translocation untested
  8. 2012 Medium

    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

    PMID:22974233

    Open questions at the time
    • Mechanism linking CORO1C to protease expression unknown
    • Direct vs. indirect regulation of MMP-9/cathepsin K unresolved
  9. 2016 High

    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

    PMID:27499521

    Open questions at the time
    • Whether CORO1C variation modifies human SMA not established
    • Mechanism by which CORO1C elevates F-actin in this context unclear
  10. 2017 Medium

    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

    PMID:28302118

    Open questions at the time
    • Regulation stated to be indirect; intermediary factors unknown
    • Single cell-line context
  11. 2021 Medium

    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

    PMID:34062216

    Open questions at the time
    • Direct vs. signaling-mediated RAD23B–CORO1C coupling not fully separated
    • Position of CORO1C within the signaling cascade inferred
  12. 2022 Medium

    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

    PMID:35593474

    Open questions at the time
    • Functional consequence of the CORO1C/RCC2 complex on actin not defined
    • Single-lab gastric cancer context
  13. 2022 High

    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

    PMID:35657370

    Open questions at the time
    • Functional redundancy with CORO1B not fully separated
    • Molecular trigger for cofilin clearance by coronins unresolved
  14. 2026 High

    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

    PMID:41968673

    Open questions at the time
    • Structural definition of the second actin-binding site pending
    • Mechanistic link from branched actin to autophagosome closure incomplete
  15. 2026 Medium

    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

    PMID:41912501

    Open questions at the time
    • Signals controlling CORO1C SUMOylation unknown
    • Whether SUMOylation regulates non-cancer functions untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • 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.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-9612973 Autophagy 1
Partners
ARPC (ARP2/3 COMPLEX)CFL1PAK4PLS3RAB27ARAD23BRCC2UBE2I

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 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. Recombinant protein biochemistry (in vitro F-actin binding/cross-linking assay), GFP-fusion live-cell imaging, subcellular fractionation, deletion mutagenesis The Journal of biological chemistry High 12377779
2000 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. Immunocytochemical staining with F-actin co-localization, FISH chromosomal mapping, cDNA sequence analysis Cytogenetics and cell genetics Medium 10828594
2005 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. GFP-tagged coronin 3 overexpression and truncation mutants in differentiating neuronal cell lines, PMA treatment The European journal of neuroscience Medium 15813925
2006 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. GFP-tagged fusion proteins, RNAi silencing, functional assays (wound healing, endocytosis), co-immunoprecipitation/pulldown for Arp2/3 and cofilin interaction Experimental cell research Medium 17274980
2008 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. Co-immunoprecipitation, RNAi knockdown, dominant-negative constructs, fluorescent endocytosis assay (FM4-64), genetic epistasis with Rab27a mutants Journal of cell science High 18768935
2008 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. shRNA knockdown, cell proliferation assay, cell motility assay, matrix invasion assay The Journal of pathology Medium 18189330
2010 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. Immunofluorescence, GFP-fusion live-cell imaging, siRNA knockdown of Rab27a, overexpression of Rab27a mutants and GAP Biochemical and biophysical research communications Medium 20362548
2012 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. Lentiviral shRNA knockdown, migration/invasion assays, tail-vein metastasis mouse model, PCR array Molecular cancer Medium 22974233
2016 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. Proteomics, co-immunoprecipitation, fluid-phase endocytosis assay, F-actin quantification, zebrafish Smn knockdown rescue experiment American journal of human genetics High 27499521
2017 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. siRNA knockdown of YBX1 and CORO1C, luciferase reporter assay, migration and invasion assays, overexpression experiments BMC cancer Medium 28302118
2021 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. Co-immunoprecipitation, immunofluorescence co-localization, invadopodia assay, matrix degradation assay, siRNA knockdown, xenograft mouse model Cancer letters Medium 34062216
2022 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. Co-immunoprecipitation, domain mapping (CE domain constructs), phosphomutant analysis, immunofluorescence localization, migration assays Acta biochimica et biophysica Sinica Medium 35593474
2022 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. Conditional knockout cell lines, live-cell imaging of lamellipodia dynamics, F-actin quantification, fluorescence microscopy, haptotaxis assay, Arp2/3 inhibition The Journal of cell biology High 35657370
2026 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. Genome-wide haploid loss-of-function screen, CRISPR/KO mouse model, immunoprecipitation, immunofluorescence, transmission electron microscopy, autophagy flux assays Autophagy High 41968673
2026 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. Immunoprecipitation-mass spectrometry identification, mutagenesis of SUMOylation sites (K19/K311/K440), functional assays (migration, invasion, proliferation), in vivo tumorigenesis, UBC9 genetic ablation Cell death & disease Medium 41912501

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 The Power of Human Protective Modifiers: PLS3 and CORO1C Unravel Impaired Endocytosis in Spinal Muscular Atrophy and Rescue SMA Phenotype. American journal of human genetics 133 27499521
2002 Oligomerization, F-actin interaction, and membrane association of the ubiquitous mammalian coronin 3 are mediated by its carboxyl terminus. The Journal of biological chemistry 77 12377779
2017 YBX1 gene silencing inhibits migratory and invasive potential via CORO1C in breast cancer in vitro. BMC cancer 67 28302118
2008 The GDP-dependent Rab27a effector coronin 3 controls endocytosis of secretory membrane in insulin-secreting cell lines. Journal of cell science 59 18768935
2012 Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K. Molecular cancer 53 22974233
2010 Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration. The Journal of pathology 52 20690162
2020 MiR-206 may suppress non-small lung cancer metastasis by targeting CORO1C. Cellular & molecular biology letters 51 32206066
2008 Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy. The Journal of pathology 49 18189330
2006 Coronin 3 involvement in F-actin-dependent processes at the cell cortex. Experimental cell research 49 17274980
2021 A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis. The Journal of biological chemistry 47 34534547
2021 Circ_0003998 Regulates the Progression and Docetaxel Sensitivity of DTX-Resistant Non-Small Cell Lung Cancer Cells by the miR-136-5p/CORO1C Axis. Technology in cancer research & treatment 32 33511909
2020 Suppression of long non-coding RNA MALAT1 inhibits survival and metastasis of esophagus cancer cells by sponging miR-1-3p/CORO1C/TPM3 axis. Molecular and cellular biochemistry 28 32468237
2021 Cytoplasmic RAD23B interacts with CORO1C to synergistically promote colorectal cancer progression and metastasis. Cancer letters 25 34062216
2000 Isolation and chromosomal assignment of a novel human gene, CORO1C, homologous to coronin-like actin-binding proteins. Cytogenetics and cell genetics 24 10828594
2005 Coronin 3 and its role in murine brain morphogenesis. The European journal of neuroscience 23 15813925
2022 Coro1B and Coro1C regulate lamellipodia dynamics and cell motility by tuning branched actin turnover. The Journal of cell biology 21 35657370
2020 miR-133a-3p Regulates Hepatocellular Carcinoma Progression Through Targeting CORO1C. Cancer management and research 20 33061567
2022 Circ_0020123 plays an oncogenic role in non-small cell lung cancer depending on the regulation of miR-512-3p/CORO1C. Thoracic cancer 13 35388975
2019 miR-26 suppresses renal cell cancer via down-regulating coronin-3. Molecular and cellular biochemistry 13 31595425
2010 Glucose-induced translocation of coronin 3 regulates the retrograde transport of the secretory membrane in the pancreatic beta-cells. Biochemical and biophysical research communications 13 20362548
2021 Depletion of Circular RNA circ_CORO1C Suppresses Gastric Cancer Development by Modulating miR-138-5p/KLF12 Axis. Cancer management and research 10 34007212
2022 CircRNA CORO1C Regulates miR-654-3p/USP7 Axis to Mediate Laryngeal Squamous Cell Carcinoma Progression. Biochemical genetics 9 35064359
2020 Coronin 3 Promotes the Development of Oncogenic Properties in Glioma Through the Wnt/β-Catenin Signaling Pathway. OncoTargets and therapy 8 32764958
2022 Circ_0025039 acts an oncogenic role in the progression of non-small cell lung cancer through miR-636-dependent regulation of CORO1C. Molecular and cellular biochemistry 6 35034254
2022 CORO1C, a novel PAK4 binding protein, recruits phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells. Acta biochimica et biophysica Sinica 5 35593474
2024 Down-regulation of CORO1C mediated by lncMALAT1/miR-133a-3p axis contributes to trophoblast dysfunction and preeclampsia. Placenta 4 39278098
2023 Molecular characterization of the unusual peptide CORO1C-47aa encoded by the circular RNA and docking simulations with its binding partner. Gene 4 37286017
2017 Coronin 3 negatively regulates G6PC3 in HepG2 cells, as identified by label‑free mass‑spectrometry. Molecular medicine reports 4 28713988
2024 The neurodevelopmental regulatory role and clinical value of hsa-circ-CORO1C-hsa-miR-708-3p-JARID2 + LNPEP axis in early-onset schizophrenia. Schizophrenia (Heidelberg, Germany) 3 39702523
2022 DLEU7-AS1 promotes renal cell cancer by silencing the miR-26a-5p/coronin-3 axis. Clinical kidney journal 3 35892027
2026 UBC9-mediated SUMOylation of CORO1C drives lung adenocarcinoma progression via Arp2/3-dependent cytoskeletal remodeling. Cell death & disease 0 41912501
2026 CORO1C (coronin 1C) promotes autophagosome formation by coordinating branched actin network dynamics. Autophagy 0 41968673
2024 Coronin 3 Promotes the Development of Oncogenic Properties in Glioma Through the Wnt/β-Catenin Signaling Pathway [Retraction]. OncoTargets and therapy 0 38414760

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