{"gene":"CORO1A","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":2007,"finding":"Coronin 1 is actively recruited to mycobacterial phagosomes and blocks lysosomal delivery by activating the Ca2+-dependent phosphatase calcineurin; in coronin 1-deficient macrophages, calcineurin activity does not occur upon mycobacterial infection, resulting in lysosomal delivery and killing of mycobacteria.","method":"Coronin 1-deficient mouse macrophages, calcineurin activity assays, cyclosporin A/FK506 pharmacological inhibition, phagosome-lysosome fusion assays","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with defined molecular mechanism (calcineurin activation), pharmacological validation, replicated across multiple approaches in one rigorous study","pmids":["17632055"],"is_preprint":false},{"year":2006,"finding":"Coronin 1 exerts an inhibitory effect on cellular steady-state F-actin formation via an Arp2/3-dependent mechanism and is required for chemokine-mediated T cell migration, but is dispensable for T cell antigen receptor functions.","method":"Coronin 1-deficient (knockout) mice, F-actin quantification, chemotaxis assays, TCR functional assays","journal":"Science","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with multiple orthogonal cellular readouts including Arp2/3-dependent mechanism and migration assays","pmids":["16902139"],"is_preprint":false},{"year":2008,"finding":"Upon T cell receptor triggering, coronin 1 is required for generation of inositol-1,4,5-trisphosphate (IP3) from PIP2, thereby enabling Ca2+ mobilization from intracellular stores, IL-2 production, T cell proliferation, and T cell survival.","method":"Coronin 1-deficient mice, IP3 measurement, Ca2+ mobilization assays, T cell functional assays (proliferation, IL-2 production, survival)","journal":"Nature immunology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with multiple orthogonal functional readouts establishing direct pathway placement (TCR→coronin1→IP3→Ca2+)","pmids":["18345003"],"is_preprint":false},{"year":2005,"finding":"Coronin 1 forms coiled-coil-mediated homotrimeric complexes that associate with the plasma membrane via the N-terminal WD repeat domain and with the cytoskeleton via positively charged residues in a linker region between the WD domain and C-terminal coiled coil.","method":"Domain deletion mutagenesis, co-immunoprecipitation, fractionation assays, biochemical reconstitution of trimeric complexes","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — mutagenesis of distinct domains combined with biochemical fractionation and co-IP, single lab with multiple orthogonal methods","pmids":["15800061"],"is_preprint":false},{"year":2006,"finding":"Crystal structure of murine coronin 1 (without leucine zipper) at 1.75 Å resolution reveals a seven-bladed beta propeller composed of five canonical WD40 repeats and two additional non-canonical blades; the C-terminal extension packs against the bottom of the propeller and is required for structural stability; conserved surface residues delineate potential F-actin binding sites.","method":"X-ray crystallography at 1.75 Å resolution","journal":"Structure","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution crystal structure with structural validation","pmids":["16407068"],"is_preprint":false},{"year":2005,"finding":"Coronin 1 (p57) forms homodimers mediated by a leucine zipper structure in its C-terminal coiled-coil domain; mutation of two leucines in the zipper abolishes dimerization, and the C-terminal region enables co-localization with cortical F-actin only when full-length coronin 1 is co-expressed.","method":"Size-exclusion chromatography, sucrose density gradient, co-immunoprecipitation in COS-1 cells, leucine-to-alanine mutagenesis, GFP fusion co-localization","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro biochemical assays plus mutagenesis and co-IP, multiple orthogonal methods in one study","pmids":["15601263"],"is_preprint":false},{"year":2005,"finding":"Coronin 1 is required for an early step of phagosome formation: TAT-WD dominant-negative constructs diminish lamellipodial extensions, actin accumulation at the base of bound particles, and Arp3 accumulation at the phagosome, without affecting opsonized RBC binding or receptor clustering.","method":"Dominant-negative TAT-fusion protein introduction into RAW 264.7 cells, phagocytosis assays, Arp3 localization by immunofluorescence","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — dominant-negative approach with multiple cellular readouts, single lab","pmids":["15829569"],"is_preprint":false},{"year":2007,"finding":"Mycobacterial lipoamide dehydrogenase C (LpdC) binds coronin 1 in a cholesterol-dependent manner (identified by GST-coronin 1 pulldown and mass spectrometry), retaining coronin 1 on the phagosomal membrane to arrest phagosome maturation; M. smegmatis overexpressing LpdC acquired the capacity to retain coronin 1 and prolong intracellular survival.","method":"GST pulldown, mass spectrometry identification, cell-free binding assays, IFNγ-induced phagolysosome fusion assays, M. smegmatis LpdC overexpression","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical pulldown with MS identification plus functional gain-of-function in bacteria, single lab","pmids":["17652161"],"is_preprint":false},{"year":2007,"finding":"RNA interference knockdown of coronin 1 in J774 macrophages does not affect phagocytosis, macropinocytosis, cell locomotion, or NADPH oxidase activity, but causes rapid lysosomal delivery and killing of internalized mycobacteria, demonstrating that coronin 1's role in mycobacterial phagosome regulation is distinct from its (dispensable) role in actin-mediated processes.","method":"siRNA knockdown in J774 macrophages, phagocytosis/macropinocytosis/locomotion assays, NADPH oxidase activity assays, lysosomal delivery and bacterial killing assays","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — RNAi loss-of-function with multiple orthogonal functional readouts, corroborating prior genetic evidence","pmids":["18162581"],"is_preprint":false},{"year":2008,"finding":"Phorbol ester (PMA) stimulation induces phosphorylation of p57/coronin 1 via protein kinase C, which reduces the protein's association with the actin cytoskeleton; phosphorylated coronin 1 showed lower affinity for F-actin in co-sedimentation assays, and during phagocytosis in differentiated HL60 cells coronin 1 dissociation from the actin cytoskeleton was concurrent with enhanced phosphorylation.","method":"Cell fractionation, 2D gel electrophoresis, co-sedimentation with F-actin, affinity chromatography, fluorescence microscopy in HL60 cells","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — multiple orthogonal biochemical methods (fractionation, F-actin co-sedimentation, affinity chromatography) in a single rigorous study","pmids":["18693254"],"is_preprint":false},{"year":2013,"finding":"In sympathetic neurons, the NGF-TrkA signaling endosome induces expression and recruitment of Coronin 1 upon arrival at the cell body; Coronin 1 prevents premature lysosomal fusion of the signaling endosome (6–10-fold faster fusion in absence), enables endosomal recycling/re-internalization, and is required for NGF-TrkA-dependent calcium release, calcineurin activation, and CREB phosphorylation.","method":"Mouse sympathetic neuron culture with Coro1a KO, live imaging of endosome trafficking, lysosomal fusion kinetics, calcium imaging, calcineurin activity assays, CREB phosphorylation by Western blot","journal":"Nature neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with multiple orthogonal functional readouts including live imaging, signaling assays, and quantified trafficking kinetics","pmids":["24270184"],"is_preprint":false},{"year":2014,"finding":"Coronin 1 interacts with the G protein subtype Gαs upon cell surface stimulation to activate the cAMP/PKA pathway in neurons; coronin 1-deficient mice lack cAMP/PKA-dependent presynaptic plasticity and exhibit neurobehavioral deficits that are rescued by membrane-permeable cAMP analogue infusion; coronin 1 mutants unable to bind Gαs fail to stimulate cAMP signaling.","method":"Co-immunoprecipitation (coronin 1–Gαs interaction), cAMP measurement, electrophysiology in amygdala, behavioral assays, in vivo cAMP analogue rescue in Coro1a KO mice, mutagenesis of Gαs-binding interface","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, mutagenesis, in vivo rescue, and electrophysiology in one study, single lab with multiple orthogonal methods","pmids":["24667537"],"is_preprint":false},{"year":2011,"finding":"Coronin 1 does not modulate F-actin levels in naive T cells and F-actin induction does not cause apoptosis; instead, coronin 1 provides pro-survival signals whose absence leads to rapid T cell apoptosis.","method":"Coronin 1 KO mice, F-actin quantification, apoptosis assays, pharmacological F-actin manipulation","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO with functional readouts, explicitly refuting prior F-actin model; single lab","pmids":["21339362"],"is_preprint":false},{"year":2009,"finding":"Coronin 1 is essential for IgM-induced intracellular Ca2+ mobilization and B cell proliferation upon BCR triggering, but is dispensable when costimulatory signals are present, consistent with normal in vivo B cell immune responses in coronin 1-deficient mice.","method":"Coronin 1 KO mice, Ca2+ mobilization assays, B cell proliferation assays, in vivo immunization","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO with multiple readouts, single lab","pmids":["19201848"],"is_preprint":false},{"year":2012,"finding":"Phosphorylation of coronin 1 at Thr-412 constitutively turns over in HL60 cells; the Thr-412-phosphorylated form fails to co-immunoprecipitate with β-actin, and the phosphomimetic T412D mutant shows reduced actin affinity compared to wild-type or the non-phosphorylatable T412A mutant, demonstrating that Thr-412 phosphorylation controls coronin 1–actin interaction.","method":"MALDI-TOF-MS, Phos-tag gel electrophoresis, site-directed mutagenesis (T412D, T412A), co-immunoprecipitation with β-actin, calyculin A treatment","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — mass spectrometry-identified site with mutagenesis, co-IP, and phosphatase inhibitor validation; multiple orthogonal methods in one study","pmids":["23100250"],"is_preprint":false},{"year":2015,"finding":"Upon cytokine stimulation of macrophages, phosphorylated coronin 1 transiently associates with 14-3-3ζ (and RACK1); 14-3-3ζ (but not RACK1) is required for coronin 1 relocation from the cell cortex to the cytoplasm, PI3-kinase activation, and induction of macropinocytosis.","method":"Co-immunoprecipitation of phospho-coronin 1 with 14-3-3ζ/RACK1, siRNA knockdown of 14-3-3ζ and RACK1, coronin 1 localization by imaging, PI3K activity assay, macropinocytosis assay","journal":"The FEBS journal","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP plus siRNA knockdown with functional readouts, single lab","pmids":["25645340"],"is_preprint":false},{"year":2014,"finding":"Coronin 1 trimerization (via C-terminal coiled coil) is essential for protecting mycobacteria from lysosomal delivery and for calcineurin activation in macrophages; macrophage activation induces serine phosphorylation of coronin 1 that causes monomerization, thereby relieving protection.","method":"Trimerization-defective coronin 1 mutants expressed in macrophages, calcineurin activity assays, mycobacterial survival assays, phosphorylation analysis","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis with functional calcineurin and survival assays, single lab","pmids":["25217836"],"is_preprint":false},{"year":2016,"finding":"Cyclin-dependent kinase 5 (CDK5) phosphorylates coronin 1 on Thr418/424, and this phosphorylation is required for coronin 1–Gαs association and subsequent cAMP/PKA pathway activation.","method":"Phosphorylation site mutagenesis (Thr418/424), CDK5 activity modulation, co-immunoprecipitation of coronin 1 with Gαs, cAMP measurement","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mutagenesis plus Co-IP and cAMP assay, single lab","pmids":["26823173"],"is_preprint":false},{"year":2015,"finding":"In sympathetic neurons, Coronin 1 (downstream of NGF-TrkA) suppresses axon growth and branching by activating PLC-γ1-dependent calcium release, which releases PI3K-dependent suppression of GSK3β; Coro1a−/− mice display sympathetic axon overgrowth and overbranching in the developing heart.","method":"Coro1a KO mice, in vivo axon morphology analysis in developing heart, PLC-γ1/PI3K/GSK3β signaling pathway epistasis assays, calcium imaging","journal":"The Journal of neuroscience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO with in vivo phenotype and signaling pathway placement, single lab","pmids":["25740518"],"is_preprint":false},{"year":2019,"finding":"Coronin 1 deficiency increases cyclic AMP (cAMP) concentrations in T cells (by relieving PDE4-mediated cAMP degradation), which suppresses allo-specific T cell responses; costimulation induced on microbe-infected APCs overcomes cAMP-mediated immunosuppression to maintain anti-pathogen immunity.","method":"Coronin 1 KO mice, cAMP measurement, pharmacological cAMP/PDE4 modulation, allograft models, T cell transfer experiments","journal":"Immunity","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with multiple orthogonal mechanistic validations (cAMP measurement, pharmacological, in vivo rescue), single lab but multiple methods","pmids":["30611611"],"is_preprint":false},{"year":2021,"finding":"Coronin 1 maintains basal PI3Kδ activity in naive T cells, thereby suppressing caspase 8-mediated apoptosis; this pathway operates independently of TCR and IL-7 signaling.","method":"Coronin 1 KO mice, PI3Kδ activity assay, caspase 8 activity assay, genetic and pharmacological PI3Kδ inhibition, epistasis analysis with TCR/IL-7 pathways","journal":"Science signaling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO with pathway epistasis and caspase activity assays, single lab","pmids":["34932374"],"is_preprint":false},{"year":2021,"finding":"Coronin 1 (CORO1A) is phosphorylated at Thr-412 specifically by PKCα (not PKCβ) in human phagocytic cells; this phosphorylation prevents dissociation of coronin 1 from phagosomes when PKCα is inhibited, linking PKCα-mediated Thr-412 phosphorylation to coronin 1 intracellular redistribution during phagocytosis.","method":"PKC isoform-specific inhibitors, siRNA knockdown of PKCα vs. PKCβ, in vitro kinase assay with recombinant PKCα/PKCβ, confocal fluorescence microscopy of coronin 1 localization during phagocytosis","journal":"Biochemistry and biophysics reports","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro kinase assay plus isoform-specific siRNA with functional localization readout, multiple orthogonal methods in one study","pmids":["34189278"],"is_preprint":false},{"year":2015,"finding":"A CORO1A frameshift mutation (S401fs) that replaces the last 61 C-terminal amino acids abolishes oligomerization and impairs cytoskeletal association of coronin 1 in patient lymphocytes, resulting in increased filamentous actin accumulation, severely defective thymic output, and impaired T cell survival, but normal calcium flux and cytotoxicity; demonstrating that C-terminal domain integrity is required for oligomerization and T cell homeostasis.","method":"Whole-genome sequencing, Western blot, biochemical oligomerization assay, cytoskeletal association assay (fractionation), flow cytometry of F-actin, T cell survival and thymic output analyses in patient cells","journal":"The Journal of allergy and clinical immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — patient mutation with biochemical dissection of domain function (oligomerization, cytoskeletal association) and functional readouts; single kindred","pmids":["26476480"],"is_preprint":false},{"year":2004,"finding":"Coronin 1 is in equilibrium between the cytosol and the cell cortex in T lymphocytes and accumulates in F-actin-rich membrane protrusions upon polarized TCR-CD3 stimulation, placing it at sites of actin remodeling during T cell activation.","method":"Subcellular fractionation, immunofluorescence and confocal microscopy of Coronin 1 localization in TCR-stimulated T cells","journal":"International immunology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by immunofluorescence and fractionation, multiple cell contexts, single lab","pmids":["14734608"],"is_preprint":false},{"year":2008,"finding":"p57/coronin 1 and F-actin co-localize at sites of L. pneumophila adherence to macrophage-like cells (an actin polymerization-dependent event), but live L. pneumophila actively excludes p57/coronin 1 from its phagosome throughout infection, in contrast to opsonized zymosan or heat-killed bacteria which show transient coronin 1 accumulation.","method":"Fluorescence microscopy, cytochalasin D (actin polymerization inhibitor) treatment, comparison of live vs. heat-killed bacteria, U937 macrophage-like cells","journal":"Biological & pharmaceutical bulletin","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single imaging study with pharmacological inhibitor, single lab, no mechanistic dissection of exclusion mechanism","pmids":["18451508"],"is_preprint":false},{"year":2023,"finding":"CREBH transcriptionally represses Coro1a expression; overexpression of Coro1a in liver cells inhibited autophagic flux and elevated inflammatory cytokines upon palmitic acid stimulation, identifying Coro1a as a negative regulator of autophagosome-lysosome fusion in hepatocytes.","method":"Luciferase reporter assay (CREBH on Coro1a promoter), Coro1a overexpression in LO2 liver cells, autophagy flux assays (LC3-II, p62, LAMP1), inflammatory cytokine measurement","journal":"Biochimica et biophysica acta. Molecular basis of disease","confidence":"Low","confidence_rationale":"Tier 3 / Weak — overexpression with functional readouts but no KO rescue or mechanistic dissection, single lab, single paper","pmids":["37837948"],"is_preprint":false},{"year":2025,"finding":"Coronin 1A (Coro1A) localizes to growth cones and filopodia, interacts with TRIM67 (a brain-enriched E3 ubiquitin ligase that binds the netrin receptor DCC), and is required for netrin-1-dependent axon turning, branching, and corpus callosum development; a Coro1A mutant deficient in TRIM67 binding cannot rescue loss-of-Coro1A phenotypes.","method":"Coro1a KO mice, live imaging and immunofluorescence (growth cone localization), TRIM67-binding deficient Coro1A mutant rescue experiments, in vivo corpus callosum analysis","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO with mutant rescue and in vivo phenotype, single lab; peer-reviewed publication","pmids":["41085995"],"is_preprint":false},{"year":2020,"finding":"In coronin 1-deficient platelets, integrin β2 translocation to the platelet surface upon thrombin stimulation is impaired, while morphological changes, Arp2/3 localization, and cAMP-dependent signaling are unaffected, indicating a specific role for coronin 1 in integrin β2 surface translocation.","method":"Coronin 1 KO mouse platelets, flow cytometry of integrin β2 surface expression, Arp2/3 localization by immunofluorescence, cAMP measurement","journal":"International journal of molecular sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genetic KO with flow cytometry readout, single lab, limited mechanistic follow-up on translocation mechanism","pmids":["31948107"],"is_preprint":false},{"year":2025,"finding":"Coro1a promotes MVB-plasma membrane fusion and exosome biogenesis by activating PKM2 to phosphorylate SNAP-23, which drives SNAP-23 to recruit STX-12 and VAMP7, increasing assembly of the STX-12-SNAP-23-VAMP7 SNARE complex; this function is independent of coronin 1 neddylation.","method":"Co-immunoprecipitation, siRNA knockdown of SNAP-23 and PKM2, PKM2 inhibitor, Coro1a KO in vivo tumor model, neddylation inhibitor MLN4924, EV quantification","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 2–3 / Weak — Co-IP and functional assays with multiple genetic/pharmacological interventions but preprint only, not yet peer-reviewed","pmids":[],"is_preprint":true},{"year":2009,"finding":"Coronin 1 overexpression in differentiated PLB985 cells decreases mitochondrial depolarization and caspase-3/caspase-9 (but not caspase-8 or Bid cleavage) induced by gliotoxin or TRAIL, indicating that coronin 1 protects against the intrinsic (mitochondrial) apoptotic pathway.","method":"Coronin 1 overexpression in PLB985 cells, mitochondrial depolarization assay, caspase activity assays (caspase-3, -8, -9), Bid truncation Western blot","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — overexpression with multiple orthogonal apoptosis readouts dissecting intrinsic vs. extrinsic pathway, single lab","pmids":["19454722"],"is_preprint":false},{"year":2026,"finding":"Coro1a transcription requires both the core promoter (containing GC boxes bound by Sp3 transcription factor at GC box 4) and gene body/intronic regions (containing ETS-binding sequences in introns 1 and 2); mutations in intronic ETS sequences decrease Coro1a transcription, and active histone marks (H3K4me3, H3K27ac) at the intronic region decrease during macrophage-to-osteoclast differentiation concurrent with reduced Coro1a expression.","method":"Reporter (luciferase) assays, promoter deletion analysis, chromatin immunoprecipitation for Sp3, DNase sequencing (chromatin accessibility), histone modification ChIP, site-directed mutagenesis of ETS sites","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (reporter assay, mutagenesis, ChIP) establishing transcriptional regulation mechanism, single lab","pmids":["41456103"],"is_preprint":false}],"current_model":"CORO1A (coronin 1) is a leukocyte-enriched, seven-bladed WD40 beta-propeller protein that homotrimerizes via a C-terminal coiled coil/leucine zipper; it associates with the plasma membrane through its WD domain and with the actin cytoskeleton through a positively charged linker region, and its cytoskeletal association is negatively regulated by PKCα-mediated phosphorylation at Thr-412. In macrophages, coronin 1 is recruited to mycobacterial phagosomes where it activates calcineurin via Ca2+ signaling to block phagosome-lysosome fusion, protecting pathogenic mycobacteria—an activity dependent on its trimeric state that is disrupted by serine phosphorylation-induced monomerization. In T cells, coronin 1 is required downstream of TCR stimulation to generate IP3 from PIP2, mobilize intracellular Ca2+, and sustain pro-survival signaling; independently, it maintains basal PI3Kδ activity to suppress caspase 8-mediated apoptosis, and its CDK5-phosphorylation-dependent interaction with Gαs activates the cAMP/PKA pathway important for synaptic plasticity and behavior. In neurons, coronin 1 acts as an effector of the NGF-TrkA signaling endosome to prevent premature lysosomal fusion, enable endosomal recycling, activate calcineurin and CREB, and suppress axon overgrowth through PLC-γ1/Ca2+-dependent inhibition of PI3K-GSK3β signaling; it also collaborates with the E3 ligase TRIM67 downstream of netrin-1 to mediate axon turning and branching."},"narrative":{"mechanistic_narrative":"CORO1A (coronin 1) is a leukocyte-enriched, seven-bladed WD40 beta-propeller protein that functions as a signaling scaffold coupling membrane receptor activation to Ca2+ and cAMP signaling, cytoskeletal regulation, and the control of organelle fusion across immune cells and neurons [PMID:16407068, PMID:18345003, PMID:24270184]. The protein homo-oligomerizes through a C-terminal coiled-coil/leucine zipper, associates with the plasma membrane via its WD domain, and binds the actin cytoskeleton through a positively charged linker; this actin association is negatively regulated by Thr-412 phosphorylation carried out specifically by PKCalpha [PMID:15800061, PMID:15601263, PMID:23100250, PMID:34189278]. In macrophages, coronin 1 is recruited to mycobacterial phagosomes where it activates the Ca2+-dependent phosphatase calcineurin to block phagosome-lysosome fusion and protect pathogenic mycobacteria, an activity that depends on its trimeric state and is relieved by serine-phosphorylation-induced monomerization [PMID:17632055, PMID:18162581, PMID:25217836]. In T cells, coronin 1 acts downstream of TCR triggering to generate IP3 from PIP2 and mobilize intracellular Ca2+ for proliferation, IL-2 production, and survival, while independently sustaining pro-survival signaling by maintaining basal PI3Kdelta activity that suppresses caspase-8-mediated apoptosis and by restraining cAMP through PDE4 to permit alloreactive T cell responses [PMID:18345003, PMID:34932374, PMID:30611611]. Through a CDK5-phosphorylation-dependent interaction with Galphas, coronin 1 activates the cAMP/PKA pathway underlying presynaptic plasticity and behavior [PMID:24667537, PMID:26823173]. In neurons it serves as an effector of the NGF-TrkA signaling endosome, preventing premature lysosomal fusion and enabling recycling, calcineurin activation, and CREB phosphorylation, and it suppresses axon overgrowth via PLC-gamma1/Ca2+-dependent inhibition of PI3K-GSK3beta signaling and collaborates with the E3 ligase TRIM67 downstream of netrin-1 to direct axon turning and branching [PMID:24270184, PMID:25740518, PMID:41085995]. A C-terminal frameshift mutation (S401fs) that abolishes oligomerization causes defective thymic output and impaired T cell survival in patients, linking C-terminal integrity to human T cell homeostasis [PMID:26476480].","teleology":[{"year":2004,"claim":"Establishing where coronin 1 acts in T cells: it was unknown whether the protein was positioned at sites of actin remodeling during T cell activation.","evidence":"Subcellular fractionation and confocal imaging of TCR-stimulated T lymphocytes","pmids":["14734608"],"confidence":"Medium","gaps":["Localization alone did not establish a functional requirement","No molecular partners at the protrusion site identified"]},{"year":2005,"claim":"Defining the molecular architecture: the question was how coronin 1 oligomerizes and engages membrane versus cytoskeleton, resolved by mapping distinct domains for trimerization, membrane, and actin association.","evidence":"Domain-deletion mutagenesis, leucine-zipper mutations, co-IP, fractionation, and biochemical reconstitution in COS-1 cells","pmids":["15800061","15601263"],"confidence":"High","gaps":["Trimer versus dimer stoichiometry described differently across studies","Functional consequence of each domain interaction not yet tested in vivo"]},{"year":2006,"claim":"Determining the three-dimensional fold: the structural basis for WD40 propeller assembly and putative F-actin contacts was unknown until a high-resolution crystal structure resolved the seven-bladed propeller and stabilizing C-terminal extension.","evidence":"X-ray crystallography of murine coronin 1 at 1.75 A","pmids":["16407068"],"confidence":"High","gaps":["Structure lacked the leucine zipper","Predicted F-actin binding surface not validated functionally"]},{"year":2006,"claim":"Testing the cytoskeletal role in vivo: whether coronin 1 governs actin dynamics and migration was resolved by showing it inhibits steady-state F-actin via Arp2/3 and is required for chemokine-driven migration but not TCR function.","evidence":"Coronin 1 knockout mice with F-actin quantification, chemotaxis, and TCR assays","pmids":["16902139"],"confidence":"High","gaps":["Mechanism of Arp2/3-dependent inhibition not detailed","Apparent dispensability for TCR later revised"]},{"year":2007,"claim":"Identifying the pathogen-protective mechanism: it was unknown how coronin 1 blocks mycobacterial killing, answered by demonstrating it activates calcineurin to prevent phagosome-lysosome fusion.","evidence":"Coronin 1-deficient macrophages with calcineurin assays, cyclosporin A/FK506 inhibition, and fusion assays","pmids":["17632055"],"confidence":"High","gaps":["How phagosomal coronin 1 triggers Ca2+/calcineurin not fully resolved","Link between membrane recruitment and calcineurin activation incomplete"]},{"year":2007,"claim":"Identifying a bacterial ligand: the basis for coronin 1 retention on the mycobacterial phagosome was addressed by identifying LpdC as a cholesterol-dependent binding partner that prolongs intracellular survival.","evidence":"GST-coronin 1 pulldown with mass spectrometry, cell-free binding, and M. smegmatis LpdC gain-of-function","pmids":["17652161"],"confidence":"Medium","gaps":["Single lab biochemical interaction without genetic confirmation in pathogenic mycobacteria","Cholesterol-dependence mechanism not structurally defined"]},{"year":2008,"claim":"Separating actin and pathogen functions: RNAi showed coronin 1 is dispensable for phagocytosis, macropinocytosis, locomotion, and oxidase activity but essential to keep mycobacteria from lysosomal killing, isolating its phagosome-regulatory role.","evidence":"siRNA knockdown in J774 macrophages with multiple actin-process and bacterial-killing readouts","pmids":["18162581"],"confidence":"High","gaps":["Does not address coronin 1 actin roles in other phagocyte subtypes"]},{"year":2008,"claim":"Placing coronin 1 in TCR signaling: the prior view that it was dispensable for TCR function was revised by showing it is required to generate IP3 and mobilize Ca2+ for T cell proliferation and survival.","evidence":"Coronin 1 KO mice with IP3 measurement, Ca2+ mobilization, and T cell functional assays","pmids":["18345003"],"confidence":"High","gaps":["Direct biochemical step at which coronin 1 enables IP3 generation unresolved","Whether the effect is through PLC recruitment or another route unclear"]},{"year":2008,"claim":"Defining phosphoregulation of actin binding: PKC-mediated phosphorylation was shown to lower coronin 1 affinity for F-actin and drive its dissociation during phagocytosis.","evidence":"Fractionation, 2D gels, F-actin co-sedimentation, and affinity chromatography in HL60 cells","pmids":["18693254"],"confidence":"High","gaps":["Specific phosphosite not yet identified at this stage","Responsible PKC isoform not yet defined"]},{"year":2009,"claim":"Defining the anti-apoptotic pathway: coronin 1 was shown to protect against the intrinsic mitochondrial apoptotic pathway rather than the extrinsic pathway.","evidence":"Coronin 1 overexpression in PLB985 cells with mitochondrial depolarization and caspase-3/-8/-9 assays","pmids":["19454722"],"confidence":"Medium","gaps":["Overexpression-based; molecular link to mitochondria not defined","Apparent contrast with later caspase-8 findings in T cells unresolved"]},{"year":2009,"claim":"Extending Ca2+ function to B cells: coronin 1 was shown to be required for BCR-induced Ca2+ mobilization and proliferation but bypassable by costimulation, explaining intact in vivo B cell responses.","evidence":"Coronin 1 KO mice with Ca2+ mobilization, proliferation, and immunization assays","pmids":["19201848"],"confidence":"Medium","gaps":["Molecular step in BCR-to-Ca2+ coupling not defined","Costimulatory bypass mechanism unidentified"]},{"year":2011,"claim":"Revising the death model in T cells: it was shown F-actin levels are not altered in naive T cells and do not drive apoptosis; instead coronin 1 provides distinct pro-survival signals.","evidence":"Coronin 1 KO mice with F-actin quantification, apoptosis assays, and pharmacological actin manipulation","pmids":["21339362"],"confidence":"Medium","gaps":["The pro-survival signal itself not molecularly identified here","Single lab refutation of prior model"]},{"year":2012,"claim":"Pinpointing the regulatory phosphosite: Thr-412 phosphorylation was identified as the switch controlling coronin 1-actin interaction.","evidence":"MALDI-TOF-MS, Phos-tag gels, T412D/T412A mutagenesis, and beta-actin co-IP in HL60 cells","pmids":["23100250"],"confidence":"High","gaps":["Kinase responsible not yet assigned in this study","Effect on oligomerization versus actin binding not separated"]},{"year":2013,"claim":"Establishing a neuronal endosome function: coronin 1 was shown to be an NGF-TrkA signaling endosome effector that prevents premature lysosomal fusion and enables Ca2+/calcineurin/CREB signaling.","evidence":"Coro1a KO sympathetic neurons with live imaging, fusion kinetics, calcium imaging, and CREB Western blot","pmids":["24270184"],"confidence":"High","gaps":["Molecular mechanism delaying lysosomal fusion unresolved","How coronin 1 is recruited to the signaling endosome unclear"]},{"year":2014,"claim":"Linking coronin 1 to cAMP/PKA: a Galphas interaction was shown to activate cAMP/PKA signaling required for presynaptic plasticity and behavior, rescuable by cAMP analogues in vivo.","evidence":"Reciprocal co-IP, cAMP measurement, amygdala electrophysiology, behavior, and in vivo cAMP rescue in Coro1a KO mice","pmids":["24667537"],"confidence":"High","gaps":["Stimulus that triggers coronin 1-Galphas coupling not fully defined","Relationship to its actin/Ca2+ roles unclear"]},{"year":2014,"claim":"Connecting oligomeric state to pathogen protection: trimerization was shown to be essential for calcineurin activation and mycobacterial protection, with macrophage-induced serine phosphorylation causing monomerization that relieves protection.","evidence":"Trimerization-defective mutants in macrophages with calcineurin and survival assays","pmids":["25217836"],"confidence":"Medium","gaps":["Specific monomerizing phosphosite not identified","Kinase driving monomerization unknown"]},{"year":2015,"claim":"Defining cytokine-induced relocalization machinery: phospho-coronin 1 was shown to bind 14-3-3zeta, which drives its cortex-to-cytoplasm relocation, PI3K activation, and macropinocytosis.","evidence":"Co-IP of phospho-coronin 1 with 14-3-3zeta/RACK1, siRNA knockdown, and macropinocytosis assays","pmids":["25645340"],"confidence":"Medium","gaps":["Single lab Co-IP-based interaction","How 14-3-3zeta binding couples to PI3K activation unresolved"]},{"year":2015,"claim":"Defining the axon-suppression pathway: coronin 1 was shown to restrain axon growth and branching by PLC-gamma1/Ca2+-dependent inhibition of PI3K-GSK3beta signaling, with KO causing cardiac sympathetic axon overgrowth.","evidence":"Coro1a KO mice with in vivo axon morphology and PLC-gamma1/PI3K/GSK3beta epistasis plus calcium imaging","pmids":["25740518"],"confidence":"Medium","gaps":["Direct molecular target of coronin 1 in this cascade unidentified","Single lab pathway placement"]},{"year":2016,"claim":"Assigning the kinase for Galphas coupling: CDK5 was shown to phosphorylate coronin 1 at Thr418/424, a modification required for Galphas association and cAMP/PKA activation.","evidence":"Phosphosite mutagenesis, CDK5 modulation, coronin 1-Galphas co-IP, and cAMP measurement","pmids":["26823173"],"confidence":"Medium","gaps":["Structural basis of the phospho-dependent Galphas interface unknown","Single lab"]},{"year":2015,"claim":"Connecting domain integrity to human disease: a C-terminal frameshift (S401fs) was shown to abolish oligomerization and cytoskeletal association, producing defective thymic output and impaired T cell survival in patients.","evidence":"Whole-genome sequencing, oligomerization and fractionation assays, and patient T cell phenotyping","pmids":["26476480"],"confidence":"Medium","gaps":["Single kindred","Normal Ca2+ flux despite oligomerization loss not fully reconciled with prior models"]},{"year":2019,"claim":"Refining cAMP control in T cells: coronin 1 deficiency was shown to raise cAMP by relieving PDE4-mediated degradation, suppressing alloreactive T cell responses while sparing anti-pathogen immunity.","evidence":"Coronin 1 KO mice with cAMP measurement, PDE4 pharmacology, allograft, and T cell transfer models","pmids":["30611611"],"confidence":"High","gaps":["How coronin 1 regulates PDE4 activity mechanistically unresolved","Reconciliation with Galphas-mediated cAMP activation in neurons unclear"]},{"year":2021,"claim":"Defining a TCR-independent survival mechanism: coronin 1 was shown to maintain basal PI3Kdelta activity that suppresses caspase-8-mediated apoptosis independently of TCR and IL-7.","evidence":"Coronin 1 KO mice with PI3Kdelta and caspase-8 assays plus genetic/pharmacological epistasis","pmids":["34932374"],"confidence":"Medium","gaps":["How coronin 1 sustains basal PI3Kdelta unknown","Relationship to the earlier intrinsic-apoptosis finding unresolved"]},{"year":2021,"claim":"Assigning the Thr-412 kinase in phagocytes: PKCalpha (not PKCbeta) was shown to phosphorylate Thr-412, controlling coronin 1 redistribution from phagosomes.","evidence":"Isoform-specific inhibitors and siRNA, in vitro kinase assays, and confocal localization in human phagocytes","pmids":["34189278"],"confidence":"High","gaps":["Upstream activation of PKCalpha during phagocytosis not defined","Single lab"]},{"year":2025,"claim":"Extending the neuronal role to guidance: coronin 1 was shown to act with the E3 ligase TRIM67 downstream of netrin-1/DCC for axon turning, branching, and corpus callosum development.","evidence":"Coro1a KO mice, growth cone imaging, TRIM67-binding-deficient rescue, and in vivo corpus callosum analysis","pmids":["41085995"],"confidence":"Medium","gaps":["Whether coronin 1 is a TRIM67 ubiquitination substrate unresolved","Single lab"]},{"year":2026,"claim":"Defining transcriptional control of CORO1A: combined core-promoter Sp3/GC-box and intronic ETS elements were shown to drive expression, with active histone marks declining during osteoclast differentiation.","evidence":"Luciferase reporters, promoter deletions, Sp3 ChIP, DNase-seq, and histone ChIP","pmids":["41456103"],"confidence":"Medium","gaps":["ETS factor identity not pinned down","Link between expression decline and osteoclast function not established"]},{"year":null,"claim":"How coronin 1 functionally integrates its actin-binding, oligomerization, and phospho-switch states into the divergent calcineurin, IP3/Ca2+, cAMP/PKA, and PI3K outputs across cell types remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified biochemical model connecting oligomeric state to each signaling output","Direct enzymatic targets versus scaffolding roles not separated","Apparent opposite effects on cAMP (PDE4 versus Galphas) not mechanistically reconciled"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[3,9,14]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[11,26,15]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[4,3]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,2,19]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[3,23]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[3,23,15]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[3,5,9]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[0,10]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[2,19,13]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[11,18,10]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,10]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[20,29]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[11,18,26]}],"complexes":["coronin 1 homotrimer"],"partners":["GNAS (GALPHAS)","TRIM67","YWHAZ (14-3-3ZETA)","ACTB (BETA-ACTIN)","CDK5","PRKCA (PKCALPHA)","LPDC (MYCOBACTERIAL)"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P31146","full_name":"Coronin-1A","aliases":["Coronin-like protein A","Clipin-A","Coronin-like protein p57","Tryptophan aspartate-containing coat protein","TACO"],"length_aa":461,"mass_kda":51.0,"function":"May be a crucial component of the cytoskeleton of highly motile cells, functioning both in the invagination of large pieces of plasma membrane, as well as in forming protrusions of the plasma membrane involved in cell locomotion. In mycobacteria-infected cells, its retention on the phagosomal membrane prevents fusion between phagosomes and lysosomes","subcellular_location":"Cytoplasm, cytoskeleton; Cytoplasm, cell cortex; Cytoplasmic vesicle, phagosome membrane","url":"https://www.uniprot.org/uniprotkb/P31146/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CORO1A","classification":"Not Classified","n_dependent_lines":23,"n_total_lines":1208,"dependency_fraction":0.01903973509933775},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CORO1A","total_profiled":1310},"omim":[{"mim_id":"615401","title":"IMMUNODEFICIENCY 8 WITH LYMPHOPROLIFERATION; IMD8","url":"https://www.omim.org/entry/615401"},{"mim_id":"611913","title":"CHROMOSOME 16p11.2 DELETION SYNDROME, 593-KB","url":"https://www.omim.org/entry/611913"},{"mim_id":"609888","title":"LEPROSY, SUSCEPTIBILITY TO, 1; LPRS1","url":"https://www.omim.org/entry/609888"},{"mim_id":"605269","title":"CORONIN 1C; CORO1C","url":"https://www.omim.org/entry/605269"},{"mim_id":"605002","title":"CORONIN 2B; CORO2B","url":"https://www.omim.org/entry/605002"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"bone marrow","ntpm":525.4},{"tissue":"lymphoid tissue","ntpm":544.1}],"url":"https://www.proteinatlas.org/search/CORO1A"},"hgnc":{"alias_symbol":["HCORO1","p57","coronin-1"],"prev_symbol":[]},"alphafold":{"accession":"P31146","domains":[{"cath_id":"2.130.10.10","chopping":"14-376","consensus_level":"medium","plddt":96.9515,"start":14,"end":376}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P31146","model_url":"https://alphafold.ebi.ac.uk/files/AF-P31146-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P31146-F1-predicted_aligned_error_v6.png","plddt_mean":93.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CORO1A","jax_strain_url":"https://www.jax.org/strain/search?query=CORO1A"},"sequence":{"accession":"P31146","fasta_url":"https://rest.uniprot.org/uniprotkb/P31146.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P31146/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P31146"}},"corpus_meta":[{"pmid":"17632055","id":"PMC_17632055","title":"Survival of 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Allograft Tolerance While Maintaining Immunity Against Microbial Pathogens: Does Coronin 1 Hold a Key?","date":"2020","source":"Transplantation","url":"https://pubmed.ncbi.nlm.nih.gov/31895336","citation_count":4,"is_preprint":false},{"pmid":"39709909","id":"PMC_39709909","title":"Kif15 regulates Coro1a+ cell migration and phagocytosis in zebrafish after spinal cord injury.","date":"2024","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/39709909","citation_count":3,"is_preprint":false},{"pmid":"34189278","id":"PMC_34189278","title":"Coronin-1 is phosphorylated at Thr-412 by protein kinase Cα in human phagocytic cells.","date":"2021","source":"Biochemistry and biophysics reports","url":"https://pubmed.ncbi.nlm.nih.gov/34189278","citation_count":3,"is_preprint":false},{"pmid":"35526384","id":"PMC_35526384","title":"Carbamazepine-modified HLA-A*24:02-bound peptidome: Implication of CORO1A in skin rash.","date":"2022","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/35526384","citation_count":3,"is_preprint":false},{"pmid":"41085995","id":"PMC_41085995","title":"Coro1A and TRIM67 collaborate in netrin-dependent neuronal morphogenesis.","date":"2025","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/41085995","citation_count":2,"is_preprint":false},{"pmid":"34812410","id":"PMC_34812410","title":"Major Outer Membrane Protein from Legionella pneumophila Inhibits Phagocytosis but Enhances Chemotaxis of RAW 264.7 Macrophages by Regulating the FOXO1/Coronin-1 Axis.","date":"2021","source":"Journal of immunology research","url":"https://pubmed.ncbi.nlm.nih.gov/34812410","citation_count":2,"is_preprint":false},{"pmid":"38030242","id":"PMC_38030242","title":"Coronin-1 promotes directional cell rearrangement in Drosophila wing epithelium.","date":"2023","source":"Cell structure and function","url":"https://pubmed.ncbi.nlm.nih.gov/38030242","citation_count":1,"is_preprint":false},{"pmid":"38737939","id":"PMC_38737939","title":"Coronin 1-dependent cell density sensing and regulation of the peripheral T cell population size.","date":"2024","source":"Oxford open immunology","url":"https://pubmed.ncbi.nlm.nih.gov/38737939","citation_count":1,"is_preprint":false},{"pmid":"40696745","id":"PMC_40696745","title":"Coronin 1 deficiency protects from the development of autoimmune myocarditis by reducing CD4+ T cells.","date":"2025","source":"ESC heart failure","url":"https://pubmed.ncbi.nlm.nih.gov/40696745","citation_count":1,"is_preprint":false},{"pmid":"40166342","id":"PMC_40166342","title":"Coro1A and TRIM67 collaborate in netrin-dependent neuronal morphogenesis.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40166342","citation_count":0,"is_preprint":false},{"pmid":"41456103","id":"PMC_41456103","title":"Dual regulation of coronin-1 expression by the core promoter and intronic regions.","date":"2026","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/41456103","citation_count":0,"is_preprint":false},{"pmid":"42153148","id":"PMC_42153148","title":"Integrated analysis of programmed cell death-related genes identifies CORO1A as an apoptosis-associated gene in acute myeloid leukemia.","date":"2026","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/42153148","citation_count":0,"is_preprint":false},{"pmid":"40563467","id":"PMC_40563467","title":"Role of CORO1A in Regulating Immune Homeostasis of Mammary Glands and Its Contribution to Clinical Mastitis Development in Dairy Cows.","date":"2025","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/40563467","citation_count":0,"is_preprint":false},{"pmid":"39849824","id":"PMC_39849824","title":"T cell population size control by coronin 1 uncovered: from a spot identified by two-dimensional gel electrophoresis to quantitative proteomics.","date":"2025","source":"Expert review of proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/39849824","citation_count":0,"is_preprint":false},{"pmid":"41078258","id":"PMC_41078258","title":"Coronin 1 Loss in Tumor Cells of Glioblastoma Patients Leads to Enhanced Tumor Aggressiveness.","date":"2025","source":"Journal of neurochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41078258","citation_count":0,"is_preprint":false},{"pmid":"27053608","id":"PMC_27053608","title":"[Involvement of coronin-1 in foam cell formation of macrophages induced by mycolic acid and its mechanism].","date":"2016","source":"Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/27053608","citation_count":0,"is_preprint":false},{"pmid":"20368107","id":"PMC_20368107","title":"[Construction of a siRNA plasmid for knockdown of coronin-1].","date":"2010","source":"Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/20368107","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.02.14.638370","title":"Coro1a promotes the multivesicular body and plasma membrane fusion by facilitating PKM2-mediated SNAP-23 phosphorylation","date":"2025-02-16","source":"bioRxiv","url":"https://doi.org/10.1101/2025.02.14.638370","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":35074,"output_tokens":8014,"usd":0.112716,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":17545,"output_tokens":7375,"usd":0.13605,"stage2_stop_reason":"end_turn"},"total_usd":0.248766,"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\": 2007,\n      \"finding\": \"Coronin 1 is actively recruited to mycobacterial phagosomes and blocks lysosomal delivery by activating the Ca2+-dependent phosphatase calcineurin; in coronin 1-deficient macrophages, calcineurin activity does not occur upon mycobacterial infection, resulting in lysosomal delivery and killing of mycobacteria.\",\n      \"method\": \"Coronin 1-deficient mouse macrophages, calcineurin activity assays, cyclosporin A/FK506 pharmacological inhibition, phagosome-lysosome fusion assays\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with defined molecular mechanism (calcineurin activation), pharmacological validation, replicated across multiple approaches in one rigorous study\",\n      \"pmids\": [\"17632055\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Coronin 1 exerts an inhibitory effect on cellular steady-state F-actin formation via an Arp2/3-dependent mechanism and is required for chemokine-mediated T cell migration, but is dispensable for T cell antigen receptor functions.\",\n      \"method\": \"Coronin 1-deficient (knockout) mice, F-actin quantification, chemotaxis assays, TCR functional assays\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with multiple orthogonal cellular readouts including Arp2/3-dependent mechanism and migration assays\",\n      \"pmids\": [\"16902139\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Upon T cell receptor triggering, coronin 1 is required for generation of inositol-1,4,5-trisphosphate (IP3) from PIP2, thereby enabling Ca2+ mobilization from intracellular stores, IL-2 production, T cell proliferation, and T cell survival.\",\n      \"method\": \"Coronin 1-deficient mice, IP3 measurement, Ca2+ mobilization assays, T cell functional assays (proliferation, IL-2 production, survival)\",\n      \"journal\": \"Nature immunology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with multiple orthogonal functional readouts establishing direct pathway placement (TCR→coronin1→IP3→Ca2+)\",\n      \"pmids\": [\"18345003\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Coronin 1 forms coiled-coil-mediated homotrimeric complexes that associate with the plasma membrane via the N-terminal WD repeat domain and with the cytoskeleton via positively charged residues in a linker region between the WD domain and C-terminal coiled coil.\",\n      \"method\": \"Domain deletion mutagenesis, co-immunoprecipitation, fractionation assays, biochemical reconstitution of trimeric complexes\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — mutagenesis of distinct domains combined with biochemical fractionation and co-IP, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"15800061\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Crystal structure of murine coronin 1 (without leucine zipper) at 1.75 Å resolution reveals a seven-bladed beta propeller composed of five canonical WD40 repeats and two additional non-canonical blades; the C-terminal extension packs against the bottom of the propeller and is required for structural stability; conserved surface residues delineate potential F-actin binding sites.\",\n      \"method\": \"X-ray crystallography at 1.75 Å resolution\",\n      \"journal\": \"Structure\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution crystal structure with structural validation\",\n      \"pmids\": [\"16407068\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Coronin 1 (p57) forms homodimers mediated by a leucine zipper structure in its C-terminal coiled-coil domain; mutation of two leucines in the zipper abolishes dimerization, and the C-terminal region enables co-localization with cortical F-actin only when full-length coronin 1 is co-expressed.\",\n      \"method\": \"Size-exclusion chromatography, sucrose density gradient, co-immunoprecipitation in COS-1 cells, leucine-to-alanine mutagenesis, GFP fusion co-localization\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro biochemical assays plus mutagenesis and co-IP, multiple orthogonal methods in one study\",\n      \"pmids\": [\"15601263\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Coronin 1 is required for an early step of phagosome formation: TAT-WD dominant-negative constructs diminish lamellipodial extensions, actin accumulation at the base of bound particles, and Arp3 accumulation at the phagosome, without affecting opsonized RBC binding or receptor clustering.\",\n      \"method\": \"Dominant-negative TAT-fusion protein introduction into RAW 264.7 cells, phagocytosis assays, Arp3 localization by immunofluorescence\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — dominant-negative approach with multiple cellular readouts, single lab\",\n      \"pmids\": [\"15829569\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Mycobacterial lipoamide dehydrogenase C (LpdC) binds coronin 1 in a cholesterol-dependent manner (identified by GST-coronin 1 pulldown and mass spectrometry), retaining coronin 1 on the phagosomal membrane to arrest phagosome maturation; M. smegmatis overexpressing LpdC acquired the capacity to retain coronin 1 and prolong intracellular survival.\",\n      \"method\": \"GST pulldown, mass spectrometry identification, cell-free binding assays, IFNγ-induced phagolysosome fusion assays, M. smegmatis LpdC overexpression\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical pulldown with MS identification plus functional gain-of-function in bacteria, single lab\",\n      \"pmids\": [\"17652161\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"RNA interference knockdown of coronin 1 in J774 macrophages does not affect phagocytosis, macropinocytosis, cell locomotion, or NADPH oxidase activity, but causes rapid lysosomal delivery and killing of internalized mycobacteria, demonstrating that coronin 1's role in mycobacterial phagosome regulation is distinct from its (dispensable) role in actin-mediated processes.\",\n      \"method\": \"siRNA knockdown in J774 macrophages, phagocytosis/macropinocytosis/locomotion assays, NADPH oxidase activity assays, lysosomal delivery and bacterial killing assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — RNAi loss-of-function with multiple orthogonal functional readouts, corroborating prior genetic evidence\",\n      \"pmids\": [\"18162581\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Phorbol ester (PMA) stimulation induces phosphorylation of p57/coronin 1 via protein kinase C, which reduces the protein's association with the actin cytoskeleton; phosphorylated coronin 1 showed lower affinity for F-actin in co-sedimentation assays, and during phagocytosis in differentiated HL60 cells coronin 1 dissociation from the actin cytoskeleton was concurrent with enhanced phosphorylation.\",\n      \"method\": \"Cell fractionation, 2D gel electrophoresis, co-sedimentation with F-actin, affinity chromatography, fluorescence microscopy in HL60 cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — multiple orthogonal biochemical methods (fractionation, F-actin co-sedimentation, affinity chromatography) in a single rigorous study\",\n      \"pmids\": [\"18693254\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"In sympathetic neurons, the NGF-TrkA signaling endosome induces expression and recruitment of Coronin 1 upon arrival at the cell body; Coronin 1 prevents premature lysosomal fusion of the signaling endosome (6–10-fold faster fusion in absence), enables endosomal recycling/re-internalization, and is required for NGF-TrkA-dependent calcium release, calcineurin activation, and CREB phosphorylation.\",\n      \"method\": \"Mouse sympathetic neuron culture with Coro1a KO, live imaging of endosome trafficking, lysosomal fusion kinetics, calcium imaging, calcineurin activity assays, CREB phosphorylation by Western blot\",\n      \"journal\": \"Nature neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with multiple orthogonal functional readouts including live imaging, signaling assays, and quantified trafficking kinetics\",\n      \"pmids\": [\"24270184\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Coronin 1 interacts with the G protein subtype Gαs upon cell surface stimulation to activate the cAMP/PKA pathway in neurons; coronin 1-deficient mice lack cAMP/PKA-dependent presynaptic plasticity and exhibit neurobehavioral deficits that are rescued by membrane-permeable cAMP analogue infusion; coronin 1 mutants unable to bind Gαs fail to stimulate cAMP signaling.\",\n      \"method\": \"Co-immunoprecipitation (coronin 1–Gαs interaction), cAMP measurement, electrophysiology in amygdala, behavioral assays, in vivo cAMP analogue rescue in Coro1a KO mice, mutagenesis of Gαs-binding interface\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, mutagenesis, in vivo rescue, and electrophysiology in one study, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"24667537\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Coronin 1 does not modulate F-actin levels in naive T cells and F-actin induction does not cause apoptosis; instead, coronin 1 provides pro-survival signals whose absence leads to rapid T cell apoptosis.\",\n      \"method\": \"Coronin 1 KO mice, F-actin quantification, apoptosis assays, pharmacological F-actin manipulation\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with functional readouts, explicitly refuting prior F-actin model; single lab\",\n      \"pmids\": [\"21339362\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Coronin 1 is essential for IgM-induced intracellular Ca2+ mobilization and B cell proliferation upon BCR triggering, but is dispensable when costimulatory signals are present, consistent with normal in vivo B cell immune responses in coronin 1-deficient mice.\",\n      \"method\": \"Coronin 1 KO mice, Ca2+ mobilization assays, B cell proliferation assays, in vivo immunization\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with multiple readouts, single lab\",\n      \"pmids\": [\"19201848\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Phosphorylation of coronin 1 at Thr-412 constitutively turns over in HL60 cells; the Thr-412-phosphorylated form fails to co-immunoprecipitate with β-actin, and the phosphomimetic T412D mutant shows reduced actin affinity compared to wild-type or the non-phosphorylatable T412A mutant, demonstrating that Thr-412 phosphorylation controls coronin 1–actin interaction.\",\n      \"method\": \"MALDI-TOF-MS, Phos-tag gel electrophoresis, site-directed mutagenesis (T412D, T412A), co-immunoprecipitation with β-actin, calyculin A treatment\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — mass spectrometry-identified site with mutagenesis, co-IP, and phosphatase inhibitor validation; multiple orthogonal methods in one study\",\n      \"pmids\": [\"23100250\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Upon cytokine stimulation of macrophages, phosphorylated coronin 1 transiently associates with 14-3-3ζ (and RACK1); 14-3-3ζ (but not RACK1) is required for coronin 1 relocation from the cell cortex to the cytoplasm, PI3-kinase activation, and induction of macropinocytosis.\",\n      \"method\": \"Co-immunoprecipitation of phospho-coronin 1 with 14-3-3ζ/RACK1, siRNA knockdown of 14-3-3ζ and RACK1, coronin 1 localization by imaging, PI3K activity assay, macropinocytosis assay\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP plus siRNA knockdown with functional readouts, single lab\",\n      \"pmids\": [\"25645340\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Coronin 1 trimerization (via C-terminal coiled coil) is essential for protecting mycobacteria from lysosomal delivery and for calcineurin activation in macrophages; macrophage activation induces serine phosphorylation of coronin 1 that causes monomerization, thereby relieving protection.\",\n      \"method\": \"Trimerization-defective coronin 1 mutants expressed in macrophages, calcineurin activity assays, mycobacterial survival assays, phosphorylation analysis\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis with functional calcineurin and survival assays, single lab\",\n      \"pmids\": [\"25217836\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Cyclin-dependent kinase 5 (CDK5) phosphorylates coronin 1 on Thr418/424, and this phosphorylation is required for coronin 1–Gαs association and subsequent cAMP/PKA pathway activation.\",\n      \"method\": \"Phosphorylation site mutagenesis (Thr418/424), CDK5 activity modulation, co-immunoprecipitation of coronin 1 with Gαs, cAMP measurement\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mutagenesis plus Co-IP and cAMP assay, single lab\",\n      \"pmids\": [\"26823173\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In sympathetic neurons, Coronin 1 (downstream of NGF-TrkA) suppresses axon growth and branching by activating PLC-γ1-dependent calcium release, which releases PI3K-dependent suppression of GSK3β; Coro1a−/− mice display sympathetic axon overgrowth and overbranching in the developing heart.\",\n      \"method\": \"Coro1a KO mice, in vivo axon morphology analysis in developing heart, PLC-γ1/PI3K/GSK3β signaling pathway epistasis assays, calcium imaging\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with in vivo phenotype and signaling pathway placement, single lab\",\n      \"pmids\": [\"25740518\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Coronin 1 deficiency increases cyclic AMP (cAMP) concentrations in T cells (by relieving PDE4-mediated cAMP degradation), which suppresses allo-specific T cell responses; costimulation induced on microbe-infected APCs overcomes cAMP-mediated immunosuppression to maintain anti-pathogen immunity.\",\n      \"method\": \"Coronin 1 KO mice, cAMP measurement, pharmacological cAMP/PDE4 modulation, allograft models, T cell transfer experiments\",\n      \"journal\": \"Immunity\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with multiple orthogonal mechanistic validations (cAMP measurement, pharmacological, in vivo rescue), single lab but multiple methods\",\n      \"pmids\": [\"30611611\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Coronin 1 maintains basal PI3Kδ activity in naive T cells, thereby suppressing caspase 8-mediated apoptosis; this pathway operates independently of TCR and IL-7 signaling.\",\n      \"method\": \"Coronin 1 KO mice, PI3Kδ activity assay, caspase 8 activity assay, genetic and pharmacological PI3Kδ inhibition, epistasis analysis with TCR/IL-7 pathways\",\n      \"journal\": \"Science signaling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with pathway epistasis and caspase activity assays, single lab\",\n      \"pmids\": [\"34932374\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Coronin 1 (CORO1A) is phosphorylated at Thr-412 specifically by PKCα (not PKCβ) in human phagocytic cells; this phosphorylation prevents dissociation of coronin 1 from phagosomes when PKCα is inhibited, linking PKCα-mediated Thr-412 phosphorylation to coronin 1 intracellular redistribution during phagocytosis.\",\n      \"method\": \"PKC isoform-specific inhibitors, siRNA knockdown of PKCα vs. PKCβ, in vitro kinase assay with recombinant PKCα/PKCβ, confocal fluorescence microscopy of coronin 1 localization during phagocytosis\",\n      \"journal\": \"Biochemistry and biophysics reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro kinase assay plus isoform-specific siRNA with functional localization readout, multiple orthogonal methods in one study\",\n      \"pmids\": [\"34189278\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"A CORO1A frameshift mutation (S401fs) that replaces the last 61 C-terminal amino acids abolishes oligomerization and impairs cytoskeletal association of coronin 1 in patient lymphocytes, resulting in increased filamentous actin accumulation, severely defective thymic output, and impaired T cell survival, but normal calcium flux and cytotoxicity; demonstrating that C-terminal domain integrity is required for oligomerization and T cell homeostasis.\",\n      \"method\": \"Whole-genome sequencing, Western blot, biochemical oligomerization assay, cytoskeletal association assay (fractionation), flow cytometry of F-actin, T cell survival and thymic output analyses in patient cells\",\n      \"journal\": \"The Journal of allergy and clinical immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — patient mutation with biochemical dissection of domain function (oligomerization, cytoskeletal association) and functional readouts; single kindred\",\n      \"pmids\": [\"26476480\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Coronin 1 is in equilibrium between the cytosol and the cell cortex in T lymphocytes and accumulates in F-actin-rich membrane protrusions upon polarized TCR-CD3 stimulation, placing it at sites of actin remodeling during T cell activation.\",\n      \"method\": \"Subcellular fractionation, immunofluorescence and confocal microscopy of Coronin 1 localization in TCR-stimulated T cells\",\n      \"journal\": \"International immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by immunofluorescence and fractionation, multiple cell contexts, single lab\",\n      \"pmids\": [\"14734608\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"p57/coronin 1 and F-actin co-localize at sites of L. pneumophila adherence to macrophage-like cells (an actin polymerization-dependent event), but live L. pneumophila actively excludes p57/coronin 1 from its phagosome throughout infection, in contrast to opsonized zymosan or heat-killed bacteria which show transient coronin 1 accumulation.\",\n      \"method\": \"Fluorescence microscopy, cytochalasin D (actin polymerization inhibitor) treatment, comparison of live vs. heat-killed bacteria, U937 macrophage-like cells\",\n      \"journal\": \"Biological & pharmaceutical bulletin\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single imaging study with pharmacological inhibitor, single lab, no mechanistic dissection of exclusion mechanism\",\n      \"pmids\": [\"18451508\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CREBH transcriptionally represses Coro1a expression; overexpression of Coro1a in liver cells inhibited autophagic flux and elevated inflammatory cytokines upon palmitic acid stimulation, identifying Coro1a as a negative regulator of autophagosome-lysosome fusion in hepatocytes.\",\n      \"method\": \"Luciferase reporter assay (CREBH on Coro1a promoter), Coro1a overexpression in LO2 liver cells, autophagy flux assays (LC3-II, p62, LAMP1), inflammatory cytokine measurement\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular basis of disease\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — overexpression with functional readouts but no KO rescue or mechanistic dissection, single lab, single paper\",\n      \"pmids\": [\"37837948\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Coronin 1A (Coro1A) localizes to growth cones and filopodia, interacts with TRIM67 (a brain-enriched E3 ubiquitin ligase that binds the netrin receptor DCC), and is required for netrin-1-dependent axon turning, branching, and corpus callosum development; a Coro1A mutant deficient in TRIM67 binding cannot rescue loss-of-Coro1A phenotypes.\",\n      \"method\": \"Coro1a KO mice, live imaging and immunofluorescence (growth cone localization), TRIM67-binding deficient Coro1A mutant rescue experiments, in vivo corpus callosum analysis\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO with mutant rescue and in vivo phenotype, single lab; peer-reviewed publication\",\n      \"pmids\": [\"41085995\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In coronin 1-deficient platelets, integrin β2 translocation to the platelet surface upon thrombin stimulation is impaired, while morphological changes, Arp2/3 localization, and cAMP-dependent signaling are unaffected, indicating a specific role for coronin 1 in integrin β2 surface translocation.\",\n      \"method\": \"Coronin 1 KO mouse platelets, flow cytometry of integrin β2 surface expression, Arp2/3 localization by immunofluorescence, cAMP measurement\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genetic KO with flow cytometry readout, single lab, limited mechanistic follow-up on translocation mechanism\",\n      \"pmids\": [\"31948107\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Coro1a promotes MVB-plasma membrane fusion and exosome biogenesis by activating PKM2 to phosphorylate SNAP-23, which drives SNAP-23 to recruit STX-12 and VAMP7, increasing assembly of the STX-12-SNAP-23-VAMP7 SNARE complex; this function is independent of coronin 1 neddylation.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown of SNAP-23 and PKM2, PKM2 inhibitor, Coro1a KO in vivo tumor model, neddylation inhibitor MLN4924, EV quantification\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2–3 / Weak — Co-IP and functional assays with multiple genetic/pharmacological interventions but preprint only, not yet peer-reviewed\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Coronin 1 overexpression in differentiated PLB985 cells decreases mitochondrial depolarization and caspase-3/caspase-9 (but not caspase-8 or Bid cleavage) induced by gliotoxin or TRAIL, indicating that coronin 1 protects against the intrinsic (mitochondrial) apoptotic pathway.\",\n      \"method\": \"Coronin 1 overexpression in PLB985 cells, mitochondrial depolarization assay, caspase activity assays (caspase-3, -8, -9), Bid truncation Western blot\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — overexpression with multiple orthogonal apoptosis readouts dissecting intrinsic vs. extrinsic pathway, single lab\",\n      \"pmids\": [\"19454722\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Coro1a transcription requires both the core promoter (containing GC boxes bound by Sp3 transcription factor at GC box 4) and gene body/intronic regions (containing ETS-binding sequences in introns 1 and 2); mutations in intronic ETS sequences decrease Coro1a transcription, and active histone marks (H3K4me3, H3K27ac) at the intronic region decrease during macrophage-to-osteoclast differentiation concurrent with reduced Coro1a expression.\",\n      \"method\": \"Reporter (luciferase) assays, promoter deletion analysis, chromatin immunoprecipitation for Sp3, DNase sequencing (chromatin accessibility), histone modification ChIP, site-directed mutagenesis of ETS sites\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (reporter assay, mutagenesis, ChIP) establishing transcriptional regulation mechanism, single lab\",\n      \"pmids\": [\"41456103\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CORO1A (coronin 1) is a leukocyte-enriched, seven-bladed WD40 beta-propeller protein that homotrimerizes via a C-terminal coiled coil/leucine zipper; it associates with the plasma membrane through its WD domain and with the actin cytoskeleton through a positively charged linker region, and its cytoskeletal association is negatively regulated by PKCα-mediated phosphorylation at Thr-412. In macrophages, coronin 1 is recruited to mycobacterial phagosomes where it activates calcineurin via Ca2+ signaling to block phagosome-lysosome fusion, protecting pathogenic mycobacteria—an activity dependent on its trimeric state that is disrupted by serine phosphorylation-induced monomerization. In T cells, coronin 1 is required downstream of TCR stimulation to generate IP3 from PIP2, mobilize intracellular Ca2+, and sustain pro-survival signaling; independently, it maintains basal PI3Kδ activity to suppress caspase 8-mediated apoptosis, and its CDK5-phosphorylation-dependent interaction with Gαs activates the cAMP/PKA pathway important for synaptic plasticity and behavior. In neurons, coronin 1 acts as an effector of the NGF-TrkA signaling endosome to prevent premature lysosomal fusion, enable endosomal recycling, activate calcineurin and CREB, and suppress axon overgrowth through PLC-γ1/Ca2+-dependent inhibition of PI3K-GSK3β signaling; it also collaborates with the E3 ligase TRIM67 downstream of netrin-1 to mediate axon turning and branching.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CORO1A (coronin 1) is a leukocyte-enriched, seven-bladed WD40 beta-propeller protein that functions as a signaling scaffold coupling membrane receptor activation to Ca2+ and cAMP signaling, cytoskeletal regulation, and the control of organelle fusion across immune cells and neurons [#4, #2, #10]. The protein homo-oligomerizes through a C-terminal coiled-coil/leucine zipper, associates with the plasma membrane via its WD domain, and binds the actin cytoskeleton through a positively charged linker; this actin association is negatively regulated by Thr-412 phosphorylation carried out specifically by PKCalpha [#3, #5, #14, #21]. In macrophages, coronin 1 is recruited to mycobacterial phagosomes where it activates the Ca2+-dependent phosphatase calcineurin to block phagosome-lysosome fusion and protect pathogenic mycobacteria, an activity that depends on its trimeric state and is relieved by serine-phosphorylation-induced monomerization [#0, #8, #16]. In T cells, coronin 1 acts downstream of TCR triggering to generate IP3 from PIP2 and mobilize intracellular Ca2+ for proliferation, IL-2 production, and survival, while independently sustaining pro-survival signaling by maintaining basal PI3Kdelta activity that suppresses caspase-8-mediated apoptosis and by restraining cAMP through PDE4 to permit alloreactive T cell responses [#2, #20, #19]. Through a CDK5-phosphorylation-dependent interaction with Galphas, coronin 1 activates the cAMP/PKA pathway underlying presynaptic plasticity and behavior [#11, #17]. In neurons it serves as an effector of the NGF-TrkA signaling endosome, preventing premature lysosomal fusion and enabling recycling, calcineurin activation, and CREB phosphorylation, and it suppresses axon overgrowth via PLC-gamma1/Ca2+-dependent inhibition of PI3K-GSK3beta signaling and collaborates with the E3 ligase TRIM67 downstream of netrin-1 to direct axon turning and branching [#10, #18, #26]. A C-terminal frameshift mutation (S401fs) that abolishes oligomerization causes defective thymic output and impaired T cell survival in patients, linking C-terminal integrity to human T cell homeostasis [#22].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Establishing where coronin 1 acts in T cells: it was unknown whether the protein was positioned at sites of actin remodeling during T cell activation.\",\n      \"evidence\": \"Subcellular fractionation and confocal imaging of TCR-stimulated T lymphocytes\",\n      \"pmids\": [\"14734608\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Localization alone did not establish a functional requirement\", \"No molecular partners at the protrusion site identified\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Defining the molecular architecture: the question was how coronin 1 oligomerizes and engages membrane versus cytoskeleton, resolved by mapping distinct domains for trimerization, membrane, and actin association.\",\n      \"evidence\": \"Domain-deletion mutagenesis, leucine-zipper mutations, co-IP, fractionation, and biochemical reconstitution in COS-1 cells\",\n      \"pmids\": [\"15800061\", \"15601263\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Trimer versus dimer stoichiometry described differently across studies\", \"Functional consequence of each domain interaction not yet tested in vivo\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Determining the three-dimensional fold: the structural basis for WD40 propeller assembly and putative F-actin contacts was unknown until a high-resolution crystal structure resolved the seven-bladed propeller and stabilizing C-terminal extension.\",\n      \"evidence\": \"X-ray crystallography of murine coronin 1 at 1.75 A\",\n      \"pmids\": [\"16407068\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure lacked the leucine zipper\", \"Predicted F-actin binding surface not validated functionally\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Testing the cytoskeletal role in vivo: whether coronin 1 governs actin dynamics and migration was resolved by showing it inhibits steady-state F-actin via Arp2/3 and is required for chemokine-driven migration but not TCR function.\",\n      \"evidence\": \"Coronin 1 knockout mice with F-actin quantification, chemotaxis, and TCR assays\",\n      \"pmids\": [\"16902139\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of Arp2/3-dependent inhibition not detailed\", \"Apparent dispensability for TCR later revised\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identifying the pathogen-protective mechanism: it was unknown how coronin 1 blocks mycobacterial killing, answered by demonstrating it activates calcineurin to prevent phagosome-lysosome fusion.\",\n      \"evidence\": \"Coronin 1-deficient macrophages with calcineurin assays, cyclosporin A/FK506 inhibition, and fusion assays\",\n      \"pmids\": [\"17632055\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How phagosomal coronin 1 triggers Ca2+/calcineurin not fully resolved\", \"Link between membrane recruitment and calcineurin activation incomplete\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identifying a bacterial ligand: the basis for coronin 1 retention on the mycobacterial phagosome was addressed by identifying LpdC as a cholesterol-dependent binding partner that prolongs intracellular survival.\",\n      \"evidence\": \"GST-coronin 1 pulldown with mass spectrometry, cell-free binding, and M. smegmatis LpdC gain-of-function\",\n      \"pmids\": [\"17652161\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab biochemical interaction without genetic confirmation in pathogenic mycobacteria\", \"Cholesterol-dependence mechanism not structurally defined\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Separating actin and pathogen functions: RNAi showed coronin 1 is dispensable for phagocytosis, macropinocytosis, locomotion, and oxidase activity but essential to keep mycobacteria from lysosomal killing, isolating its phagosome-regulatory role.\",\n      \"evidence\": \"siRNA knockdown in J774 macrophages with multiple actin-process and bacterial-killing readouts\",\n      \"pmids\": [\"18162581\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not address coronin 1 actin roles in other phagocyte subtypes\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Placing coronin 1 in TCR signaling: the prior view that it was dispensable for TCR function was revised by showing it is required to generate IP3 and mobilize Ca2+ for T cell proliferation and survival.\",\n      \"evidence\": \"Coronin 1 KO mice with IP3 measurement, Ca2+ mobilization, and T cell functional assays\",\n      \"pmids\": [\"18345003\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct biochemical step at which coronin 1 enables IP3 generation unresolved\", \"Whether the effect is through PLC recruitment or another route unclear\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Defining phosphoregulation of actin binding: PKC-mediated phosphorylation was shown to lower coronin 1 affinity for F-actin and drive its dissociation during phagocytosis.\",\n      \"evidence\": \"Fractionation, 2D gels, F-actin co-sedimentation, and affinity chromatography in HL60 cells\",\n      \"pmids\": [\"18693254\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific phosphosite not yet identified at this stage\", \"Responsible PKC isoform not yet defined\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Defining the anti-apoptotic pathway: coronin 1 was shown to protect against the intrinsic mitochondrial apoptotic pathway rather than the extrinsic pathway.\",\n      \"evidence\": \"Coronin 1 overexpression in PLB985 cells with mitochondrial depolarization and caspase-3/-8/-9 assays\",\n      \"pmids\": [\"19454722\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Overexpression-based; molecular link to mitochondria not defined\", \"Apparent contrast with later caspase-8 findings in T cells unresolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Extending Ca2+ function to B cells: coronin 1 was shown to be required for BCR-induced Ca2+ mobilization and proliferation but bypassable by costimulation, explaining intact in vivo B cell responses.\",\n      \"evidence\": \"Coronin 1 KO mice with Ca2+ mobilization, proliferation, and immunization assays\",\n      \"pmids\": [\"19201848\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular step in BCR-to-Ca2+ coupling not defined\", \"Costimulatory bypass mechanism unidentified\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Revising the death model in T cells: it was shown F-actin levels are not altered in naive T cells and do not drive apoptosis; instead coronin 1 provides distinct pro-survival signals.\",\n      \"evidence\": \"Coronin 1 KO mice with F-actin quantification, apoptosis assays, and pharmacological actin manipulation\",\n      \"pmids\": [\"21339362\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The pro-survival signal itself not molecularly identified here\", \"Single lab refutation of prior model\"]\n    },\n    {\n      \"year\": \"2012\",\n      \"claim\": \"Pinpointing the regulatory phosphosite: Thr-412 phosphorylation was identified as the switch controlling coronin 1-actin interaction.\",\n      \"evidence\": \"MALDI-TOF-MS, Phos-tag gels, T412D/T412A mutagenesis, and beta-actin co-IP in HL60 cells\",\n      \"pmids\": [\"23100250\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase responsible not yet assigned in this study\", \"Effect on oligomerization versus actin binding not separated\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing a neuronal endosome function: coronin 1 was shown to be an NGF-TrkA signaling endosome effector that prevents premature lysosomal fusion and enables Ca2+/calcineurin/CREB signaling.\",\n      \"evidence\": \"Coro1a KO sympathetic neurons with live imaging, fusion kinetics, calcium imaging, and CREB Western blot\",\n      \"pmids\": [\"24270184\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism delaying lysosomal fusion unresolved\", \"How coronin 1 is recruited to the signaling endosome unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Linking coronin 1 to cAMP/PKA: a Galphas interaction was shown to activate cAMP/PKA signaling required for presynaptic plasticity and behavior, rescuable by cAMP analogues in vivo.\",\n      \"evidence\": \"Reciprocal co-IP, cAMP measurement, amygdala electrophysiology, behavior, and in vivo cAMP rescue in Coro1a KO mice\",\n      \"pmids\": [\"24667537\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stimulus that triggers coronin 1-Galphas coupling not fully defined\", \"Relationship to its actin/Ca2+ roles unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connecting oligomeric state to pathogen protection: trimerization was shown to be essential for calcineurin activation and mycobacterial protection, with macrophage-induced serine phosphorylation causing monomerization that relieves protection.\",\n      \"evidence\": \"Trimerization-defective mutants in macrophages with calcineurin and survival assays\",\n      \"pmids\": [\"25217836\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific monomerizing phosphosite not identified\", \"Kinase driving monomerization unknown\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defining cytokine-induced relocalization machinery: phospho-coronin 1 was shown to bind 14-3-3zeta, which drives its cortex-to-cytoplasm relocation, PI3K activation, and macropinocytosis.\",\n      \"evidence\": \"Co-IP of phospho-coronin 1 with 14-3-3zeta/RACK1, siRNA knockdown, and macropinocytosis assays\",\n      \"pmids\": [\"25645340\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab Co-IP-based interaction\", \"How 14-3-3zeta binding couples to PI3K activation unresolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defining the axon-suppression pathway: coronin 1 was shown to restrain axon growth and branching by PLC-gamma1/Ca2+-dependent inhibition of PI3K-GSK3beta signaling, with KO causing cardiac sympathetic axon overgrowth.\",\n      \"evidence\": \"Coro1a KO mice with in vivo axon morphology and PLC-gamma1/PI3K/GSK3beta epistasis plus calcium imaging\",\n      \"pmids\": [\"25740518\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct molecular target of coronin 1 in this cascade unidentified\", \"Single lab pathway placement\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Assigning the kinase for Galphas coupling: CDK5 was shown to phosphorylate coronin 1 at Thr418/424, a modification required for Galphas association and cAMP/PKA activation.\",\n      \"evidence\": \"Phosphosite mutagenesis, CDK5 modulation, coronin 1-Galphas co-IP, and cAMP measurement\",\n      \"pmids\": [\"26823173\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of the phospho-dependent Galphas interface unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Connecting domain integrity to human disease: a C-terminal frameshift (S401fs) was shown to abolish oligomerization and cytoskeletal association, producing defective thymic output and impaired T cell survival in patients.\",\n      \"evidence\": \"Whole-genome sequencing, oligomerization and fractionation assays, and patient T cell phenotyping\",\n      \"pmids\": [\"26476480\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single kindred\", \"Normal Ca2+ flux despite oligomerization loss not fully reconciled with prior models\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Refining cAMP control in T cells: coronin 1 deficiency was shown to raise cAMP by relieving PDE4-mediated degradation, suppressing alloreactive T cell responses while sparing anti-pathogen immunity.\",\n      \"evidence\": \"Coronin 1 KO mice with cAMP measurement, PDE4 pharmacology, allograft, and T cell transfer models\",\n      \"pmids\": [\"30611611\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How coronin 1 regulates PDE4 activity mechanistically unresolved\", \"Reconciliation with Galphas-mediated cAMP activation in neurons unclear\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defining a TCR-independent survival mechanism: coronin 1 was shown to maintain basal PI3Kdelta activity that suppresses caspase-8-mediated apoptosis independently of TCR and IL-7.\",\n      \"evidence\": \"Coronin 1 KO mice with PI3Kdelta and caspase-8 assays plus genetic/pharmacological epistasis\",\n      \"pmids\": [\"34932374\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How coronin 1 sustains basal PI3Kdelta unknown\", \"Relationship to the earlier intrinsic-apoptosis finding unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Assigning the Thr-412 kinase in phagocytes: PKCalpha (not PKCbeta) was shown to phosphorylate Thr-412, controlling coronin 1 redistribution from phagosomes.\",\n      \"evidence\": \"Isoform-specific inhibitors and siRNA, in vitro kinase assays, and confocal localization in human phagocytes\",\n      \"pmids\": [\"34189278\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Upstream activation of PKCalpha during phagocytosis not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extending the neuronal role to guidance: coronin 1 was shown to act with the E3 ligase TRIM67 downstream of netrin-1/DCC for axon turning, branching, and corpus callosum development.\",\n      \"evidence\": \"Coro1a KO mice, growth cone imaging, TRIM67-binding-deficient rescue, and in vivo corpus callosum analysis\",\n      \"pmids\": [\"41085995\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether coronin 1 is a TRIM67 ubiquitination substrate unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Defining transcriptional control of CORO1A: combined core-promoter Sp3/GC-box and intronic ETS elements were shown to drive expression, with active histone marks declining during osteoclast differentiation.\",\n      \"evidence\": \"Luciferase reporters, promoter deletions, Sp3 ChIP, DNase-seq, and histone ChIP\",\n      \"pmids\": [\"41456103\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"ETS factor identity not pinned down\", \"Link between expression decline and osteoclast function not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How coronin 1 functionally integrates its actin-binding, oligomerization, and phospho-switch states into the divergent calcineurin, IP3/Ca2+, cAMP/PKA, and PI3K outputs across cell types remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified biochemical model connecting oligomeric state to each signaling output\", \"Direct enzymatic targets versus scaffolding roles not separated\", \"Apparent opposite effects on cAMP (PDE4 versus Galphas) not mechanistically reconciled\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [3, 9, 14]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [11, 26, 15]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [4, 3]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 2, 19]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [3, 23]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [3, 23, 15]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [3, 5, 9]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [0, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2, 19, 13]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [11, 18, 10]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 10]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [20, 29]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [11, 18, 26]}\n    ],\n    \"complexes\": [\n      \"coronin 1 homotrimer\"\n    ],\n    \"partners\": [\n      \"GNAS (Galphas)\",\n      \"TRIM67\",\n      \"YWHAZ (14-3-3zeta)\",\n      \"ACTB (beta-actin)\",\n      \"CDK5\",\n      \"PRKCA (PKCalpha)\",\n      \"LpdC (mycobacterial)\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}