{"gene":"CAPRIN2","run_date":"2026-06-09T22:57:17","timeline":{"discoveries":[{"year":2008,"finding":"Caprin-2 was identified as a LRP5/6-binding protein that stabilizes cytosolic β-catenin, enhances LEF1/TCF-dependent reporter gene activity, facilitates GSK3-dependent LRP5/6 phosphorylation, and enhances the interaction between Axin and LRP5/6, thereby promoting canonical Wnt signaling. Morpholino-mediated knockdown of Caprin-2 in zebrafish embryos inhibits Wnt/β-catenin signaling and causes a dorsalized phenotype.","method":"Co-immunoprecipitation, reporter gene assay, morpholino knockdown in zebrafish, Western blotting for β-catenin stabilization and LRP5/6 phosphorylation","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, multiple orthogonal methods (reporter assay, phosphorylation assay, in vivo knockdown), replicated in two biological systems (mammalian cells and zebrafish)","pmids":["18762581"],"is_preprint":false},{"year":2016,"finding":"Caprin-2 positively regulates constitutive LRP5/6 Ser-1490 phosphorylation by forming a quaternary complex with CDK14, Cyclin Y, and LRP5/6 at G2/M phase of the cell cycle. Knockdown of Caprin-2 disrupts both the CDK14–Cyclin Y interaction and the CDK14/Cyclin Y–LRP6 interaction.","method":"Co-immunoprecipitation, knockdown experiments, cell cycle synchronization assays, phosphorylation assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, cell-cycle-dependent phosphorylation assay, knockdown with two distinct interaction readouts, single lab with multiple orthogonal methods","pmids":["27821587"],"is_preprint":false},{"year":2014,"finding":"The C-terminal C1q-related domain (Cap2_CRD) of Caprin-2 forms a calcium-stabilized homotrimer (crystal structures solved for human and zebrafish). Mutations disrupting the homotrimer impair Caprin-2's ability to promote LRP5/6 phosphorylation, whereas a calcium-binding-deficient mutant retains this activity, demonstrating that trimeric assembly (not calcium binding per se) is required for Caprin-2's function in Wnt signaling.","method":"X-ray crystallography, site-directed mutagenesis, LRP5/6 phosphorylation assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure combined with mutagenesis and functional phosphorylation assay, single lab but multiple orthogonal methods","pmids":["25331957"],"is_preprint":false},{"year":2024,"finding":"The HR1 domain of human Caprin-2 forms a homodimer with a 'scissors'-like structure as determined by X-ray crystallography. Residues R200 and R201 within a basic cluster in the N-terminal 'blades' region are critical for Caprin-2's localization to the plasma membrane; mutations at these residues decrease Caprin-2 plasma membrane localization and reduce its activity in canonical Wnt signaling.","method":"X-ray crystallography, site-directed mutagenesis, subcellular localization imaging, Wnt signaling activity assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure plus mutagenesis with localization and functional readout, single lab with multiple orthogonal methods","pmids":["39159816"],"is_preprint":false},{"year":2019,"finding":"The HR1 region of Caprin-2 contains a dimerization domain with an all α-helical fold that self-associates to form a homodimer, as revealed by crystal structure. The dimeric fold is similar to Caprin-1 but with distinct molecular surface properties that may dictate different protein–protein interactions.","method":"X-ray crystallography, structural comparison","journal":"Journal of biomolecular structure & dynamics","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — crystal structure determined but functional validation of surface differences was not experimentally confirmed, single lab","pmids":["30304999"],"is_preprint":false},{"year":2010,"finding":"RNG140 (Caprin-2) is an RNA-binding protein that binds mRNAs, inhibits translation in vitro, induces RNA granule formation, and localizes to dendritic RNA granules distinct from those containing RNG105. Knockdown of RNG140 in cultured neurons reduces dendrite length and spine density, and this effect is not rescued by RNG105, indicating non-redundant functions.","method":"In vitro translation assay, RNA granule induction assay, immunofluorescence/localization, shRNA knockdown in cultured neurons with morphological readout","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — in vitro translation assay, localization experiments, and knockdown with cellular phenotype in neurons; multiple orthogonal methods in a single study","pmids":["20516077"],"is_preprint":false},{"year":2020,"finding":"RNG140 (Caprin-2) binds to the translation initiation factor eIF3 and suppresses translation through mechanisms involving inhibition of eIF3-dependent translation initiation. Ribosome profiling revealed that RNG140 overexpression reduces translation of long mRNAs (associated with cell proliferation), while RNG140 knockout in mouse eye increases translation of long mRNAs; short crystallin mRNAs escape this inhibition and are translated during lens differentiation.","method":"Co-immunoprecipitation (RNG140–eIF3 interaction), ribosome profiling (comprehensive translational analysis), RNG140 knockout mouse analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — eIF3 binding by Co-IP, genome-wide ribosome profiling in overexpression and knockout systems, confirmed in vivo in mouse eye; multiple orthogonal methods","pmids":["32839273"],"is_preprint":false},{"year":2015,"finding":"Caprin-2 binds AVP (arginine vasopressin) mRNAs in the hypothalamus and regulates their poly(A) tail length and abundance. Lentiviral shRNA knockdown of Caprin-2 in the osmotically stimulated hypothalamus shortened AVP mRNA poly(A) tails and reduced transcript abundance, while over-expression enhanced AVP mRNA abundance and poly(A) tail length. Caprin-2 knockdown decreased urine output and fluid intake and increased urine osmolality and plasma AVP levels, demonstrating a role in the central osmotic defense response.","method":"RNA immunoprecipitation (Caprin-2–AVP mRNA binding), lentiviral shRNA knockdown in vivo, in vitro overexpression system, poly(A) tail length assay, physiological measurements","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Moderate — in vivo lentiviral knockdown with physiological phenotype, RNA binding confirmed, recapitulated in vitro; multiple orthogonal methods in single study","pmids":["26559902"],"is_preprint":false},{"year":2015,"finding":"Lens-specific conditional knockout of Caprin-2 in mouse causes an abnormally compact lens nucleus and at 8% penetrance a Peters anomaly-like defect (lens–cornea attachment), establishing a required role for Caprin-2 in lens fiber cell morphogenesis and lens–cornea separation during eye development.","method":"Conditional knockout (Pax6GFPCre-driven), wheat germ agglutinin staining, scanning electron microscopy, phenotypic analysis","journal":"Developmental dynamics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined morphological phenotype, multiple imaging methods; no molecular mechanism identified in this study, single lab","pmids":["26177727"],"is_preprint":false},{"year":2009,"finding":"FGF signaling (specifically FGF8 activity from prospective retinal cells) is required and sufficient to induce Caprin-2 expression in lens fiber cells during vertebrate lens development, placing Caprin-2 downstream of FGF receptor signaling in the lens differentiation pathway.","method":"In vitro lens fiber cell differentiation assays, FGF8 addition/inhibition experiments, in situ hybridization in mouse and chick","journal":"Differentiation; research in biological diversity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro gain-of-function and inhibition experiments in two species establishing epistatic relationship; pathway placement supported but molecular mechanism not fully detailed","pmids":["19275872"],"is_preprint":false},{"year":2015,"finding":"Chlamydia pneumoniae inclusion membrane protein Cpn1027 interacts with Caprin-2 (mapped to C-termini of both proteins) and co-precipitates GSK3β. RFP-Caprin2 fusion protein is recruited to the chlamydial inclusion along with endogenous GSK3β, and C. pneumoniae-infected cells show enhanced apoptosis resistance dependent on β-catenin.","method":"Yeast two-hybrid screen, co-immunoprecipitation, GST pull-down, live-cell imaging of RFP-Caprin2 recruitment, apoptosis assays","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — interaction mapped by reciprocal Co-IP and GST pull-down, live imaging of recruitment, functional apoptosis assay; single lab with multiple orthogonal methods","pmids":["25996495"],"is_preprint":false},{"year":2025,"finding":"GATA1 potentially regulates Caprin2 transcription in erythroid cells, and Caprin2 loss boosts erythroid production and maturation during gestation and adulthood, an effect enhanced under stress erythropoiesis conditions. Overexpression of CAPRIN2 in CHO cells causes reduced growth, cell cycle arrest, and apoptosis, consistent with its role in translational regulation of key mRNAs during erythropoiesis.","method":"Caprin2 knockout mouse analysis (erythroid phenotype), CAPRIN2 overexpression in CHO cells (growth/apoptosis assay), GATA1 transcriptional regulation analysis","journal":"Transfusion and apheresis science","confidence":"Low","confidence_rationale":"Tier 3 / Weak — KO phenotype described and overexpression effects noted, but molecular mechanism for GATA1 regulation and mRNA targets is proposed but not experimentally confirmed in this study; single lab, limited mechanistic follow-up","pmids":["39922087"],"is_preprint":false}],"current_model":"CAPRIN2 (RNG140/Caprin-2) is a multifunctional RNA-binding protein and Wnt pathway regulator: it directly binds LRP5/6 co-receptors, facilitating both GSK3-dependent Wnt-induced phosphorylation and CDK14/Cyclin Y-dependent constitutive Ser-1490 phosphorylation by forming a quaternary complex, thereby promoting canonical Wnt/β-catenin signaling; its C-terminal C1q domain forms a calcium-stabilized homotrimer required for this activity, and its HR1 domain forms a homodimer whose basic residues (R200/R201) mediate plasma membrane localization essential for Wnt signaling function; as an RNA-binding protein, it suppresses translation of long mRNAs by binding eIF3 and inhibiting translation initiation, regulates AVP mRNA poly(A) tail length and stability in the hypothalamus to control osmotic homeostasis, and localizes to distinct dendritic RNA granules in neurons where it maintains dendrite length and spine density."},"narrative":{"mechanistic_narrative":"CAPRIN2 (RNG140/Caprin-2) is a dual-function protein that acts both as a positive regulator of canonical Wnt/β-catenin signaling and as an RNA-binding translational repressor [PMID:18762581, PMID:32839273]. In Wnt signaling, it binds the LRP5/6 co-receptors, stabilizes cytosolic β-catenin, enhances Axin–LRP5/6 association, and facilitates GSK3-dependent LRP5/6 phosphorylation to promote LEF1/TCF-dependent transcription, with knockdown in zebrafish causing a dorsalized phenotype [PMID:18762581]. It additionally drives constitutive LRP5/6 Ser-1490 phosphorylation by assembling a quaternary complex with CDK14, Cyclin Y, and LRP5/6 during G2/M [PMID:27821587]. This signaling activity depends on two structurally defined self-association modules: a C-terminal C1q-related domain that forms a calcium-stabilized homotrimer required for promoting LRP5/6 phosphorylation [PMID:25331957], and an HR1 domain that forms a 'scissors'-like homodimer whose basic residues R200/R201 direct plasma membrane localization essential for Wnt activity [PMID:39159816, PMID:30304999]. As an RNA-binding protein, CAPRIN2 binds mRNAs and the translation initiation factor eIF3 to suppress translation initiation, selectively repressing long mRNAs while sparing short crystallin transcripts during lens differentiation [PMID:20516077, PMID:32839273]. It binds AVP mRNA in the hypothalamus to control poly(A) tail length and abundance, governing the central osmotic defense response [PMID:26559902]. CAPRIN2 localizes to dendritic RNA granules distinct from RNG105-containing granules and is required for dendrite length and spine density [PMID:20516077], and is required in vivo for lens fiber cell morphogenesis downstream of FGF8 signaling [PMID:26177727, PMID:19275872].","teleology":[{"year":2008,"claim":"Established CAPRIN2 as a positive regulator of canonical Wnt signaling, answering how a novel LRP5/6-binding protein influences β-catenin stability.","evidence":"Co-IP, reporter assays, LRP5/6 phosphorylation assays in mammalian cells and morpholino knockdown in zebrafish","pmids":["18762581"],"confidence":"High","gaps":["Did not define the structural basis of LRP5/6 binding","Mechanism linking CAPRIN2 to Axin recruitment not resolved"]},{"year":2009,"claim":"Placed CAPRIN2 downstream of FGF receptor signaling in lens differentiation, defining an upstream inducer of its expression.","evidence":"In vitro lens fiber differentiation with FGF8 gain/loss and in situ hybridization in mouse and chick","pmids":["19275872"],"confidence":"Medium","gaps":["Transcriptional intermediates between FGF8 and CAPRIN2 not identified","Whether CAPRIN2's lens role is RNA-binding or Wnt-related not addressed"]},{"year":2010,"claim":"Revealed CAPRIN2 as an RNA-binding translational repressor in neurons, distinguishing its dendritic granule role from the paralog RNG105.","evidence":"In vitro translation assays, RNA granule induction, immunofluorescence, and shRNA knockdown with morphological readout in cultured neurons","pmids":["20516077"],"confidence":"High","gaps":["mRNA targets in neurons not identified","Molecular mechanism of translation inhibition not yet defined"]},{"year":2014,"claim":"Defined the C1q-related domain homotrimer as the structural unit required for Wnt function, separating assembly from calcium binding.","evidence":"X-ray crystallography of human and zebrafish domains with mutagenesis and LRP5/6 phosphorylation assay","pmids":["25331957"],"confidence":"High","gaps":["How trimerization couples to LRP5/6 phosphorylation mechanistically unclear","Full-length assembly state not determined"]},{"year":2015,"claim":"Demonstrated CAPRIN2 controls AVP mRNA polyadenylation and stability, linking its RNA-binding activity to systemic osmotic homeostasis.","evidence":"RNA-IP, in vivo lentiviral shRNA knockdown, overexpression, poly(A) tail assays, and physiological measurements in hypothalamus","pmids":["26559902"],"confidence":"High","gaps":["Mechanism by which CAPRIN2 promotes poly(A) lengthening unknown","Whether eIF3-mediated repression applies to AVP mRNA not tested"]},{"year":2015,"claim":"Established a required in vivo role for CAPRIN2 in lens fiber cell morphogenesis and lens-cornea separation.","evidence":"Lens-specific conditional knockout with WGA staining, scanning electron microscopy, and phenotypic analysis in mouse","pmids":["26177727"],"confidence":"Medium","gaps":["No molecular mechanism identified for the lens phenotype","Low (8%) penetrance of the Peters anomaly-like defect"]},{"year":2015,"claim":"Showed CAPRIN2 can be hijacked by a pathogen, with Chlamydia pneumoniae Cpn1027 recruiting CAPRIN2 and GSK3β to promote β-catenin-dependent apoptosis resistance.","evidence":"Yeast two-hybrid, reciprocal Co-IP, GST pull-down, live-cell imaging of recruitment, and apoptosis assays","pmids":["25996495"],"confidence":"Medium","gaps":["Physiological relevance to native CAPRIN2 function unclear","Whether recruitment alters host Wnt signaling output not quantified"]},{"year":2016,"claim":"Identified a cell-cycle-coupled mechanism whereby CAPRIN2 scaffolds CDK14/Cyclin Y onto LRP6 to drive constitutive Ser-1490 phosphorylation.","evidence":"Reciprocal Co-IP, cell cycle synchronization, and phosphorylation assays with knockdown readouts","pmids":["27821587"],"confidence":"High","gaps":["Structural basis of the quaternary complex not resolved","How signaling and RNA-binding functions are coordinated unknown"]},{"year":2019,"claim":"Resolved the HR1 dimerization fold and noted surface differences from Caprin-1 that may dictate distinct partner interactions.","evidence":"X-ray crystallography and structural comparison","pmids":["30304999"],"confidence":"Medium","gaps":["Functional consequences of surface differences not experimentally tested","Partners differentiated by these surfaces not identified"]},{"year":2020,"claim":"Defined the mechanism of CAPRIN2 translational repression, showing eIF3 binding selectively suppresses long mRNAs and shapes lens crystallin expression.","evidence":"Co-IP for eIF3 binding, genome-wide ribosome profiling in overexpression and knockout cells, and knockout mouse eye analysis","pmids":["32839273"],"confidence":"High","gaps":["How mRNA length is sensed mechanistically not fully resolved","Whether RNA-binding and Wnt functions occur in the same cells unclear"]},{"year":2024,"claim":"Established that the HR1 basic cluster (R200/R201) directs plasma membrane localization essential for CAPRIN2 Wnt activity.","evidence":"X-ray crystallography, mutagenesis, subcellular localization imaging, and Wnt signaling assays","pmids":["39159816"],"confidence":"High","gaps":["The membrane lipid or partner bound by the basic cluster not identified","How HR1 dimerization and C1q trimerization integrate spatially unresolved"]},{"year":2025,"claim":"Linked CAPRIN2 to erythropoiesis, with loss boosting erythroid production and overexpression triggering cell cycle arrest and apoptosis.","evidence":"Caprin2 knockout mouse erythroid phenotyping, CAPRIN2 overexpression growth/apoptosis assays in CHO cells, and GATA1 regulation analysis","pmids":["39922087"],"confidence":"Low","gaps":["GATA1 transcriptional regulation proposed but not experimentally confirmed","mRNA targets mediating the erythroid phenotype not identified","Single lab, limited mechanistic follow-up"]},{"year":null,"claim":"It remains unknown how CAPRIN2's two distinct activities—membrane-associated Wnt co-receptor scaffolding and cytoplasmic eIF3-dependent translational repression—are spatially and temporally partitioned within a single cell.","evidence":"","pmids":[],"confidence":"Low","gaps":["No study reconciles the membrane-localized Wnt role with the RNA granule/eIF3 translational role","Direct mRNA target catalog across tissues incomplete"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[5,6,7]},{"term_id":"GO:0045182","term_label":"translation regulator activity","supporting_discovery_ids":[5,6]},{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,1]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,3]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[3]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,5]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[5,6,7]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[8,9]}],"complexes":["CAPRIN2-CDK14-Cyclin Y-LRP6 quaternary complex","dendritic RNA granule"],"partners":["LRP5","LRP6","CDK14","CCNY","AXIN1","EIF3","GSK3B"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6IMN6","full_name":"Caprin-2","aliases":["C1q domain-containing protein 1","Cytoplasmic activation/proliferation-associated protein 2","Gastric cancer multidrug resistance-associated protein","Protein EEG-1","RNA granule protein 140"],"length_aa":1127,"mass_kda":125.9,"function":"Promotes phosphorylation of the Wnt coreceptor LRP6, leading to increased activity of the canonical Wnt signaling pathway (PubMed:18762581). Facilitates constitutive LRP6 phosphorylation by CDK14/CCNY during G2/M stage of the cell cycle, which may potentiate cells for Wnt signaling (PubMed:27821587). May regulate the transport and translation of mRNAs, modulating for instance the expression of proteins involved in synaptic plasticity in neurons (By similarity). Involved in regulation of growth as erythroblasts shift from a highly proliferative state towards their terminal phase of differentiation (PubMed:14593112). May be involved in apoptosis (PubMed:14593112)","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q6IMN6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CAPRIN2","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/CAPRIN2","total_profiled":1310},"omim":[{"mim_id":"610375","title":"CAPRIN FAMILY, MEMBER 2; CAPRIN2","url":"https://www.omim.org/entry/610375"},{"mim_id":"601178","title":"CELL CYCLE-ASSOCIATED PROTEIN 1; CAPRIN1","url":"https://www.omim.org/entry/601178"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Centrosome","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CAPRIN2"},"hgnc":{"alias_symbol":["EEG1","FLJ22569","FLJ11391","caprin-2","RNG140"],"prev_symbol":["C1QDC1"]},"alphafold":{"accession":"Q6IMN6","domains":[{"cath_id":"-","chopping":"230-316","consensus_level":"high","plddt":92.9454,"start":230,"end":316},{"cath_id":"2.60.120.40","chopping":"1000-1127","consensus_level":"high","plddt":91.672,"start":1000,"end":1127},{"cath_id":"1.10.287","chopping":"2-36_118-210","consensus_level":"medium","plddt":77.0608,"start":2,"end":210}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6IMN6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6IMN6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6IMN6-F1-predicted_aligned_error_v6.png","plddt_mean":51.81},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CAPRIN2","jax_strain_url":"https://www.jax.org/strain/search?query=CAPRIN2"},"sequence":{"accession":"Q6IMN6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6IMN6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6IMN6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6IMN6"}},"corpus_meta":[{"pmid":"18762581","id":"PMC_18762581","title":"Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation.","date":"2008","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/18762581","citation_count":51,"is_preprint":false},{"pmid":"26177727","id":"PMC_26177727","title":"Deficiency of the RNA binding protein caprin2 causes lens defects and features of Peters anomaly.","date":"2015","source":"Developmental dynamics : an official publication of the American Association of Anatomists","url":"https://pubmed.ncbi.nlm.nih.gov/26177727","citation_count":45,"is_preprint":false},{"pmid":"32691935","id":"PMC_32691935","title":"LINC00941 promotes oral squamous cell carcinoma progression via activating CAPRIN2 and canonical WNT/β-catenin signaling pathway.","date":"2020","source":"Journal of cellular and molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32691935","citation_count":41,"is_preprint":false},{"pmid":"20516077","id":"PMC_20516077","title":"RNA granule protein 140 (RNG140), a paralog of RNG105 localized to distinct RNA granules in neuronal dendrites in the adult vertebrate brain.","date":"2010","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20516077","citation_count":31,"is_preprint":false},{"pmid":"19275872","id":"PMC_19275872","title":"FGF signals induce Caprin2 expression in the vertebrate lens.","date":"2009","source":"Differentiation; research in biological diversity","url":"https://pubmed.ncbi.nlm.nih.gov/19275872","citation_count":22,"is_preprint":false},{"pmid":"27821587","id":"PMC_27821587","title":"Activation/Proliferation-associated Protein 2 (Caprin-2) Positively Regulates CDK14/Cyclin Y-mediated Lipoprotein Receptor-related Protein 5 and 6 (LRP5/6) Constitutive Phosphorylation.","date":"2016","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27821587","citation_count":21,"is_preprint":false},{"pmid":"25331957","id":"PMC_25331957","title":"Structural insights into the C1q domain of Caprin-2 in canonical Wnt signaling.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25331957","citation_count":18,"is_preprint":false},{"pmid":"36276162","id":"PMC_36276162","title":"CAPRIN2 upregulation by LINC00941 promotes nasopharyngeal carcinoma ferroptosis resistance and metastatic colonization through HMGCR.","date":"2022","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36276162","citation_count":17,"is_preprint":false},{"pmid":"26559902","id":"PMC_26559902","title":"RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response.","date":"2015","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/26559902","citation_count":16,"is_preprint":false},{"pmid":"25996495","id":"PMC_25996495","title":"The Chlamydia pneumoniae Inclusion Membrane Protein Cpn1027 Interacts with Host Cell Wnt Signaling Pathway Regulator Cytoplasmic Activation/Proliferation-Associated Protein 2 (Caprin2).","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25996495","citation_count":15,"is_preprint":false},{"pmid":"32839273","id":"PMC_32839273","title":"Implications of RNG140 (caprin2)-mediated translational regulation in eye lens differentiation.","date":"2020","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/32839273","citation_count":13,"is_preprint":false},{"pmid":"34511033","id":"PMC_34511033","title":"Upregulated lncRNA Cyclin-dependent kinase inhibitor 2B antisense RNA 1 induces the proliferation and migration of colorectal cancer by miR-378b/CAPRIN2 axis.","date":"2021","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/34511033","citation_count":9,"is_preprint":false},{"pmid":"30304999","id":"PMC_30304999","title":"Crystal structure of a dimerization domain of human Caprin-2: similar overall dimeric fold but different molecular surface properties to that of human Caprin-1.","date":"2019","source":"Journal of biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/30304999","citation_count":3,"is_preprint":false},{"pmid":"36710479","id":"PMC_36710479","title":"Polymorphisms in TRIB2 and CAPRIN2 Genes Contribute to the Susceptibility to High Myopia-Induced Cataract in Han Chinese Population.","date":"2023","source":"Medical science monitor : international medical journal of experimental and clinical research","url":"https://pubmed.ncbi.nlm.nih.gov/36710479","citation_count":2,"is_preprint":false},{"pmid":"39159816","id":"PMC_39159816","title":"Structural insights into the Caprin-2 HR1 domain in canonical Wnt signaling.","date":"2024","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/39159816","citation_count":0,"is_preprint":false},{"pmid":"39922087","id":"PMC_39922087","title":"CAPRIN2 RNA-binding protein contributes to balance erythroid production: Implications in the fine-tuning of proteostasis during erythropoiesis.","date":"2025","source":"Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis","url":"https://pubmed.ncbi.nlm.nih.gov/39922087","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9856,"output_tokens":3353,"usd":0.039932,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11052,"output_tokens":3997,"usd":0.077592,"stage2_stop_reason":"end_turn"},"total_usd":0.117524,"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\": 2008,\n      \"finding\": \"Caprin-2 was identified as a LRP5/6-binding protein that stabilizes cytosolic β-catenin, enhances LEF1/TCF-dependent reporter gene activity, facilitates GSK3-dependent LRP5/6 phosphorylation, and enhances the interaction between Axin and LRP5/6, thereby promoting canonical Wnt signaling. Morpholino-mediated knockdown of Caprin-2 in zebrafish embryos inhibits Wnt/β-catenin signaling and causes a dorsalized phenotype.\",\n      \"method\": \"Co-immunoprecipitation, reporter gene assay, morpholino knockdown in zebrafish, Western blotting for β-catenin stabilization and LRP5/6 phosphorylation\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, multiple orthogonal methods (reporter assay, phosphorylation assay, in vivo knockdown), replicated in two biological systems (mammalian cells and zebrafish)\",\n      \"pmids\": [\"18762581\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Caprin-2 positively regulates constitutive LRP5/6 Ser-1490 phosphorylation by forming a quaternary complex with CDK14, Cyclin Y, and LRP5/6 at G2/M phase of the cell cycle. Knockdown of Caprin-2 disrupts both the CDK14–Cyclin Y interaction and the CDK14/Cyclin Y–LRP6 interaction.\",\n      \"method\": \"Co-immunoprecipitation, knockdown experiments, cell cycle synchronization assays, phosphorylation assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, cell-cycle-dependent phosphorylation assay, knockdown with two distinct interaction readouts, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"27821587\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The C-terminal C1q-related domain (Cap2_CRD) of Caprin-2 forms a calcium-stabilized homotrimer (crystal structures solved for human and zebrafish). Mutations disrupting the homotrimer impair Caprin-2's ability to promote LRP5/6 phosphorylation, whereas a calcium-binding-deficient mutant retains this activity, demonstrating that trimeric assembly (not calcium binding per se) is required for Caprin-2's function in Wnt signaling.\",\n      \"method\": \"X-ray crystallography, site-directed mutagenesis, LRP5/6 phosphorylation assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure combined with mutagenesis and functional phosphorylation assay, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"25331957\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The HR1 domain of human Caprin-2 forms a homodimer with a 'scissors'-like structure as determined by X-ray crystallography. Residues R200 and R201 within a basic cluster in the N-terminal 'blades' region are critical for Caprin-2's localization to the plasma membrane; mutations at these residues decrease Caprin-2 plasma membrane localization and reduce its activity in canonical Wnt signaling.\",\n      \"method\": \"X-ray crystallography, site-directed mutagenesis, subcellular localization imaging, Wnt signaling activity assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure plus mutagenesis with localization and functional readout, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"39159816\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The HR1 region of Caprin-2 contains a dimerization domain with an all α-helical fold that self-associates to form a homodimer, as revealed by crystal structure. The dimeric fold is similar to Caprin-1 but with distinct molecular surface properties that may dictate different protein–protein interactions.\",\n      \"method\": \"X-ray crystallography, structural comparison\",\n      \"journal\": \"Journal of biomolecular structure & dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — crystal structure determined but functional validation of surface differences was not experimentally confirmed, single lab\",\n      \"pmids\": [\"30304999\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"RNG140 (Caprin-2) is an RNA-binding protein that binds mRNAs, inhibits translation in vitro, induces RNA granule formation, and localizes to dendritic RNA granules distinct from those containing RNG105. Knockdown of RNG140 in cultured neurons reduces dendrite length and spine density, and this effect is not rescued by RNG105, indicating non-redundant functions.\",\n      \"method\": \"In vitro translation assay, RNA granule induction assay, immunofluorescence/localization, shRNA knockdown in cultured neurons with morphological readout\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro translation assay, localization experiments, and knockdown with cellular phenotype in neurons; multiple orthogonal methods in a single study\",\n      \"pmids\": [\"20516077\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"RNG140 (Caprin-2) binds to the translation initiation factor eIF3 and suppresses translation through mechanisms involving inhibition of eIF3-dependent translation initiation. Ribosome profiling revealed that RNG140 overexpression reduces translation of long mRNAs (associated with cell proliferation), while RNG140 knockout in mouse eye increases translation of long mRNAs; short crystallin mRNAs escape this inhibition and are translated during lens differentiation.\",\n      \"method\": \"Co-immunoprecipitation (RNG140–eIF3 interaction), ribosome profiling (comprehensive translational analysis), RNG140 knockout mouse analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — eIF3 binding by Co-IP, genome-wide ribosome profiling in overexpression and knockout systems, confirmed in vivo in mouse eye; multiple orthogonal methods\",\n      \"pmids\": [\"32839273\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Caprin-2 binds AVP (arginine vasopressin) mRNAs in the hypothalamus and regulates their poly(A) tail length and abundance. Lentiviral shRNA knockdown of Caprin-2 in the osmotically stimulated hypothalamus shortened AVP mRNA poly(A) tails and reduced transcript abundance, while over-expression enhanced AVP mRNA abundance and poly(A) tail length. Caprin-2 knockdown decreased urine output and fluid intake and increased urine osmolality and plasma AVP levels, demonstrating a role in the central osmotic defense response.\",\n      \"method\": \"RNA immunoprecipitation (Caprin-2–AVP mRNA binding), lentiviral shRNA knockdown in vivo, in vitro overexpression system, poly(A) tail length assay, physiological measurements\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo lentiviral knockdown with physiological phenotype, RNA binding confirmed, recapitulated in vitro; multiple orthogonal methods in single study\",\n      \"pmids\": [\"26559902\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Lens-specific conditional knockout of Caprin-2 in mouse causes an abnormally compact lens nucleus and at 8% penetrance a Peters anomaly-like defect (lens–cornea attachment), establishing a required role for Caprin-2 in lens fiber cell morphogenesis and lens–cornea separation during eye development.\",\n      \"method\": \"Conditional knockout (Pax6GFPCre-driven), wheat germ agglutinin staining, scanning electron microscopy, phenotypic analysis\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined morphological phenotype, multiple imaging methods; no molecular mechanism identified in this study, single lab\",\n      \"pmids\": [\"26177727\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"FGF signaling (specifically FGF8 activity from prospective retinal cells) is required and sufficient to induce Caprin-2 expression in lens fiber cells during vertebrate lens development, placing Caprin-2 downstream of FGF receptor signaling in the lens differentiation pathway.\",\n      \"method\": \"In vitro lens fiber cell differentiation assays, FGF8 addition/inhibition experiments, in situ hybridization in mouse and chick\",\n      \"journal\": \"Differentiation; research in biological diversity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro gain-of-function and inhibition experiments in two species establishing epistatic relationship; pathway placement supported but molecular mechanism not fully detailed\",\n      \"pmids\": [\"19275872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Chlamydia pneumoniae inclusion membrane protein Cpn1027 interacts with Caprin-2 (mapped to C-termini of both proteins) and co-precipitates GSK3β. RFP-Caprin2 fusion protein is recruited to the chlamydial inclusion along with endogenous GSK3β, and C. pneumoniae-infected cells show enhanced apoptosis resistance dependent on β-catenin.\",\n      \"method\": \"Yeast two-hybrid screen, co-immunoprecipitation, GST pull-down, live-cell imaging of RFP-Caprin2 recruitment, apoptosis assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — interaction mapped by reciprocal Co-IP and GST pull-down, live imaging of recruitment, functional apoptosis assay; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"25996495\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GATA1 potentially regulates Caprin2 transcription in erythroid cells, and Caprin2 loss boosts erythroid production and maturation during gestation and adulthood, an effect enhanced under stress erythropoiesis conditions. Overexpression of CAPRIN2 in CHO cells causes reduced growth, cell cycle arrest, and apoptosis, consistent with its role in translational regulation of key mRNAs during erythropoiesis.\",\n      \"method\": \"Caprin2 knockout mouse analysis (erythroid phenotype), CAPRIN2 overexpression in CHO cells (growth/apoptosis assay), GATA1 transcriptional regulation analysis\",\n      \"journal\": \"Transfusion and apheresis science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — KO phenotype described and overexpression effects noted, but molecular mechanism for GATA1 regulation and mRNA targets is proposed but not experimentally confirmed in this study; single lab, limited mechanistic follow-up\",\n      \"pmids\": [\"39922087\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CAPRIN2 (RNG140/Caprin-2) is a multifunctional RNA-binding protein and Wnt pathway regulator: it directly binds LRP5/6 co-receptors, facilitating both GSK3-dependent Wnt-induced phosphorylation and CDK14/Cyclin Y-dependent constitutive Ser-1490 phosphorylation by forming a quaternary complex, thereby promoting canonical Wnt/β-catenin signaling; its C-terminal C1q domain forms a calcium-stabilized homotrimer required for this activity, and its HR1 domain forms a homodimer whose basic residues (R200/R201) mediate plasma membrane localization essential for Wnt signaling function; as an RNA-binding protein, it suppresses translation of long mRNAs by binding eIF3 and inhibiting translation initiation, regulates AVP mRNA poly(A) tail length and stability in the hypothalamus to control osmotic homeostasis, and localizes to distinct dendritic RNA granules in neurons where it maintains dendrite length and spine density.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CAPRIN2 (RNG140/Caprin-2) is a dual-function protein that acts both as a positive regulator of canonical Wnt/\\u03b2-catenin signaling and as an RNA-binding translational repressor [#0, #6]. In Wnt signaling, it binds the LRP5/6 co-receptors, stabilizes cytosolic \\u03b2-catenin, enhances Axin\\u2013LRP5/6 association, and facilitates GSK3-dependent LRP5/6 phosphorylation to promote LEF1/TCF-dependent transcription, with knockdown in zebrafish causing a dorsalized phenotype [#0]. It additionally drives constitutive LRP5/6 Ser-1490 phosphorylation by assembling a quaternary complex with CDK14, Cyclin Y, and LRP5/6 during G2/M [#1]. This signaling activity depends on two structurally defined self-association modules: a C-terminal C1q-related domain that forms a calcium-stabilized homotrimer required for promoting LRP5/6 phosphorylation [#2], and an HR1 domain that forms a 'scissors'-like homodimer whose basic residues R200/R201 direct plasma membrane localization essential for Wnt activity [#3, #4]. As an RNA-binding protein, CAPRIN2 binds mRNAs and the translation initiation factor eIF3 to suppress translation initiation, selectively repressing long mRNAs while sparing short crystallin transcripts during lens differentiation [#5, #6]. It binds AVP mRNA in the hypothalamus to control poly(A) tail length and abundance, governing the central osmotic defense response [#7]. CAPRIN2 localizes to dendritic RNA granules distinct from RNG105-containing granules and is required for dendrite length and spine density [#5], and is required in vivo for lens fiber cell morphogenesis downstream of FGF8 signaling [#8, #9].\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Established CAPRIN2 as a positive regulator of canonical Wnt signaling, answering how a novel LRP5/6-binding protein influences \\u03b2-catenin stability.\",\n      \"evidence\": \"Co-IP, reporter assays, LRP5/6 phosphorylation assays in mammalian cells and morpholino knockdown in zebrafish\",\n      \"pmids\": [\"18762581\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the structural basis of LRP5/6 binding\", \"Mechanism linking CAPRIN2 to Axin recruitment not resolved\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Placed CAPRIN2 downstream of FGF receptor signaling in lens differentiation, defining an upstream inducer of its expression.\",\n      \"evidence\": \"In vitro lens fiber differentiation with FGF8 gain/loss and in situ hybridization in mouse and chick\",\n      \"pmids\": [\"19275872\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Transcriptional intermediates between FGF8 and CAPRIN2 not identified\", \"Whether CAPRIN2's lens role is RNA-binding or Wnt-related not addressed\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Revealed CAPRIN2 as an RNA-binding translational repressor in neurons, distinguishing its dendritic granule role from the paralog RNG105.\",\n      \"evidence\": \"In vitro translation assays, RNA granule induction, immunofluorescence, and shRNA knockdown with morphological readout in cultured neurons\",\n      \"pmids\": [\"20516077\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"mRNA targets in neurons not identified\", \"Molecular mechanism of translation inhibition not yet defined\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined the C1q-related domain homotrimer as the structural unit required for Wnt function, separating assembly from calcium binding.\",\n      \"evidence\": \"X-ray crystallography of human and zebrafish domains with mutagenesis and LRP5/6 phosphorylation assay\",\n      \"pmids\": [\"25331957\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How trimerization couples to LRP5/6 phosphorylation mechanistically unclear\", \"Full-length assembly state not determined\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Demonstrated CAPRIN2 controls AVP mRNA polyadenylation and stability, linking its RNA-binding activity to systemic osmotic homeostasis.\",\n      \"evidence\": \"RNA-IP, in vivo lentiviral shRNA knockdown, overexpression, poly(A) tail assays, and physiological measurements in hypothalamus\",\n      \"pmids\": [\"26559902\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which CAPRIN2 promotes poly(A) lengthening unknown\", \"Whether eIF3-mediated repression applies to AVP mRNA not tested\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Established a required in vivo role for CAPRIN2 in lens fiber cell morphogenesis and lens-cornea separation.\",\n      \"evidence\": \"Lens-specific conditional knockout with WGA staining, scanning electron microscopy, and phenotypic analysis in mouse\",\n      \"pmids\": [\"26177727\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No molecular mechanism identified for the lens phenotype\", \"Low (8%) penetrance of the Peters anomaly-like defect\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Showed CAPRIN2 can be hijacked by a pathogen, with Chlamydia pneumoniae Cpn1027 recruiting CAPRIN2 and GSK3\\u03b2 to promote \\u03b2-catenin-dependent apoptosis resistance.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal Co-IP, GST pull-down, live-cell imaging of recruitment, and apoptosis assays\",\n      \"pmids\": [\"25996495\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological relevance to native CAPRIN2 function unclear\", \"Whether recruitment alters host Wnt signaling output not quantified\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified a cell-cycle-coupled mechanism whereby CAPRIN2 scaffolds CDK14/Cyclin Y onto LRP6 to drive constitutive Ser-1490 phosphorylation.\",\n      \"evidence\": \"Reciprocal Co-IP, cell cycle synchronization, and phosphorylation assays with knockdown readouts\",\n      \"pmids\": [\"27821587\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the quaternary complex not resolved\", \"How signaling and RNA-binding functions are coordinated unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Resolved the HR1 dimerization fold and noted surface differences from Caprin-1 that may dictate distinct partner interactions.\",\n      \"evidence\": \"X-ray crystallography and structural comparison\",\n      \"pmids\": [\"30304999\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequences of surface differences not experimentally tested\", \"Partners differentiated by these surfaces not identified\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Defined the mechanism of CAPRIN2 translational repression, showing eIF3 binding selectively suppresses long mRNAs and shapes lens crystallin expression.\",\n      \"evidence\": \"Co-IP for eIF3 binding, genome-wide ribosome profiling in overexpression and knockout cells, and knockout mouse eye analysis\",\n      \"pmids\": [\"32839273\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How mRNA length is sensed mechanistically not fully resolved\", \"Whether RNA-binding and Wnt functions occur in the same cells unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established that the HR1 basic cluster (R200/R201) directs plasma membrane localization essential for CAPRIN2 Wnt activity.\",\n      \"evidence\": \"X-ray crystallography, mutagenesis, subcellular localization imaging, and Wnt signaling assays\",\n      \"pmids\": [\"39159816\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The membrane lipid or partner bound by the basic cluster not identified\", \"How HR1 dimerization and C1q trimerization integrate spatially unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Linked CAPRIN2 to erythropoiesis, with loss boosting erythroid production and overexpression triggering cell cycle arrest and apoptosis.\",\n      \"evidence\": \"Caprin2 knockout mouse erythroid phenotyping, CAPRIN2 overexpression growth/apoptosis assays in CHO cells, and GATA1 regulation analysis\",\n      \"pmids\": [\"39922087\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"GATA1 transcriptional regulation proposed but not experimentally confirmed\", \"mRNA targets mediating the erythroid phenotype not identified\", \"Single lab, limited mechanistic follow-up\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how CAPRIN2's two distinct activities\\u2014membrane-associated Wnt co-receptor scaffolding and cytoplasmic eIF3-dependent translational repression\\u2014are spatially and temporally partitioned within a single cell.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No study reconciles the membrane-localized Wnt role with the RNA granule/eIF3 translational role\", \"Direct mRNA target catalog across tissues incomplete\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [5, 6, 7]},\n      {\"term_id\": \"GO:0045182\", \"supporting_discovery_ids\": [5, 6]},\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [5, 6, 7]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [8, 9]}\n    ],\n    \"complexes\": [\n      \"CAPRIN2-CDK14-Cyclin Y-LRP6 quaternary complex\",\n      \"dendritic RNA granule\"\n    ],\n    \"partners\": [\n      \"LRP5\",\n      \"LRP6\",\n      \"CDK14\",\n      \"CCNY\",\n      \"AXIN1\",\n      \"EIF3\",\n      \"GSK3B\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":7,"faith_pct":85.71428571428571}}