{"gene":"CTTNBP2NL","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":2012,"finding":"CTTNBP2NL interacts with cortactin (though this interaction does not promote dendritic spinogenesis), and CTTNBP2NL is associated with stress fibers rather than cortical/punctate distributions seen with CTTNBP2. CTTNBP2NL shows no activity in regulation of dendritic spinogenesis.","method":"Co-immunoprecipitation, subcellular localization experiments in neurons and HEK293 cells, overexpression/knockdown with dendritic spine morphology readout","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and localization with functional readout (spinogenesis assay), single lab with two orthogonal methods","pmids":["23015759"],"is_preprint":false},{"year":2012,"finding":"CTTNBP2NL interacts with striatin and zinedin (regulatory B subunits of PP2A) in HEK293 cells, placing it in a striatin-PP2A complex.","method":"Co-immunoprecipitation in HEK293 cells","journal":"Molecular biology of the cell","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP in heterologous cells, single lab, single method","pmids":["23015759"],"is_preprint":false},{"year":2011,"finding":"CTTNBP2NL physically interacts with STRN (striatin), as validated experimentally by immunoprecipitation from IP-MS proteomics data.","method":"Experimental validation of IP-MS predicted interaction (Co-IP/pull-down)","journal":"PLoS computational biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single experimental validation from a pan-proteomics study, single method","pmids":["22219718"],"is_preprint":false},{"year":2013,"finding":"CTTNBP2NL dephosphorylates connexin 43 (a gap junction protein), and overexpression of CTTNBP2NL inhibits embryo implantation in mice.","method":"Biochemical dephosphorylation assay for connexin 43 phosphorylation status; mouse embryo implantation model with CTTNBP2NL overexpression","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical activity assay plus in vivo functional readout, single lab","pmids":["24218568"],"is_preprint":false},{"year":2026,"finding":"CTTNBP2NL is identified as a negative regulator of autophagy that localizes to the nucleus/nucleolus; interaction with the peptide Tat-HSPE1 promotes translocation of CTTNBP2NL from the nucleus to the cytoplasm, facilitating activation of autophagic processes in ccRCC cells.","method":"Peptidomics, cellular fractionation/localization, interaction assay (Tat-HSPE1 co-treatment), autophagy activation assay in ccRCC cells","journal":"Frontiers in pharmacology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, indirect evidence of CTTNBP2NL autophagy regulatory role via peptide interaction, limited mechanistic detail in abstract","pmids":["42147335"],"is_preprint":false},{"year":2025,"finding":"TEAD1 transcriptionally regulates CTTNBP2NL expression in papillary thyroid carcinoma cells; overexpression of TEAD1 compensates for CTTNBP2NL deficiency to promote cell survival and reduce apoptosis.","method":"qPCR, Western blot, overexpression/knockdown in TPC1 cells with proliferation and apoptosis assays, colony formation assay","journal":"CytoJournal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, indirect transcriptional regulatory relationship established by expression modulation without direct promoter binding assay described in abstract","pmids":["41216228"],"is_preprint":false}],"current_model":"CTTNBP2NL is a cortactin-binding protein that associates with stress fibers, interacts with striatin-PP2A complex components (striatin, zinedin), dephosphorylates connexin 43 to regulate gap junction signaling, localizes to the nucleus/nucleolus where it negatively regulates autophagy, and is transcriptionally regulated by TEAD1; unlike its paralog CTTNBP2, it does not regulate dendritic spinogenesis."},"narrative":{"mechanistic_narrative":"CTTNBP2NL is a cortactin-binding protein that associates with stress fibers and functions as a scaffolding component of striatin-PP2A signaling, distinguishing it functionally from its paralog CTTNBP2 in that it does not regulate dendritic spinogenesis [PMID:23015759]. It binds cortactin and assembles with the PP2A regulatory B subunits striatin (STRN) and zinedin, placing CTTNBP2NL within a striatin-PP2A complex [PMID:23015759]. Consistent with a role in directing phosphatase activity, CTTNBP2NL mediates dephosphorylation of the gap junction protein connexin 43, and its overexpression inhibits embryo implantation in mice [PMID:24218568]. Beyond these activities, the broader mechanistic logic linking its cortactin/stress-fiber association, striatin-PP2A scaffolding, and connexin 43 dephosphorylation has not been integrated in the available corpus.","teleology":[{"year":2011,"claim":"Establishing whether CTTNBP2NL is a bona fide striatin-associated protein anchored the gene to the striatin interaction network and gave it a candidate scaffolding context.","evidence":"Experimental Co-IP/pull-down validation of an IP-MS-predicted CTTNBP2NL-STRN interaction","pmids":["22219718"],"confidence":"Low","gaps":["Single experimental validation from a pan-proteomics study, single method","Stoichiometry and direct versus indirect nature of the STRN interaction not resolved","Functional consequence of the interaction not tested"]},{"year":2012,"claim":"Defining CTTNBP2NL's partners and localization separated it from its paralog CTTNBP2, showing it binds cortactin and decorates stress fibers without driving dendritic spinogenesis.","evidence":"Reciprocal Co-IP, subcellular localization in neurons and HEK293 cells, and spine-morphology functional readout","pmids":["23015759"],"confidence":"Medium","gaps":["Mechanism by which CTTNBP2NL is targeted to stress fibers rather than cortical actin is unknown","The functional output of cortactin binding for CTTNBP2NL is not defined","No structural basis for partner selection established"]},{"year":2012,"claim":"Co-IP of CTTNBP2NL with striatin and zinedin placed it in a striatin-PP2A complex, providing a candidate route to phosphatase-directed signaling.","evidence":"Co-immunoprecipitation in HEK293 cells","pmids":["23015759"],"confidence":"Low","gaps":["Single Co-IP in heterologous cells, single method","Whether CTTNBP2NL recruits or modulates PP2A catalytic activity not shown","Substrate targeting by the complex not addressed"]},{"year":2013,"claim":"Demonstrating CTTNBP2NL-dependent dephosphorylation of connexin 43 linked the protein to gap junction regulation and provided an in vivo phenotype.","evidence":"Biochemical connexin 43 dephosphorylation assay plus a mouse embryo implantation model with CTTNBP2NL overexpression","pmids":["24218568"],"confidence":"Medium","gaps":["Whether dephosphorylation is direct or via the associated PP2A complex is not resolved","Connexin 43 residues targeted not mapped","Mechanistic link between connexin 43 status and implantation failure unclear"]},{"year":2025,"claim":"Identifying TEAD1 as an upstream regulator of CTTNBP2NL expression connected the gene to a transcriptional control axis affecting tumor cell survival.","evidence":"qPCR, Western blot, and overexpression/knockdown in TPC1 papillary thyroid carcinoma cells with proliferation, apoptosis, and colony formation assays","pmids":["41216228"],"confidence":"Low","gaps":["Indirect transcriptional relationship without a direct promoter-binding assay","Single cell line and single lab","Mechanistic role of CTTNBP2NL downstream of TEAD1 not defined"]},{"year":2026,"claim":"Reporting CTTNBP2NL as a nuclear/nucleolar negative regulator of autophagy whose cytoplasmic translocation activates autophagy proposed a new localization-dependent function.","evidence":"Peptidomics, cellular fractionation, Tat-HSPE1 interaction assay, and autophagy activation readout in ccRCC cells","pmids":["42147335"],"confidence":"Low","gaps":["Indirect evidence via peptide interaction with limited mechanistic detail","How nuclear CTTNBP2NL suppresses autophagy is not defined","Relationship between this nuclear role and its cytoplasmic stress-fiber/striatin functions unknown"]},{"year":null,"claim":"It remains unknown how CTTNBP2NL's cortactin/stress-fiber association, striatin-PP2A scaffolding, connexin 43 dephosphorylation, and reported nuclear autophagy regulation are mechanistically unified.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of CTTNBP2NL or its complexes","Direct catalytic versus adaptor contribution to dephosphorylation unresolved","Whether nuclear and cytoskeletal functions reflect distinct pools or a single regulated mechanism is untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0]}],"pathway":[],"complexes":["striatin-PP2A complex"],"partners":["CTTN","STRN","STRN4"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9P2B4","full_name":"CTTNBP2 N-terminal-like protein","aliases":[],"length_aa":639,"mass_kda":70.2,"function":"Regulates lamellipodial actin dynamics in a CTTN-dependent manner (By similarity). Associates with core striatin-interacting phosphatase and kinase (STRIPAK) complex to form CTTNBP2NL-STRIPAK complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753)","subcellular_location":"Cell projection, lamellipodium; Cytoplasm, cytoskeleton, stress fiber","url":"https://www.uniprot.org/uniprotkb/Q9P2B4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CTTNBP2NL","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DYNLL2","stoichiometry":10.0},{"gene":"DYNLL1","stoichiometry":4.0},{"gene":"MAP4K4","stoichiometry":4.0},{"gene":"CALM3","stoichiometry":0.2},{"gene":"CTTN","stoichiometry":0.2},{"gene":"PPP2CA","stoichiometry":0.2},{"gene":"PPP2CB","stoichiometry":0.2},{"gene":"STK25","stoichiometry":0.2},{"gene":"STK26","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CTTNBP2NL","total_profiled":1310},"omim":[{"mim_id":"615100","title":"CTTNBP2 N TERMINUS-LIKE PROTEIN; CTTNBP2NL","url":"https://www.omim.org/entry/615100"},{"mim_id":"609772","title":"CORTACTIN-BINDING PROTEIN 2; CTTNBP2","url":"https://www.omim.org/entry/609772"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli fibrillar center","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CTTNBP2NL"},"hgnc":{"alias_symbol":["DKFZp547A023"],"prev_symbol":[]},"alphafold":{"accession":"Q9P2B4","domains":[{"cath_id":"-","chopping":"9-67","consensus_level":"medium","plddt":86.309,"start":9,"end":67}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P2B4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P2B4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P2B4-F1-predicted_aligned_error_v6.png","plddt_mean":65.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CTTNBP2NL","jax_strain_url":"https://www.jax.org/strain/search?query=CTTNBP2NL"},"sequence":{"accession":"Q9P2B4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9P2B4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9P2B4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P2B4"}},"corpus_meta":[{"pmid":"23015759","id":"PMC_23015759","title":"CTTNBP2, but not CTTNBP2NL, regulates dendritic spinogenesis and synaptic distribution of the striatin-PP2A complex.","date":"2012","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/23015759","citation_count":51,"is_preprint":false},{"pmid":"21334929","id":"PMC_21334929","title":"Genetic alterations in oral squamous cell carcinoma progression detected by combining array-based comparative genomic hybridization and multiplex ligation-dependent probe amplification.","date":"2011","source":"Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics","url":"https://pubmed.ncbi.nlm.nih.gov/21334929","citation_count":36,"is_preprint":false},{"pmid":"29955027","id":"PMC_29955027","title":"Genomic and transcriptomic analyses reveal selection of genes for puberty in Bama Xiang pigs.","date":"2018","source":"Zoological research","url":"https://pubmed.ncbi.nlm.nih.gov/29955027","citation_count":29,"is_preprint":false},{"pmid":"24218568","id":"PMC_24218568","title":"Genetic variants related to gap junctions and hormone secretion influence conception rates in cows.","date":"2013","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24218568","citation_count":24,"is_preprint":false},{"pmid":"22219718","id":"PMC_22219718","title":"Recovering protein-protein and domain-domain interactions from aggregation of IP-MS proteomics of coregulator complexes.","date":"2011","source":"PLoS computational biology","url":"https://pubmed.ncbi.nlm.nih.gov/22219718","citation_count":14,"is_preprint":false},{"pmid":"31164339","id":"PMC_31164339","title":"The Drosophila protein, Nausicaa, regulates lamellipodial actin dynamics in a Cortactin-dependent manner.","date":"2019","source":"Biology open","url":"https://pubmed.ncbi.nlm.nih.gov/31164339","citation_count":9,"is_preprint":false},{"pmid":"36276268","id":"PMC_36276268","title":"Pan-Cancer Analysis on the Oncogenic Role of Programmed Cell Death 10.","date":"2022","source":"Journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/36276268","citation_count":3,"is_preprint":false},{"pmid":"22029168","id":"PMC_22029168","title":"Mosaic supernumerary r(1)(p13.2q23.3) in a 10-year-old girl with epilepsy facial asymmetry psychomotor retardation kyphoscoliosis dermatofibrosarcoma and multiple exostoses.","date":"2011","source":"Genetic counseling (Geneva, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/22029168","citation_count":3,"is_preprint":false},{"pmid":"41892289","id":"PMC_41892289","title":"Proteomic Profiling of Endometrial Cancer Tissues Reveals Differential Expression of Proteomes in Obese Versus Non-Obese Patients.","date":"2026","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/41892289","citation_count":1,"is_preprint":false},{"pmid":"42147335","id":"PMC_42147335","title":"Tat-HSPE1 suppresses clear cell renal cell carcinoma growth through lysosome-dependent cell death.","date":"2026","source":"Frontiers in pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/42147335","citation_count":0,"is_preprint":false},{"pmid":"41216228","id":"PMC_41216228","title":"Transcriptional enhanced associate domain factor 1 regulates cortactin-binding protein 2 N-terminal-like to control cell apoptosis in thyroid cancer.","date":"2025","source":"CytoJournal","url":"https://pubmed.ncbi.nlm.nih.gov/41216228","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8021,"output_tokens":1348,"usd":0.022142,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7977,"output_tokens":2325,"usd":0.049005,"stage2_stop_reason":"end_turn"},"total_usd":0.071147,"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\": 2012,\n      \"finding\": \"CTTNBP2NL interacts with cortactin (though this interaction does not promote dendritic spinogenesis), and CTTNBP2NL is associated with stress fibers rather than cortical/punctate distributions seen with CTTNBP2. CTTNBP2NL shows no activity in regulation of dendritic spinogenesis.\",\n      \"method\": \"Co-immunoprecipitation, subcellular localization experiments in neurons and HEK293 cells, overexpression/knockdown with dendritic spine morphology readout\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and localization with functional readout (spinogenesis assay), single lab with two orthogonal methods\",\n      \"pmids\": [\"23015759\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CTTNBP2NL interacts with striatin and zinedin (regulatory B subunits of PP2A) in HEK293 cells, placing it in a striatin-PP2A complex.\",\n      \"method\": \"Co-immunoprecipitation in HEK293 cells\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP in heterologous cells, single lab, single method\",\n      \"pmids\": [\"23015759\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"CTTNBP2NL physically interacts with STRN (striatin), as validated experimentally by immunoprecipitation from IP-MS proteomics data.\",\n      \"method\": \"Experimental validation of IP-MS predicted interaction (Co-IP/pull-down)\",\n      \"journal\": \"PLoS computational biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single experimental validation from a pan-proteomics study, single method\",\n      \"pmids\": [\"22219718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"CTTNBP2NL dephosphorylates connexin 43 (a gap junction protein), and overexpression of CTTNBP2NL inhibits embryo implantation in mice.\",\n      \"method\": \"Biochemical dephosphorylation assay for connexin 43 phosphorylation status; mouse embryo implantation model with CTTNBP2NL overexpression\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical activity assay plus in vivo functional readout, single lab\",\n      \"pmids\": [\"24218568\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CTTNBP2NL is identified as a negative regulator of autophagy that localizes to the nucleus/nucleolus; interaction with the peptide Tat-HSPE1 promotes translocation of CTTNBP2NL from the nucleus to the cytoplasm, facilitating activation of autophagic processes in ccRCC cells.\",\n      \"method\": \"Peptidomics, cellular fractionation/localization, interaction assay (Tat-HSPE1 co-treatment), autophagy activation assay in ccRCC cells\",\n      \"journal\": \"Frontiers in pharmacology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, indirect evidence of CTTNBP2NL autophagy regulatory role via peptide interaction, limited mechanistic detail in abstract\",\n      \"pmids\": [\"42147335\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"TEAD1 transcriptionally regulates CTTNBP2NL expression in papillary thyroid carcinoma cells; overexpression of TEAD1 compensates for CTTNBP2NL deficiency to promote cell survival and reduce apoptosis.\",\n      \"method\": \"qPCR, Western blot, overexpression/knockdown in TPC1 cells with proliferation and apoptosis assays, colony formation assay\",\n      \"journal\": \"CytoJournal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, indirect transcriptional regulatory relationship established by expression modulation without direct promoter binding assay described in abstract\",\n      \"pmids\": [\"41216228\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CTTNBP2NL is a cortactin-binding protein that associates with stress fibers, interacts with striatin-PP2A complex components (striatin, zinedin), dephosphorylates connexin 43 to regulate gap junction signaling, localizes to the nucleus/nucleolus where it negatively regulates autophagy, and is transcriptionally regulated by TEAD1; unlike its paralog CTTNBP2, it does not regulate dendritic spinogenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CTTNBP2NL is a cortactin-binding protein that associates with stress fibers and functions as a scaffolding component of striatin-PP2A signaling, distinguishing it functionally from its paralog CTTNBP2 in that it does not regulate dendritic spinogenesis [#0]. It binds cortactin and assembles with the PP2A regulatory B subunits striatin (STRN) and zinedin, placing CTTNBP2NL within a striatin-PP2A complex [#0, #1]. Consistent with a role in directing phosphatase activity, CTTNBP2NL mediates dephosphorylation of the gap junction protein connexin 43, and its overexpression inhibits embryo implantation in mice [#3]. Beyond these activities, the broader mechanistic logic linking its cortactin/stress-fiber association, striatin-PP2A scaffolding, and connexin 43 dephosphorylation has not been integrated in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Establishing whether CTTNBP2NL is a bona fide striatin-associated protein anchored the gene to the striatin interaction network and gave it a candidate scaffolding context.\",\n      \"evidence\": \"Experimental Co-IP/pull-down validation of an IP-MS-predicted CTTNBP2NL-STRN interaction\",\n      \"pmids\": [\"22219718\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single experimental validation from a pan-proteomics study, single method\",\n        \"Stoichiometry and direct versus indirect nature of the STRN interaction not resolved\",\n        \"Functional consequence of the interaction not tested\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Defining CTTNBP2NL's partners and localization separated it from its paralog CTTNBP2, showing it binds cortactin and decorates stress fibers without driving dendritic spinogenesis.\",\n      \"evidence\": \"Reciprocal Co-IP, subcellular localization in neurons and HEK293 cells, and spine-morphology functional readout\",\n      \"pmids\": [\"23015759\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism by which CTTNBP2NL is targeted to stress fibers rather than cortical actin is unknown\",\n        \"The functional output of cortactin binding for CTTNBP2NL is not defined\",\n        \"No structural basis for partner selection established\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Co-IP of CTTNBP2NL with striatin and zinedin placed it in a striatin-PP2A complex, providing a candidate route to phosphatase-directed signaling.\",\n      \"evidence\": \"Co-immunoprecipitation in HEK293 cells\",\n      \"pmids\": [\"23015759\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP in heterologous cells, single method\",\n        \"Whether CTTNBP2NL recruits or modulates PP2A catalytic activity not shown\",\n        \"Substrate targeting by the complex not addressed\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstrating CTTNBP2NL-dependent dephosphorylation of connexin 43 linked the protein to gap junction regulation and provided an in vivo phenotype.\",\n      \"evidence\": \"Biochemical connexin 43 dephosphorylation assay plus a mouse embryo implantation model with CTTNBP2NL overexpression\",\n      \"pmids\": [\"24218568\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether dephosphorylation is direct or via the associated PP2A complex is not resolved\",\n        \"Connexin 43 residues targeted not mapped\",\n        \"Mechanistic link between connexin 43 status and implantation failure unclear\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identifying TEAD1 as an upstream regulator of CTTNBP2NL expression connected the gene to a transcriptional control axis affecting tumor cell survival.\",\n      \"evidence\": \"qPCR, Western blot, and overexpression/knockdown in TPC1 papillary thyroid carcinoma cells with proliferation, apoptosis, and colony formation assays\",\n      \"pmids\": [\"41216228\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Indirect transcriptional relationship without a direct promoter-binding assay\",\n        \"Single cell line and single lab\",\n        \"Mechanistic role of CTTNBP2NL downstream of TEAD1 not defined\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Reporting CTTNBP2NL as a nuclear/nucleolar negative regulator of autophagy whose cytoplasmic translocation activates autophagy proposed a new localization-dependent function.\",\n      \"evidence\": \"Peptidomics, cellular fractionation, Tat-HSPE1 interaction assay, and autophagy activation readout in ccRCC cells\",\n      \"pmids\": [\"42147335\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Indirect evidence via peptide interaction with limited mechanistic detail\",\n        \"How nuclear CTTNBP2NL suppresses autophagy is not defined\",\n        \"Relationship between this nuclear role and its cytoplasmic stress-fiber/striatin functions unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how CTTNBP2NL's cortactin/stress-fiber association, striatin-PP2A scaffolding, connexin 43 dephosphorylation, and reported nuclear autophagy regulation are mechanistically unified.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of CTTNBP2NL or its complexes\",\n        \"Direct catalytic versus adaptor contribution to dephosphorylation unresolved\",\n        \"Whether nuclear and cytoskeletal functions reflect distinct pools or a single regulated mechanism is untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"striatin-PP2A complex\"],\n    \"partners\": [\"CTTN\", \"STRN\", \"STRN4\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}