{"gene":"CEP85","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2018,"finding":"CEP85 directly binds STIL through a conserved interaction interface involving a previously uncharacterised domain of STIL; this interaction is essential for efficient centriolar targeting of STIL, PLK4 activation, and faithful daughter centriole assembly.","method":"Protein proximity mapping (BioID), NMR/structural methods, structure-guided mutational analyses in vivo, Co-IP","journal":"Nature Communications","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (proximity mapping, high-resolution structural determination, mutagenesis, in vivo functional rescue) in a single rigorous study","pmids":["29712910"],"is_preprint":false},{"year":2015,"finding":"CEP85 localizes to centrosomes, colocalizes with Nek2A at the proximal ends of centrioles forming a granule meshwork, directly binds Nek2A, and inhibits Nek2A kinase activity in vitro; depletion of CEP85 causes precocious centrosome separation while overexpression (with Eg5 inhibition) blocks centrosome disjunction. CEP85 cooperates with PP1γ to antagonize Nek2A activity during interphase.","method":"Co-immunoprecipitation, in vitro kinase assay, immunofluorescence/localization, siRNA depletion, overexpression with domain-mapping","journal":"Journal of Cell Science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, in vitro kinase assay, loss-of-function and gain-of-function with defined phenotype, domain mapping; single lab but multiple orthogonal methods","pmids":["26220856"],"is_preprint":false},{"year":2018,"finding":"PLK1 interacts with CEP85 and forms a ternary complex with CEP85–Nek2A. Nek2A binding to CEP85 is required (but not Nek2A kinase activity) for CEP85 to be phosphorylated by PLK1. PLK1-mediated phosphorylation of CEP85 causes its dissociation specifically from phospho-Nek2A, freeing phospho-Nek2A to become active. Both PLK1 and Nek2A are required for endogenous CEP85 phosphorylation, and timely CEP85 phosphorylation at G2/M is essential for centrosome disjunction.","method":"Co-immunoprecipitation, in vitro kinase assay, phospho-specific analyses, cell-based functional assays with mutant forms","journal":"iScience","confidence":"High","confidence_rationale":"Tier 2 / Moderate — Co-IP establishing ternary complex, in vitro kinase assays, endogenous phosphorylation validated in cells, multiple orthogonal methods in single lab","pmids":["30611117"],"is_preprint":false},{"year":2020,"finding":"The CEP85–STIL interaction is required for directional cancer cell migration. PLK4 drives recruitment of CEP85 and STIL to the leading edge of migrating cells to promote protrusive activity; disruption of the CEP85–STIL–PLK4 interaction reduces ARP2 (ACTR2) phosphorylation and impairs actin cytoskeleton reorganization, thereby impairing directional cell motility.","method":"Mutational analyses, fluorescence localization (leading-edge recruitment), siRNA knockdown, phosphorylation assays (ARP2), directed cell migration assays","journal":"Journal of Cell Science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — structure-guided mutational analyses, localization experiments, loss-of-function with defined molecular readout (ARP2 phosphorylation) and cellular phenotype, building on prior structural work","pmids":["32107292"],"is_preprint":false},{"year":2025,"finding":"CEP85 overexpression in monocyte-derived macrophages disrupts phagocytosis, indicating a functional role in phagocytic activity.","method":"In vitro overexpression in monocyte-derived macrophages with phagocytosis assay","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single functional in vitro assay reported in a preprint with no mechanistic pathway placement, no molecular detail provided in abstract","pmids":[],"is_preprint":true}],"current_model":"CEP85 is a centrosomal scaffold protein that directly binds STIL to promote PLK4 activation, centriolar STIL recruitment, and daughter centriole assembly; it also acts as a relay in centrosome disjunction by forming a PLK1–CEP85–Nek2A ternary complex in which PLK1 phosphorylates CEP85 in a Nek2A-binding-dependent manner, causing CEP85 to dissociate from phospho-Nek2A and thereby freeing active phospho-Nek2A to initiate centrosome separation at G2/M, while in interphase CEP85 cooperates with PP1γ to antagonize Nek2A and maintain centrosome integrity; additionally, the CEP85–STIL complex is recruited by PLK4 to the leading edge of migrating cells to sustain ARP2 phosphorylation and actin-dependent directional motility."},"narrative":{"mechanistic_narrative":"CEP85 is a centrosomal scaffold protein that governs both centriole biogenesis and centrosome separation through direct, mutually exclusive kinase-coupled interactions [PMID:26220856, PMID:29712910]. In centriole assembly, CEP85 directly binds STIL through a conserved interface, and this interaction is essential for centriolar targeting of STIL, PLK4 activation, and faithful daughter centriole formation [PMID:29712910]. In centrosome integrity control, CEP85 localizes to the proximal ends of centrioles, directly binds Nek2A, and inhibits its kinase activity, cooperating with PP1γ to antagonize Nek2A and suppress precocious centrosome separation during interphase [PMID:26220856]. At G2/M this restraint is relieved: CEP85 forms a PLK1–CEP85–Nek2A ternary complex in which PLK1 phosphorylates CEP85 in a Nek2A-binding-dependent manner, driving CEP85 to dissociate from phospho-Nek2A and freeing active Nek2A to initiate centrosome disjunction [PMID:30611117]. Beyond the centrosome, the CEP85–STIL complex is recruited by PLK4 to the leading edge of migrating cells, where it sustains ARP2 (ACTR2) phosphorylation and actin-dependent directional motility [PMID:32107292].","teleology":[{"year":2015,"claim":"Established CEP85 as a centrosomal negative regulator of centrosome separation, answering how Nek2A activity is restrained during interphase.","evidence":"Co-IP, in vitro kinase assay, immunofluorescence, and siRNA/overexpression phenotyping with domain mapping in cells","pmids":["26220856"],"confidence":"High","gaps":["Structural basis of the CEP85–Nek2A interface not defined","Mechanism by which PP1γ cooperates with CEP85 not resolved","How the inhibition is relieved at mitotic entry not addressed"]},{"year":2018,"claim":"Defined the direct CEP85–STIL interface and showed it is required for STIL centriolar targeting, PLK4 activation, and daughter centriole assembly, placing CEP85 in the centriole biogenesis pathway.","evidence":"BioID proximity mapping, structural determination, structure-guided mutagenesis with in vivo rescue, and Co-IP","pmids":["29712910"],"confidence":"High","gaps":["Temporal coordination between the STIL-binding and Nek2A-binding roles of CEP85 not addressed","Whether the same CEP85 molecules participate in both functions unknown"]},{"year":2018,"claim":"Resolved how interphase inhibition of Nek2A is switched off, showing PLK1 phosphorylates CEP85 within a ternary complex to release active Nek2A and trigger disjunction at G2/M.","evidence":"Co-IP establishing ternary complex, in vitro kinase assays, phospho-specific analyses, and cell-based assays with mutant forms","pmids":["30611117"],"confidence":"High","gaps":["Specific PLK1 phosphosites on CEP85 and their structural consequences not fully mapped","How phosphorylation selectively dissociates CEP85 from phospho-Nek2A but not unphosphorylated Nek2A unresolved"]},{"year":2020,"claim":"Extended CEP85 function beyond the centrosome by showing the CEP85–STIL complex drives directional migration through PLK4-dependent leading-edge recruitment and ARP2 phosphorylation.","evidence":"Structure-guided mutagenesis, leading-edge localization, siRNA knockdown, ARP2 phosphorylation assays, and directed migration assays","pmids":["32107292"],"confidence":"High","gaps":["Direct link between CEP85–STIL and ARP2 kinase not established","Whether this role is separable from centriolar duplication function unclear"]},{"year":2025,"claim":"Implicated CEP85 in macrophage phagocytosis, hinting at a function outside cell-division contexts.","evidence":"Overexpression in monocyte-derived macrophages with phagocytosis assay (preprint)","pmids":[],"confidence":"Low","gaps":["Single overexpression assay in a preprint with no mechanistic pathway placement","No molecular partners or signaling readout identified","Not independently confirmed"]},{"year":null,"claim":"How CEP85 partitions its centriole-biogenesis (STIL/PLK4), centrosome-disjunction (Nek2A/PLK1/PP1γ), and migration roles across the cell cycle and cell types remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model integrating the STIL- and Nek2A-binding regions","Spatiotemporal regulation distinguishing the functions not defined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[1]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,1,2]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[0]}],"complexes":["PLK1–CEP85–Nek2A ternary complex","CEP85–STIL complex"],"partners":["STIL","NEK2","PLK1","PLK4","PPP1CC"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6P2H3","full_name":"Centrosomal protein of 85 kDa","aliases":["Coiled-coil domain-containing protein 21"],"length_aa":762,"mass_kda":85.6,"function":"Acts as a regulator of centriole duplication through a direct interaction with STIL, a key factor involved in the early steps of centriole formation. The CEP85-STIL protein complex acts as a modulator of PLK4-driven cytoskeletal rearrangements and directional cell motility (PubMed:29712910, PubMed:32107292). Acts as a negative regulator of NEK2 to maintain the centrosome integrity in interphase. Suppresses centrosome disjunction by inhibiting NEK2 kinase activity (PubMed:26220856)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle pole; Nucleus, nucleolus; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Cytoplasm, cell cortex","url":"https://www.uniprot.org/uniprotkb/Q6P2H3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP85","classification":"Not Classified","n_dependent_lines":418,"n_total_lines":1208,"dependency_fraction":0.34602649006622516},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000130695","cell_line_id":"CID000194","localizations":[{"compartment":"centrosome","grade":3},{"compartment":"cytoplasmic","grade":1}],"interactors":[{"gene":"MIF","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000194","total_profiled":1310},"omim":[{"mim_id":"618898","title":"CENTROSOMAL PROTEIN, 85-KD; CEP85","url":"https://www.omim.org/entry/618898"},{"mim_id":"618873","title":"LISSENCEPHALY 10; LIS10","url":"https://www.omim.org/entry/618873"},{"mim_id":"618865","title":"CEP85-LIKE PROTEIN; CEP85L","url":"https://www.omim.org/entry/618865"},{"mim_id":"604043","title":"NIMA-RELATED KINASE 2; NEK2","url":"https://www.omim.org/entry/604043"},{"mim_id":"181590","title":"SCL/TAL1-INTERRUPTING LOCUS; STIL","url":"https://www.omim.org/entry/181590"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"},{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Vesicles","reliability":"Additional"},{"location":"Centrosome","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"skeletal muscle","ntpm":124.5},{"tissue":"tongue","ntpm":61.6}],"url":"https://www.proteinatlas.org/search/CEP85"},"hgnc":{"alias_symbol":["DKFZP434L0117"],"prev_symbol":["CCDC21"]},"alphafold":{"accession":"Q6P2H3","domains":[{"cath_id":"1.20.58","chopping":"665-758","consensus_level":"medium","plddt":76.523,"start":665,"end":758}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6P2H3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6P2H3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6P2H3-F1-predicted_aligned_error_v6.png","plddt_mean":66.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP85","jax_strain_url":"https://www.jax.org/strain/search?query=CEP85"},"sequence":{"accession":"Q6P2H3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6P2H3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6P2H3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6P2H3"}},"corpus_meta":[{"pmid":"29712910","id":"PMC_29712910","title":"Direct binding of CEP85 to STIL ensures robust PLK4 activation and efficient centriole assembly.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29712910","citation_count":38,"is_preprint":false},{"pmid":"26220856","id":"PMC_26220856","title":"Characterization of Cep85 - a new antagonist of Nek2A that is involved in the regulation of centrosome disjunction.","date":"2015","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/26220856","citation_count":17,"is_preprint":false},{"pmid":"22276910","id":"PMC_22276910","title":"Identification of endometriosis-related genes by representational difference analysis of cDNA.","date":"2012","source":"The Australian & New Zealand journal of obstetrics & gynaecology","url":"https://pubmed.ncbi.nlm.nih.gov/22276910","citation_count":17,"is_preprint":false},{"pmid":"32107292","id":"PMC_32107292","title":"Direct interaction between CEP85 and STIL mediates PLK4-driven directed cell migration.","date":"2020","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/32107292","citation_count":13,"is_preprint":false},{"pmid":"36718820","id":"PMC_36718820","title":"circRNA-SMO upregulates CEP85 to promote proliferation and migration of glioblastoma via sponging miR-326.","date":"2023","source":"Histology and histopathology","url":"https://pubmed.ncbi.nlm.nih.gov/36718820","citation_count":10,"is_preprint":false},{"pmid":"36793728","id":"PMC_36793728","title":"Transcriptome-wide association study of circulating IgE levels identifies novel targets for asthma and allergic diseases.","date":"2023","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/36793728","citation_count":8,"is_preprint":false},{"pmid":"30611117","id":"PMC_30611117","title":"Cep85 Relays Plk1 Activity to Phosphorylated Nek2A for Its Timely Activation in Centrosome Disjunction.","date":"2018","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/30611117","citation_count":7,"is_preprint":false},{"pmid":"22491241","id":"PMC_22491241","title":"Reduced expression of Sytl 1 and Ccdc21 and impaired induction of Mt I by oxidative stress in SII-K1 knockout mice.","date":"2010","source":"Drug discoveries & therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/22491241","citation_count":3,"is_preprint":false},{"pmid":"39932629","id":"PMC_39932629","title":"Genetic insights into non-obstructive azoospermia: Implications for diagnosis and TESE outcomes.","date":"2025","source":"Journal of assisted reproduction and genetics","url":"https://pubmed.ncbi.nlm.nih.gov/39932629","citation_count":3,"is_preprint":false},{"pmid":"38891632","id":"PMC_38891632","title":"Integrated miRNA and mRNA Sequencing Reveals the Sterility Mechanism in Hybrid Yellow Catfish Resulting from Pelteobagrus fulvidraco (♀) × Pelteobagrus vachelli (♂).","date":"2024","source":"Animals : an open access journal from MDPI","url":"https://pubmed.ncbi.nlm.nih.gov/38891632","citation_count":3,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.04.25332125","title":"Multi-omic triangulation identifies molecular candidates of atopic dermatitis severity","date":"2025-08-06","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.04.25332125","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7455,"output_tokens":1485,"usd":0.02232,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8184,"output_tokens":2279,"usd":0.048947,"stage2_stop_reason":"end_turn"},"total_usd":0.071267,"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\": 2018,\n      \"finding\": \"CEP85 directly binds STIL through a conserved interaction interface involving a previously uncharacterised domain of STIL; this interaction is essential for efficient centriolar targeting of STIL, PLK4 activation, and faithful daughter centriole assembly.\",\n      \"method\": \"Protein proximity mapping (BioID), NMR/structural methods, structure-guided mutational analyses in vivo, Co-IP\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (proximity mapping, high-resolution structural determination, mutagenesis, in vivo functional rescue) in a single rigorous study\",\n      \"pmids\": [\"29712910\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"CEP85 localizes to centrosomes, colocalizes with Nek2A at the proximal ends of centrioles forming a granule meshwork, directly binds Nek2A, and inhibits Nek2A kinase activity in vitro; depletion of CEP85 causes precocious centrosome separation while overexpression (with Eg5 inhibition) blocks centrosome disjunction. CEP85 cooperates with PP1γ to antagonize Nek2A activity during interphase.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, immunofluorescence/localization, siRNA depletion, overexpression with domain-mapping\",\n      \"journal\": \"Journal of Cell Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, in vitro kinase assay, loss-of-function and gain-of-function with defined phenotype, domain mapping; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"26220856\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PLK1 interacts with CEP85 and forms a ternary complex with CEP85–Nek2A. Nek2A binding to CEP85 is required (but not Nek2A kinase activity) for CEP85 to be phosphorylated by PLK1. PLK1-mediated phosphorylation of CEP85 causes its dissociation specifically from phospho-Nek2A, freeing phospho-Nek2A to become active. Both PLK1 and Nek2A are required for endogenous CEP85 phosphorylation, and timely CEP85 phosphorylation at G2/M is essential for centrosome disjunction.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, phospho-specific analyses, cell-based functional assays with mutant forms\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP establishing ternary complex, in vitro kinase assays, endogenous phosphorylation validated in cells, multiple orthogonal methods in single lab\",\n      \"pmids\": [\"30611117\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The CEP85–STIL interaction is required for directional cancer cell migration. PLK4 drives recruitment of CEP85 and STIL to the leading edge of migrating cells to promote protrusive activity; disruption of the CEP85–STIL–PLK4 interaction reduces ARP2 (ACTR2) phosphorylation and impairs actin cytoskeleton reorganization, thereby impairing directional cell motility.\",\n      \"method\": \"Mutational analyses, fluorescence localization (leading-edge recruitment), siRNA knockdown, phosphorylation assays (ARP2), directed cell migration assays\",\n      \"journal\": \"Journal of Cell Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — structure-guided mutational analyses, localization experiments, loss-of-function with defined molecular readout (ARP2 phosphorylation) and cellular phenotype, building on prior structural work\",\n      \"pmids\": [\"32107292\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CEP85 overexpression in monocyte-derived macrophages disrupts phagocytosis, indicating a functional role in phagocytic activity.\",\n      \"method\": \"In vitro overexpression in monocyte-derived macrophages with phagocytosis assay\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single functional in vitro assay reported in a preprint with no mechanistic pathway placement, no molecular detail provided in abstract\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"CEP85 is a centrosomal scaffold protein that directly binds STIL to promote PLK4 activation, centriolar STIL recruitment, and daughter centriole assembly; it also acts as a relay in centrosome disjunction by forming a PLK1–CEP85–Nek2A ternary complex in which PLK1 phosphorylates CEP85 in a Nek2A-binding-dependent manner, causing CEP85 to dissociate from phospho-Nek2A and thereby freeing active phospho-Nek2A to initiate centrosome separation at G2/M, while in interphase CEP85 cooperates with PP1γ to antagonize Nek2A and maintain centrosome integrity; additionally, the CEP85–STIL complex is recruited by PLK4 to the leading edge of migrating cells to sustain ARP2 phosphorylation and actin-dependent directional motility.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP85 is a centrosomal scaffold protein that governs both centriole biogenesis and centrosome separation through direct, mutually exclusive kinase-coupled interactions [#1, #0]. In centriole assembly, CEP85 directly binds STIL through a conserved interface, and this interaction is essential for centriolar targeting of STIL, PLK4 activation, and faithful daughter centriole formation [#0]. In centrosome integrity control, CEP85 localizes to the proximal ends of centrioles, directly binds Nek2A, and inhibits its kinase activity, cooperating with PP1\\u03b3 to antagonize Nek2A and suppress precocious centrosome separation during interphase [#1]. At G2/M this restraint is relieved: CEP85 forms a PLK1\\u2013CEP85\\u2013Nek2A ternary complex in which PLK1 phosphorylates CEP85 in a Nek2A-binding-dependent manner, driving CEP85 to dissociate from phospho-Nek2A and freeing active Nek2A to initiate centrosome disjunction [#2]. Beyond the centrosome, the CEP85\\u2013STIL complex is recruited by PLK4 to the leading edge of migrating cells, where it sustains ARP2 (ACTR2) phosphorylation and actin-dependent directional motility [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Established CEP85 as a centrosomal negative regulator of centrosome separation, answering how Nek2A activity is restrained during interphase.\",\n      \"evidence\": \"Co-IP, in vitro kinase assay, immunofluorescence, and siRNA/overexpression phenotyping with domain mapping in cells\",\n      \"pmids\": [\"26220856\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of the CEP85\\u2013Nek2A interface not defined\",\n        \"Mechanism by which PP1\\u03b3 cooperates with CEP85 not resolved\",\n        \"How the inhibition is relieved at mitotic entry not addressed\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Defined the direct CEP85\\u2013STIL interface and showed it is required for STIL centriolar targeting, PLK4 activation, and daughter centriole assembly, placing CEP85 in the centriole biogenesis pathway.\",\n      \"evidence\": \"BioID proximity mapping, structural determination, structure-guided mutagenesis with in vivo rescue, and Co-IP\",\n      \"pmids\": [\"29712910\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Temporal coordination between the STIL-binding and Nek2A-binding roles of CEP85 not addressed\",\n        \"Whether the same CEP85 molecules participate in both functions unknown\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Resolved how interphase inhibition of Nek2A is switched off, showing PLK1 phosphorylates CEP85 within a ternary complex to release active Nek2A and trigger disjunction at G2/M.\",\n      \"evidence\": \"Co-IP establishing ternary complex, in vitro kinase assays, phospho-specific analyses, and cell-based assays with mutant forms\",\n      \"pmids\": [\"30611117\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Specific PLK1 phosphosites on CEP85 and their structural consequences not fully mapped\",\n        \"How phosphorylation selectively dissociates CEP85 from phospho-Nek2A but not unphosphorylated Nek2A unresolved\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended CEP85 function beyond the centrosome by showing the CEP85\\u2013STIL complex drives directional migration through PLK4-dependent leading-edge recruitment and ARP2 phosphorylation.\",\n      \"evidence\": \"Structure-guided mutagenesis, leading-edge localization, siRNA knockdown, ARP2 phosphorylation assays, and directed migration assays\",\n      \"pmids\": [\"32107292\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct link between CEP85\\u2013STIL and ARP2 kinase not established\",\n        \"Whether this role is separable from centriolar duplication function unclear\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Implicated CEP85 in macrophage phagocytosis, hinting at a function outside cell-division contexts.\",\n      \"evidence\": \"Overexpression in monocyte-derived macrophages with phagocytosis assay (preprint)\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single overexpression assay in a preprint with no mechanistic pathway placement\",\n        \"No molecular partners or signaling readout identified\",\n        \"Not independently confirmed\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CEP85 partitions its centriole-biogenesis (STIL/PLK4), centrosome-disjunction (Nek2A/PLK1/PP1\\u03b3), and migration roles across the cell cycle and cell types remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model integrating the STIL- and Nek2A-binding regions\",\n        \"Spatiotemporal regulation distinguishing the functions not defined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005813\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"PLK1\\u2013CEP85\\u2013Nek2A ternary complex\",\n      \"CEP85\\u2013STIL complex\"\n    ],\n    \"partners\": [\n      \"STIL\",\n      \"NEK2\",\n      \"PLK1\",\n      \"PLK4\",\n      \"PPP1CC\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}