{"gene":"CEP350","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2005,"finding":"CAP350 (CEP350) and FOP form a centrosomal complex required for microtubule anchoring. The C-terminal domain of CAP350 directly interacts with FOP. FOP also binds EB1 and is required for localizing EB1 to the centrosome. siRNA depletion of either CAP350, FOP, or EB1 causes loss of MT anchoring and profound disorganization of the MT network.","method":"Co-immunoprecipitation, siRNA knockdown, immunofluorescence, direct binding assay","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, direct binding mapped to C-terminal domain, siRNA phenotype replicated across multiple proteins, replicated by subsequent studies","pmids":["16314388"],"is_preprint":false},{"year":2007,"finding":"CAP350 (CEP350) binds microtubules through an N-terminal basic region (not its CAP-Gly domain). CAP-Gly-containing domains target CAP350 to the centrosome and a Golgi-like network. Overexpression of CAP350 promotes microtubule stability (decreased EB1 comets, enhanced nocodazole resistance). Depletion of CAP350 decreases microtubule stability. Both depletion and overexpression cause Golgi fragmentation, suggesting CAP350 specifically stabilises Golgi-associated microtubules.","method":"In vitro and in vivo expression of partial constructs, siRNA knockdown, nocodazole resistance assay, EB1 comet counting, immunofluorescence","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — domain mapping with partial constructs, multiple orthogonal functional assays (MT stability, Golgi morphology), single lab","pmids":["17878239"],"is_preprint":false},{"year":2005,"finding":"CAP350 (CEP350) interacts with PPARα, PPARδ, PPARγ, and liver-X-receptor α (but not RXRα) and recruits PPARα to discrete nuclear foci and to the centrosome/perinuclear region/intermediate filaments. CAP350 inhibits PPARα-mediated transactivation in an LXXLL motif-dependent manner. The LXXLL motif in CAP350 is required for subnuclear recruitment of PPARα but is dispensable for direct binding of PPARα in vitro.","method":"Co-immunoprecipitation, immunofluorescence co-localization, in vitro binding assay, transactivation reporter assay, LXXLL point mutation","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, in vitro binding, mutagenesis, and functional transactivation assay all in single lab study","pmids":["15615782"],"is_preprint":false},{"year":2007,"finding":"Expression of a C-terminal fragment of CAP350 (CEP350), which removes EB1 from the centrosome but not from MT plus ends, inhibits primary cilia assembly in NIH3T3 fibroblasts, demonstrating that centrosomal/centriolar localization of EB1 — promoted by CAP350 — is required for ciliogenesis.","method":"Dominant-negative CAP350 fragment expression, siRNA knockdown, immunofluorescence, cilia assembly assay","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — dominant-negative construct plus siRNA, single lab, functional ciliogenesis readout","pmids":["17600711"],"is_preprint":false},{"year":2008,"finding":"CAP350 (CEP350) stabilises growing procentrioles independently of hSAS-6 and CPAP; siRNA depletion of CAP350 renders procentrioles sensitive to nocodazole-induced depolymerisation, indicating CAP350 belongs to a class of proteins that associate with and stabilise centriolar tubules to control centriole duplication.","method":"siRNA knockdown, nocodazole-sensitivity assay for procentriole stability, epistasis with hSAS-6/CPAP knockdowns","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with hSAS-6 and CPAP plus drug-sensitivity assay, single lab","pmids":["19052644"],"is_preprint":false},{"year":2008,"finding":"The oncogenic FOP-FGFR1 fusion kinase interacts with CAP350 (CEP350), and CAP350 is necessary for FOP-FGFR1 localization at the centrosome.","method":"Co-immunoprecipitation, siRNA knockdown of CAP350, immunofluorescence","journal":"Molecular cancer","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP plus CAP350 knockdown showing loss of FOP-FGFR1 centrosomal localization, single lab","pmids":["18412956"],"is_preprint":false},{"year":2014,"finding":"The deubiquitinating enzyme CYLD localizes to centrosomes and basal bodies via direct interaction with CAP350 (CEP350). In transgenic mice mimicking the smallest cylindromatosis-associated CYLD truncation, CYLD-CAP350 interaction is lost, disrupting CYLD centrosome localization and causing cilia formation defects due to impaired basal body migration and docking. CYLD must be both centrosomally localized and catalytically active to promote ciliogenesis independently of NF-κB.","method":"Co-immunoprecipitation, transgenic mouse model, immunofluorescence, ciliogenesis assay","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — Co-IP, in vivo transgenic mouse model, epistasis with NF-κB pathway, multiple orthogonal methods","pmids":["25134987"],"is_preprint":false},{"year":2015,"finding":"CAP350 (CEP350) localises at adherens junctions in epithelial cells through a direct interaction with α-catenin identified by two-hybrid screening and confirmed by co-immunoprecipitation. Blocking E-cadherin-mediated adhesion or depleting α-catenin prevents CAP350 junctional localisation. Knockdown of junction-located CAP350 inhibits establishment of apico-basal microtubule arrays and impairs columnar shape acquisition in MDCKII cells; cystogenesis is also defective, with smaller cysts containing multiple or no lumens and failure of cortical MT bundle formation.","method":"Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, immunofluorescence, 3D cyst assay","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid plus Co-IP for interaction, siRNA with multiple orthogonal phenotypic readouts (MT arrays, columnar shape, cystogenesis), single lab","pmids":["25764135"],"is_preprint":false},{"year":2017,"finding":"CEP350 forms a complex with FOP at the centriolar base that recruits CEP19. CEP19 is recruited to the ciliary base by the CEP350/FOP complex and then specifically captures GTP-bound RABL2B, which initiates ciliary entry of the IFT-B holocomplex. CEP350/FOP thus constitutes part of the first known mechanism directing ciliary entry of IFT complexes.","method":"Affinity-purification mass spectrometry, co-immunoprecipitation, siRNA knockdown, IFT trafficking assays","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — AP-MS identification, Co-IP validation, loss-of-function with defined IFT entry phenotype, multiple proteins validated","pmids":["28625565"],"is_preprint":false},{"year":2016,"finding":"CFAP157 interacts with the centrosomal protein CEP350 (as well as tubulin) at basal bodies in mouse spermatozoa and motile cilia; this interaction is part of a mechanism required for correct flagellum ultrastructure and sperm motility.","method":"Co-immunoprecipitation, immunofluorescence localization in knockout mouse tissue","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP plus co-localization with functional KO phenotype, single lab","pmids":["27965440"],"is_preprint":false},{"year":2018,"finding":"Talpid3 and C2CD3 regulate the assembly of the CEP350/FOP/CEP19 module at the distal centriole. Loss of Talpid3 or C2CD3 disrupts assembly of this module, linking the CEP350/FOP/CEP19 complex to distal centriole maturation, distal appendage assembly, and ciliogenesis.","method":"siRNA knockdown, immunofluorescence, structured illumination microscopy, epistasis analysis in Talpid3/C2CD3 mutant cells","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with multiple proteins, super-resolution imaging, single lab","pmids":["30258116"],"is_preprint":false},{"year":2021,"finding":"CEP350 promotes centrosomal recruitment and stability of CEP78, which in turn recruits EDD1 to the centrosome. Cells lacking CEP78 display increased centrosomal levels of CP110, and depletion of CP110 in CEP78-deficient cells restores ciliation frequency. CEP350 thus functions upstream of CEP78 in a pathway that negatively regulates CP110 to promote ciliogenesis.","method":"Co-immunoprecipitation, siRNA/CRISPR knockdown, immunofluorescence, epistasis rescue experiment (CP110 depletion restoring ciliation)","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Moderate — epistatic rescue, Co-IP, multiple loss-of-function conditions, quantitative centrosomal protein level measurements, single lab with multiple orthogonal methods","pmids":["34259627"],"is_preprint":false},{"year":2022,"finding":"CEP350 functions as a scaffold at the distal end of centrioles, coordinating centriole length, stability, and formation of distal and subdistal appendages. CEP350 ensures centriolar localisation of WDR90 and recruits CEP78 and OFD1 to the distal centriole end. The CEP350-FOP complex in association with CEP78 or OFD1 controls centriole microtubule length. CEP350-FOP-WDR90 axis secures centriole integrity. CEP350 knockout does not affect the proximal PCM.","method":"CRISPR knockout, immunofluorescence, super-resolution microscopy, epistasis analysis, protein recruitment assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — CRISPR KO with multiple orthogonal phenotypic readouts, super-resolution imaging, systematic epistasis with several partners, single lab with rigorous controls","pmids":["36315013"],"is_preprint":false},{"year":2024,"finding":"PPP2R3C (a PP2A phosphatase subunit) is a distal centriole protein and functional partner of CEP350 and FOP. PPP2R3C counteracts MAP3K1 kinase activity at the centrosome; MAP3K1 knockout suppresses growth defects from PPP2R3C inactivation. Overexpression of MAP3K1 inhibits centrosome function and triggers rapid centriole disintegration. A syndromic PPP2R3C variant defective in centriolar localization cannot bind FOP, implicating this CEP350/FOP-anchored kinase-phosphatase balance in gonadal development.","method":"Systems genetics, co-immunoprecipitation, CRISPR knockout epistasis, MAP3K1 overexpression, immunofluorescence, JNK signaling assay","journal":"Current biology : CB","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, genetic epistasis (MAP3K1 KO rescues PPP2R3C defects), functional overexpression phenotype, single lab","pmids":["39317195"],"is_preprint":false},{"year":2024,"finding":"PPP2R3C is a distal centriole protein and functional partner of CEP350 and FOP (preprint version, same findings as published paper above).","method":"Functional genomics, co-immunoprecipitation, CRISPR knockout epistasis, immunofluorescence","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 2 / Weak — preprint, same findings replicated in peer-reviewed version (PMID:39317195); lower confidence as preprint","pmids":["38617270"],"is_preprint":true},{"year":2025,"finding":"CEP78 truncating variants associated with CAKUT abrogate binding to CEP350 and VPRBP, demonstrating that CEP78-CEP350 interaction is required for normal CEP78 function in ciliogenesis.","method":"Co-immunoprecipitation of CAKUT mutant CEP78 variants with CEP350","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP experiment in preprint, no independent replication reported","pmids":["40777246"],"is_preprint":true},{"year":2026,"finding":"CEP350 mRNA localizes to centrosomes during S phase via the centriolar satellite protein CEP131 and the RNA-binding protein Unkempt (UNK) in a microtubule-dependent manner. CEP131 and UNK stabilize CEP350 mRNA steady-state levels and promote normal CEP350 protein levels at centrosomes. CEP350 is required for PLK4-induced centriole overduplication but is less important for canonical centriole duplication. CEP131, UNK, and CEP350 are important for centrosome amplification in triple-negative breast cancer cells.","method":"FISH for mRNA localization, siRNA knockdown, PLK4-induced overduplication assay, immunofluorescence, mRNA stability assay","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — preprint with multiple orthogonal methods (FISH, siRNA epistasis, mRNA stability, overduplication assay), single lab","pmids":["41929017"],"is_preprint":true}],"current_model":"CEP350 (CAP350) is a large scaffolding protein of the distal centriole that (1) forms a core complex with FOP to anchor microtubules to the centrosome, stabilize centriolar tubules, and recruit CEP19/RABL2B to initiate IFT-complex entry into cilia; (2) coordinates distal centriole length, stability, and appendage assembly by recruiting WDR90, CEP78, and OFD1 while promoting subdistal appendage formation; (3) anchors CYLD at the centrosome to control ciliogenesis via Lys63-deubiquitination; (4) acts upstream of CEP78 in a pathway that negatively regulates CP110 to permit ciliation; (5) stabilises Golgi-associated microtubules through an N-terminal MT-binding region; (6) redistributes PPARα to centrosomal and nuclear compartments and represses its transcriptional activity; and (7) functions as a platform for a balanced PPP2R3C phosphatase–MAP3K1 kinase module that maintains centriole integrity."},"narrative":{"mechanistic_narrative":"CEP350 (CAP350) is a large scaffolding protein of the distal centriole that organizes microtubule anchoring, centriole integrity, and ciliogenesis [PMID:16314388, PMID:36315013]. Through its C-terminal domain it forms a core complex with FOP that anchors microtubules to the centrosome and, together with EB1, maintains the radial microtubule network [PMID:16314388]; a distinct N-terminal basic region binds microtubules directly and stabilizes Golgi-associated microtubules, with CEP350 perturbation causing Golgi fragmentation [PMID:17878239]. At the distal centriole CEP350 acts as a platform coordinating centriole length, stability, and appendage formation by ensuring centriolar localization of WDR90 and recruiting CEP78 and OFD1, without affecting the proximal pericentriolar material [PMID:36315013]; it functions upstream of CEP78 in a pathway that limits centrosomal CP110 to permit ciliation [PMID:34259627]. The CEP350/FOP complex recruits CEP19, which captures GTP-bound RABL2B to initiate ciliary entry of the IFT-B holocomplex, and assembly of this distal module depends on Talpid3 and C2CD3 [PMID:28625565, PMID:30258116]. CEP350 additionally anchors the deubiquitinase CYLD at centrosomes and basal bodies to support basal body migration and docking during ciliogenesis [PMID:25134987], and it serves as a docking site for a balanced PPP2R3C phosphatase–MAP3K1 kinase module that maintains centriole integrity [PMID:39317195]. Beyond the centrosome, CEP350 localizes to epithelial adherens junctions via direct binding to α-catenin, where it directs apico-basal microtubule array formation and epithelial morphogenesis [PMID:25764135], and it binds nuclear receptors including PPARα, redistributing PPARα to centrosomal and nuclear compartments and repressing its transactivation through an LXXLL motif [PMID:15615782].","teleology":[{"year":2005,"claim":"Established the founding mechanistic role of CEP350: how the radial microtubule network is anchored at the centrosome.","evidence":"Co-IP and direct binding mapping the CAP350 C-terminus to FOP, with siRNA of CAP350/FOP/EB1 disrupting MT anchoring","pmids":["16314388"],"confidence":"High","gaps":["Structural basis of the CAP350-FOP-EB1 module not resolved","Does not address centriolar substructure where the complex acts"]},{"year":2005,"claim":"Revealed an unexpected nuclear-receptor function, showing CEP350 binds PPARs/LXRα and represses PPARα transcription, linking a centrosomal scaffold to transcriptional control.","evidence":"Co-IP, in vitro binding, transactivation reporter assays and LXXLL point mutation","pmids":["15615782"],"confidence":"Medium","gaps":["Physiological significance of PPARα repression unclear","Connection between centrosomal and nuclear pools of CEP350 unresolved"]},{"year":2007,"claim":"Distinguished CEP350's microtubule-binding and targeting modules and tied it specifically to Golgi microtubule stability.","evidence":"Partial construct expression, nocodazole resistance, EB1 comet counting and Golgi morphology assays","pmids":["17878239"],"confidence":"High","gaps":["Mechanism coupling Golgi MT stabilization to Golgi integrity not defined","Relationship of N-terminal MT binding to centrosomal anchoring unclear"]},{"year":2007,"claim":"Connected CEP350-dependent centrosomal EB1 localization to primary cilium assembly, providing the first link between this scaffold and ciliogenesis.","evidence":"Dominant-negative C-terminal fragment plus siRNA with cilia assembly readout in NIH3T3","pmids":["17600711"],"confidence":"Medium","gaps":["Downstream ciliary machinery not identified at this stage","Dominant-negative interpretation limited without rescue"]},{"year":2008,"claim":"Showed CEP350 stabilizes nascent procentrioles independently of hSAS-6 and CPAP, placing it among centriolar tubule-stabilizing factors controlling duplication.","evidence":"siRNA with nocodazole-sensitivity assay and epistasis against hSAS-6/CPAP","pmids":["19052644"],"confidence":"Medium","gaps":["Molecular contacts with centriolar tubules unmapped","Single-lab study"]},{"year":2014,"claim":"Identified CEP350 as the centrosomal anchor for the deubiquitinase CYLD, mechanistically tying CYLD-mediated ciliogenesis to a defined docking interaction.","evidence":"Co-IP plus a transgenic mouse mimicking a cylindromatosis CYLD truncation, with ciliogenesis assays","pmids":["25134987"],"confidence":"High","gaps":["Centrosomal substrates of CYLD not identified","How CYLD activity feeds into basal body docking mechanistically unresolved"]},{"year":2015,"claim":"Extended CEP350 function beyond the centrosome by showing it localizes to adherens junctions via α-catenin to build apico-basal microtubule arrays and drive epithelial morphogenesis.","evidence":"Yeast two-hybrid, Co-IP, siRNA, and 3D cyst assays in MDCKII cells","pmids":["25764135"],"confidence":"High","gaps":["How the junctional and centrosomal pools are partitioned unclear","Single-lab study"]},{"year":2016,"claim":"Implicated CEP350 in motile cilia/flagellum biology through a basal-body interaction with CFAP157.","evidence":"Co-IP and immunofluorescence in CFAP157 knockout mouse spermatozoa and motile cilia","pmids":["27965440"],"confidence":"Medium","gaps":["Direct vs indirect nature of CEP350-CFAP157 contact not established","Role of CEP350 in flagellar ultrastructure not directly tested"]},{"year":2017,"claim":"Defined the CEP350/FOP complex as the recruiter of CEP19, establishing the first mechanism directing IFT-B entry into cilia via RABL2B capture.","evidence":"AP-MS, Co-IP, siRNA and IFT trafficking assays","pmids":["28625565"],"confidence":"High","gaps":["Structural details of CEP19 capture of GTP-RABL2B at the base not resolved","How IFT entry timing is gated unclear"]},{"year":2018,"claim":"Placed assembly of the CEP350/FOP/CEP19 module downstream of Talpid3 and C2CD3, connecting it to distal centriole maturation and appendage assembly.","evidence":"siRNA, structured illumination microscopy and epistasis in Talpid3/C2CD3 mutant cells","pmids":["30258116"],"confidence":"Medium","gaps":["Direct biochemical link between Talpid3/C2CD3 and CEP350 not shown","Order of appendage versus module assembly not fully resolved"]},{"year":2021,"claim":"Positioned CEP350 upstream of CEP78 in a pathway that negatively regulates CP110, explaining how this scaffold permits ciliation.","evidence":"Co-IP, siRNA/CRISPR, and epistatic rescue where CP110 depletion restores ciliation in CEP78-deficient cells","pmids":["34259627"],"confidence":"High","gaps":["Mechanism by which CEP78/EDD1 reduce CP110 not defined","Direct CEP350-CEP78 interface not mapped here"]},{"year":2022,"claim":"Consolidated CEP350 as the master distal-centriole scaffold coordinating length, stability, and appendage formation through WDR90, CEP78, and OFD1 recruitment.","evidence":"CRISPR knockout, super-resolution microscopy and systematic epistasis/recruitment assays","pmids":["36315013"],"confidence":"High","gaps":["Stoichiometry and spatial arrangement of the CEP350-FOP-WDR90 axis not solved","Mechanism of subdistal appendage promotion unclear"]},{"year":2024,"claim":"Revealed a kinase-phosphatase module anchored by CEP350/FOP, where PPP2R3C counteracts MAP3K1 to maintain centriole integrity, with a disease variant linking this balance to gonadal development.","evidence":"Systems genetics, Co-IP, CRISPR epistasis (MAP3K1 KO rescues PPP2R3C defects), and MAP3K1 overexpression","pmids":["39317195"],"confidence":"Medium","gaps":["Centriolar substrates of the MAP3K1/PPP2R3C module not identified","How phospho-balance maintains tubule integrity mechanistically unclear"]},{"year":2025,"claim":"Provided disease-linked evidence that CEP78-CEP350 binding is required for CEP78 function, with CAKUT truncating variants abrogating the interaction.","evidence":"Co-IP of CAKUT mutant CEP78 with CEP350 (preprint)","pmids":["40777246"],"confidence":"Low","gaps":["Single Co-IP without independent replication","Functional ciliogenesis consequence of lost binding not directly tested here"]},{"year":2026,"claim":"Uncovered an mRNA-level regulatory layer in which CEP350 transcript is localized and stabilized at centrosomes by CEP131 and Unkempt, coupling local translation to centriole overduplication in cancer cells.","evidence":"FISH, siRNA epistasis, mRNA stability and PLK4-induced overduplication assays (preprint)","pmids":["41929017"],"confidence":"Medium","gaps":["Mechanism of UNK/CEP131-dependent mRNA targeting not fully resolved","Selective requirement in overduplication vs canonical duplication needs orthogonal validation"]},{"year":null,"claim":"How CEP350's many spatially distinct functions (distal centriole scaffolding, Golgi MT stabilization, junctional MT organization, nuclear-receptor repression) are partitioned and regulated within a single protein remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of full-length CEP350 or its multi-partner interfaces","Mechanism switching CEP350 between centrosomal, Golgi, junctional, and nuclear pools unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,8,12]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,8,12]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[7]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[8,12]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[4,16]}],"complexes":["CEP350-FOP complex","CEP350/FOP/CEP19 distal centriole module"],"partners":["FOP","EB1","CEP19","CEP78","WDR90","OFD1","CYLD","CTNNA1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q5VT06","full_name":"Centrosome-associated protein 350","aliases":["Centrosome-associated protein of 350 kDa"],"length_aa":3117,"mass_kda":350.9,"function":"Plays an essential role in centriole growth by stabilizing a procentriolar seed composed of at least, SASS6 and CPAP (PubMed:19052644). Required for anchoring microtubules to the centrosomes and for the integrity of the microtubule network (PubMed:16314388, PubMed:17878239, PubMed:28659385). Recruits PPARA to discrete subcellular compartments and thereby modulates PPARA activity (PubMed:15615782). Required for ciliation (PubMed:28659385)","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle; Nucleus; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Cytoplasm, cytoskeleton, cilium basal body","url":"https://www.uniprot.org/uniprotkb/Q5VT06/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CEP350","classification":"Not Classified","n_dependent_lines":119,"n_total_lines":1208,"dependency_fraction":0.09850993377483444},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000135837","cell_line_id":"CID000198","localizations":[{"compartment":"centrosome","grade":3},{"compartment":"cytoskeleton","grade":1}],"interactors":[{"gene":"FGFR1OP","stoichiometry":0.2},{"gene":"PPP2R3C;C14ORF10","stoichiometry":0.2},{"gene":"EIF4G1","stoichiometry":0.2},{"gene":"MAPRE1","stoichiometry":0.2},{"gene":"PPP2CA","stoichiometry":0.2},{"gene":"PPP2CB","stoichiometry":0.2},{"gene":"RNF40","stoichiometry":0.2},{"gene":"VCP","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000198","total_profiled":1310},"omim":[{"mim_id":"617870","title":"CENTROSOMAL PROTEIN 350; CEP350","url":"https://www.omim.org/entry/617870"},{"mim_id":"615586","title":"CENTROSOMAL PROTEIN, 19-KD; CEP19","url":"https://www.omim.org/entry/615586"},{"mim_id":"605413","title":"RAB, MEMBER OF RAS ONCOGENE FAMILY-LIKE 2B; RABL2B","url":"https://www.omim.org/entry/605413"},{"mim_id":"605392","title":"FIBROBLAST GROWTH FACTOR RECEPTOR 1 ONCOGENE PARTNER; FGFR1OP","url":"https://www.omim.org/entry/605392"},{"mim_id":"170998","title":"PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-ALPHA; PPARA","url":"https://www.omim.org/entry/170998"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Centrosome","reliability":"Supported"},{"location":"Basal body","reliability":"Additional"},{"location":"End piece","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CEP350"},"hgnc":{"alias_symbol":["KIAA0480","CAP350"],"prev_symbol":[]},"alphafold":{"accession":"Q5VT06","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5VT06","model_url":"","pae_url":"","plddt_mean":null},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CEP350","jax_strain_url":"https://www.jax.org/strain/search?query=CEP350"},"sequence":{"accession":"Q5VT06","fasta_url":"https://rest.uniprot.org/uniprotkb/Q5VT06.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q5VT06/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q5VT06"}},"corpus_meta":[{"pmid":"26147620","id":"PMC_26147620","title":"The OsSPL16-GW7 regulatory module determines grain shape and simultaneously improves rice yield and grain quality.","date":"2015","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/26147620","citation_count":464,"is_preprint":false},{"pmid":"16314388","id":"PMC_16314388","title":"A complex of two centrosomal proteins, CAP350 and FOP, cooperates with EB1 in microtubule anchoring.","date":"2005","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/16314388","citation_count":121,"is_preprint":false},{"pmid":"28625565","id":"PMC_28625565","title":"The CEP19-RABL2 GTPase Complex Binds IFT-B to Initiate Intraflagellar Transport at the Ciliary Base.","date":"2017","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/28625565","citation_count":94,"is_preprint":false},{"pmid":"27038408","id":"PMC_27038408","title":"GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN.","date":"2016","source":"Depression and anxiety","url":"https://pubmed.ncbi.nlm.nih.gov/27038408","citation_count":89,"is_preprint":false},{"pmid":"30617275","id":"PMC_30617275","title":"Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.","date":"2019","source":"Molecular psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/30617275","citation_count":88,"is_preprint":false},{"pmid":"23456457","id":"PMC_23456457","title":"CEP proteins: the knights of centrosome dynasty.","date":"2013","source":"Protoplasma","url":"https://pubmed.ncbi.nlm.nih.gov/23456457","citation_count":81,"is_preprint":false},{"pmid":"32586373","id":"PMC_32586373","title":"Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets.","date":"2020","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/32586373","citation_count":66,"is_preprint":false},{"pmid":"17600711","id":"PMC_17600711","title":"EB1 is required for primary cilia assembly in fibroblasts.","date":"2007","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/17600711","citation_count":55,"is_preprint":false},{"pmid":"25848750","id":"PMC_25848750","title":"Transposon mutagenesis identifies genetic drivers of Braf(V600E) melanoma.","date":"2015","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/25848750","citation_count":54,"is_preprint":false},{"pmid":"17878239","id":"PMC_17878239","title":"Centrosomal CAP350 protein stabilises microtubules associated with the Golgi complex.","date":"2007","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/17878239","citation_count":49,"is_preprint":false},{"pmid":"27998958","id":"PMC_27998958","title":"Bisphenol A and its analogues disrupt centrosome cycle and microtubule dynamics in prostate cancer.","date":"2016","source":"Endocrine-related cancer","url":"https://pubmed.ncbi.nlm.nih.gov/27998958","citation_count":44,"is_preprint":false},{"pmid":"30258116","id":"PMC_30258116","title":"A distal centriolar protein network controls organelle maturation and asymmetry.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/30258116","citation_count":41,"is_preprint":false},{"pmid":"25134987","id":"PMC_25134987","title":"The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells.","date":"2014","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25134987","citation_count":40,"is_preprint":false},{"pmid":"34259627","id":"PMC_34259627","title":"CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels.","date":"2021","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/34259627","citation_count":33,"is_preprint":false},{"pmid":"15615782","id":"PMC_15615782","title":"Activity and subcellular compartmentalization of peroxisome proliferator-activated receptor alpha are altered by the centrosome-associated protein CAP350.","date":"2005","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/15615782","citation_count":27,"is_preprint":false},{"pmid":"19052644","id":"PMC_19052644","title":"Role of CAP350 in centriolar tubule stability and centriole assembly.","date":"2008","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/19052644","citation_count":23,"is_preprint":false},{"pmid":"27965440","id":"PMC_27965440","title":"CFAP157 is a murine downstream effector of FOXJ1 that is specifically required for flagellum morphogenesis and sperm motility.","date":"2016","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/27965440","citation_count":22,"is_preprint":false},{"pmid":"25764135","id":"PMC_25764135","title":"Alpha-catenin-dependent recruitment of the centrosomal protein CAP350 to adherens junctions allows epithelial cells to acquire a columnar shape.","date":"2015","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/25764135","citation_count":18,"is_preprint":false},{"pmid":"36315013","id":"PMC_36315013","title":"The central scaffold protein CEP350 coordinates centriole length, stability, and maturation.","date":"2022","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/36315013","citation_count":17,"is_preprint":false},{"pmid":"18412956","id":"PMC_18412956","title":"Myeloproliferative disorder FOP-FGFR1 fusion kinase recruits phosphoinositide-3 kinase and phospholipase Cgamma at the centrosome.","date":"2008","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/18412956","citation_count":16,"is_preprint":false},{"pmid":"28606843","id":"PMC_28606843","title":"The effect of Diosmin on the blood proteome in a rat model of venous thrombosis.","date":"2017","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/28606843","citation_count":7,"is_preprint":false},{"pmid":"34955918","id":"PMC_34955918","title":"Construction and Analysis of a Diagnostic Model Based on Differential Expression Genes in Patients With Major Depressive Disorder.","date":"2021","source":"Frontiers in psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/34955918","citation_count":6,"is_preprint":false},{"pmid":"32507013","id":"PMC_32507013","title":"A novel microRNA boosts hyper-β-oxidation of fatty acids in liver by impeding CEP350-mediated sequestration of PPARα and thus restricts chronic hepatitis C.","date":"2020","source":"RNA biology","url":"https://pubmed.ncbi.nlm.nih.gov/32507013","citation_count":5,"is_preprint":false},{"pmid":"36291689","id":"PMC_36291689","title":"Exome and Sputum Microbiota as Predictive Markers of Frequent Exacerbations in Chronic Obstructive Pulmonary Disease.","date":"2022","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/36291689","citation_count":5,"is_preprint":false},{"pmid":"39317195","id":"PMC_39317195","title":"A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function.","date":"2024","source":"Current biology : CB","url":"https://pubmed.ncbi.nlm.nih.gov/39317195","citation_count":2,"is_preprint":false},{"pmid":"40777246","id":"PMC_40777246","title":"CAKUT variants in PRPF8, DYRK2, and CEP78: implications for splicing and ciliogenesis.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40777246","citation_count":1,"is_preprint":false},{"pmid":"36241435","id":"PMC_36241435","title":"Blood transcriptome analysis and identification of genes associated with supernumerary teats in Chinese Holstein cows.","date":"2022","source":"Journal of dairy science","url":"https://pubmed.ncbi.nlm.nih.gov/36241435","citation_count":1,"is_preprint":false},{"pmid":"41929017","id":"PMC_41929017","title":"Centriolar satellites regulate CEP350 mRNA localization and centrosome amplification.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41929017","citation_count":0,"is_preprint":false},{"pmid":"38617270","id":"PMC_38617270","title":"A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38617270","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.07.16.665151","title":"CAKUT variants in  <i>PRPF8, DYRK2</i>  , and  <i>CEP78</i>  : implications for splicing and ciliogenesis","date":"2025-07-21","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.16.665151","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17509,"output_tokens":4494,"usd":0.059969,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":12502,"output_tokens":4620,"usd":0.089005,"stage2_stop_reason":"end_turn"},"total_usd":0.148974,"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\": 2005,\n      \"finding\": \"CAP350 (CEP350) and FOP form a centrosomal complex required for microtubule anchoring. The C-terminal domain of CAP350 directly interacts with FOP. FOP also binds EB1 and is required for localizing EB1 to the centrosome. siRNA depletion of either CAP350, FOP, or EB1 causes loss of MT anchoring and profound disorganization of the MT network.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, immunofluorescence, direct binding assay\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, direct binding mapped to C-terminal domain, siRNA phenotype replicated across multiple proteins, replicated by subsequent studies\",\n      \"pmids\": [\"16314388\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"CAP350 (CEP350) binds microtubules through an N-terminal basic region (not its CAP-Gly domain). CAP-Gly-containing domains target CAP350 to the centrosome and a Golgi-like network. Overexpression of CAP350 promotes microtubule stability (decreased EB1 comets, enhanced nocodazole resistance). Depletion of CAP350 decreases microtubule stability. Both depletion and overexpression cause Golgi fragmentation, suggesting CAP350 specifically stabilises Golgi-associated microtubules.\",\n      \"method\": \"In vitro and in vivo expression of partial constructs, siRNA knockdown, nocodazole resistance assay, EB1 comet counting, immunofluorescence\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — domain mapping with partial constructs, multiple orthogonal functional assays (MT stability, Golgi morphology), single lab\",\n      \"pmids\": [\"17878239\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"CAP350 (CEP350) interacts with PPARα, PPARδ, PPARγ, and liver-X-receptor α (but not RXRα) and recruits PPARα to discrete nuclear foci and to the centrosome/perinuclear region/intermediate filaments. CAP350 inhibits PPARα-mediated transactivation in an LXXLL motif-dependent manner. The LXXLL motif in CAP350 is required for subnuclear recruitment of PPARα but is dispensable for direct binding of PPARα in vitro.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence co-localization, in vitro binding assay, transactivation reporter assay, LXXLL point mutation\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, in vitro binding, mutagenesis, and functional transactivation assay all in single lab study\",\n      \"pmids\": [\"15615782\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Expression of a C-terminal fragment of CAP350 (CEP350), which removes EB1 from the centrosome but not from MT plus ends, inhibits primary cilia assembly in NIH3T3 fibroblasts, demonstrating that centrosomal/centriolar localization of EB1 — promoted by CAP350 — is required for ciliogenesis.\",\n      \"method\": \"Dominant-negative CAP350 fragment expression, siRNA knockdown, immunofluorescence, cilia assembly assay\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — dominant-negative construct plus siRNA, single lab, functional ciliogenesis readout\",\n      \"pmids\": [\"17600711\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"CAP350 (CEP350) stabilises growing procentrioles independently of hSAS-6 and CPAP; siRNA depletion of CAP350 renders procentrioles sensitive to nocodazole-induced depolymerisation, indicating CAP350 belongs to a class of proteins that associate with and stabilise centriolar tubules to control centriole duplication.\",\n      \"method\": \"siRNA knockdown, nocodazole-sensitivity assay for procentriole stability, epistasis with hSAS-6/CPAP knockdowns\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with hSAS-6 and CPAP plus drug-sensitivity assay, single lab\",\n      \"pmids\": [\"19052644\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"The oncogenic FOP-FGFR1 fusion kinase interacts with CAP350 (CEP350), and CAP350 is necessary for FOP-FGFR1 localization at the centrosome.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown of CAP350, immunofluorescence\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP plus CAP350 knockdown showing loss of FOP-FGFR1 centrosomal localization, single lab\",\n      \"pmids\": [\"18412956\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The deubiquitinating enzyme CYLD localizes to centrosomes and basal bodies via direct interaction with CAP350 (CEP350). In transgenic mice mimicking the smallest cylindromatosis-associated CYLD truncation, CYLD-CAP350 interaction is lost, disrupting CYLD centrosome localization and causing cilia formation defects due to impaired basal body migration and docking. CYLD must be both centrosomally localized and catalytically active to promote ciliogenesis independently of NF-κB.\",\n      \"method\": \"Co-immunoprecipitation, transgenic mouse model, immunofluorescence, ciliogenesis assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — Co-IP, in vivo transgenic mouse model, epistasis with NF-κB pathway, multiple orthogonal methods\",\n      \"pmids\": [\"25134987\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"CAP350 (CEP350) localises at adherens junctions in epithelial cells through a direct interaction with α-catenin identified by two-hybrid screening and confirmed by co-immunoprecipitation. Blocking E-cadherin-mediated adhesion or depleting α-catenin prevents CAP350 junctional localisation. Knockdown of junction-located CAP350 inhibits establishment of apico-basal microtubule arrays and impairs columnar shape acquisition in MDCKII cells; cystogenesis is also defective, with smaller cysts containing multiple or no lumens and failure of cortical MT bundle formation.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, immunofluorescence, 3D cyst assay\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid plus Co-IP for interaction, siRNA with multiple orthogonal phenotypic readouts (MT arrays, columnar shape, cystogenesis), single lab\",\n      \"pmids\": [\"25764135\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CEP350 forms a complex with FOP at the centriolar base that recruits CEP19. CEP19 is recruited to the ciliary base by the CEP350/FOP complex and then specifically captures GTP-bound RABL2B, which initiates ciliary entry of the IFT-B holocomplex. CEP350/FOP thus constitutes part of the first known mechanism directing ciliary entry of IFT complexes.\",\n      \"method\": \"Affinity-purification mass spectrometry, co-immunoprecipitation, siRNA knockdown, IFT trafficking assays\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — AP-MS identification, Co-IP validation, loss-of-function with defined IFT entry phenotype, multiple proteins validated\",\n      \"pmids\": [\"28625565\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"CFAP157 interacts with the centrosomal protein CEP350 (as well as tubulin) at basal bodies in mouse spermatozoa and motile cilia; this interaction is part of a mechanism required for correct flagellum ultrastructure and sperm motility.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence localization in knockout mouse tissue\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP plus co-localization with functional KO phenotype, single lab\",\n      \"pmids\": [\"27965440\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Talpid3 and C2CD3 regulate the assembly of the CEP350/FOP/CEP19 module at the distal centriole. Loss of Talpid3 or C2CD3 disrupts assembly of this module, linking the CEP350/FOP/CEP19 complex to distal centriole maturation, distal appendage assembly, and ciliogenesis.\",\n      \"method\": \"siRNA knockdown, immunofluorescence, structured illumination microscopy, epistasis analysis in Talpid3/C2CD3 mutant cells\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with multiple proteins, super-resolution imaging, single lab\",\n      \"pmids\": [\"30258116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"CEP350 promotes centrosomal recruitment and stability of CEP78, which in turn recruits EDD1 to the centrosome. Cells lacking CEP78 display increased centrosomal levels of CP110, and depletion of CP110 in CEP78-deficient cells restores ciliation frequency. CEP350 thus functions upstream of CEP78 in a pathway that negatively regulates CP110 to promote ciliogenesis.\",\n      \"method\": \"Co-immunoprecipitation, siRNA/CRISPR knockdown, immunofluorescence, epistasis rescue experiment (CP110 depletion restoring ciliation)\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — epistatic rescue, Co-IP, multiple loss-of-function conditions, quantitative centrosomal protein level measurements, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"34259627\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CEP350 functions as a scaffold at the distal end of centrioles, coordinating centriole length, stability, and formation of distal and subdistal appendages. CEP350 ensures centriolar localisation of WDR90 and recruits CEP78 and OFD1 to the distal centriole end. The CEP350-FOP complex in association with CEP78 or OFD1 controls centriole microtubule length. CEP350-FOP-WDR90 axis secures centriole integrity. CEP350 knockout does not affect the proximal PCM.\",\n      \"method\": \"CRISPR knockout, immunofluorescence, super-resolution microscopy, epistasis analysis, protein recruitment assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — CRISPR KO with multiple orthogonal phenotypic readouts, super-resolution imaging, systematic epistasis with several partners, single lab with rigorous controls\",\n      \"pmids\": [\"36315013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PPP2R3C (a PP2A phosphatase subunit) is a distal centriole protein and functional partner of CEP350 and FOP. PPP2R3C counteracts MAP3K1 kinase activity at the centrosome; MAP3K1 knockout suppresses growth defects from PPP2R3C inactivation. Overexpression of MAP3K1 inhibits centrosome function and triggers rapid centriole disintegration. A syndromic PPP2R3C variant defective in centriolar localization cannot bind FOP, implicating this CEP350/FOP-anchored kinase-phosphatase balance in gonadal development.\",\n      \"method\": \"Systems genetics, co-immunoprecipitation, CRISPR knockout epistasis, MAP3K1 overexpression, immunofluorescence, JNK signaling assay\",\n      \"journal\": \"Current biology : CB\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, genetic epistasis (MAP3K1 KO rescues PPP2R3C defects), functional overexpression phenotype, single lab\",\n      \"pmids\": [\"39317195\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PPP2R3C is a distal centriole protein and functional partner of CEP350 and FOP (preprint version, same findings as published paper above).\",\n      \"method\": \"Functional genomics, co-immunoprecipitation, CRISPR knockout epistasis, immunofluorescence\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — preprint, same findings replicated in peer-reviewed version (PMID:39317195); lower confidence as preprint\",\n      \"pmids\": [\"38617270\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CEP78 truncating variants associated with CAKUT abrogate binding to CEP350 and VPRBP, demonstrating that CEP78-CEP350 interaction is required for normal CEP78 function in ciliogenesis.\",\n      \"method\": \"Co-immunoprecipitation of CAKUT mutant CEP78 variants with CEP350\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP experiment in preprint, no independent replication reported\",\n      \"pmids\": [\"40777246\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"CEP350 mRNA localizes to centrosomes during S phase via the centriolar satellite protein CEP131 and the RNA-binding protein Unkempt (UNK) in a microtubule-dependent manner. CEP131 and UNK stabilize CEP350 mRNA steady-state levels and promote normal CEP350 protein levels at centrosomes. CEP350 is required for PLK4-induced centriole overduplication but is less important for canonical centriole duplication. CEP131, UNK, and CEP350 are important for centrosome amplification in triple-negative breast cancer cells.\",\n      \"method\": \"FISH for mRNA localization, siRNA knockdown, PLK4-induced overduplication assay, immunofluorescence, mRNA stability assay\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — preprint with multiple orthogonal methods (FISH, siRNA epistasis, mRNA stability, overduplication assay), single lab\",\n      \"pmids\": [\"41929017\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"CEP350 (CAP350) is a large scaffolding protein of the distal centriole that (1) forms a core complex with FOP to anchor microtubules to the centrosome, stabilize centriolar tubules, and recruit CEP19/RABL2B to initiate IFT-complex entry into cilia; (2) coordinates distal centriole length, stability, and appendage assembly by recruiting WDR90, CEP78, and OFD1 while promoting subdistal appendage formation; (3) anchors CYLD at the centrosome to control ciliogenesis via Lys63-deubiquitination; (4) acts upstream of CEP78 in a pathway that negatively regulates CP110 to permit ciliation; (5) stabilises Golgi-associated microtubules through an N-terminal MT-binding region; (6) redistributes PPARα to centrosomal and nuclear compartments and represses its transcriptional activity; and (7) functions as a platform for a balanced PPP2R3C phosphatase–MAP3K1 kinase module that maintains centriole integrity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CEP350 (CAP350) is a large scaffolding protein of the distal centriole that organizes microtubule anchoring, centriole integrity, and ciliogenesis [#0, #12]. Through its C-terminal domain it forms a core complex with FOP that anchors microtubules to the centrosome and, together with EB1, maintains the radial microtubule network [#0]; a distinct N-terminal basic region binds microtubules directly and stabilizes Golgi-associated microtubules, with CEP350 perturbation causing Golgi fragmentation [#1]. At the distal centriole CEP350 acts as a platform coordinating centriole length, stability, and appendage formation by ensuring centriolar localization of WDR90 and recruiting CEP78 and OFD1, without affecting the proximal pericentriolar material [#12]; it functions upstream of CEP78 in a pathway that limits centrosomal CP110 to permit ciliation [#11]. The CEP350/FOP complex recruits CEP19, which captures GTP-bound RABL2B to initiate ciliary entry of the IFT-B holocomplex, and assembly of this distal module depends on Talpid3 and C2CD3 [#8, #10]. CEP350 additionally anchors the deubiquitinase CYLD at centrosomes and basal bodies to support basal body migration and docking during ciliogenesis [#6], and it serves as a docking site for a balanced PPP2R3C phosphatase–MAP3K1 kinase module that maintains centriole integrity [#13]. Beyond the centrosome, CEP350 localizes to epithelial adherens junctions via direct binding to \\u03b1-catenin, where it directs apico-basal microtubule array formation and epithelial morphogenesis [#7], and it binds nuclear receptors including PPAR\\u03b1, redistributing PPAR\\u03b1 to centrosomal and nuclear compartments and repressing its transactivation through an LXXLL motif [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Established the founding mechanistic role of CEP350: how the radial microtubule network is anchored at the centrosome.\",\n      \"evidence\": \"Co-IP and direct binding mapping the CAP350 C-terminus to FOP, with siRNA of CAP350/FOP/EB1 disrupting MT anchoring\",\n      \"pmids\": [\"16314388\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the CAP350-FOP-EB1 module not resolved\", \"Does not address centriolar substructure where the complex acts\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Revealed an unexpected nuclear-receptor function, showing CEP350 binds PPARs/LXR\\u03b1 and represses PPAR\\u03b1 transcription, linking a centrosomal scaffold to transcriptional control.\",\n      \"evidence\": \"Co-IP, in vitro binding, transactivation reporter assays and LXXLL point mutation\",\n      \"pmids\": [\"15615782\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological significance of PPAR\\u03b1 repression unclear\", \"Connection between centrosomal and nuclear pools of CEP350 unresolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Distinguished CEP350's microtubule-binding and targeting modules and tied it specifically to Golgi microtubule stability.\",\n      \"evidence\": \"Partial construct expression, nocodazole resistance, EB1 comet counting and Golgi morphology assays\",\n      \"pmids\": [\"17878239\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism coupling Golgi MT stabilization to Golgi integrity not defined\", \"Relationship of N-terminal MT binding to centrosomal anchoring unclear\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Connected CEP350-dependent centrosomal EB1 localization to primary cilium assembly, providing the first link between this scaffold and ciliogenesis.\",\n      \"evidence\": \"Dominant-negative C-terminal fragment plus siRNA with cilia assembly readout in NIH3T3\",\n      \"pmids\": [\"17600711\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream ciliary machinery not identified at this stage\", \"Dominant-negative interpretation limited without rescue\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Showed CEP350 stabilizes nascent procentrioles independently of hSAS-6 and CPAP, placing it among centriolar tubule-stabilizing factors controlling duplication.\",\n      \"evidence\": \"siRNA with nocodazole-sensitivity assay and epistasis against hSAS-6/CPAP\",\n      \"pmids\": [\"19052644\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular contacts with centriolar tubules unmapped\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified CEP350 as the centrosomal anchor for the deubiquitinase CYLD, mechanistically tying CYLD-mediated ciliogenesis to a defined docking interaction.\",\n      \"evidence\": \"Co-IP plus a transgenic mouse mimicking a cylindromatosis CYLD truncation, with ciliogenesis assays\",\n      \"pmids\": [\"25134987\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Centrosomal substrates of CYLD not identified\", \"How CYLD activity feeds into basal body docking mechanistically unresolved\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Extended CEP350 function beyond the centrosome by showing it localizes to adherens junctions via \\u03b1-catenin to build apico-basal microtubule arrays and drive epithelial morphogenesis.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP, siRNA, and 3D cyst assays in MDCKII cells\",\n      \"pmids\": [\"25764135\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How the junctional and centrosomal pools are partitioned unclear\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Implicated CEP350 in motile cilia/flagellum biology through a basal-body interaction with CFAP157.\",\n      \"evidence\": \"Co-IP and immunofluorescence in CFAP157 knockout mouse spermatozoa and motile cilia\",\n      \"pmids\": [\"27965440\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect nature of CEP350-CFAP157 contact not established\", \"Role of CEP350 in flagellar ultrastructure not directly tested\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined the CEP350/FOP complex as the recruiter of CEP19, establishing the first mechanism directing IFT-B entry into cilia via RABL2B capture.\",\n      \"evidence\": \"AP-MS, Co-IP, siRNA and IFT trafficking assays\",\n      \"pmids\": [\"28625565\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural details of CEP19 capture of GTP-RABL2B at the base not resolved\", \"How IFT entry timing is gated unclear\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Placed assembly of the CEP350/FOP/CEP19 module downstream of Talpid3 and C2CD3, connecting it to distal centriole maturation and appendage assembly.\",\n      \"evidence\": \"siRNA, structured illumination microscopy and epistasis in Talpid3/C2CD3 mutant cells\",\n      \"pmids\": [\"30258116\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical link between Talpid3/C2CD3 and CEP350 not shown\", \"Order of appendage versus module assembly not fully resolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Positioned CEP350 upstream of CEP78 in a pathway that negatively regulates CP110, explaining how this scaffold permits ciliation.\",\n      \"evidence\": \"Co-IP, siRNA/CRISPR, and epistatic rescue where CP110 depletion restores ciliation in CEP78-deficient cells\",\n      \"pmids\": [\"34259627\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which CEP78/EDD1 reduce CP110 not defined\", \"Direct CEP350-CEP78 interface not mapped here\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Consolidated CEP350 as the master distal-centriole scaffold coordinating length, stability, and appendage formation through WDR90, CEP78, and OFD1 recruitment.\",\n      \"evidence\": \"CRISPR knockout, super-resolution microscopy and systematic epistasis/recruitment assays\",\n      \"pmids\": [\"36315013\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and spatial arrangement of the CEP350-FOP-WDR90 axis not solved\", \"Mechanism of subdistal appendage promotion unclear\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed a kinase-phosphatase module anchored by CEP350/FOP, where PPP2R3C counteracts MAP3K1 to maintain centriole integrity, with a disease variant linking this balance to gonadal development.\",\n      \"evidence\": \"Systems genetics, Co-IP, CRISPR epistasis (MAP3K1 KO rescues PPP2R3C defects), and MAP3K1 overexpression\",\n      \"pmids\": [\"39317195\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Centriolar substrates of the MAP3K1/PPP2R3C module not identified\", \"How phospho-balance maintains tubule integrity mechanistically unclear\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Provided disease-linked evidence that CEP78-CEP350 binding is required for CEP78 function, with CAKUT truncating variants abrogating the interaction.\",\n      \"evidence\": \"Co-IP of CAKUT mutant CEP78 with CEP350 (preprint)\",\n      \"pmids\": [\"40777246\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP without independent replication\", \"Functional ciliogenesis consequence of lost binding not directly tested here\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Uncovered an mRNA-level regulatory layer in which CEP350 transcript is localized and stabilized at centrosomes by CEP131 and Unkempt, coupling local translation to centriole overduplication in cancer cells.\",\n      \"evidence\": \"FISH, siRNA epistasis, mRNA stability and PLK4-induced overduplication assays (preprint)\",\n      \"pmids\": [\"41929017\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of UNK/CEP131-dependent mRNA targeting not fully resolved\", \"Selective requirement in overduplication vs canonical duplication needs orthogonal validation\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CEP350's many spatially distinct functions (distal centriole scaffolding, Golgi MT stabilization, junctional MT organization, nuclear-receptor repression) are partitioned and regulated within a single protein remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of full-length CEP350 or its multi-partner interfaces\", \"Mechanism switching CEP350 between centrosomal, Golgi, junctional, and nuclear pools unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 8, 12]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 8, 12]},\n      {\"term_id\": \"GO:0005814\", \"supporting_discovery_ids\": [4, 12]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [8, 12]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [4, 16]}\n    ],\n    \"complexes\": [\n      \"CEP350-FOP complex\",\n      \"CEP350/FOP/CEP19 distal centriole module\"\n    ],\n    \"partners\": [\n      \"FOP\",\n      \"EB1\",\n      \"CEP19\",\n      \"CEP78\",\n      \"WDR90\",\n      \"OFD1\",\n      \"CYLD\",\n      \"CTNNA1\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":6,"faith_pct":83.33333333333333}}