Affinage

CEP350

Centrosome-associated protein 350 · UniProt Q5VT06

Length
3117 aa
Mass
350.9 kDa
Annotated
2026-06-09
29 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2005 High

    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

    PMID:16314388

    Open questions at the time
    • Structural basis of the CAP350-FOP-EB1 module not resolved
    • Does not address centriolar substructure where the complex acts
  2. 2005 Medium

    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

    PMID:15615782

    Open questions at the time
    • Physiological significance of PPARα repression unclear
    • Connection between centrosomal and nuclear pools of CEP350 unresolved
  3. 2007 High

    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

    PMID:17878239

    Open questions at the time
    • Mechanism coupling Golgi MT stabilization to Golgi integrity not defined
    • Relationship of N-terminal MT binding to centrosomal anchoring unclear
  4. 2007 Medium

    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

    PMID:17600711

    Open questions at the time
    • Downstream ciliary machinery not identified at this stage
    • Dominant-negative interpretation limited without rescue
  5. 2008 Medium

    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

    PMID:19052644

    Open questions at the time
    • Molecular contacts with centriolar tubules unmapped
    • Single-lab study
  6. 2014 High

    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

    PMID:25134987

    Open questions at the time
    • Centrosomal substrates of CYLD not identified
    • How CYLD activity feeds into basal body docking mechanistically unresolved
  7. 2015 High

    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

    PMID:25764135

    Open questions at the time
    • How the junctional and centrosomal pools are partitioned unclear
    • Single-lab study
  8. 2016 Medium

    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

    PMID:27965440

    Open questions at the time
    • Direct vs indirect nature of CEP350-CFAP157 contact not established
    • Role of CEP350 in flagellar ultrastructure not directly tested
  9. 2017 High

    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

    PMID:28625565

    Open questions at the time
    • Structural details of CEP19 capture of GTP-RABL2B at the base not resolved
    • How IFT entry timing is gated unclear
  10. 2018 Medium

    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

    PMID:30258116

    Open questions at the time
    • Direct biochemical link between Talpid3/C2CD3 and CEP350 not shown
    • Order of appendage versus module assembly not fully resolved
  11. 2021 High

    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

    PMID:34259627

    Open questions at the time
    • Mechanism by which CEP78/EDD1 reduce CP110 not defined
    • Direct CEP350-CEP78 interface not mapped here
  12. 2022 High

    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

    PMID:36315013

    Open questions at the time
    • Stoichiometry and spatial arrangement of the CEP350-FOP-WDR90 axis not solved
    • Mechanism of subdistal appendage promotion unclear
  13. 2024 Medium

    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

    PMID:39317195

    Open questions at the time
    • Centriolar substrates of the MAP3K1/PPP2R3C module not identified
    • How phospho-balance maintains tubule integrity mechanistically unclear
  14. 2025 Low

    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)

    PMID:40777246

    Open questions at the time
    • Single Co-IP without independent replication
    • Functional ciliogenesis consequence of lost binding not directly tested here
  15. 2026 Medium

    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)

    PMID:41929017

    Open questions at the time
    • Mechanism of UNK/CEP131-dependent mRNA targeting not fully resolved
    • Selective requirement in overduplication vs canonical duplication needs orthogonal validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • 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.
  • No structure of full-length CEP350 or its multi-partner interfaces
  • Mechanism switching CEP350 between centrosomal, Golgi, junctional, and nuclear pools unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005815 microtubule organizing center 3 GO:0005634 nucleus 1 GO:0005794 Golgi apparatus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1640170 Cell Cycle 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
CEP19CEP78CTNNA1CYLDEB1FOPOFD1WDR90
Complex memberships
CEP350-FOP complexCEP350/FOP/CEP19 distal centriole module

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 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. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, direct binding assay Molecular biology of the cell High 16314388
2007 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. In vitro and in vivo expression of partial constructs, siRNA knockdown, nocodazole resistance assay, EB1 comet counting, immunofluorescence Journal of cell science High 17878239
2005 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. Co-immunoprecipitation, immunofluorescence co-localization, in vitro binding assay, transactivation reporter assay, LXXLL point mutation Journal of cell science Medium 15615782
2007 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. Dominant-negative CAP350 fragment expression, siRNA knockdown, immunofluorescence, cilia assembly assay Current biology : CB Medium 17600711
2008 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. siRNA knockdown, nocodazole-sensitivity assay for procentriole stability, epistasis with hSAS-6/CPAP knockdowns PloS one Medium 19052644
2008 The oncogenic FOP-FGFR1 fusion kinase interacts with CAP350 (CEP350), and CAP350 is necessary for FOP-FGFR1 localization at the centrosome. Co-immunoprecipitation, siRNA knockdown of CAP350, immunofluorescence Molecular cancer Medium 18412956
2014 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. Co-immunoprecipitation, transgenic mouse model, immunofluorescence, ciliogenesis assay Nature communications High 25134987
2015 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. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, immunofluorescence, 3D cyst assay PLoS biology High 25764135
2017 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. Affinity-purification mass spectrometry, co-immunoprecipitation, siRNA knockdown, IFT trafficking assays Developmental cell High 28625565
2016 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. Co-immunoprecipitation, immunofluorescence localization in knockout mouse tissue Development (Cambridge, England) Medium 27965440
2018 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. siRNA knockdown, immunofluorescence, structured illumination microscopy, epistasis analysis in Talpid3/C2CD3 mutant cells Nature communications Medium 30258116
2021 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. Co-immunoprecipitation, siRNA/CRISPR knockdown, immunofluorescence, epistasis rescue experiment (CP110 depletion restoring ciliation) eLife High 34259627
2022 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. CRISPR knockout, immunofluorescence, super-resolution microscopy, epistasis analysis, protein recruitment assays The Journal of cell biology High 36315013
2024 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. Systems genetics, co-immunoprecipitation, CRISPR knockout epistasis, MAP3K1 overexpression, immunofluorescence, JNK signaling assay Current biology : CB Medium 39317195
2024 PPP2R3C is a distal centriole protein and functional partner of CEP350 and FOP (preprint version, same findings as published paper above). Functional genomics, co-immunoprecipitation, CRISPR knockout epistasis, immunofluorescence bioRxivpreprint Low 38617270
2025 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. Co-immunoprecipitation of CAKUT mutant CEP78 variants with CEP350 bioRxivpreprint Low 40777246
2026 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. FISH for mRNA localization, siRNA knockdown, PLK4-induced overduplication assay, immunofluorescence, mRNA stability assay bioRxivpreprint Medium 41929017

Source papers

Stage 0 corpus · 29 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 The OsSPL16-GW7 regulatory module determines grain shape and simultaneously improves rice yield and grain quality. Nature genetics 464 26147620
2005 A complex of two centrosomal proteins, CAP350 and FOP, cooperates with EB1 in microtubule anchoring. Molecular biology of the cell 121 16314388
2017 The CEP19-RABL2 GTPase Complex Binds IFT-B to Initiate Intraflagellar Transport at the Ciliary Base. Developmental cell 94 28625565
2016 GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN. Depression and anxiety 89 27038408
2019 Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci. Molecular psychiatry 88 30617275
2013 CEP proteins: the knights of centrosome dynasty. Protoplasma 81 23456457
2020 Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets. Clinical epigenetics 66 32586373
2007 EB1 is required for primary cilia assembly in fibroblasts. Current biology : CB 55 17600711
2015 Transposon mutagenesis identifies genetic drivers of Braf(V600E) melanoma. Nature genetics 54 25848750
2007 Centrosomal CAP350 protein stabilises microtubules associated with the Golgi complex. Journal of cell science 49 17878239
2016 Bisphenol A and its analogues disrupt centrosome cycle and microtubule dynamics in prostate cancer. Endocrine-related cancer 44 27998958
2018 A distal centriolar protein network controls organelle maturation and asymmetry. Nature communications 41 30258116
2014 The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells. Nature communications 40 25134987
2021 CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels. eLife 33 34259627
2005 Activity and subcellular compartmentalization of peroxisome proliferator-activated receptor alpha are altered by the centrosome-associated protein CAP350. Journal of cell science 27 15615782
2008 Role of CAP350 in centriolar tubule stability and centriole assembly. PloS one 23 19052644
2016 CFAP157 is a murine downstream effector of FOXJ1 that is specifically required for flagellum morphogenesis and sperm motility. Development (Cambridge, England) 22 27965440
2015 Alpha-catenin-dependent recruitment of the centrosomal protein CAP350 to adherens junctions allows epithelial cells to acquire a columnar shape. PLoS biology 18 25764135
2022 The central scaffold protein CEP350 coordinates centriole length, stability, and maturation. The Journal of cell biology 17 36315013
2008 Myeloproliferative disorder FOP-FGFR1 fusion kinase recruits phosphoinositide-3 kinase and phospholipase Cgamma at the centrosome. Molecular cancer 16 18412956
2017 The effect of Diosmin on the blood proteome in a rat model of venous thrombosis. International journal of biological macromolecules 7 28606843
2021 Construction and Analysis of a Diagnostic Model Based on Differential Expression Genes in Patients With Major Depressive Disorder. Frontiers in psychiatry 6 34955918
2022 Exome and Sputum Microbiota as Predictive Markers of Frequent Exacerbations in Chronic Obstructive Pulmonary Disease. Biomolecules 5 36291689
2020 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. RNA biology 5 32507013
2024 A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function. Current biology : CB 2 39317195
2025 CAKUT variants in PRPF8, DYRK2, and CEP78: implications for splicing and ciliogenesis. bioRxiv : the preprint server for biology 1 40777246
2022 Blood transcriptome analysis and identification of genes associated with supernumerary teats in Chinese Holstein cows. Journal of dairy science 1 36241435
2026 Centriolar satellites regulate CEP350 mRNA localization and centrosome amplification. bioRxiv : the preprint server for biology 0 41929017
2024 A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function. bioRxiv : the preprint server for biology 0 38617270

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