Affinage

CEP295

Centrosomal protein of 295 kDa · UniProt Q9C0D2

Length
2601 aa
Mass
295.2 kDa
Annotated
2026-06-09
21 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEP295 (Drosophila Ana1) is a conserved centriole wall protein that serves as the central scaffold for centriole-to-centrosome conversion (CCC), the process that endows newly formed centrioles with the capacity to organize pericentriolar material and to duplicate (PMID:25131205, PMID:26595382). Recruited to the proximal end of procentrioles in early S phase, CEP295 is irreversibly incorporated into the centriolar microtubule wall surrounding the SAS6 cartwheel hub, where it directly binds microtubules (PMID:27185865, PMID:27206860). There it acts as a molecular strut spanning the inner to outermost centriole, sequentially bridging Cep135 and Cep152/Asterless—the receptor for the master duplication kinase Plk4—to license centriole duplication (PMID:26595382). CEP295 directly binds and recruits CEP192 onto the daughter centriole wall, conferring PCM-assembly and microtubule-organizing-center activity on the new mother centriole (PMID:27562453). Beyond conversion, CEP295 governs construction of the distal centriole half by loading POC5 and POC1B and enabling tubulin acetylation and glutamylation, with its N-terminal domain controlling centriole elongation (PMID:27185865, PMID:28811500). CEP295 also recruits Polo/Plk kinase to mother centrioles to drive mitotic centrosome maturation and G2 centriole elongation, functions separable from its role in duplication and ciliogenesis (PMID:34156068, PMID:35505659). In the male germline it directs conversion of microtubule doublets to triplets by recruiting centrobin through its C-terminal region (PMID:42159626). CEP295 is positioned downstream of RTTN/STIL and PPP1R35 in the assembly pathway and acts in parallel with a CEP44–POC1B structural pathway, such that CEP295 binding alone is insufficient for conversion when the centriole wall is disrupted (PMID:28811500, PMID:30230954, PMID:32060285). Loss of CEP295 in human cells causes failure of CCC, progressive centriole disintegration, ciliogenesis defects, and p53-dependent G1 arrest; bi-allelic CEP295 variants underlie a primary microcephaly syndrome, and wild-type but not a disease-associated mutant rescues the centriole and cilia defects of patient cells (PMID:25131205, PMID:38154379).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2010 Medium

    Established CEP295 (KIAA1731) as a centrosomal protein whose depletion perturbs centriole formation/stability, providing the first link between this uncharacterized gene and the centriole.

    Evidence Exogenous expression localization and RNAi phenotypic scoring in human cells

    PMID:20844083

    Open questions at the time
    • No molecular mechanism or interaction partners identified
    • Localization shown only by overexpression
    • Single lab, limited follow-up
  2. 2014 High

    Defined the specific cellular role of CEP295 as the factor required for centriole-to-centrosome conversion, resolving why centrioles lacking it disintegrate—they fail to recruit PCM after cartwheel removal.

    Evidence RNAi knockdown with cell-cycle staging, immunofluorescence and electron microscopy in human cells

    PMID:25131205

    Open questions at the time
    • Direct binding partners mediating PCM recruitment not yet identified
    • Molecular nature of the conversion event undefined
  3. 2015 High

    Placed CEP295/Ana1 within an ordered Cep135–Ana1–Asterless/Cep152 loading hierarchy, showing it acts as a structural bridge essential for recruiting the Plk4 partner Cep152 and thus for duplication.

    Evidence Epistasis/rescue, Co-IP, super-resolution microscopy and engineered bridge constructs in Drosophila and human cells

    PMID:26595382

    Open questions at the time
    • Atomic/structural basis of the bridge not resolved
    • Whether interactions with Cep135 and Cep152 are direct or indirect not fully defined
  4. 2016 High

    Showed CEP295 directly binds microtubules and builds the distal centriole half, identifying POC5/POC1B loading and tubulin modification as downstream events and mapping elongation control to the N-terminal domain.

    Evidence siRNA depletion, super-resolution/immunogold EM, in vitro microtubule-binding assay, domain overexpression in human cells

    PMID:27185865

    Open questions at the time
    • Mechanism by which microtubule binding controls elongation not defined
    • How POC5/POC1B recruitment is achieved at molecular level unknown
  5. 2016 High

    Identified the molecular basis of conversion: CEP295 directly binds and recruits CEP192, the factor that confers PCM-assembly and MTOC capacity on the new mother centriole.

    Evidence siRNA/RNAi depletion, direct binding/pull-down assays, MTOC functional readouts in human/Drosophila cells

    PMID:27562453

    Open questions at the time
    • Structural details of the CEP295–CEP192 interface not resolved
    • Coordination between CEP192 recruitment and Cep152 loading unclear
  6. 2016 High

    Demonstrated in vivo that Ana1 is irreversibly incorporated and that centrosome/cilium function is separable from its dose-dependent role in centriole over-elongation, mapping the latter to the N-terminal 639 residues.

    Evidence Drosophila ana1 mutant analysis, truncation rescue, FRAP, fluorescence microscopy

    PMID:27206860

    Open questions at the time
    • Molecular distinction between maintaining vs initially recruiting Asl not defined
    • Mechanism of irreversible incorporation unknown
  7. 2017 Medium

    Positioned CEP295 in the assembly hierarchy as downstream of RTTN/STIL-mediated assembly and upstream of POC1B/POC5 loading, clarifying the order of distal-half construction.

    Evidence CRISPR/Cas9 knockout, super-resolution microscopy, Co-IP and epistasis in human cells

    PMID:28811500

    Open questions at the time
    • CEP295 pathway position partly inferred from orthogonal KOs
    • Direct vs indirect connection to RTTN/STIL not established
  8. 2018 Medium

    Identified PPP1R35 as a factor upstream of CEP295 recruitment, showing that nascent centrioles initiate normally but require PPP1R35 to load CEP295 and undergo conversion.

    Evidence CRISPR/Cas9 knockout, immunofluorescence, epistasis by marker recruitment

    PMID:30230954

    Open questions at the time
    • Whether PPP1R35 recruits CEP295 directly is unknown
    • Single lab
  9. 2020 Medium

    Showed that CEP295 binding is necessary but not sufficient for conversion: a parallel CEP44–POC1B–TUBD1/TUBE1 wall-integrity pathway is also required, refining the conversion model.

    Evidence siRNA depletion, epistasis and centriole structural analysis in human cells

    PMID:32060285

    Open questions at the time
    • How wall integrity gates CEP295 function mechanistically unclear
    • Single lab
  10. 2021 High

    Established that Ana1 recruits Polo kinase to mother centrioles to specifically drive mitotic PCM assembly and G2 elongation, separable from its roles in duplication and cilia.

    Evidence Drosophila genetics with Polo-binding-deficient Ana1 mutants and multiple functional readouts

    PMID:34156068

    Open questions at the time
    • Whether human CEP295 recruits Plk in the same manner not directly shown
    • Structural basis of Ana1–Polo interaction undefined
  11. 2022 Medium

    Provided a quantitative model in which Ana1 acts as the centriole receptor generating a local pulse of Polo activity that times centrosome maturation prior to mitosis.

    Evidence Live imaging of Drosophila embryos, quantitative microscopy, mathematical modeling and genetic perturbation

    PMID:35505659

    Open questions at the time
    • Model partly inferred from fitting
    • Direct measurement of Polo activity dynamics not achieved
    • Single lab
  12. 2023 High

    Connected CEP295 loss to human disease, showing depletion causes reduced centriole/centrosome numbers, p53-dependent G1 arrest and ciliary defects, with isogenic rescue distinguishing pathogenic from wild-type alleles.

    Evidence Patient exome sequencing, patient-derived fibroblasts, siRNA in U2OS/RPE1, mRNA complementation, cell-cycle analysis

    PMID:38154379

    Open questions at the time
    • Tissue specificity of microcephaly phenotype not mechanistically explained
    • Link between centriole loss and p53 activation undefined
  13. 2024 Medium

    Demonstrated Ana1 is required to maintain centriole structural integrity (in a Polo-dependent manner) but that centrioles maintained by Ana1 alone are MTOC-inactive, separating structural maintenance from MTOC activity.

    Evidence Drosophila overexpression and tethering genetics with MTOC functional readout in an oogenesis centriole-loss model

    PMID:38200359

    Open questions at the time
    • Molecular basis of structural maintenance vs MTOC activity not defined
    • Single lab
  14. 2024 Medium

    Intragenic complementation genetics dissected CEP295 into separable functional modules, showing radial expansion/Asl recruitment can be rescued by overlapping fragments while centriole elongation requires continuous full-length sequence including a defined internal region.

    Evidence Drosophila intragenic complementation, domain deletion, EM, fertility assays (preprint)

    PMID:bio_10.1101_2024.10.28.620588

    Open questions at the time
    • Preprint, not peer-reviewed
    • Molecular identity of the elongation-required internal region not characterized
  15. 2026 High

    Identified a germline-specific role in which Ana1 drives microtubule doublet-to-triplet conversion by recruiting centrobin through its C-terminal region, with centrobin tethering sufficient to restore C-tubule formation.

    Evidence Drosophila deletion mutants, domain truncations, EM, centrobin tethering rescue and fertility assays

    PMID:42159626

    Open questions at the time
    • Whether human CEP295 recruits centrobin similarly not shown
    • Mechanism of C-tubule template formation downstream of centrobin undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of how CEP295 simultaneously bridges multiple partners (Cep135, Cep152, CEP192, Polo, centrobin) along the centriole wall, and how its distinct domains coordinate conversion, elongation and tissue-specific functions, remains unresolved.
  • No high-resolution structure of CEP295 or its interfaces
  • Mechanism linking centriole loss to p53/G1 arrest unknown
  • Human relevance of germline centrobin/triplet functions untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005815 microtubule organizing center 2 GO:0005929 cilium 2
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1266738 Developmental Biology 2
Partners
CEP135CEP152CEP192CNTROBPOC1BPOC5POLORTTN
Complex memberships
centriolecentrosome

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 CEP295 (KIAA1731) is a newborn centriole-enriched protein specifically required for centriole-to-centrosome conversion (CCC) but dispensable for cartwheel removal. In its absence, centrioles form and lose their cartwheel in mitosis but fail to recruit pericentriolar material (PCM), resulting in progressive loss of centriolar components. Centrioles associating with either the cartwheel or PCM alone remain stable, but cartwheel-less centrioles without PCM disintegrate, demonstrating that CEP295-mediated CCC maintains centriole stability for duplication. RNAi knockdown in human cells, cell cycle staging, immunofluorescence, electron microscopy Cell reports High 25131205
2015 Centriole-to-centrosome conversion requires sequential loading of Cep135, Ana1 (CEP295), and Asterless (Cep152) onto daughter centrioles during mitotic progression in both Drosophila and human cells. Ana1/CEP295 forms a molecular strut within this network spanning the inner to outermost centriole, and its essential role can be substituted by an engineered fragment providing an alternative linkage between Asterless/Cep152 and Cep135. This framework is essential for loading Cep152, the partner of the master regulator of centriole duplication, Plk4. Epistasis/genetic rescue experiments, co-immunoprecipitation, super-resolution microscopy, engineered molecular bridge constructs in Drosophila and human cells Nature cell biology High 26595382
2016 CEP295 directly interacts with microtubules and is required for building the distal half of centrioles during S and G2. CEP295 is recruited to the proximal end of procentrioles in early S phase and localizes at the centriolar microtubule wall surrounding the SAS6 cartwheel hub. Depletion of CEP295 inhibits recruitment of POC5 and POC1B to distal half centrioles, resulting in shorter centrioles, and blocks post-translational modifications of centriolar microtubules (acetylation and glutamylation). Excess CEP295 induces overly long centrioles; the N-terminal domain exerts a dominant-negative effect on centriole elongation. siRNA depletion, super-resolution and immunogold electron microscopy, in vitro microtubule-binding assay, overexpression of domains, immunofluorescence Journal of cell science High 27185865
2016 Cep295 is recruited to the proximal centriole wall in early stages of procentriole assembly and acts as a scaffold for proper daughter centriole assembly. Cep295 directly binds to and recruits Cep192 onto the daughter centriole wall, which endows the new mother centriole with PCM assembly capacity, microtubule-organizing centre activity, and the ability to support centriole formation. Depletion by siRNA/RNAi, direct binding assay (pull-down/Co-IP), immunofluorescence, functional assays for MTOC activity Nature communications High 27562453
2016 Drosophila Ana1 (CEP295 ortholog) is irreversibly incorporated into centrioles during assembly and is required for assembling functional centrosomes and cilia. Ana1 plays a more important role in maintaining Asl (Cep152) at centrioles than in initially recruiting it. Ana1 promotes centriole elongation in a dose-dependent manner; a GFP-Ana1 fusion lacking the N-terminal 639 amino acids can support centrosome assembly and cilium function but cannot promote centriole over-elongation, indicating these are separable functions. Drosophila ana1 mutant analysis, GFP-Ana1 truncation rescue experiments, fluorescence microscopy, FRAP (irreversible incorporation) Journal of cell science High 27206860
2017 CEP295 acts as an upstream effector of POC1B and POC5 loading onto distal-half centrioles. RTTN, which directly interacts with STIL, acts upstream of CEP295 in centriole assembly; CEP295 is downstream of STIL-mediated assembly and upstream of POC1B/POC5 recruitment. CRISPR/Cas9 knockout, super-resolution microscopy, co-immunoprecipitation (RTTN-STIL interaction), epistasis analysis Nature communications Medium 28811500
2018 PPP1R35 acts upstream of CEP295 to induce centriole-to-centrosome conversion. In PPP1R35-null cells, centriole assembly initiates normally but CEP295 is not recruited to nascent centrioles, and centrioles disintegrate after mitosis upon cartwheel removal, placing PPP1R35 upstream of CEP295 in the CCC pathway. CRISPR/Cas9 knockout, immunofluorescence, epistasis analysis by marker recruitment Molecular biology of the cell Medium 30230954
2020 CEP44, which binds A-microtubules in the centriole lumen and interacts with POC1B, is required for centriole-to-centrosome conversion even when CEP295 is bound to centrioles. This places a centriole structural pathway (CEP44–POC1B–TUBE1–TUBD1) alongside CEP295 as required for CCC, and shows that CEP295 binding alone is insufficient for conversion if the centriole wall is disrupted. siRNA depletion, immunofluorescence, epistasis analysis, centriole structural analysis Nature communications Medium 32060285
2021 Ana1 (Drosophila CEP295 ortholog) helps recruit Polo kinase to mother centrioles. When Ana1-dependent Polo recruitment is specifically impaired, mother centrioles can duplicate, disengage from daughters, and form functional cilia, but they fail to efficiently assemble mitotic PCM or elongate during G2. This demonstrates that Ana1 specifically promotes mitotic centrosome assembly and G2 centriole elongation via Polo recruitment, independently of centriole duplication or cilia assembly. Drosophila genetics, domain-specific Ana1 mutants disrupting Polo binding, immunofluorescence, functional assays for PCM assembly, centriole duplication, cilia formation Journal of cell science High 34156068
2022 In Drosophila syncytial blastoderm embryos, centrosomal Polo levels rise and fall during PCM assembly, peaking then declining while PCM scaffold levels continue to rise. Mathematical modeling and experiments indicate that a centriolar pulse of Polo activity, generated by the interaction between Polo and its centriole receptor Ana1 (CEP295 in humans), explains these scaffold assembly dynamics. This supports a model where centrioles generate a local pulse of Polo activity prior to mitotic entry to initiate centrosome maturation. Live imaging of Drosophila embryos, quantitative fluorescence microscopy, mathematical modeling, genetic perturbation The EMBO journal Medium 35505659
2023 Depletion of CEP295 in human cells decreases centriole and centrosome numbers and triggers p53-dependent G1 cell cycle arrest. Loss of CEP295 also causes extensive primary ciliary defects in patient-derived fibroblasts and RPE1 cells. Wild-type CEP295, but not a disease-associated missense mutant, can rescue centrosome/centriole developmental defects and cilia defects in patient cells. Whole-exome sequencing of patients, patient-derived fibroblast analysis, siRNA depletion in U2OS and RPE1 cells, mRNA complementation assay, immunofluorescence, cell cycle analysis EBioMedicine High 38154379
2024 Ana1/CEP295 is essential for maintaining centrosome integrity in Drosophila. Polo kinase requires Ana1 to promote centriole stability. Ana1 expression prevents centriole loss upon PCM downregulation. However, centrioles maintained solely by ANA1 overexpression are inactive as MTOCs, unlike those maintained by Polo kinase tethering, indicating that CEP295/Ana1 maintains centriole structure but not MTOC activity independently. Drosophila genetics (overexpression, tethering experiments), immunofluorescence, oogenesis model of centriole loss EMBO reports Medium 38200359
2010 Exogenously expressed KIAA1731 (CEP295) localizes to the centrosome in human cells. RNAi-mediated depletion of KIAA1731 affects centriole formation/stability, suggesting a role in maintaining centriole structure. Exogenous expression with immunofluorescence, RNAi depletion with phenotypic scoring Molecular biology of the cell Medium 20844083
2026 In Drosophila male germline cells, Ana1 (CEP295) is required for the conversion of microtubule doublets to triplets (C-tubule assembly) during spermatogenesis. The Ana1 N-terminal region localizes adjacent to microtubule doublets and promotes modest elongation, while the C-terminal region extends outward and is sufficient for C-tubule assembly. Ana1 recruits centrobin to centrioles via its C-terminal region, and targeted recruitment of centrobin to centrioles restores C-tubule formation in Ana1-deficient cells. Triplet microtubule integrity is critical for male fertility. Drosophila genetics (Ana1 deletion mutants), domain-mapping with truncation constructs, electron microscopy, centrobin tethering rescue experiments, fertility assays The Journal of cell biology High 42159626
2024 Mutant alleles encoding overlapping N- and C-terminal parts of Ana1 (CEP295) can complement intragенically to rescue centriole radial expansion and Asl (Cep152) recruitment, thereby restoring centriole duplication and mechanosensory cilia formation, but not elongation of triplet-microtubule-containing centrioles in primary spermatocytes. Full-length continuous Ana1 sequence is required for centriole elongation. A defined internal region, when deleted from otherwise intact Ana1, prevents primary spermatocyte centriole elongation but still allows Asl recruitment, showing that radial expansion and elongation have distinct structural requirements within CEP295. Drosophila intragenic complementation genetics, domain deletion analysis, electron microscopy, immunofluorescence, fertility assays bioRxivpreprint Medium bio_10.1101_2024.10.28.620588

Source papers

Stage 0 corpus · 21 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Conserved molecular interactions in centriole-to-centrosome conversion. Nature cell biology 110 26595382
2014 Stabilization of cartwheel-less centrioles for duplication requires CEP295-mediated centriole-to-centrosome conversion. Cell reports 91 25131205
2010 Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731. Molecular biology of the cell 89 20844083
2018 ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits. Journal of molecular medicine (Berlin, Germany) 84 30421101
2016 CEP295 interacts with microtubules and is required for centriole elongation. Journal of cell science 63 27185865
2015 Gene-based meta-analysis of genome-wide association studies implicates new loci involved in obesity. Human molecular genetics 55 26376864
2016 Cep295 is a conserved scaffold protein required for generation of a bona fide mother centriole. Nature communications 54 27562453
2020 CEP44 ensures the formation of bona fide centriole wall, a requirement for the centriole-to-centrosome conversion. Nature communications 40 32060285
2017 Human microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles. Nature communications 39 28811500
2016 Drosophila Ana1 is required for centrosome assembly and centriole elongation. Journal of cell science 34 27206860
2022 Centrioles generate a local pulse of Polo/PLK1 activity to initiate mitotic centrosome assembly. The EMBO journal 23 35505659
2022 Modeling Human Primary Microcephaly With hiPSC-Derived Brain Organoids Carrying CPAP-E1235V Disease-Associated Mutant Protein. Frontiers in cell and developmental biology 22 35309908
2018 PPP1R35 ensures centriole homeostasis by promoting centriole-to-centrosome conversion. Molecular biology of the cell 13 30230954
2021 Ana1 helps recruit Polo to centrioles to promote mitotic PCM assembly and centriole elongation. Journal of cell science 12 34156068
2023 IQUB deficiency causes male infertility by affecting the activity of p-ERK1/2/RSPH3. Human reproduction (Oxford, England) 8 36355624
2024 Ana1/CEP295 is an essential player in the centrosome maintenance program regulated by Polo kinase and the PCM. EMBO reports 7 38200359
2023 Heritable Risk and Protective Genetic Components of Glaucoma Medication Non-Adherence. International journal of molecular sciences 6 36982708
2023 Bi-allelic variants in CEP295 cause Seckel-like syndrome presenting with primary microcephaly, developmental delay, intellectual disability, short stature, craniofacial and digital abnormalities. EBioMedicine 6 38154379
2021 Triple deletion of TP53, PCNT, and CEP215 promotes centriole amplification in the M phase. Cell cycle (Georgetown, Tex.) 5 34233584
2021 Coding variants in the PCNT and CEP295 genes contribute to breast cancer risk in Chinese women. Pathology, research and practice 3 34418690
2026 Ana1/CEP295 regulates centriolar doublet-to-triplet conversion during spermatogenesis. The Journal of cell biology 0 42159626

Missed literature

Know a paper Affinage missed for CEP295? Flag it for the maintainers and the community.

No submissions yet.