Affinage

CEP120

Centrosomal protein of 120 kDa · UniProt Q8N960

Length
986 aa
Mass
112.6 kDa
Annotated
2026-06-09
17 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEP120 is a daughter-centriole-enriched protein that governs centriole biogenesis, elongation, and appendage assembly to support ciliogenesis and centriole-dependent signaling (PMID:20956381, PMID:23857771, PMID:30988386). It binds tubulin and microtubules through a conserved positively charged patch on its N-terminal C2A domain and directly promotes microtubule formation; the protein is organized as three atypical C2 domains (which lack the calcium- and phospholipid-binding activity of classical C2 domains) followed by a coiled-coil dimerization domain (PMID:29398280). Through direct interaction with CPAP, CEP120 drives centriole elongation, with microtubule-binding-defective and overexpression states perturbing centriole length and number (PMID:23857771). CEP120 localizes to the daughter centriole via Talpid3 and cooperates with C2CD3 and Talpid3 to recruit distal-centriole factors and build distal and subdistal appendages required for cilium formation (PMID:25251415, PMID:30988386). In quiescent cells it instead exerts an inhibitory role, restraining premature pericentriolar material accumulation, microtubule-nucleation activity, and centriolar satellite dispersal (PMID:29741480). CEP120 also recruits KIAA0753 to centrioles to coordinate cerebellar granule neuron progenitor cell-cycle exit and differentiation, and supports meiotic spindle microtubule nucleation in oocytes (PMID:34711653, PMID:32772081). Ciliopathy-causing mutations destabilize the second C2 domain or weaken partner binding, reducing CEP120 levels, impairing appendage and cilium assembly, and underlying Joubert syndrome and Jeune asphyxiating thoracic dystrophy (PMID:29847808, PMID:30988386); in vivo loss of Cep120 disrupts Hedgehog and Wnt signaling and causes cerebellar hypoplasia and hypoplastic kidneys (PMID:25251415, PMID:38177914).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2007 Medium

    Established CEP120 as a functionally important centrosomal protein in neural development by linking it to interkinetic nuclear migration and progenitor self-renewal, before its centriolar mechanism was known.

    Evidence shRNA silencing in developing neocortex with TACC Co-IP

    PMID:17920017

    Open questions at the time
    • Did not define the molecular activity at the centriole
    • TACC interaction not mapped to a domain or validated reciprocally
  2. 2010 High

    Resolved where and when CEP120 acts by showing asymmetric daughter-centriole enrichment with two kinetic pools and a requirement for centriole duplication/amplification across cell contexts.

    Evidence Immunofluorescence, FRAP, and siRNA depletion in cycling cells, MTECs, and S-phase-arrested cells

    PMID:20956381

    Open questions at the time
    • Molecular basis of daughter-centriole targeting unresolved
    • Did not identify direct binding partners driving duplication
  3. 2013 High

    Identified the elongation mechanism by showing CEP120 directly binds CPAP and that a microtubule-binding-defective mutant suppresses centriole elongation, defining its domain architecture.

    Evidence Co-IP, domain mapping, K76A mutagenesis, and overexpression/depletion in human cells

    PMID:23857771

    Open questions at the time
    • Structural basis of microtubule binding not yet determined
    • How CPAP and CEP120 are coordinated temporally unclear
  4. 2014 High

    Connected CEP120 to ciliogenesis and Hedgehog-dependent development via Talpid3-mediated daughter-centriole localization and established its essentiality in vivo.

    Evidence Conditional knockout mice, Co-IP, and Hedgehog signaling assays in cerebellar progenitors

    PMID:25251415

    Open questions at the time
    • Whether Talpid3 acts upstream or downstream in recruitment not fully separated
    • Heart-looping defect mechanism not dissected
  5. 2014 Medium

    Linked CEP120 to human ciliopathy by showing a JATD-associated missense variant reduces cilia and disrupts centriole number, with cross-species confirmation.

    Evidence Patient fibroblast analysis and zebrafish morpholino knockdown

    PMID:25361962

    Open questions at the time
    • Molecular consequence of A199P not yet defined at this stage
    • Morpholino specificity limitations
  6. 2018 High

    Provided the structural and biochemical basis for CEP120 microtubule activity, revealing three atypical C2 domains and a C2A positively charged patch that binds tubulin and promotes microtubule formation.

    Evidence X-ray crystallography, biophysical binding assays, mutagenesis, and in vitro polymerization

    PMID:29398280

    Open questions at the time
    • Roles of C2B and C2C domains not functionally assigned
    • In vitro activity not directly tied to centriole geometry in cells
  7. 2018 High

    Explained how ciliopathy point mutations cause disease by showing V194A and A199P destabilize the second C2 domain, lowering CEP120 levels and impairing distal-centriole recruitment and ciliogenesis.

    Evidence Crystallography, thermal stability assays, and CRISPR knock-in cells with marker imaging

    PMID:29847808

    Open questions at the time
    • Whether protein destabilization fully accounts for phenotype versus loss of a specific interaction not separated
  8. 2018 High

    Revealed a context-dependent inhibitory function in quiescent cells, where CEP120 restrains PCM accumulation, microtubule nucleation, and satellite dispersal to permit proper ciliogenesis.

    Evidence siRNA depletion in quiescent mouse and human cells with PCM, nucleation, and satellite readouts

    PMID:29741480

    Open questions at the time
    • Mechanism switching between elongation-promoting and inhibitory roles unclear
    • Direct PCM-restraining interactions not identified
  9. 2019 High

    Defined CEP120's role in appendage assembly by showing it interacts with C2CD3 and Talpid3 to recruit them to distal centriole ends and build appendages, with a disease mutant weakening C2CD3 binding.

    Evidence CRISPR knockout in RPE1 cells, Co-IP, appendage marker imaging, and WT vs. I975S rescue

    PMID:30988386

    Open questions at the time
    • Order of recruitment among CEP120, C2CD3, and Talpid3 not fully resolved
    • Subdistal versus distal appendage contributions not separated
  10. 2020 Medium

    Extended CEP120 function to meiosis by showing a human variant reduces spindle microtubule nucleation and increases aneuploidy in oocytes.

    Evidence Ectopic expression of CEP120 R947H in mouse oocytes with nucleation and aneuploidy assays

    PMID:32772081

    Open questions at the time
    • Ectopic expression rather than endogenous variant
    • Molecular mechanism of acentriolar spindle nucleation defect not defined
  11. 2021 High

    Identified KIAA0753 recruitment as the mechanism by which CEP120 controls cerebellar progenitor differentiation, with Joubert-syndrome mutants failing to rescue.

    Evidence Co-IP, in vivo shRNA depletion, and WT vs. JS-mutant rescue in cerebellar slices

    PMID:34711653

    Open questions at the time
    • How KIAA0753 recruitment couples to cell-cycle exit signaling unclear
  12. 2023 High

    Demonstrated tissue-level consequences of CEP120 loss in kidney stroma, linking centrosome-duplication failure to mitotic surveillance-driven apoptosis and altered Wnt/Hh and TGF-β/Smad3-Gli2 signaling.

    Evidence Conditional knockout mice with proliferation, apoptosis, signaling, and histological analysis

    PMID:38177914

    Open questions at the time
    • Direct molecular link between CEP120 and TGF-β/Smad3-Gli2 pathway not established
    • Cilia-dependent versus centriole-duplication contributions not fully separated
  13. 2026 Medium

    Validated the meiotic role of the human R947H variant in an endogenous knock-in model, showing reduced fertility, impaired microtubule regrowth, and elevated aneuploidy in a humanized-spindle context.

    Evidence Knock-in mouse, cold-induced microtubule regrowth assay, pericentrin depletion, and aneuploidy quantification

    PMID:42096526

    Open questions at the time
    • Species difference in spindle architecture caveat
    • Mechanism by which the variant lowers nucleation efficiency not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CEP120 switches between its elongation/duplication-promoting role and its quiescent-cell inhibitory role, and the functional division of labor among its three C2 domains, remain unresolved.
  • No regulatory mechanism for the context-dependent switch identified
  • C2B and C2C domain functions unassigned
  • Recruitment hierarchy at distal centriole not fully ordered

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005815 microtubule organizing center 4 GO:0005929 cilium 3 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-162582 Signal Transduction 2
Partners
C2CD3CPAPKIAA0753TACCTALPID3

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 CEP120 (Cep120) interacts with transforming acidic coiled-coil proteins (TACCs) and is required for interkinetic nuclear migration (INM) and neural progenitor self-renewal in the developing neocortex; silencing Cep120 impairs both INM and progenitor maintenance. shRNA-mediated silencing in developing neocortex, co-immunoprecipitation with TACC proteins Neuron Medium 17920017
2010 Cep120 (Ccdc100) localizes preferentially and asymmetrically to the daughter centriole in cycling cells, with two kinetically distinct pools at the centriole (by FRAP); this asymmetry is relieved coincident with new centriole assembly. Cep120 is required for centriole duplication in cycling cells, centriole amplification in multiciliated cells, and centriole overduplication in S phase-arrested cells. Immunofluorescence, FRAP (photobleaching recovery analysis), siRNA depletion in cycling cells and MTECs, S-phase arrest assay The Journal of cell biology High 20956381
2013 CEP120 directly interacts with CPAP and is required for centriole elongation; CEP120 contains an N-terminal microtubule-binding domain, a C-terminal dimerization domain, and a centriolar localization domain. A microtubule binding-defective mutant (K76A) significantly suppresses elongated centriole formation. Forced overexpression of either CEP120 or CPAP induces overly long centrioles and supernumerary centrioles. Co-immunoprecipitation, domain mapping, mutagenesis (K76A), overexpression and depletion assays in human cells The Journal of cell biology High 23857771
2014 Cep120 localizes to the daughter centriole via interaction with Talpid3 (Ta3); loss of Cep120 causes failed centriole duplication and consequent loss of ciliogenesis, abolishing Hedgehog pathway activity in cerebellar granule neuron progenitors (GNPs), leading to cerebellar hypoplasia. Cep120 null mice die in early gestation with abnormal heart looping. Conditional knockout mice, immunofluorescence, Co-IP (Cep120–Talpid3 interaction), Hedgehog signaling assays PloS one High 25251415
2014 A missense mutation in CEP120 (p.Ala199Pro) found in Jeune asphyxiating thoracic dystrophy (JATD) patients results in markedly reduced cilia number and abnormal centriole number in patient fibroblasts. Knockdown of the CEP120 ortholog in zebrafish produces cilia-defect phenotypes (body curvature, hydrocephalus, otolith defects, shortened neural tube cilia, disorganized pronephric cilia). Patient fibroblast analysis, zebrafish morpholino knockdown, cilia length/number quantification Human molecular genetics Medium 25361962
2018 CEP120 contains three C2 domains (C2A, C2B, C2C) followed by a coiled-coil dimerization domain. The N-terminal C2A domain binds tubulin and microtubules and promotes microtubule formation; a conserved positively charged patch on C2A mediates this interaction. Unlike classical C2 domains, all three Cep120 C2 domains lack calcium- and phospholipid-binding activity. X-ray crystallography, biophysical binding assays, mutagenesis of charged residues, in vitro microtubule polymerization assay Journal of structural biology High 29398280
2018 CEP120 contains three C2 domains; ciliopathy-causing point mutations V194A (Joubert syndrome) and A199P (JATD) reduce thermostability of the second C2 domain by targeting residues pointing toward its hydrophobic core, leading to reduced CEP120 protein levels, compromised distal centriole marker recruitment, and deficient cilia formation. X-ray crystallography, thermal stability assays, genome engineering (CRISPR homozygous knock-in), immunofluorescence of centriole/cilia markers Cell reports High 29847808
2018 In quiescent cells, Cep120 plays an inhibitory role at the daughter centriole, preventing premature pericentriolar material (PCM) accumulation (pericentrin, Cdk5Rap2, ninein, Cep170). Depletion of Cep120 causes increased PCM and elevated microtubule-nucleation activity, aberrant dynein-dependent trafficking of centrosomal proteins, dispersal of centriolar satellites, and defective cilia assembly and signaling. siRNA depletion in quiescent mouse and human cells, immunofluorescence, microtubule nucleation assay, centrosomal satellite localization eLife High 29741480
2019 CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly (distal and subdistal appendages) and ciliogenesis. Loss of CEP120 causes short centrioles lacking appendages and impairs C2CD3 and Talpid3 recruitment to distal centriole ends. A disease-associated CEP120 mutant (I975S) has reduced affinity for C2CD3 and perturbs cilia assembly. CRISPR/Cas9 knockout in p53-deficient RPE1 cells, Co-IP, immunofluorescence, centriole appendage marker analysis, rescue with wild-type vs. I975S mutant Scientific reports High 30988386
2020 A non-synonymous variant in CEP120 (p.Arg947His; rs2303720) causes decreased spindle microtubule nucleation efficiency and increased aneuploidy when expressed in mouse oocytes, implicating CEP120 in meiotic spindle assembly. Ectopic expression of CEP120 variant in mouse oocytes, spindle microtubule nucleation assay, chromosome segregation/aneuploidy assessment Human reproduction (Oxford, England) Medium 32772081
2021 CEP120 recruits KIAA0753 to centrioles, and loss of this interaction causes accumulation of granule neuron progenitors (GNPs) in the cerebellar germinal zone and impairs neuronal differentiation and cell cycle exit. JS-associated CEP120 mutants that hinder KIAA0753 recruitment fail to rescue these defects. Co-IP (CEP120–KIAA0753 interaction), shRNA depletion in vivo, immunofluorescence, rescue with WT vs. JS-mutant CEP120, in vivo cerebellar slice analysis Genes & development High 34711653
2023 Conditional deletion of Cep120 in kidney stromal mesenchyme impairs centrosome duplication, causing delayed mitosis, activation of the mitotic surveillance pathway leading to apoptosis, and altered Wnt and Hedgehog signaling, resulting in reduced stromal lineages, hypoplastic kidneys, and post-injury fibrosis via enhanced TGF-β/Smad3-Gli2 signaling. Conditional knockout mice, cell proliferation and apoptosis assays, signaling pathway analysis (Wnt, Hh, TGF-β/Smad3-Gli2), histology EMBO reports High 38177914
2026 A CEP120 knock-in mouse harboring the human variant (p.Arg947His) shows reduced female fertility and increased egg aneuploidy. Oocytes from variant mice have reduced microtubule nucleation efficiency after cold-induced depolymerization; in a pericentrin-depleted (humanized spindle) model, aneuploidy levels are significantly elevated in CEP120 variant eggs. Knock-in mouse model, microtubule regrowth assay after cold exposure, pericentrin depletion to model human spindle, aneuploidy quantification Biology of reproduction Medium 42096526

Source papers

Stage 0 corpus · 17 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool. Neuron 146 17920017
2013 CEP120 interacts with CPAP and positively regulates centriole elongation. The Journal of cell biology 101 23857771
2010 Cep120 is asymmetrically localized to the daughter centriole and is essential for centriole assembly. The Journal of cell biology 100 20956381
2014 A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies. Human molecular genetics 63 25361962
2016 Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes. Journal of medical genetics 52 27208211
2014 Talpid3-binding centrosomal protein Cep120 is required for centriole duplication and proliferation of cerebellar granule neuron progenitors. PloS one 40 25251415
2019 CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly and ciliogenesis. Scientific reports 37 30988386
2020 Exome sequencing links CEP120 mutation to maternally derived aneuploid conception risk. Human reproduction (Oxford, England) 21 32772081
2018 A novel Cep120-dependent mechanism inhibits centriole maturation in quiescent cells. eLife 20 29741480
2018 Disease-Associated Mutations in CEP120 Destabilize the Protein and Impair Ciliogenesis. Cell reports 18 29847808
2021 Update of genetic variants in CEP120 and CC2D2A-With an emphasis on genotype-phenotype correlations, tissue specific transcripts and exploring mutation specific exon skipping therapies. Molecular genetics & genomic medicine 13 33486889
2018 Cep120 promotes microtubule formation through a unique tubulin binding C2 domain. Journal of structural biology 12 29398280
2007 The ups and downs of neural progenitors: Cep120 and TACCs control interkinetic nuclear migration. Neuron 11 17920006
2021 CEP120-mediated KIAA0753 recruitment onto centrioles is required for timely neuronal differentiation and germinal zone exit in the developing cerebellum. Genes & development 7 34711653
2023 Cep120 is essential for kidney stromal progenitor cell growth and differentiation. EMBO reports 6 38177914
2020 Expression patterns of ciliopathy genes ARL3 and CEP120 reveal roles in multisystem development. BMC developmental biology 5 33297941
2026 A human CEP120 gene variant impairs meiotic spindle building causing aneuploidy†. Biology of reproduction 0 42096526

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