Affinage

CEP120

Centrosomal protein of 120 kDa · UniProt Q8N960

Length
986 aa
Mass
112.6 kDa
Annotated
2026-04-28
16 papers in source corpus 11 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEP120 is a daughter-centriole-enriched protein that governs centriole elongation, appendage assembly, ciliogenesis, and pericentriolar material homeostasis. It contains three tandem C2 domains—of which C2A binds tubulin and microtubules via a conserved positively charged surface patch—and a C-terminal coiled-coil dimerization domain; it directly interacts with CPAP to drive centriole elongation, with Talpid3 and C2CD3 for distal appendage assembly, and with KIAA0753 for cerebellar granule neuron differentiation (PMID:23857771, PMID:29398280, PMID:30988386, PMID:34711653). In quiescent cells CEP120 restrains premature PCM accumulation at daughter centrioles, thereby preventing aberrant microtubule nucleation and ensuring proper cilia formation and Hedgehog signaling (PMID:29741480, PMID:25251415). Destabilizing mutations in the C2B domain (V194A, A199P) cause Joubert syndrome and Jeune asphyxiating thoracic dystrophy by reducing protein levels and compromising distal centriole maturation and ciliogenesis (PMID:29847808).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2007 High

    Identifying CEP120 as a centrosomal protein that interacts with TACCs and is functionally required for interkinetic nuclear migration and neural progenitor self-renewal established its role in centrosome-dependent processes during brain development.

    Evidence In utero electroporation shRNA knockdown in mouse neocortex with Co-IP of Cep120–TACC interaction

    PMID:17920017

    Open questions at the time
    • Mechanism by which CEP120–TACC interaction supports INM not resolved
    • Role in centriole biogenesis not yet tested
  2. 2010 High

    Demonstrating that CEP120 is asymmetrically enriched on the daughter centriole and required for centriole duplication in cycling and multiciliated cells positioned it as a core centriole biogenesis factor rather than a general centrosome component.

    Evidence Immunofluorescence, siRNA knockdown, and FRAP in cycling cells and mouse tracheal epithelial cells

    PMID:20956381

    Open questions at the time
    • Molecular basis of daughter-centriole targeting unknown
    • Direct binding partners for duplication function not identified
  3. 2013 High

    Showing that CEP120 directly interacts with CPAP and that both are required for centriole elongation—with the N-terminal microtubule-binding domain essential for this activity—revealed the molecular mechanism through which CEP120 promotes centriole length control.

    Evidence Co-IP, reciprocal siRNA epistasis, overexpression-induced elongation, and K76A microtubule-binding mutant analysis

    PMID:23857771

    Open questions at the time
    • Structural basis of CEP120–CPAP interaction not determined
    • How elongation is limited to prevent over-elongation in vivo unclear
  4. 2014 High

    Identifying Talpid3 as a binding partner that mediates CEP120 daughter-centriole asymmetry, and showing that conditional Cep120 knockout in the CNS ablates centriole duplication, ciliogenesis, and Hedgehog signaling, linked CEP120 to ciliary signaling in vivo.

    Evidence Co-IP of Cep120–Talpid3; conditional Cep120 knockout in mouse CNS with Hedgehog pathway readouts

    PMID:25251415

    Open questions at the time
    • How Talpid3 directs CEP120 asymmetry at the molecular level not resolved
    • Whether Hedgehog defects are solely secondary to cilia loss not distinguished
  5. 2018 High

    Crystal structures revealed three consecutive C2 domains whose C2A domain binds tubulin/microtubules through a positively charged patch, while ciliopathy mutations in C2B destabilize the protein and compromise centriole maturation and cilia formation, providing the structural basis for CEP120 function and disease.

    Evidence X-ray crystallography; in vitro tubulin binding and microtubule polymerization assays; thermal stability assays of V194A/A199P; CRISPR knock-in of disease mutations in human cells

    PMID:29398280 PMID:29847808

    Open questions at the time
    • Functional roles of C2C domain unknown
    • Whether C2A–tubulin binding is calcium-independent in all contexts not fully tested
  6. 2018 High

    Discovering that CEP120 actively suppresses PCM accumulation at daughter centrioles in quiescent cells revealed a regulatory function distinct from its pro-duplication role in cycling cells, explaining how daughter-centriole identity is maintained.

    Evidence siRNA knockdown in quiescent mouse and human cells; PCM component quantification; microtubule nucleation and ciliogenesis assays

    PMID:29741480

    Open questions at the time
    • Molecular mechanism of PCM inhibition not identified
    • Whether this function operates through the same domains as elongation activity unknown
  7. 2019 High

    Establishing that CEP120 recruits C2CD3 and Talpid3 to distal centrioles for appendage assembly, and that the disease mutation I975S weakens C2CD3 binding, defined CEP120 as a scaffold for distal centriole maturation upstream of appendage formation.

    Evidence CRISPR KO in RPE1 cells; Co-IP; appendage marker analysis; binding affinity of I975S mutant

    PMID:30988386

    Open questions at the time
    • Order of recruitment between C2CD3 and Talpid3 not fully resolved
    • Whether CEP120 scaffolding is direct or involves additional intermediaries
  8. 2021 High

    Showing that CEP120 recruits KIAA0753 to centrioles and that Joubert-syndrome-associated CEP120 mutants failing in this recruitment cause impaired granule neuron differentiation connected CEP120-KIAA0753 to the neuropathology of Joubert syndrome.

    Evidence Co-IP; in vivo Cep120 depletion with mutant rescue in cerebellar granule neuron progenitors

    PMID:34711653

    Open questions at the time
    • Which CEP120 domain mediates KIAA0753 binding not mapped
    • Whether KIAA0753 recruitment is required in non-neural tissues unknown
  9. 2023 High

    Conditional deletion of Cep120 in kidney stromal mesenchyme causing mitotic delay, apoptosis via mitotic surveillance, and altered Wnt/Hh/TGF-β signaling extended CEP120's in vivo importance to renal interstitial lineage specification and fibrosis susceptibility.

    Evidence Conditional KO in mouse kidney stromal mesenchyme; lineage tracing; signaling pathway analysis after injury

    PMID:38177914

    Open questions at the time
    • Whether renal phenotype is cilia-dependent or reflects centrosome-intrinsic mitotic defects not distinguished
    • Relevance to human kidney disease not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanism by which CEP120 inhibits PCM accumulation at daughter centrioles, the functional role of the C2C domain, and how disease mutations differentially affect centriole elongation versus appendage assembly versus ciliogenesis remain unresolved.
  • No reconstitution of PCM-inhibitory activity
  • C2C domain function untested by mutagenesis or structure-guided experiments
  • No systematic genotype–phenotype correlation across all known CEP120 disease mutations

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005815 microtubule organizing center 5
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-162582 Signal Transduction 2
Partners
C2CD3CPAPKIAA0753KIAA1081TACC3

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 CEP120 (Cep120) localizes to centrosomes, interacts with TACC (transforming acidic coiled-coil) proteins, and is required for interkinetic nuclear migration (INM) and neural progenitor self-renewal in the developing neocortex; silencing Cep120 or TACCs impairs both INM and progenitor self-renewal. In utero electroporation-mediated shRNA knockdown in mouse neocortex; co-immunoprecipitation of Cep120 with TACCs; immunofluorescence for centrosomal localization Neuron High 17920017
2010 Cep120 (Ccdc100) is asymmetrically localized to the daughter centriole in cycling cells, with this asymmetry relieved upon new centriole assembly; it is required for centriole duplication in cycling cells, centriole amplification in multiciliated cells (MTECs), and centriole overduplication in S-phase-arrested cells. FRAP revealed two kinetically distinct pools of Cep120 at the centriole. Immunofluorescence, siRNA knockdown, FRAP (fluorescence recovery after photobleaching) in cycling cells and mouse tracheal epithelial cells (MTECs) The Journal of cell biology High 20956381
2013 CEP120 directly interacts with CPAP and positively regulates centriole elongation; CEP120 levels are cell-cycle regulated (peak at S/G2/M). Overexpression of either CEP120 or CPAP induces overly long centrioles; depletion of CEP120 inhibits CPAP-induced elongation and vice versa. CEP120 contains an N-terminal microtubule-binding domain (disrupted by K76A mutation), a C-terminal dimerization domain, and a centriolar localization domain; the K76A microtubule-binding mutant suppresses elongated centriole formation. Co-immunoprecipitation, siRNA knockdown, overexpression, mutagenesis (CEP120-K76A), immunofluorescence, cell-cycle synchronization The Journal of cell biology High 23857771
2014 Cep120 interacts with Talpid3 (Ta3), and this interaction mediates asymmetric localization of Cep120 to the daughter centriole. Conditional knockout of Cep120 in the CNS causes failed centriole duplication, loss of ciliogenesis, impaired Hedgehog pathway activity in cerebellar granule neuron progenitors (GNPs), hydrocephalus, and cerebellar hypoplasia. Co-immunoprecipitation of Cep120 with Talpid3; conditional Cep120 knockout in mouse CNS; immunofluorescence for centriole and cilia markers; Hedgehog signaling assays PloS one High 25251415
2018 CEP120 contains three consecutive 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 surface patch on C2A mediates this interaction. C2 domains lack classical calcium- and phospholipid-binding activities. X-ray crystallography; in vitro tubulin/microtubule binding assays; mutagenesis of positively charged residues; microtubule polymerization assay Journal of structural biology High 29398280
2018 X-ray crystallography confirmed that CEP120 contains three C2 domains; ciliopathy point mutations V194A (Joubert syndrome) and A199P (Jeune JATD) reduce thermostability of the second C2 domain (C2B) by targeting hydrophobic core residues. Genome-engineered cells homozygous for these mutations show reduced CEP120 protein levels, compromised recruitment of distal centriole markers, and deficient cilia formation, with largely normal centriole numbers. X-ray crystallography; thermal shift/stability assays; CRISPR/Cas9 genome engineering of disease mutations; immunofluorescence for distal centriole and cilia markers Cell reports High 29847808
2018 In quiescent cells, Cep120 plays a critical inhibitory role at daughter centrioles to prevent premature PCM accumulation (pericentrin, Cdk5Rap2, ninein, Cep170). Depletion of Cep120 in quiescent cells causes elevated PCM, increased microtubule-nucleation activity, aberrant dynein-dependent trafficking of centrosomal proteins, dispersal of centriolar satellites, and defective cilia assembly and signaling. siRNA knockdown in quiescent mouse and human cells; immunofluorescence for PCM components; microtubule nucleation assays; ciliogenesis assays eLife High 29741480
2019 CEP120 interacts with C2CD3 and Talpid3 and is required for recruitment of these proteins to the distal ends of centrioles for centriole appendage assembly and ciliogenesis. CEP120 knockout produces short centrioles lacking distal and subdistal appendages. The disease-associated mutant CEP120-I975S has reduced affinity for C2CD3 binding, perturbing cilia assembly. CRISPR/Cas9 knockout in p53-deficient RPE1 cells; co-immunoprecipitation; immunofluorescence for appendage markers (C2CD3, Talpid3); ciliogenesis assay; binding affinity assessment of I975S mutant Scientific reports High 30988386
2020 A CEP120 variant (rs2303720, p.Arg947His) impairs spindle microtubule nucleation efficiency and increases aneuploidy incidence in mouse oocytes undergoing meiotic maturation, linking CEP120 to meiotic spindle function. Ectopic expression of CEP120:p.Arg947His in mouse oocytes; spindle microtubule nucleation assays; aneuploidy scoring Human reproduction Medium 32772081
2021 CEP120 recruits KIAA0753 (a Joubert syndrome-associated protein) to centrioles; loss of this interaction leads to accumulation of granule neuron progenitors (GNPs) in the cerebellar germinal zone and impaired neuronal differentiation. JS-associated CEP120 mutants that hinder KIAA0753 recruitment fail to rescue this defect. Co-immunoprecipitation of CEP120 with KIAA0753; in vivo Cep120 depletion; rescue experiments with wild-type vs. JS-associated CEP120 mutants; immunofluorescence and cell cycle exit analyses Genes & development High 34711653
2023 Conditional deletion of Cep120 in kidney stromal mesenchyme causes delayed mitosis, activation of the mitotic surveillance pathway leading to apoptosis, and altered Wnt and Hedgehog signaling, resulting in reduction of interstitial lineages (pericytes, fibroblasts, mesangial cells), hypoplastic kidneys, and sensitization to fibrosis via enhanced TGF-β/Smad3-Gli2 signaling after renal injury. Conditional Cep120 knockout in mouse stromal mesenchyme; immunofluorescence and flow cytometry for lineage markers; signaling pathway analysis (Wnt, Hh, TGF-β/Smad3-Gli2); mitotic surveillance assay EMBO reports High 38177914

Source papers

Stage 0 corpus · 16 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 99 23857771
2010 Cep120 is asymmetrically localized to the daughter centriole and is essential for centriole assembly. The Journal of cell biology 98 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 34 30988386
2020 Exome sequencing links CEP120 mutation to maternally derived aneuploid conception risk. Human reproduction (Oxford, England) 20 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 17 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 12 33486889
2018 Cep120 promotes microtubule formation through a unique tubulin binding C2 domain. Journal of structural biology 11 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