CEP152

UniProt ID: O94986
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

CEP152 is a large coiled-coil scaffold of the pericentriolar material that organizes centriole biogenesis. Together with CEP63 it forms a higher-order cylindrical assembly around the proximal region of a parent centriole. An N-terminal PLK4-binding region recruits and spatially organizes the master centriole-duplication kinase PLK4, while CEP152 also engages CPAP/CENPJ and other centrosomal factors to support procentriole initiation. In specialized multiciliated cells, CEP152 is recruited to DEUP1-positive deuterosomes and supports large-scale centriole amplification. During mitosis, APC/C-dependent turnover of CEP152 releases CEP57 from a CEP152-CEP63-CEP57 complex, enabling pericentrin recruitment and normal spindle assembly. Biallelic CEP152 variants cause primary microcephaly 9 and Seckel syndrome 5.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0007099 centriole replication
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT node PTN000818649 is CEP152-specific, and centriole replication is independently established by human depletion and PLK4-recruitment experiments.
Reason: The phylogenetic inference has coherent scope, although O94986 itself is one of its experimental seeds.
GO:0005813 centrosome
IBA
GO_REF:0000033
ACCEPT
Summary: The CEP152-specific PAINT node and extensive human microscopy/biochemistry both place active CEP152 at the centrosome.
Reason: The propagated location agrees with multiple independent direct human studies.
GO:0005813 centrosome
IEA
GO_REF:0000044
ACCEPT
Summary: UniProt's centrosome location is supported by numerous direct human localization and loss-of-function studies.
GO:0005814 centriole
IEA
GO_REF:0000044
ACCEPT
Summary: UniProt's centriole location agrees with super-resolution placement of CEP152 around the proximal parent/daughter centriole region.
GO:0005515 protein binding
IPI
PMID:21059844
Cep152 acts as a scaffold for recruitment of Plk4 and CPAP t...
MODIFY
Summary: Direct CEP152-PLK4 interaction is well supported, but generic protein binding obscures the informative kinase-binding relationship.
Reason: Replace the uninformative generic interaction term with protein kinase binding.
Proposed replacements: protein kinase binding
GO:0005515 protein binding
IPI
PMID:24997597
Molecular basis for unidirectional scaffold switching of hum...
MODIFY
Summary: Structural and cellular experiments establish PLK4 binding by CEP152, for which protein kinase binding is the more informative term.
Reason: Replace generic protein binding with the specific supported kinase-binding activity.
Proposed replacements: protein kinase binding
GO:0005515 protein binding
IPI
PMID:26188084
STIL binding to Polo-box 3 of PLK4 regulates centriole dupli...
MODIFY
Summary: The reported interactor is the protein kinase PLK4, so the broad binding term can be made functionally specific.
Reason: Use protein kinase binding for the experimentally detected PLK4 interaction.
Proposed replacements: protein kinase binding
GO:0005515 protein binding
IPI
PMID:26297806
Centriolar satellites assemble centrosomal microcephaly prot...
MARK AS OVER ANNOTATED
Summary: CEP131 association is plausible within the centrosomal microcephaly-protein network, but generic protein binding does not describe a biological activity.
Reason: Retain the interaction as evidence in the literature record, not as an informative GO molecular function.
GO:0005515 protein binding
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz...
MODIFY
Summary: The quantitative interactome detects CEP152 with PLK4; kinase binding is more informative than generic protein binding.
Reason: Replace the generic interaction term with protein kinase binding.
Proposed replacements: protein kinase binding
GO:0005515 protein binding
IPI
PMID:26638075
A Dynamic Protein Interaction Landscape of the Human Centros...
MODIFY
Summary: The centrosome-cilium interaction map supports CEP152 association with PLK4, a relationship captured more precisely as kinase binding.
Reason: Replace generic protein binding with the specific PLK4-binding molecular function.
Proposed replacements: protein kinase binding
GO:0005515 protein binding
IPI
PMID:35709258
Spatial centrosome proteome of human neural cells uncovers d...
MARK AS OVER ANNOTATED
Summary: MOV10 was recovered in a neural-cell centrosome proximity/interactome study, but the generic binding term supplies no mechanistic function for CEP152.
Reason: The high-throughput association is contextual evidence and does not warrant an uninformative binding-function annotation.
GO:0007099 centriole replication
IEA
GO_REF:0000107
ACCEPT
Summary: Mouse-to-human orthology transfer is appropriate because direct human depletion studies independently show a requirement for centriole replication.
GO:0098535 de novo centriole assembly involved in multi-ciliated epithelial cell differentiation
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Mouse multiciliated-cell studies support a conserved CEP152 role in deuterosome-associated centriole amplification, but direct human evidence is limited.
Reason: Retain as a credible specialized epithelial context rather than the universal core function.
GO:0098536 deuterosome
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Mouse Cep152 localizes to DEUP1-positive deuterosomes during multiciliated-cell differentiation; the human call is an orthology transfer.
Reason: Retain as a specialized multiciliated-cell location, distinct from the core parent-centriole/PCM site.
GO:0030674 protein-macromolecule adaptor activity
IDA
PMID:20852615
Asterless is a scaffold for the onset of centriole assembly.
ACCEPT
Summary: CEP152 uses separated regions to engage PLK4 and CPAP/CENPJ, directly supporting a non-catalytic adaptor/scaffold activity.
Supporting Evidence:
file:human/CEP152/CEP152-deep-research-manual.md
CEP152 is a non-enzymatic, coiled-coil scaffold of the pericentriolar material and proximal parent-centriole region.
GO:0005813 centrosome
IPI
PMID:30858376
Molecular architecture of a cylindrical self-assembly at hum...
ACCEPT
Summary: Biochemical assembly with the centrosomal scaffold CEP63 and cell imaging support centrosomal localization of the complex.
GO:0007099 centriole replication
NAS
PMID:30858376
Molecular architecture of a cylindrical self-assembly at hum...
ACCEPT
Summary: The cited study shows that disrupting CEP63-CEP152 self-assembly abrogates PLK4-mediated centriole duplication.
GO:0051298 centrosome duplication
NAS
PMID:30858376
Molecular architecture of a cylindrical self-assembly at hum...
ACCEPT
Summary: Higher-order CEP63-CEP152 assembly is required for the PLK4-dependent centriole pathway that underlies centrosome duplication.
GO:0005813 centrosome
IDA
GO_REF:0000052
ACCEPT
Summary: Human Protein Atlas immunofluorescence supports centrosome localization, consistent with gene-specific microscopy studies.
GO:0036064 ciliary basal body
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: Immunofluorescence supports basal-body localization, consistent with the centriole-derived nature of basal bodies.
Reason: Basal-body localization is a differentiated ciliary context rather than CEP152's defining centriole-duplication site.
GO:0007099 centriole replication
IDA
PMID:21059844
Cep152 acts as a scaffold for recruitment of Plk4 and CPAP t...
ACCEPT
Summary: CEP152 depletion prevents centrosomal PLK4 recruitment and normal or PLK4-induced centriole duplication.
GO:0120098 procentriole
IDA
PMID:24997597
Molecular basis for unidirectional scaffold switching of hum...
ACCEPT
Summary: Super-resolution imaging places CEP152 in the outer ring assembled around the daughter centriole/procentriole site.
GO:0120099 procentriole replication complex
IPI
PMID:24997597
Molecular basis for unidirectional scaffold switching of hum...
ACCEPT
Summary: CEP152 is a structural member of the PLK4-recruiting procentriole replication scaffold demonstrated by interaction and localization experiments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-2574840
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-2574845
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-3000310
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-3000319
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380272
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380283
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380294
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380303
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380311
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380316
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380455
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-380508
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5617816
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626220
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626223
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626227
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626228
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626681
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5626699
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5638009
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8853405
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8853419
KEEP AS NON CORE
Summary: Reactome places CEP152 in a soluble cytosolic pool for this event; the location is plausible but broad and is not an independent localization experiment.
GO:0005515 protein binding
IPI
PMID:35849559
The ciliopathy protein CCDC66 controls mitotic progression a...
MARK AS OVER ANNOTATED
Summary: Overexpression co-immunoprecipitation supports association with CCDC66, but generic protein binding is not an informative CEP152 activity.
Reason: Preserve the interaction as supporting context rather than a generic GO molecular function.
GO:0005813 centrosome
IDA
PMID:35849559
The ciliopathy protein CCDC66 controls mitotic progression a...
ACCEPT
Summary: The CCDC66 study directly visualizes CEP152 at centrosomes, consistent with extensive independent localization evidence.
GO:0005814 centriole
IDA
PMID:32060285
CEP44 ensures the formation of bona fide centriole wall, a r...
ACCEPT
Summary: The CEP44 study uses CEP152 as the PLK4-recruiting centriolar adaptor and directly supports centriolar localization.
GO:0005814 centriole
IDA
PMID:22020124
The human microcephaly protein STIL interacts with CPAP and ...
ACCEPT
Summary: The cached abstract foregrounds STIL/CPAP rather than the CEP152 assay, but the curator's full-text annotation is strongly corroborated by independent CEP152 localization studies.
Reason: Do not overrule an experimental curator annotation from an abstract-only cache when the biological conclusion is independently secure.
GO:0000242 pericentriolar material
IDA
PMID:26337392
MDM1 is a microtubule-binding protein that negatively regula...
ACCEPT
Summary: Microscopy resolves CEP152 as a ring in the pericentriolar material around centrioles, matching its structural scaffold role.
GO:0005814 centriole
IDA
PMID:26337392
MDM1 is a microtubule-binding protein that negatively regula...
ACCEPT
Summary: Direct imaging in the cited study supports CEP152 localization at the centriole/pericentriolar interface.
GO:0007099 centriole replication
ISS
GO_REF:0000024
ACCEPT
Summary: Curator sequence-similarity transfer is consistent with conserved vertebrate CEP152 architecture and direct human duplication phenotypes.
GO:0098535 de novo centriole assembly involved in multi-ciliated epithelial cell differentiation
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Sequence-similarity transfer from vertebrate CEP152 is consistent with direct mouse multiciliated-cell evidence.
Reason: Retain as a specialized multiciliated epithelial role, not the ubiquitous core process.
GO:0098536 deuterosome
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: The inferred deuterosome localization agrees with direct mouse Cep152 localization during centriole amplification.
Reason: Retain as a specialized multiciliated-cell location.
GO:0005813 centrosome
IDA
PMID:21399614
Novel asymmetrically localizing components of human centroso...
ACCEPT
Summary: Complementary centrosome proteomics and localization experiments identify CEP152 as a human centrosomal component.
GO:0005515 protein binding
IPI
PMID:20852615
Asterless is a scaffold for the onset of centriole assembly.
MODIFY
Summary: CEP152 binds CENPJ/CPAP through a region distinct from its PLK4-binding region, establishing a two-ended molecular scaffold.
Reason: The mechanistic result is better represented by the existing protein-macromolecule adaptor activity annotation.
GO:0005515 protein binding
IPI
PMID:21131973
CEP152 is a genome maintenance protein disrupted in Seckel s...
MARK AS OVER ANNOTATED
Summary: The CINP interaction may contribute to the reported genome-maintenance phenotype, but generic protein binding is not an informative molecular function.
Reason: The accessible abstract does not establish a more specific CEP152 activity for this contact; do not overinterpret it.
GO:0005813 centrosome
IDA
PMID:21131973
CEP152 is a genome maintenance protein disrupted in Seckel s...
ACCEPT
Summary: The Seckel-syndrome study identifies CEP152 as a centrosomal protein, consistent with direct localization and disease-allele mislocalization evidence.
GO:0019901 protein kinase binding
IPI
PMID:20852615
Asterless is a scaffold for the onset of centriole assembly.
ACCEPT
Summary: The CEP152 N-terminal region binds the cryptic Polo-box of the protein kinase PLK4, directly supporting kinase binding.
GO:0019901 protein kinase binding
IPI
PMID:21059844
Cep152 acts as a scaffold for recruitment of Plk4 and CPAP t...
ACCEPT
Summary: Direct interaction mapping establishes binding between CEP152's N terminus and the PLK4 cryptic Polo-box.
GO:0051298 centrosome duplication
IMP
PMID:20852615
Asterless is a scaffold for the onset of centriole assembly.
ACCEPT
Summary: CEP152 depletion causes centrosome-duplication failure and overexpression drives amplification, directly supporting the process annotation.
GO:0090307 mitotic spindle assembly
IMP
PMID:34878135
The APC/C targets the Cep152-Cep63 complex at the centrosome...
NEW
Summary: APC/C-dependent turnover of centrosomal CEP152 releases CEP57 for pericentrin recruitment; stabilizing an APC/C-resistant CEP152 mutant reduces microtubule nucleation and increases chromosome mis-segregation.
Reason: This direct human-cell perturbation study establishes a CEP152-dependent mitotic spindle-assembly mechanism that is absent from the current GOA.
Supporting Evidence:
PMID:34878135
This negative feedback loop controlling APC/C localization is required for proper assembly of the mitotic spindle.

Core Functions

CEP152 is a protein-macromolecule adaptor at the pericentriolar material. It co-assembles with CEP63 into a cylindrical scaffold around the parent centriole, recruits and positions PLK4 through its N-terminal region, and engages CPAP/CENPJ to support procentriole initiation and centriole replication.

Supporting Evidence:
  • PMID:20852615
    Here we show that the centriolar protein Asterless (Asl; human orthologue CEP152) provides a conserved molecular platform, the amino terminus of which interacts with the cryptic Polo box of Plk4 whereas the carboxy terminus interacts with the centriolar protein Sas-4 (CPAP in humans).
  • PMID:21059844
    Our results suggest that Cep152 recruits Plk4 and CPAP to the centrosome to ensure a faithful centrosome duplication process.
  • PMID:30858376
    Mutations disrupting the self-assembly abrogate Plk4-mediated centriole duplication.
  • PMID:37433832
    Mutants defective in Cep63β€’Cep152 heterotetramer formation displayed crippled pericentriolar Cep152 organization, polo-like kinase 4 (Plk4) relocalization to the procentriole assembly site, and Plk4-mediated centriole duplication.

During mitosis, centrosomal CEP152 organizes a temporally regulated complex with CEP63 and CEP57 and recruits APC/C. APC/C-dependent CEP152 ubiquitylation releases CEP57 so that it can bind pericentrin, promoting microtubule nucleation and proper mitotic spindle assembly.

Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • PMID:34878135
    Recruitment of the APC/C to spindle poles requires the centrosomal protein Cep152, and we identified Cep152 as both an APC/C interaction partner and an APC/C substrate.
  • PMID:34878135
    The APC/C-mediated ubiquitylation of Cep152 at the centrosome releases Cep57 from this inhibitory complex and enables its interaction with pericentrin, a critical step in promoting microtubule nucleation.

References

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Suggested Questions for Experts

Q: How is the CEP63-CEP152 centriole-duplication scaffold remodeled at mitotic entry so that CEP57 is released to engage pericentrin without compromising centriole integrity?

Q: Is CEP152 directly required at deuterosomes in human multiciliated epithelia, and how much centriole amplification proceeds through deuterosomes versus parent-centriole-associated or deuterosome-independent routes?

Q: Do the four UniProt CEP152 isoforms differ in centrosomal targeting, partner selection, cell-cycle turnover, or tissue-specific centriole-amplification functions?

Suggested Experiments

Experiment: Engineer endogenous APC/C-resistant and separation-of-function CEP152 alleles in diploid human cells, then combine live-cell imaging of CEP57, pericentrin, microtubule nucleation, and chromosome segregation with rescue by wild-type CEP152 to resolve the mitotic handoff mechanism.

Experiment: Use CRISPR depletion and domain-specific rescue of CEP152 in differentiated human airway organoids, with quantitative imaging of DEUP1, PLK4, nascent centrioles, basal bodies, and cilia, to test the transferred deuterosome and multiciliated-cell annotations directly in human tissue.

Experiment: Compare endogenous isoform-specific tagging and rescue across proliferating cells and multiciliated-cell models, coupled to interaction proteomics, to determine whether CEP152 splice products have distinct localization or scaffold functions.

Deep Research

Manual

(CEP152-deep-research-manual.md)

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πŸ“š Additional Documentation

Notes

(CEP152-notes.md)

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