Date: 2026-07-18
Automated deep-research providers were attempted before this manual synthesis. Falcon/Edison returned HTTP 402 and the Perplexity-lite fallback returned HTTP 401, so this file records a source-grounded manual synthesis rather than masquerading as provider output.
CEP152 is a non-enzymatic, coiled-coil scaffold of the pericentriolar material and proximal parent-centriole region. Together with CEP63 it builds a higher-order cylindrical assembly. Its N-terminal PLK4-binding region recruits and positions the master centriole-biogenesis kinase PLK4, while another region engages CPAP/CENPJ. This spatial adaptor function is required for procentriole initiation and normal centrosome duplication. The direct evidence is unusually convergent: depletion phenotypes, rescue/mutant analysis, interaction mapping, super-resolution localization, biochemistry, and structural reconstitution all support the same mechanism.
CEP152 is reused in specialized centriole-amplification contexts. Mouse multiciliated-cell work places Cep152 at DEUP1-positive deuterosomes and shows that DEUP1 assemblies concentrate Cep152 and Plk4. This supports the transferred human annotations as plausible, specialized biology, while leaving direct human tissue evidence as a gap.
A separate 2022 study identifies CEP152 as both an APC/C interaction partner and substrate at centrosomes/spindle poles. Timed CEP152 ubiquitylation dismantles an inhibitory CEP152-CEP63-CEP57 complex, freeing CEP57 to recruit pericentrin and support microtubule nucleation and spindle assembly. This is a direct, annotation-worthy mitotic role, but it does not make CEP152 a ubiquitin ligase or a microtubule nucleator.
The initial human functional studies defined CEP152 as a scaffold rather than an enzyme. Drosophila Asterless and human CEP152 use separated regions to bind PLK4 and Sas-4/CPAP PMID:20852615 Human depletion blocks duplication PMID:20852615
Independent work directly mapped human CEP152 binding to the PLK4 cryptic Polo-box and showed that CEP152 loss prevents PLK4 recruitment and centriole duplication PMID:21059844 PMID:21059844 A companion human/Xenopus study similarly found that depletion prevents normal and PLK4-driven centriole formation PMID:21059850 and mapped the interaction to the N-terminal 217 residues PMID:21059850
Super-resolution work refined this into a scaffold-switch model: PLK4 moves from an inner CEP192 ring to an outer CEP152 ring as the daughter centriole matures PMID:24997597 A CEP152 mutation that weakens PLK4 binding impairs procentriole formation and chromosome segregation PMID:24997597
Biochemical and structural studies then showed that CEP63 and CEP152 form a heterotetrameric coiled-coil building block and self-assemble into a PLK4-recruiting cylinder PMID:30858376 Disrupting the assembly blocks PLK4-mediated duplication PMID:30858376 A later analysis directly resolved the stepwise assembly PMID:37433832 and linked assembly-defective mutants to abnormal CEP152 organization, PLK4 positioning, and duplication PMID:37433832
CEP152 participates in a centrosomal microcephaly-protein hierarchy with CDK5RAP2, WDR62, and CEP63 PMID:26297806 The proteins interact and are interdependent for centrosomal localization PMID:26297806 This network provides biological context for the CEP131 interaction but does not convert every physical contact into a distinct molecular activity.
Multiple microscopy and proteomics studies independently support centrosome, centriole, procentriole, and pericentriolar-material localization. The PMID:22020124 cached abstract foregrounds STIL and CPAP and does not describe the CEP152 assay; because the full text was not locally available, the associated experimental centriole annotation was retained in deference to curator access and because the location is strongly corroborated by independent direct studies.
In a mouse oviduct multiciliated-cell model, DEUP1 assemblies spatially concentrate Cep152 and Plk4 PMID:33658185 Mouse tracheal epithelial cells show Cep152 at both parent centrioles and deuterosomes PMID:33627667 This supports the orthology-based human deuterosome and multiciliated epithelial differentiation annotations as non-core/context-specific. The evidence does not establish that every human CEP152 isoform or every multiciliated cell uses an identical route.
APC/C is recruited to spindle poles through CEP152, which is both an interaction partner and substrate PMID:34878135 Timed ubiquitylation of CEP152 releases CEP57 from an inhibitory CEP152-CEP63-CEP57 complex, permitting CEP57-pericentrin interaction and microtubule nucleation PMID:34878135 This supports mitotic spindle assembly as a new biological-process annotation. The mechanistic direction is temporal and complex-dependent, so a simple positive-regulation-of-microtubule-nucleation annotation could obscure the initial inhibitory sequestration and was not proposed.
Pathogenic biallelic CEP152 variants cause primary microcephaly and Seckel syndrome. A premature-termination allele prevented centrosome localization in transfected cells PMID:20598275 The disease association supports the physiological importance of centrosomal localization but does not itself identify a separate molecular function.
UniProt lists four alternative products. None of the reviewed studies supplied sufficiently clear isoform-resolved functional comparisons to justify functional-isoform classes or isoform-specific GO decisions.
The local PANTHER PAINT table (interpro/panther/PTHR10337/PTHR10337-paint.tsv) assigns centrosome and centriole-replication functions at node PTN000818649, with human CEP152 and mouse Cep152 among the evidence sources. This node is specific to the CEP152 lineage even though the broader family contains unrelated SHC subfamilies. The two IBA annotations are therefore accepted: their propagation scope is coherent, and the functions are independently established experimentally in human CEP152. Because O94986 is itself a PAINT seed, the IBA records are corroborative rather than independent evidence.
protein-macromolecule adaptor activity (GO:0030674).centriole replication (GO:0007099), with centrosome duplication as the broader process.mitotic spindle assembly (GO:0090307).protein binding should not be retained as the final functional representation. PLK4 records can be made specific as protein kinase binding; the CENPJ record is best represented by adaptor activity; other interaction-only records remain biologically plausible but are over-annotated as GO molecular functions.