Affinage

CDK5RAP2

CDK5 regulatory subunit-associated protein 2 · UniProt Q96SN8

Length
1893 aa
Mass
215.0 kDa
Annotated
2026-04-28
83 papers in source corpus 28 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDK5RAP2 (CEP215) is a pericentriolar material scaffold protein that organizes centrosome structure, activates microtubule nucleation, and maintains centriole engagement, with loss-of-function mutations causing autosomal recessive primary microcephaly (PMID:15793586, PMID:20460369). Its CM1/γ-TuNA domain binds GCP2 within the γ-tubulin ring complex (γ-TuRC), inducing partial ring closure toward microtubule geometry to stimulate nucleation both at centrosomes and acentrosomal sites; this activation is enhanced by LRRK1-mediated phosphorylation at Ser140, which strengthens γ-tubulin binding and promotes astral microtubule formation for spindle orientation (PMID:21135143, PMID:39321808, PMID:26192437). CDK5RAP2 is recruited to centrosomes via interactions with pericentrin, AKAP450 (through its CM2-like motif), and Cep192, and is dynamically delivered by dynein-dynactin along microtubules; it additionally binds EB1 to track microtubule plus-ends and directly recruits the minus-end motor HSET for spindle pole focusing and centrosome clustering (PMID:20466722, PMID:23874654, PMID:19553473, PMID:26987684, PMID:33376154). Beyond its structural roles, CDK5RAP2 maintains centriole engagement to restrict centriole reduplication, enforces centrosome cohesion through a pericentrin-dependent mechanism, and functions in transcriptional regulation of mitotic checkpoint genes (BUBR1, MAD2) and the centromeric histone CENP-A (PMID:20627074, PMID:18042621, PMID:19282672, PMID:33725591).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2005 High

    Identification of CDK5RAP2 as a centrosomal protein whose loss causes primary microcephaly established the first link between a pericentriolar scaffold and human brain size determination.

    Evidence Homozygosity mapping and mutation identification in microcephaly families combined with immunolocalization at mitotic spindle poles

    PMID:15793586

    Open questions at the time
    • Molecular function at centrosomes unknown
    • How centrosomal defects translate to reduced neuron number not addressed
  2. 2007 High

    Demonstrating that CDK5RAP2 tethers the γ-TuRC to centrosomes via a conserved short motif answered how the nucleation machinery is anchored at the pericentriolar material, and separately revealed a role in centrosome cohesion mediated through pericentrin.

    Evidence Co-immunoprecipitation of CDK5RAP2–γ-TuRC, RNAi-mediated loss causing γ-tubulin delocalization and anastral spindles; separate RNAi demonstrating centrosome splitting phenotype

    PMID:17959831 PMID:18042621

    Open questions at the time
    • Whether CDK5RAP2 directly activates (not just recruits) γ-TuRC was untested
    • Structural basis of γ-TuRC interaction undefined
  3. 2009 High

    Discovery of CDK5RAP2 as a microtubule plus-end tracker via EB1 binding and as a transcriptional regulator of spindle checkpoint genes (BUBR1, MAD2) expanded its functional repertoire beyond a passive centrosomal scaffold.

    Evidence Direct in vitro binding to EB1 with mutagenesis abolishing interaction; ChIP showing CDK5RAP2 on BUBR1/MAD2 promoters

    PMID:19282672 PMID:19553473

    Open questions at the time
    • How a centrosomal scaffold accesses gene promoters mechanistically unclear
    • Functional significance of plus-end tracking versus centrosomal pool not dissected
  4. 2010 High

    A cluster of studies in 2010 established that CDK5RAP2 directly activates γ-TuRC nucleation via its γ-TuNA domain, maintains centriole engagement to prevent reduplication, links centrosomes to spindle poles through its CNN1/CNN2 domains, localizes to the Golgi via pericentrin/AKAP450, and is required in vivo for neural progenitor proliferation.

    Evidence In vitro nucleation assay with purified γ-TuRC and γ-TuNA domain; Cdk5rap2 mutant mouse showing centriole amplification by EM; DT40 domain deletions; Golgi localization mutational mapping; Cdk5rap2-an/an mouse microcephaly model

    PMID:20139723 PMID:20368616 PMID:20460369 PMID:20466722 PMID:20471352 PMID:20627074 PMID:21135143

    Open questions at the time
    • Structural mechanism of γ-TuRC activation by γ-TuNA unresolved
    • How centriole engagement is physically maintained unknown
    • Whether centrosomal vs. Golgi pools serve distinct functions in neural progenitors untested
  5. 2013 Medium

    Showing that CDK5RAP2 is dynamically delivered to centrosomes via dynein-dynactin along microtubules explained how steady-state centrosomal levels are maintained and revealed the protein's rapid exchange kinetics.

    Evidence FRAP live imaging, Co-IP with dynein light chain 8, dynein-dynactin inhibition reducing centrosomal CDK5RAP2

    PMID:23874654

    Open questions at the time
    • Direct binding to dynein heavy chain not demonstrated
    • Regulation of CDK5RAP2 turnover at centrosomes during cell cycle transitions not resolved
  6. 2014 High

    Defining the Cep68–CDK5RAP2–pericentrin complex and its PLK1/SCF(βTrCP)-mediated disassembly revealed the mechanism by which CDK5RAP2 is removed from PCM to permit centriole separation, while the CDK5RAP2–pericentrin interaction was shown to be essential for centrosome maturation independently of γ-tubulin binding.

    Evidence Mass spectrometry-identified complex, phospho-dependent ubiquitination of Cep68, knockdown-rescue with domain mutants

    PMID:24466316 PMID:25503564

    Open questions at the time
    • Whether Cep68 degradation is the sole trigger for CDK5RAP2 removal is uncertain
    • Temporal ordering of PCNT cleavage versus Cep68 degradation not fully resolved
  7. 2015 High

    Identifying LRRK1-mediated phosphorylation of CDK5RAP2 at Ser140 as the activating signal for γ-tubulin binding established the PLK1→LRRK1→CDK5RAP2 kinase cascade that controls astral microtubule nucleation for spindle orientation.

    Evidence In vitro kinase assay, Ser140 phospho-mutant analysis, rescue experiments showing spindle orientation defects

    PMID:26192437

    Open questions at the time
    • Whether additional phosphorylation sites on CDK5RAP2 modulate nucleation unknown
    • Phosphatase(s) opposing Ser140 phosphorylation not identified
  8. 2016 High

    Identification of CDK5RAP2 as a direct binding partner of the minus-end motor HSET explained how centrosomes recruit the pole-focusing motor and how cancer cells with supernumerary centrosomes cluster them.

    Evidence MS-based proteomics, targeted domain deletion, validation in patient-derived cells

    PMID:26987684

    Open questions at the time
    • Stoichiometry of CDK5RAP2–HSET complex at centrosomes not determined
    • Whether HSET recruitment depends on CDK5RAP2 phosphorylation state untested
  9. 2017 High

    Genetic epistasis between ASPM and CDK5RAP2 revealed a redundant spindle pole-focusing function that is independent of CDK5RAP2's known γ-TuRC activation and HSET recruitment roles.

    Evidence CRISPR knockout of ASPM combined with auxin-inducible CDK5RAP2 depletion, live-cell imaging

    PMID:28883092

    Open questions at the time
    • Molecular basis of the ASPM-redundant pole-focusing mechanism unknown
    • Whether this redundancy operates in neural progenitors untested
  10. 2020 High

    Studies showed that CDK5RAP2 and pericentrin can self-organize into acentriolar PCM foci that become essential for spindle assembly when centrioles are absent, and that a mitosis-specific N-terminal domain of CDK5RAP2 interacts with Cep192 and phospho-Aurora A for centrosome maturation.

    Evidence Centrinone-induced centriole depletion combined with PCM protein knockout; domain mapping and Co-IP of 215N with Cep192/pAurA

    PMID:33170211 PMID:33376154

    Open questions at the time
    • How PCM self-organization is templated in the absence of centrioles is structurally unresolved
    • Whether Cep192 interaction is direct or bridged by Aurora A unclear
  11. 2021 Medium

    CDK5RAP2 was found to occupy the CENP-A promoter and regulate its transcription, and separately to modulate cell senescence through a GSK3β/β-catenin/WIP1 axis, broadening its roles beyond centrosome biology.

    Evidence ChIP for CENP-A promoter occupancy plus CENP-A rescue of chromosome segregation defects; Co-IP with GSK3β and senescence assays in Cdk5rap2-an/an mouse cells

    PMID:33725591 PMID:34930892

    Open questions at the time
    • How a predominantly centrosomal protein accesses chromatin promoters mechanistically unexplained
    • Whether senescence phenotype is cell-autonomous or secondary to mitotic errors uncertain
  12. 2024 High

    Cryo-EM of the γ-TuRC bound to CDK5RAP2's CM1 domain revealed that CM1 binds GCP2 and induces partial ring constriction toward 13-protofilament geometry, providing the long-sought structural mechanism for γ-TuRC activation; separately, Arl2 GTPase was identified as an upstream regulator that positions CDK5RAP2 at centrosomes for cortical neurogenesis.

    Evidence Cryo-EM structure of porcine γ-TuRC–CM1 complex plus single-molecule nucleation assays; Co-IP and PLA for Arl2–Cdk5rap2 with in utero rescue experiments

    PMID:39137170 PMID:39321808

    Open questions at the time
    • Full-length CDK5RAP2 structure on γ-TuRC not determined
    • Whether Arl2 GTPase activity directly regulates CDK5RAP2 binding affinity unknown
    • Complete set of conformational changes needed for full ring closure not captured
  13. 2025 Medium

    Material-state analysis showed CDK5RAP2 transitions from a solid-like suppressed state in interphase to a dynamic state in mitosis controlled by PCNT interaction, and in vitro reconstitution demonstrated that CDK5RAP2 alone is sufficient to form micron-scale scaffolds that recruit and activate γ-TuRCs for aster formation.

    Evidence FRAP and light-inducible clustering with CCD truncation mutants; in vitro reconstitution of minimal centrosome with purified CDK5RAP2 (preprint)

    PMID:40270183

    Open questions at the time
    • In vivo relevance of scaffold phase behavior for centrosome size regulation untested
    • Regulatory signals controlling interphase-to-mitosis material transition incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the full-length structural architecture of CDK5RAP2 on the centrosome, the mechanism by which CDK5RAP2 accesses gene promoters for transcriptional regulation, and how its multiple interaction interfaces are coordinately regulated across the cell cycle to balance nucleation, cohesion, and spindle pole integrity.
  • No full-length structure or complete interaction map at atomic resolution
  • Transcriptional roles mechanistically disconnected from centrosomal functions
  • How distinct CDK5RAP2 pools (centrosome, Golgi, plus-end, nuclear) are partitioned and regulated is unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 5 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005815 microtubule organizing center 7 GO:0005634 nucleus 2 GO:0005794 Golgi apparatus 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1640170 Cell Cycle 6 R-HSA-1852241 Organelle biogenesis and maintenance 5 R-HSA-1266738 Developmental Biology 3
Partners
AKAP450ARL2CEP192CEP68EB1HSETPCNTTUBG1
Complex memberships
Cep68–CDK5RAP2–pericentrin complexdynein-dynactinγ-TuRC (via CM1/γ-TuNA)

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 CDK5RAP2 localizes to the spindle poles of mitotic cells (neuroepithelial cells), and homozygous mutations in CDK5RAP2 cause autosomal recessive primary microcephaly, establishing a centrosomal mechanism for control of neuron number in the developing brain. Immunolocalization in mitotic cells; human genetics (homozygosity mapping, mutation identification) Nature genetics High 15793586
2007 CDK5RAP2 is a pericentriolar protein that associates with the γ-tubulin ring complex (γTuRC) via a short conserved sequence, and this binding is required for γTuRC attachment to the centrosome (but not for γTuRC assembly); perturbing CDK5RAP2 delocalizes γ-tubulin, inhibits centrosomal microtubule nucleation, disorganizes interphase microtubule arrays, and causes anastral mitotic spindles. Co-immunoprecipitation, overexpression, RNAi knockdown, immunofluorescence, microtubule regrowth assay Molecular biology of the cell High 17959831
2007 Cep215 (CDK5RAP2) is required for centrosome cohesion; unlike rootletin and Cep68, Cep215 does not decorate centriolar fibres or interact with rootletin/C-Nap1, but instead influences centrosome cohesion through an indirect mechanism involving pericentrin and cytoskeletal dynamics. RNAi knockdown, immunofluorescence, co-immunoprecipitation, overexpression Journal of cell science High 18042621
2009 CDK5RAP2 interacts directly with EB1 via a basic and Ser-rich motif (containing an Ile/Leu-Pro dipeptide); this interaction enables CDK5RAP2 to track growing microtubule plus-ends, and the CDK5RAP2-EB1 complex regulates microtubule dynamics, stability, and bundling both in cells and in vitro. Co-immunoprecipitation, direct in vitro binding assay, site-directed mutagenesis (Ile/Leu-Pro mutant abolishes EB1 interaction), live-cell imaging, RNAi, in vitro microtubule assembly assay Molecular biology of the cell High 19553473
2009 CDK5RAP2 is required for spindle checkpoint function: its knockdown causes chromosome missegregation, reduces expression of BUBR1 and MAD2, and increases chromatin-associated CDC20; CDK5RAP2 resides on the BUBR1 and MAD2 promoters and regulates their transcription. RNAi knockdown, ChIP, RT-PCR/Western blot, rescue experiments Cell cycle Medium 19282672
2010 CDK5RAP2 stimulates the microtubule-nucleating activity of purified γTuRC via a conserved γ-TuRC-mediated nucleation activator (γ-TuNA) domain; γ-TuNA stimulates microtubule nucleation by purified γTuRC in vitro, and γTuRC bound to γ-TuNA contains NME7, FAM128A/B, and actin in addition to core components; CDK5RAP2 depletion impairs both centrosomal and acentrosomal microtubule nucleation without affecting γTuRC assembly. In vitro microtubule nucleation assay with purified γTuRC, mass spectrometry, RNAi, microtubule regrowth assay, mutagenesis of γ-TuC-binding-deficient mutant The Journal of cell biology High 21135143
2010 CDK5RAP2 localizes to the Golgi complex in an ATP- and centrosome-dependent manner; a CM2-like motif within its centrosome-targeting domain is required for both centrosomal and Golgi localization; this motif mediates binding to pericentrin (required for centrosomal and Golgi localization) and AKAP450 (required for Golgi localization). Immunofluorescence, fractionation, mutational analysis, co-immunoprecipitation The Journal of biological chemistry High 20466722
2010 CDK5RAP2's CNN1 domain is essential for linking centrosomes to mitotic spindle poles and for recruiting specific PCM components; the CNN1 domain also enforces centriole cohesion during interphase and promotes DNA damage-induced G2 arrest; the CNN2 domain is also essential for spindle pole attachment. Targeted domain deletion in avian DT40 cells, immunofluorescence, cell cycle analysis The Journal of cell biology High 20368616
2010 Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors; the an/an mouse (Cdk5rap2 exon 4 inversion causing in-frame deletion) exhibits microcephaly due to proliferative and survival defects in neuronal progenitors, impaired mitotic progression, abnormal mitotic spindle pole number, and altered mitotic orientation. Mouse genetic model (Cdk5rap2an/an), immunofluorescence, BrdU/EdU labeling, cell cycle analysis, apoptosis assay Development High 20460369
2010 Cdk5rap2 interacts with pericentrin; depletion of pericentrin in neural progenitors phenocopies Cdk5rap2 knockdown (depletion of apical progenitors, premature neuronal differentiation) and decreases recruitment of Cdk5rap2 to the centrosome, establishing pericentrin-Cdk5rap2 as a common mechanistic axis for microcephaly. RNAi knockdown, co-immunoprecipitation, immunofluorescence, in utero electroporation Neuron High 20471352
2010 CDK5RAP2 loss of function in mice causes centriole amplification with excess unpaired centrioles and daughter-daughter centriole pairs, indicating CDK5RAP2 is required to maintain centriole engagement and cohesion to restrict centriole replication; amplified centrosomes assemble multipolar spindles and excess mother centrioles template multiple primary cilia. CDK5RAP2 mutant mouse analysis, electron microscopy, immunofluorescence for centriole markers, cilia staining Developmental cell High 20627074
2010 CEP215 (CDK5RAP2) is involved in dynein-dependent accumulation of pericentriolar matrix proteins for spindle pole formation; CEP215 knockdown reduces centrosomal dynein localization throughout the cell cycle, preventing proper recruitment of selective centrosomal proteins. RNAi knockdown, immunofluorescence, live-cell imaging Cell cycle Medium 20139723
2013 CDK5RAP2 displays highly dynamic attachment to centrosomes in a microtubule-dependent manner; it associates with the retrograde transporter dynein-dynactin via a sequence motif that binds dynein light chain 8, and disruption of dynein-dynactin function reduces the centrosomal level of CDK5RAP2. FRAP (live imaging), co-immunoprecipitation, pulldown assay, dynein-dynactin inhibition PloS one Medium 23874654
2014 Cep68 forms a complex with Cep215 (CDK5RAP2) and PCNT; SCF(βTrCP)-mediated degradation of Cep68 (initiated by PLK1 phosphorylation of Cep68 Ser332) allows Cep215 removal from peripheral PCM, which is required for proper centriole separation and disengagement; PCNT cleavage mediates Cep215 removal from the core PCM. Co-immunoprecipitation, mass spectrometry, ubiquitin ligase assay, phospho-site mutagenesis, siRNA knockdown Nature cell biology High 25503564
2014 The CEP215-pericentrin interaction is required for centrosome maturation and bipolar spindle formation during mitosis; CEP215 and pericentrin are interdependent for their accumulation at spindle poles; interaction of CEP215 with γ-tubulin is dispensable for centrosome maturation. Knockdown-rescue experiments with domain mutants, immunofluorescence PloS one Medium 24466316
2015 PLK1 phosphorylates LRRK1 on Ser1790, enabling CDK1-mediated LRRK1 activation at centrosomes; activated LRRK1 in turn phosphorylates CDK5RAP2 on Ser140 within its γ-tubulin-binding motif, promoting CDK5RAP2-γ-tubulin interaction and CDK5RAP2-dependent nucleation of astral microtubules for mitotic spindle orientation. In vitro kinase assay, phospho-site mutagenesis, co-immunoprecipitation, RNAi, rescue experiments, immunofluorescence Nature cell biology High 26192437
2016 CEP215 (CDK5RAP2) directly binds the minus-end-directed microtubule motor HSET; targeted deletion of the HSET-binding domain of CEP215 causes centrosome detachment, HSET depletion at centrosomes, and failure of centrosome clustering in cancer cells with extra centrosomes. Proteomic profiling (mass spectrometry), targeted domain deletion, co-immunoprecipitation, immunofluorescence, patient-derived cells Nature communications High 26987684
2016 CDK5RAP2 interacts with the Hippo signaling pathway components MST1 kinase and the transcriptional regulator TAZ; loss of CDK5RAP2 in patient fibroblasts leads to higher TAZ and YAP levels and altered expression of Hippo target genes, linking centrosomal CDK5RAP2 to the Hippo pathway. Co-immunoprecipitation, immunofluorescence, Western blot in patient fibroblasts, RT-PCR Molecular genetics and genomics Low 28004182
2017 Human ASPM and CDK5RAP2 function redundantly in spindle pole organization during mitotic metaphase; depletion of CDK5RAP2 in ASPM knockout cells (but not ASPM KO alone) causes unfocused spindle poles and delayed anaphase onset; the pole-focusing function of CDK5RAP2 is independent of its known roles in HSET localization or γ-tubulin complex activation. CRISPR knockout, auxin-inducible degron, RNAi, live-cell imaging, immunofluorescence Journal of cell science High 28883092
2020 When centrioles are absent, the PCNT-CDK5RAP2 pericentriolar matrix self-organizes into foci via a microtubule- and PLK1-dependent process, and this matrix becomes essential for mitotic spindle assembly; CDK5RAP2's ability to recruit γ-tubulin complexes is required for acentriolar spindle assembly. Centriole depletion (centrinone inhibitor), PCNT/CDK5RAP2 RNAi/knockout, immunofluorescence, live-cell imaging in RPE1 and cancer cell lines The Journal of cell biology High 33170211
2020 A mitosis-specific centrosome-targeting domain of Cep215 (215N) interacts with Cep192 and phosphorylated Aurora A (pAurA); Cep192 is essential for targeting this domain to centrosomes, and centrosomal localization of 215N and pAurA is mutually dependent; Cep215 maintains structural integrity of the spindle pole by providing a platform for centrosome maturation molecules. Domain mapping, co-immunoprecipitation, rescue experiments with domain deletion mutants, immunofluorescence Journal of cell science Medium 33376154
2021 Cdk5rap2 acts as a positive transcriptional regulator of CENP-A: Cdk5rap2 interacts with the CENP-A promoter and upregulates CENP-A transcription; loss of Cdk5rap2 reduces centromeric CENP-A, causing lagging chromosomes, micronuclei, and chromatin bridges; exogenous CENP-A partially rescues lagging chromosomes caused by Cdk5rap2 loss. ChIP, rescue experiments, knockdown, immunofluorescence, flow cytometry Biomedicine & pharmacotherapy Medium 33725591
2021 CDK5RAP2 loss promotes premature cell senescence via GSK3β/β-catenin downregulation of WIP1: CDK5RAP2 interacts with GSK3β, causing inhibitory GSK3β Ser9 phosphorylation; loss of CDK5RAP2 increases GSK3β activity, reduces nuclear β-catenin, lowers WIP1 expression, and increases p53 Ser15 phosphorylation leading to senescence. Co-immunoprecipitation, Western blot, kinase activity assays, ectopic expression rescue, SA-β-gal staining in mouse embryonic fibroblasts and Cdk5rap2an/an mice Cell death & disease Medium 34930892
2022 Pathogenic LRRK2 causes centrosomal displacement of CDK5RAP2 (not of linker proteins rootletin/C-Nap1), resulting in centrosome cohesion deficits; this requires phospho-Rab proteins and RILPL1, which stably associate with centrosomes and displace CDK5RAP2. Immunofluorescence in transfected cells and patient-derived iPSC cells, LRRK2 kinase inhibitors, Rab mutant analysis iScience Medium 35721463
2024 CDK5RAP2's CM1 (centrosomin motif 1) binds to GCP2 within the γ-TuRC and induces a partial closure/constriction of the γ-tubulin ring, bringing it closer to the 13-protofilament geometry of the microtubule; additional CDK5RAP2 promotes γ-TuRC decoration and stimulates microtubule nucleation activity in single-molecule assays, providing a structural mechanism for CM1-mediated γ-TuRC activation. Cryo-EM structure determination of porcine γ-TuRC purified with CDK5RAP2 CM1, single-molecule microtubule nucleation assays with purified reconstituted complexes Developmental cell High 39321808
2024 MORC2 binds RBM39, which in turn interacts with pre-CDK5RAP2 exon 32 pre-mRNA, causing a splicing switch from CDK5RAP2 L to CDK5RAP2 S; the short isoform specifically recruits PHD finger protein 8 to promote Slug transcription by removing repressive histone marks at the Slug promoter, promoting epithelial-mesenchymal transition and metastasis. Co-immunoprecipitation, RNA splicing analysis, luciferase reporter, ChIP, shRNA knockdown, in vivo metastasis assays Cell death & disease Medium 39048555
2024 Mouse Arl2 GTPase physically associates with Cdk5rap2 (validated by co-immunoprecipitation and proximity ligation assay); Arl2 knockdown diminishes centrosomal microtubule growth and delocalizes Cdk5rap2 and γ-tubulin from centrosomes; overexpression of Cdk5rap2 rescues neurogenesis defects caused by Arl2 knockdown, placing Cdk5rap2 downstream of Arl2 in cortical development. Co-immunoprecipitation, proximity ligation assay, AlphaFold multimer prediction, in utero RNAi, overexpression rescue, immunofluorescence PLoS biology Medium 39137170
2025 CDK5RAP2 is sufficient to form micron-scale scaffolds around a nanometer-scale nucleator in vitro in a PLK1-regulated manner; these scaffolds recruit and activate γ-TuRCs to generate microtubule asters; residue F75 is partially needed for γ-TuRC recruitment but is indispensable for γ-TuRC activation; CDK5RAP2 scaffolds selectively recruit HSET, which enhances α/β-tubulin concentration, microtubule polymerization, and clustering. In vitro reconstitution of minimal centrosome, microtubule aster formation assay, mutagenesis (F75 mutant), purified component analysis bioRxivpreprint High
2025 CEP215 (CDK5RAP2) exhibits a dynamically suppressed, solid-like state in interphase centrosomes that transitions to a more dynamic state in mitotic centrosomes; specific interaction with PCNT is crucial for diffusible molecular dynamicity of CEP215; CEP215's coiled-coil domains (CCDs) are required for its cluster formation activity and for spindle pole assembly. FRAP, light-inducible clustering system, CCD truncation mutants, immunofluorescence, live-cell imaging Journal of cell science Medium 40270183

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. Nature genetics 446 15793586
2010 CDK5RAP2 stimulates microtubule nucleation by the gamma-tubulin ring complex. The Journal of cell biology 237 21135143
2007 CDK5RAP2 is a pericentriolar protein that functions in centrosomal attachment of the gamma-tubulin ring complex. Molecular biology of the cell 232 17959831
2010 Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors. Development (Cambridge, England) 218 20460369
2007 Cep68 and Cep215 (Cdk5rap2) are required for centrosome cohesion. Journal of cell science 176 18042621
2010 Cdk5rap2 interacts with pericentrin to maintain the neural progenitor pool in the developing neocortex. Neuron 147 20471352
2010 CDK5RAP2 regulates centriole engagement and cohesion in mice. Developmental cell 141 20627074
2010 Conserved motif of CDK5RAP2 mediates its localization to centrosomes and the Golgi complex. The Journal of biological chemistry 112 20466722
2011 Cdk5rap2 exposes the centrosomal root of microcephaly syndromes. Trends in cell biology 100 21632253
2010 CDK5RAP2 functions in centrosome to spindle pole attachment and DNA damage response. The Journal of cell biology 100 20368616
2001 Purification and properties of two chitinolytic enzymes of Serratia plymuthica HRO-C48. Archives of microbiology 75 11734885
2016 A CEP215-HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer. Nature communications 73 26987684
2007 Mg2+ binding and archaeosine modification stabilize the G15 C48 Levitt base pair in tRNAs. RNA (New York, N.Y.) 72 17652139
2014 Degradation of Cep68 and PCNT cleavage mediate Cep215 removal from the PCM to allow centriole separation, disengagement and licensing. Nature cell biology 70 25503564
2014 Importance of the CEP215-pericentrin interaction for centrosome maturation during mitosis. PloS one 67 24466316
2015 Development of a novel adjuvanted nasal vaccine: C48/80 associated with chitosan nanoparticles as a path to enhance mucosal immunity. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 64 25818119
2006 Molecular evolution of the brain size regulator genes CDK5RAP2 and CENPJ. Gene 64 16631324
2015 PLK1-dependent activation of LRRK1 regulates spindle orientation by phosphorylating CDK5RAP2. Nature cell biology 59 26192437
2009 Interaction of CDK5RAP2 with EB1 to track growing microtubule tips and to regulate microtubule dynamics. Molecular biology of the cell 59 19553473
2006 Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9;4)(q33;q12q25) and a CDK5RAP2-PDGFRA fusion gene. Genes, chromosomes & cancer 54 16845659
2015 Mutations in CDK5RAP2 cause Seckel syndrome. Molecular genetics & genomic medicine 53 26436113
2009 CDK5RAP2 is required for spindle checkpoint function. Cell cycle (Georgetown, Tex.) 40 19282672
2010 CEP215 is involved in the dynein-dependent accumulation of pericentriolar matrix proteins for spindle pole formation. Cell cycle (Georgetown, Tex.) 39 20139723
2020 Centriole-independent mitotic spindle assembly relies on the PCNT-CDK5RAP2 pericentriolar matrix. The Journal of cell biology 37 33170211
2012 A novel nonsense CDK5RAP2 mutation in a Somali child with primary microcephaly and sensorineural hearing loss. American journal of medical genetics. Part A 35 22887808
1979 12alpha-Hydroxysteroid dehydrogenase from Clostridium group P strain C48-50 ATCC No. 29733: partial purification and characterization. Journal of lipid research 35 438663
2007 Previously described sequence variant in CDK5RAP2 gene in a Pakistani family with autosomal recessive primary microcephaly. BMC medical genetics 31 17764569
2020 An update of pathogenic variants in ASPM, WDR62, CDK5RAP2, STIL, CENPJ, and CEP135 underlying autosomal recessive primary microcephaly in 32 consanguineous families from Pakistan. Molecular genetics & genomic medicine 30 32677750
2012 CDK5RAP2 expression during murine and human brain development correlates with pathology in primary autosomal recessive microcephaly. Cerebral cortex (New York, N.Y. : 1991) 30 22806269
2017 Human microcephaly ASPM protein is a spindle pole-focusing factor that functions redundantly with CDK5RAP2. Journal of cell science 27 28883092
2013 Clinical and cellular features in patients with primary autosomal recessive microcephaly and a novel CDK5RAP2 mutation. Orphanet journal of rare diseases 27 23587236
2013 The first case of CDK5RAP2-related primary microcephaly in a non-consanguineous patient identified by next generation sequencing. Brain & development 27 23726037
2011 What's the hype about CDK5RAP2? Cellular and molecular life sciences : CMLS 27 21327915
2011 Intranasal immunization with recombinant HA and mast cell activator C48/80 elicits protective immunity against 2009 pandemic H1N1 influenza in mice. PloS one 25 21625486
2015 Loss of γ-tubulin, GCP-WD/NEDD1 and CDK5RAP2 from the Centrosome of Neurons in Developing Mouse Cerebral and Cerebellar Cortex. Acta histochemica et cytochemica 23 26633906
2013 Dynamic recruitment of CDK5RAP2 to centrosomes requires its association with dynein. PloS one 23 23874654
2020 CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects. Journal of medical genetics 22 32015000
2024 Partial closure of the γ-tubulin ring complex by CDK5RAP2 activates microtubule nucleation. Developmental cell 21 39321808
2016 CDK5RAP2 interaction with components of the Hippo signaling pathway may play a role in primary microcephaly. Molecular genetics and genomics : MGG 20 28004182
2015 Exome sequencing identifies recessive CDK5RAP2 variants in patients with isolated agenesis of corpus callosum. European journal of human genetics : EJHG 20 26197979
2015 Cep169, a Novel Microtubule Plus-End-Tracking Centrosomal Protein, Binds to CDK5RAP2 and Regulates Microtubule Stability. PloS one 19 26485573
2022 Pathogenic LRRK2 regulates centrosome cohesion via Rab10/RILPL1-mediated CDK5RAP2 displacement. iScience 18 35721463
2020 CEP215 and AURKA regulate spindle pole focusing and aMTOC organization in mouse oocytes. Reproduction (Cambridge, England) 18 31895686
2017 CDK5RAP2 Is Required to Maintain the Germ Cell Pool during Embryonic Development. Stem cell reports 18 28162995
2018 CDK5RAP2 Is an Essential Scaffolding Protein of the Corona of the Dictyostelium Centrosome. Cells 16 29690637
2018 CDK5RAP2 gene and tau pathophysiology in late-onset sporadic Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association 15 29360470
2015 Loss of CDK5RAP2 affects neural but not non-neural mESC differentiation into cardiomyocytes. Cell cycle (Georgetown, Tex.) 15 25942099
2023 CDK5RAP2 is a Wnt target gene and promotes stemness and progression of oral squamous cell carcinoma. Cell death & disease 14 36774351
2017 A new association between CDK5RAP2 microcephaly and congenital cataracts. Annals of human genetics 12 29271474
2024 Inhibitory effect of phellodendrine on C48/80-induced allergic reaction in vitro and in vivo. International immunopharmacology 11 38744172
2024 MORC2 regulates RBM39-mediated CDK5RAP2 alternative splicing to promote EMT and metastasis in colon cancer. Cell death & disease 11 39048555
2017 A novel mutation in CDK5RAP2 gene causes primary microcephaly with speech impairment and sparse eyebrows in a consanguineous Pakistani family. European journal of medical genetics 11 28778786
2022 Whole exome sequencing identifies a novel mutation in ASPM and ultra-rare mutation in CDK5RAP2 causing Primary microcephaly in consanguineous Pakistani families. Pakistan journal of medical sciences 10 35035405
2013 Intranasal immunization of mice with inactivated virus and mast cell activator C48/80 elicits protective immunity against influenza H1 but not H5. Immunological investigations 10 24295504
2021 CDK5RAP2 loss-of-function causes premature cell senescence via the GSK3β/β-catenin-WIP1 pathway. Cell death & disease 9 34930892
2021 Centromeric chromatin integrity is compromised by loss of Cdk5rap2, a transcriptional activator of CENP-A. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 7 33725591
2019 Congenital microcephaly-linked CDK5RAP2 affects eye development. Annals of human genetics 7 31355417
2001 Dermal fibroblast morphology is affected by stretching and not by C48/80. Connective tissue research 7 11913768
2023 A novel missense variant in CDK5RAP2 associated with non-obstructive azoospermia. Taiwanese journal of obstetrics & gynecology 6 38008501
2021 A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation. Frontiers in genetics 6 33815457
2021 Further insights into the spectrum phenotype of TRAPPC9 and CDK5RAP2 genes, segregating independently in a large Tunisian family with intellectual disability and microcephaly. European journal of medical genetics 6 34737153
2020 A novel mitosis-specific Cep215 domain interacts with Cep192 and phosphorylated Aurora A for organization of spindle poles. Journal of cell science 6 33376154
2021 Triple deletion of TP53, PCNT, and CEP215 promotes centriole amplification in the M phase. Cell cycle (Georgetown, Tex.) 5 34233584
2021 Study on degranulation of mast cells under C48/80 treatment by electroporation-assisted and ultrasound-assisted surface-enhanced Raman spectrascopy. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 5 34536894
2015 Novel Alternative Splice Variants of Mouse Cdk5rap2. PloS one 5 26322982
2015 Species-Specific Expression of Full-Length and Alternatively Spliced Variant Forms of CDK5RAP2. PloS one 5 26550838
2023 Hominoid SVA-lncRNA AK057321 targets human-specific SVA retrotransposons in SCN8A and CDK5RAP2 to initiate neuronal maturation. Communications biology 4 36997626
2023 Inhibitory effect of daphnetin on the C48/80-induced pseudo-allergic reaction. International immunopharmacology 4 37690236
2025 A Rare Cause of Primary Microcephaly: 4 New Variants in CDK5RAP2 Gene and Review of the Literature. American journal of medical genetics. Part A 3 40243280
2025 Sea buckthorn leaves and gallic acid inhibit C48/80-induced pseudo-allergic reaction via the PLC/IP3 signaling pathway both in vitro and in vivo. International immunopharmacology 2 40163943
2025 Enhancement of CEP215 dynamics for spindle pole assembly during mitosis. Journal of cell science 2 40270183
2024 Arl2 GTPase associates with the centrosomal protein Cdk5rap2 to regulate cortical development via microtubule organization. PLoS biology 2 39137170
2024 Roles of Cep215/Cdk5rap2 in establishing testicular architecture for mouse male germ cell development. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 39569992
2022 An alternative splice isoform of mouse CDK5RAP2 induced cytoplasmic microtubule nucleation. IBRO neuroscience reports 2 36164503
2020 Cep215 is essential for morphological differentiation of astrocytes. Scientific reports 2 33046744
1981 On the production of 12 alpha-hydroxysteroid dehydrogenase from Clostridium group P, strain C48-50 ATCC 29733. Experientia 2 6941897
2018 The regulatory subunit phr2AB of Dictyostelium discoideum phosphatase PP2A interacts with the centrosomal protein CEP161, a CDK5RAP2 ortholog. Genes to cells : devoted to molecular & cellular mechanisms 1 30133996
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2025 Tomatidine Attenuates C48/80-induced Inflammatory Responses in HMC-1 Cells and is Associated with Modulation of the JNK/AP-1/ NF-κB/Caspase-1 Pathway. Current topics in medicinal chemistry 0 40444630
2025 Identification of CDK5RAP2 as a causative gene of focal epilepsy without microcephaly. Seizure 0 40848503
2025 Expanding the Clinical and Molecular Spectrum of Primary Autosomal Recessive Microcephaly: Novel CDK5RAP2 Gene Variants and Functional Insights on the Intronic Variants. Genes 0 41153337
2025 STARD9 and CDK5RAP2-Novel Candidate Genes for 46,XY Complete Gonadal Dysgenesis. International journal of molecular sciences 0 41373726