Affinage

PCNT

Pericentrin · UniProt O95613

Length
3336 aa
Mass
378.0 kDa
Annotated
2026-06-10
69 papers in source corpus 11 papers cited in narrative 11 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

PCNT (pericentrin) is a large centrosomal scaffold protein that organizes the pericentriolar material (PCM) and governs centriole engagement and duplication across the mitotic cycle (PMID:25503564, PMID:30814333). Its mRNA localizes to centrosomes and is translated locally, with the nascent protein delivered co-translationally to centrosomes by cytoplasmic dynein during early mitosis in a polysome-dependent manner (PMID:29708497). Within the PCM, PCNT forms a complex with Cep68 and CDK5RAP2 (Cep215), and this PCNT–CDK5RAP2 matrix recruits γ-tubulin complexes; the matrix is dispensable for spindle assembly when centrioles are present but becomes essential, through a microtubule- and PLK1-dependent foci-forming process, when centrioles are absent (PMID:25503564, PMID:33170211). PCNT couples centriole behavior to mitotic progression through regulated proteolysis: PLK1 phosphorylates PCNT as a priming step required for separase-mediated cleavage during mitotic exit, and this cleavage is necessary for PCM disintegration, centriole separation, and centriole-to-mother-centriole conversion that licenses subsequent centriole duplication (PMID:26647647, PMID:30814333). Loss of PCNT causes premature centriole separation and centriole amplification, while in combination with TP53 and CEP215 loss it drives supernumerary centriole assembly (PMID:30814333, PMID:34233584). PCNT also anchors Chk1 at centrosomes to restrain centrosomal cyclin B–Cdk1 activation and mitotic entry (PMID:23798705). Biallelic loss-of-function mutations in PCNT cause microcephalic osteodysplastic primordial dwarfism type II (MOPD II), accompanied by disorganized mitotic spindles and chromosome missegregation (PMID:18174396).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1996 Medium

    Establishing the genomic location and centrosomal nature of human pericentrin set the foundation for studying it as a microtubule-organizing scaffold.

    Evidence Exon trapping, FISH, and Southern blot mapping PCNT to chromosome 21q

    PMID:8812505

    Open questions at the time
    • Functional role inferred from mouse precedent rather than direct human experiment
    • No mechanism of PCM organization established
  2. 2008 High

    Linking PCNT loss to a human disease with defined mitotic defects established that PCNT is required for faithful spindle organization and chromosome segregation.

    Evidence Genetic linkage and patient cell studies in MOPD II

    PMID:18174396

    Open questions at the time
    • Molecular pathway connecting PCNT loss to spindle disorganization not resolved
    • Specific PCM partners mediating the defect not identified
  3. 2013 Medium

    Identifying PCNT as the centrosomal anchor for Chk1 explained how it gates mitotic entry through local cyclin B–Cdk1 control.

    Evidence Co-IP of Chk1 with PCNT, Che-1 knockdown, centrosomal Cdk1 activity assays

    PMID:23798705

    Open questions at the time
    • Single lab with two methods; reciprocal validation limited
    • Direct binding interface between Chk1 and PCNT not mapped
  4. 2014 High

    Defining the PCNT–Cep68–CDK5RAP2 complex and the consequence of PCNT cleavage revealed how PCNT restrains centriole disengagement and duplication.

    Evidence Reciprocal Co-IP, mass spectrometry, RNAi, centriole engagement assays

    PMID:25503564

    Open questions at the time
    • Protease responsible for cleavage not identified in this study
    • Stoichiometry and architecture of the complex unresolved
  5. 2015 High

    Demonstrating that PLK1 phosphorylation primes separase cleavage of PCNT established the regulatory switch that times PCM disassembly to mitotic exit.

    Evidence Phospho-resistant/phospho-mimetic mutants, separase cleavage assays, PLK1 inhibitor treatment

    PMID:26647647

    Open questions at the time
    • Precise phosphosites and cleavage sites within full-length PCNT not fully mapped
    • Quantitative contribution of cleavage to overall PCM turnover unknown
  6. 2019 High

    Showing that PCNT maintains centriole association at spindle poles and that its cleavage drives centriole-to-mother conversion connected PCNT proteolysis directly to the centriole duplication licensing step.

    Evidence CRISPR KO, non-cleavable mutants, TEV-induced artificial cleavage, live-cell imaging

    PMID:30814333

    Open questions at the time
    • Mechanism linking PCM disintegration to centriole conversion not fully detailed
    • Whether all PCNT pools are subject to cleavage unknown
  7. 2020 High

    Genetic epistasis established that the PCNT–CDK5RAP2 matrix is conditionally essential — required for acentriolar spindle assembly via γ-tubulin recruitment but dispensable when centrioles are present.

    Evidence PCNT/CDK5RAP2 double KO, centriole depletion, auxin degron, γ-tubulin recruitment assays

    PMID:33170211

    Open questions at the time
    • Molecular basis of PLK1-dependent PCNT foci formation not defined
    • Redundancy with other PCM scaffolds in centriole-containing cells unresolved
  8. 2021 Medium

    Triple-knockout analysis clarified that PCNT loss causes precocious centriole separation and, combined with TP53/CEP215 loss, promotes supernumerary centriole formation, refining its role in centriole number control.

    Evidence Triple CRISPR KO, cell cycle synchronization, centriole marker immunofluorescence

    PMID:34233584

    Open questions at the time
    • Single lab; mechanism of cooperation between TP53, PCNT, and CEP215 not dissected
    • Whether supernumerary centrioles are functional unknown
  9. 2025 Medium

    Identifying a centrosome-independent PCNT–LC3 dynein adaptor complex in influenza uncoating expanded PCNT's function beyond the centrosome.

    Evidence Co-IP, dynein adaptor reconstitution, IAV uncoating assays

    PMID:41060632

    Open questions at the time
    • Abstract-level detail limits mechanistic resolution
    • How non-lipidated LC3 engages PCNT structurally not defined
  10. 2025 Low

    Implicating PCNT with CEP152/CEP63 as ALMS1-interacting cartwheel seeds proposed a role in de novo centriole biogenesis independent of pre-existing centrioles.

    Evidence Co-IP, super-resolution imaging, depletion/rescue for de novo centriole formation (preprint)

    PMID:40667363

    Open questions at the time
    • Preprint, not yet peer-reviewed; single study
    • Direct PCNT contribution to cartwheel seeding versus passive association unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PCNT's distinct functional pools — centrosomal PCM scaffolding, Chk1 anchoring, and centrosome-independent dynein adaptor roles — are spatially and temporally partitioned remains unresolved.
  • No integrated model distinguishing centrosomal and non-centrosomal PCNT functions
  • Structural basis of PCNT scaffolding not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005815 microtubule organizing center 4 GO:0005768 endosome 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
ALMS1CDK5RAP2CEP152CEP63CEP68CHEK1PLK1
Complex memberships
PCNT-Cep68-CDK5RAP2 (Cep215) PCM complexPCNT-LC3 dynein adaptor complex

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 Biallelic loss-of-function mutations in PCNT cause microcephalic osteodysplastic primordial dwarfism type II (MOPD II); absence of PCNT results in disorganized mitotic spindles and missegregation of chromosomes. Genetic linkage analysis, patient cell studies showing mitotic spindle disorganization and chromosome missegregation Science High 18174396
2018 PCNT is delivered co-translationally to centrosomes during early mitosis by cytoplasmic dynein; PCNT mRNA localizes to centrosomes, is translated near centrosomes, and this localization requires intact polysomes. Live imaging of PCNT mRNA localization, centrosomal enrichment assays, polysome disruption experiments, co-translational targeting assays eLife High 29708497
2014 PCNT forms a complex with Cep68 and Cep215 (CDK5RAP2) at the pericentriolar material; PCNT cleavage mediates Cep215 removal from the core PCM to inhibit centriole disengagement and duplication, while Cep68 degradation removes Cep215 from the peripheral PCM. Co-immunoprecipitation, mass spectrometry, RNAi knockdown, cell biology assays for centriole engagement/separation Nature Cell Biology High 25503564
2015 PLK1 phosphorylates PCNT as a priming step required for separase-mediated cleavage of PCNT during mitotic exit; phospho-resistant PCNT mutants are not cleaved by separase and inhibit centriole separation, while phospho-mimetic mutants rescue centriole separation even in the presence of PLK1 inhibitor. Phospho-resistant and phospho-mimetic PCNT mutants, separase cleavage assays, PLK1 inhibitor treatment, centriole separation assays Nature Communications High 26647647
2019 PCNT is critical for maintaining centriole association within spindle poles during mitosis; deletion of PCNT causes premature centriole separation and centriole amplification during mitosis. Separase-mediated cleavage of PCNT during mitotic exit is required for centriole separation and centriole-to-mother-centriole conversion. PCNT deletion (CRISPR/KO), non-cleavable PCNT mutants, TEV protease-induced artificial cleavage, live-cell imaging of centriole behavior Journal of Cell Science High 30814333
2020 The PCNT-CDK5RAP2 pericentriolar matrix is dispensable for spindle formation when centrioles are present, but becomes essential for spindle assembly when centrioles are absent; acentriolar spindle assembly involves formation of PCNT- and CDK5RAP2-containing foci through a microtubule- and PLK1-dependent process, and requires CDK5RAP2-dependent γ-tubulin complex recruitment. PCNT and CDK5RAP2 knockout, centriole depletion, auxin-inducible degron, spindle assembly assays, γ-tubulin recruitment assays Journal of Cell Biology High 33170211
2013 PCNT is required at centrosomes for Chk1 localization to centrosomes; depletion of Che-1 abolishes Chk1 binding to pericentrin and centrosomal localization, deregulating centrosomal cyclin B-Cdk1 activation and advancing mitotic entry. Co-immunoprecipitation of Chk1 with PCNT, siRNA knockdown of Che-1, immunofluorescence localization, centrosomal Cdk1 activity assays Journal of Biological Chemistry Medium 23798705
1996 The human PCNT gene was mapped to chromosome 21q between marker PFKL and 21qter; pericentrin is described as a conserved protein component of the filamentous matrix of the centrosome involved in the initial establishment of the organized microtubule array. Exon trapping, PCR amplification, Southern blot, FISH Genomics Medium 8812505
2021 Triple deletion of TP53, PCNT, and CEP215 promotes supernumerary centriole assembly during M phase; PCNT deletion alone causes precocious centriole separation; only two centrioles (formed in S phase) per cell maintain an intact composition including CEP135, CEP192, CEP295, and CEP152. Triple knockout (CRISPR), cell cycle synchronization, centriole marker immunofluorescence Cell Cycle Medium 34233584
2025 PCNT forms a dynein adaptor complex with non-lipidated LC3 proteins that facilitates influenza A virus (IAV) uncoating at late endosomes; PCNT's role in this process is independent of its centrosomal localization. Co-immunoprecipitation, dynein adaptor complex reconstitution, IAV uncoating assays; PCNT localization studies Autophagy Medium 41060632
2025 CEP152, CEP63, and PCNT are ALMS1-interacting proteins that form aggregates (cartwheel seeds) devoid of ALMS1, which function as seeds for cartwheel assembly and centriole biogenesis independently of pre-existing centrioles. Co-immunoprecipitation (ALMS1-PCNT interaction), super-resolution imaging, genetic depletion and rescue experiments for de novo centriole formation bioRxivpreprint Low 40667363

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1. Genes & development 552 10733526
2005 5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal. Molecular and cellular biology 344 15899874
2008 Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. Science (New York, N.Y.) 310 18174396
2001 D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p. Genes & development 152 11562348
2005 Mechanism of Aurora-B degradation and its dependency on intact KEN and A-boxes: identification of an aneuploidy-promoting property. Molecular and cellular biology 135 15923616
2007 Mad3 KEN boxes mediate both Cdc20 and Mad3 turnover, and are critical for the spindle checkpoint. PloS one 115 17406666
2011 BubR1 blocks substrate recruitment to the APC/C in a KEN-box-dependent manner. Journal of cell science 90 22193957
2009 Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. Journal of medical genetics 88 19643772
2018 Co-translational protein targeting facilitates centrosomal recruitment of PCNT during centrosome maturation in vertebrates. eLife 84 29708497
2008 The spindle checkpoint functions of Mad3 and Mad2 depend on a Mad3 KEN box-mediated interaction with Cdc20-anaphase-promoting complex (APC/C). The Journal of biological chemistry 79 18556659
2002 Arsenite-induced Cdc25C degradation is through the KEN-box and ubiquitin-proteasome pathway. Proceedings of the National Academy of Sciences of the United States of America 77 11842186
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
2006 KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome. The Journal of biological chemistry 62 17158872
2003 Xkid is degraded in a D-box, KEN-box, and A-box-independent pathway. Molecular and cellular biology 57 12773557
2015 PLK1 regulation of PCNT cleavage ensures fidelity of centriole separation during mitotic exit. Nature communications 55 26647647
2010 Cdc20 is required for the post-anaphase, KEN-dependent degradation of centromere protein F. Journal of cell science 47 20053638
2021 Single-dose HPV vaccination efficacy among adolescent girls and young women in Kenya (the KEN SHE Study): study protocol for a randomized controlled trial. Trials 42 34579786
2006 Ken & barbie selectively regulates the expression of a subset of Jak/STAT pathway target genes. Current biology : CB 41 16401426
2012 GPS-ARM: computational analysis of the APC/C recognition motif by predicting D-boxes and KEN-boxes. PloS one 40 22479614
2011 Mechanism of action of the suppression of influenza virus replication by Ko-Ken Tang through inhibition of the phosphatidylinositol 3-kinase/Akt signaling pathway and viral RNP nuclear export. Journal of ethnopharmacology 39 21232589
2020 Centriole-independent mitotic spindle assembly relies on the PCNT-CDK5RAP2 pericentriolar matrix. The Journal of cell biology 37 33170211
2008 Unique D box and KEN box sequences limit ubiquitination of Acm1 and promote pseudosubstrate inhibition of the anaphase-promoting complex. The Journal of biological chemistry 34 18596038
2011 The smallest teeth in the world are caused by mutations in the PCNT gene. American journal of medical genetics. Part A 33 21567919
2009 Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome previously diagnosed as Seckel syndrome: report of a novel mutation of the PCNT gene. American journal of medical genetics. Part A 31 19839044
2003 Drosophila securin destruction involves a D-box and a KEN-box and promotes anaphase in parallel with Cyclin A degradation. Journal of cell science 29 12724352
2001 The KEN box regulates Clb2 proteolysis in G1 and at the metaphase-to-anaphase transition. Current biology : CB 29 11719221
2008 Discovery of candidate KEN-box motifs using cell cycle keyword enrichment combined with native disorder prediction and motif conservation. Bioinformatics (Oxford, England) 28 18184688
2007 Gene and expression analyses reveal enhanced expression of pericentrin 2 (PCNT2) in bipolar disorder. Biological psychiatry 26 17884020
2012 The Drosophila BCL6 homolog Ken and Barbie promotes somatic stem cell self-renewal in the testis niche. Developmental biology 24 22580161
2019 PCNT is critical for the association and conversion of centrioles to centrosomes during mitosis. Journal of cell science 23 30814333
2018 PCNT point mutations and familial intracranial aneurysms. Neurology 20 30413633
2009 Positive association of the pericentrin (PCNT) gene with major depressive disorder in the Japanese population. Journal of psychiatry & neuroscience : JPN 20 19448849
2003 The ken and barbie gene encoding a putative transcription factor with a BTB domain and three zinc finger motifs functions in terminalia development of Drosophila. Archives of insect biochemistry and physiology 20 14518006
2012 The beneficial effects of Kampo medicine Dai-ken-chu-to after hepatic resection: a prospective randomized control study. Hepato-gastroenterology 19 23435143
2015 Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms. Metabolic brain disease 18 26231886
2013 Centrosomal Che-1 protein is involved in the regulation of mitosis and DNA damage response by mediating pericentrin (PCNT)-dependent Chk1 protein localization. The Journal of biological chemistry 16 23798705
2013 The Putzig partners DREF, TRF2 and KEN are involved in the regulation of the Drosophila telomere retrotransposons, HeT-A and TART. Mobile DNA 12 23822164
2023 The miR-184-3p promotes rice black-streaked dwarf virus infection by suppressing Ken in Laodelphax striatellus (Fallén). Pest management science 10 38050810
2021 Modifier Genes in Microcephaly: A Report on WDR62, CEP63, RAD50 and PCNT Variants Exacerbating Disease Caused by Biallelic Mutations of ASPM and CENPJ. Genes 9 34068194
2014 A new mutation of the PCNT gene in a Colombian patient with microcephalic osteodysplastic primordial dwarfism type II: a case report. Journal of medical case reports 9 24928221
2009 Association study between the pericentrin (PCNT) gene and schizophrenia. Neuromolecular medicine 9 19937158
1998 A transcription unit at the ken and barbie gene locus encodes a novel Drosophila zinc finger protein. Mechanisms of development 9 10349629
2022 Transcriptome profile of spleen tissues from locally-adapted Kenyan pigs (Sus scrofa) experimentally infected with three varying doses of a highly virulent African swine fever virus genotype IX isolate: Ken12/busia.1 (ken-1033). BMC genomics 7 35854219
2006 JAK/STAT signalling: STAT cannot play with Ken and Barbie. Current biology : CB 7 16461274
1996 Localization of a human homolog of the mouse pericentrin gene (PCNT) to chromosome 21qter. Genomics 7 8812505
2024 A structure-based designed small molecule depletes hRpn13Pru and a select group of KEN box proteins. Nature communications 6 38509117
2020 A Novel PCNT Frame Shift Variant (c.7511delA) Causing Osteodysplastic Primordial Dwarfism of Majewski Type 2 (MOPD II). Frontiers in pediatrics 6 32671003
2021 Triple deletion of TP53, PCNT, and CEP215 promotes centriole amplification in the M phase. Cell cycle (Georgetown, Tex.) 5 34233584
2021 RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature. BMC musculoskeletal disorders 5 34284742
2021 A novel homozygous mutation of the PCNT gene in a Chinese patient with microcephalic osteodysplastic primordial dwarfism type II. Molecular genetics & genomic medicine 5 34331829
2020 Novel PCNT variants in MOPDII with attenuated growth restriction and pachygyria. Clinical genetics 5 32557621
2019 Identification of a novel PCNT founder pathogenic variant in the Israeli Druze population. European journal of medical genetics 5 30922925
2021 Identification of three novel mutations in PCNT in vietnamese patients with microcephalic osteodysplastic primordial dwarfism type II. Genes & genomics 4 33460028
2020 Novel compound heterozygous mutations of PCNT gene in MOPD type II with central precocious puberty. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 4 33016782
2019 Majewski dwarfism type II: an atypical neuroradiological presentation with a novel variant in the PCNT gene. BMJ case reports 4 31151966
2022 Novel frameshift variant in the PCNT gene associated with Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II and small kidneys. BMC medical genomics 3 35422036
2021 Coding variants in the PCNT and CEP295 genes contribute to breast cancer risk in Chinese women. Pathology, research and practice 3 34418690
2019 New PCNT candidate missense variant in a patient with oral and maxillofacial osteodysplasia: a case report. BMC medical genetics 3 31311520
2023 Crawling, waving, inch worming, dilating, and pivoting mechanics of migrating cells: Lessons from Ken Jacobson. Biophysical journal 2 36934300
2023 Case Report: short stature, kidney anomalies, and cerebral aneurysms in a novel homozygous mutation in the PCNT gene associated with microcephalic osteodysplastic primordial dwarfism type II. Frontiers in endocrinology 2 37234811
2019 Schizophrenia in microcephalic osteodysplastic primordial dwarfism type II syndrome: supporting evidence for an association between the PCNT gene and schizophrenia. Psychiatric genetics 2 30531648
2026 The crazy ovary 2: a tribute to Ken McNatty. Biology of reproduction 0 41408696
2026 Hsa_circ_PCNT sponges hsa-miR-133b to promote SHH medulloblastoma via TAGLN2. Cellular and molecular life sciences : CMLS 0 41483179
2026 High agreement of Seegene Anyplex™ HPV 28 and Allplex™ HPV 28 for high-risk vaccine-type HPV detection in the KEN SHE Study. Journal of virological methods 0 41962590
2025 Centriole biogenesis is seeded by CEP152-CEP63-PCNT aggregates propagating outside the centriole through the Alström syndrome protein ALMS1. bioRxiv : the preprint server for biology 0 40667363
2025 BIM-Ken: Identifying Disease-Related miRNA Biomarkers Based on Knowledge-Enhanced Bio-Network. Genes 0 40869950
2025 Hijacking a cellular highway: non-lipidated LC3 proteins and PCNT (pericentrin) drive influenza a virus uncoating. Autophagy 0 41060632
2025 Two Siblings With Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPDII) Caused by Compound Heterozygous Pericentrin (PCNT) Gene Variants. Cureus 0 41583253
2020 An interview with Ken Poss. Development (Cambridge, England) 0 32561666

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