Affinage

CEP83

Centrosomal protein of 83 kDa · UniProt Q9Y592

Length
701 aa
Mass
82.9 kDa
Annotated
2026-06-09
30 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEP83 is a core structural component of the distal appendages (DAPs) of the mother centriole and functions as an early, essential organizer of ciliogenesis and centriole docking to the plasma membrane (PMID:23530209, PMID:39882846). It localizes to the distal end of the mother centriole, where its own positioning depends on an upstream CEP90/FOPNL/OFD1 module, and together with SCLT1 it constitutes one of the two critical modules for DAP structural assembly, hierarchically recruiting downstream appendage proteins including LRRC45 and RABL2 (PMID:30131441, PMID:30578315, PMID:36070319, PMID:39882846). Through these appendages CEP83 tethers preciliary/ciliary vesicles to the mother centriole and coordinates IFT recruitment — interacting with and recruiting IFT20 and supporting Rabin8/TRAPPII-dependent vesicle accumulation — and its loss compromises all four steps of cilium formation: vesicle recruitment, IFT recruitment, IFT initiation, and CP110 removal (PMID:23530209, PMID:31467083, PMID:39882846). CEP83 is a direct substrate of TTBK2, which is recruited to appendages in a CEP164-dependent manner and phosphorylates CEP83 at four sites to drive ciliary vesicle docking and CP110 removal (PMID:31455668, PMID:32129703). Functionally, CEP83 distinguishes a ciliary-assembly subgroup of DAP proteins distinct from disassembly regulators, mediates mother-centriole contact with the plasma membrane in non-ciliary contexts such as the immunological synapse in cytotoxic T lymphocytes, and in radial glial progenitors anchors the centrosome to the apical membrane to set cell mechanical properties and suppress YAP-driven proliferation (PMID:26670998, PMID:32238932, PMID:39696441). Biallelic CEP83 mutations cause altered distal appendage composition and ciliary defects in patients, and CEP83 is required for primary cilia-dependent intermediate mesoderm specification during iPSC differentiation (PMID:24882706, PMID:36222666, PMID:41073425).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2013 High

    Established CEP83 as a distal-appendage protein physically linked to the ciliogenesis machinery, answering where it acts and what step it controls.

    Evidence Immunofluorescence, reciprocal co-IP with CEP164, siRNA knockdown and EM in human cells

    PMID:23530209

    Open questions at the time
    • Direct binding interface with CEP164 not mapped
    • Mechanism of IFT20 recruitment not resolved
  2. 2014 Medium

    Linked CEP83 loss-of-function to human disease, establishing that altered DAP composition underlies patient ciliary defects.

    Evidence Patient fibroblast/renal cell analysis with DAP marker immunofluorescence and targeted sequencing

    PMID:24882706

    Open questions at the time
    • Genotype-phenotype relationship of specific alleles not dissected
    • Tissue specificity of phenotype unexplained
  3. 2015 Medium

    Showed CEP83 mediates centrosome docking to the plasma membrane beyond ciliogenesis, generalizing its appendage-tethering function.

    Evidence siRNA knockdown, TEM tomography and secretion assays at the immunological synapse in CTLs

    PMID:26670998

    Open questions at the time
    • Molecular partners for plasma-membrane docking in CTLs not identified
    • Single lab
  4. 2018 Medium

    Placed CEP83 upstream in the DAP assembly hierarchy by defining LRRC45 recruitment dependency.

    Evidence siRNA knockdown and epistasis of protein recruitment by immunofluorescence

    PMID:30131441

    Open questions at the time
    • Direct vs indirect recruitment of LRRC45 unresolved
    • Single lab
  5. 2019 High

    Identified CEP83 as a TTBK2 substrate phosphorylated at four sites and extended its role to RABL2/Rabin8-dependent vesicle tethering, connecting kinase regulation to vesicle docking and CP110 removal.

    Evidence In vitro kinase assays, mass spectrometry phosphosite mapping, site-directed mutagenesis, knockdown/rescue, and live imaging of Rabin8/RABL2

    PMID:30578315 PMID:31455668 PMID:31467083

    Open questions at the time
    • Functional contribution of each individual phosphosite not separated
    • Direct CEP83-RABL2/Rabin8 binding not established
  6. 2020 High

    Independently confirmed CEP83 as a TTBK2 substrate within a broader phosphorylation network and defined the centrosome-anchoring/YAP mechanotransduction role in neural progenitors.

    Evidence In vitro/in vivo kinase and phosphosite assays; conditional knockout mouse with CEP83/YAP epistasis, EM, and mechanical measurements

    PMID:32129703 PMID:32238932

    Open questions at the time
    • How appendage loss leads to apical membrane stiffening mechanically not fully resolved
    • Link between phosphorylation and the in vivo progenitor phenotype not connected
  7. 2022 Medium

    Defined the module upstream of CEP83 (CEP90/FOPNL/OFD1) and showed CEP83 is required for cilia-dependent intermediate mesoderm specification, extending its role to lineage differentiation.

    Evidence CRISPR knockouts with expansion microscopy epistasis; hiPSC inactivation with single-cell/bulk transcriptomics and kidney organoids

    PMID:36070319 PMID:36222666

    Open questions at the time
    • Cilia-dependent signaling pathway driving IM gene expression not identified
    • Direct interactions within the upstream module not mapped
  8. 2025 High

    Comprehensive CRISPR analysis established CEP83-SCLT1 as a critical DAP assembly module controlling all four ciliogenesis steps, and functionally separated it from disassembly regulators.

    Evidence CRISPR-Cas9 knockout panels, superresolution microscopy, four-step ciliogenesis assays and epistasis across 12+ proteins; ciliation/deciliation kinetics with Aurora A analysis

    PMID:39696441 PMID:39882846

    Open questions at the time
    • Structural basis of the CEP83-SCLT1 module not solved
    • Mechanism distinguishing assembly from disassembly roles not defined
  9. 2025 Medium

    Revealed dosage-dependent control of cilia length, with complete loss producing elongated cilia versus shorter/absent cilia from partial loss.

    Evidence Patient fibroblast analysis with whole genome sequencing, RT-PCR, Western blot and cilia immunofluorescence

    PMID:41073425

    Open questions at the time
    • Molecular basis of dosage-dependent length regulation unknown
    • Single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CEP83 mechanically integrates appendage assembly, vesicle docking, TTBK2 phosphorylation, and downstream cilia-dependent signaling into tissue-level outcomes remains unresolved.
  • No high-resolution structure of CEP83 or the CEP83-SCLT1 module
  • Direct physical partners largely inferred from recruitment epistasis rather than biochemistry
  • Causal chain from phosphosites to in vivo phenotypes incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005815 microtubule organizing center 4 GO:0005929 cilium 3 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1266738 Developmental Biology 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
CEP164IFT20LRRC45PCM1RABL2SCLT1TTBK2
Complex memberships
CEP83-SCLT1 moduledistal appendage

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 CCDC41 (CEP83) localizes specifically to the distal end of the mother centriole and interacts with CEP164, a distal appendage component. A pool of CCDC41 colocalizes with IFT20 at the Golgi complex. Knockdown of CCDC41 inhibits recruitment of IFT20 to the centrosome and blocks ciliogenesis at the ciliary vesicle docking step. Immunofluorescence, co-immunoprecipitation, siRNA knockdown, electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 23530209
2014 Biallelic mutations in CEP83 cause altered distal appendage (DAP) composition and ciliary defects in patient fibroblasts and tubular renal cells, establishing CEP83 as a key component of distal appendages required for ciliogenesis. Patient fibroblast and renal cell analysis, immunofluorescence of distal appendage markers, targeted exon sequencing American journal of human genetics Medium 24882706
2015 CEP83, as a distal appendage protein, is required for the mother centriole to contact the plasma membrane at the immunological synapse in cytotoxic T lymphocytes (CTLs). siRNA knockdown of CEP83 impairs CTL secretion, demonstrating a role in centrosome docking without full ciliogenesis. siRNA knockdown, high-resolution TEM tomography, functional secretion assay Current biology : CB Medium 26670998
2018 CEP83 and SCLT1 are core distal appendage proteins that recruit LRRC45 to the mother centriole, placing CEP83 upstream of LRRC45 in the distal appendage assembly hierarchy. siRNA knockdown, immunofluorescence, epistasis analysis of protein recruitment Journal of cell science Medium 30131441
2019 TTBK2 phosphorylates CEP83 at four specific phosphorylation sites. CEP164-dependent TTBK2 recruitment to distal appendages is required for CEP83 phosphorylation. TTBK2-dependent CEP83 phosphorylation is important for ciliary vesicle docking and CP110 removal during early ciliogenesis. Biochemical phosphorylation assays, mass spectrometry, superresolution microscopy, site-directed mutagenesis of phosphorylation sites, knockdown/rescue The Journal of cell biology High 31455668
2019 RABL2 recruitment to the mother centriole is dependent on the distal appendage proteins CEP164 and CEP83, placing CEP83 upstream of RABL2 in the pathway controlling ciliary GPCR trafficking. Immunofluorescence, siRNA knockdown, epistasis analysis of protein recruitment Journal of cell science Medium 30578315
2019 CEP83 (FBF1) and distal appendage proteins are required for GFP-Rabin8 centrosomal accumulation, supporting a role for CEP83 in tethering preciliary vesicles to the mother centriole via the TRAPPII complex pathway. siRNA knockdown, live-cell fluorescence imaging of GFP-Rabin8, co-immunoprecipitation The Journal of biological chemistry Medium 31467083
2020 CEP83 is a substrate of TTBK2 kinase in vitro and in vivo, with specific phosphosites characterized. TTBK2-induced phosphorylations of CEP83 are part of a broader substrate set including CEP89, CCDC92, Rabin8, and DVL3 that regulate ciliogenesis. In vitro kinase assay, mass spectrometry phosphosite mapping, cell-based phosphorylation assays Molecular biology of the cell High 32129703
2020 Selective removal of CEP83 in mouse radial glial progenitors (RGPs) eliminates distal appendages and disrupts centrosome anchorage to the apical membrane, resulting in microtubule disorganization, apical membrane stiffening, YAP activation, excessive RGP proliferation, overproduction of intermediate progenitor cells, and cortical enlargement with abnormal folding. Simultaneous elimination of YAP suppresses these cortical phenotypes. Conditional knockout mouse, genetic epistasis (CEP83 KO + YAP KO), electron microscopy, live imaging, mechanical measurements, immunofluorescence Nature High 32238932
2022 CEP90, FOPNL, and OFD1, recruited by MNR (Moonraker), are required upstream of CEP83, CEP89, and CEP164 for distal appendage assembly. CEP83 localization to the distal centriole depends on this upstream module. CRISPR-Cas9 knockouts, ultrastructure expansion microscopy, epistasis analysis of protein recruitment in mammalian cells and Paramecium PLoS biology Medium 36070319
2022 CEP83 inactivation in human iPSCs causes absent or elongated primary cilia in induced mesodermal cells and perturbs differentiation toward intermediate mesoderm (IM) progenitors, with decreased expression of IM genes (PAX8, EYA1, HOXB7) and aberrant induction of lateral plate mesoderm markers, leading to failure to generate kidney cell types in organoid culture. CRISPR-Cas9 inactivating deletions in hiPSCs, single-cell and bulk transcriptomics, organoid culture, immunofluorescence of cilia eLife Medium 36222666
2023 CEP83 and SCLT1 form a critical module for structural assembly of distal appendages. Deletion of CEP83-SCLT1-CEP164-TTBK2 severely compromises all four steps of cilium formation: preciliary vesicle recruitment, IFT recruitment, IFT initiation, and CP110 removal. CEP83 knockout disrupts recruitment of downstream distal appendage proteins in a hierarchical manner. CRISPR-Cas9 knockouts, superresolution microscopy, functional ciliogenesis assays (preprint version of PMID:39882846) bioRxivpreprint Medium 36711481
2024 CEP83 belongs to a functional subgroup of distal appendage proteins (with SCLT1 and CEP164) primarily essential for ciliary assembly and centriole docking, distinct from CEP89/FBF1 which regulate ciliary disassembly. siRNA-mediated depletion of CEP83 impairs ciliogenesis but does not affect Aurora A kinase-mediated ciliary disassembly. siRNA knockdown, immunofluorescence, kinetics of ciliation/deciliation assays, Aurora A kinase localization analysis Cell communication and signaling : CCS Medium 39696441
2025 Comprehensive CRISPR-Cas9 analysis confirms CEP83-SCLT1 as one of two critical modules for distal appendage structural assembly. CEP83 deletion severely compromises all four steps of cilium formation (RAB34+ vesicle recruitment, IFT recruitment, IFT initiation, CP110 removal) and disrupts recruitment of multiple downstream distal appendage proteins. CRISPR-Cas9 knockouts, superresolution microscopy, functional ciliogenesis assays for four distinct steps, epistasis analysis of 12+ proteins eLife High 39882846
2025 In zebrafish RGPs, Pcm1 is asymmetrically associated with Cep83 as a mother centrosome marker. CEP83 is used as a marker distinguishing mother from daughter centrioles, with conserved PARD3-PCM1-CEP83-RAB11 associations detected in human cortical brain organoids. In vivo time-lapse imaging, nanoscale expansion microscopy, co-localization analysis in zebrafish and human brain organoids Nature communications Low 41315244
2025 Complete biallelic loss-of-function of CEP83 (abrogating CEP83 mRNA and protein expression) results in aberrantly long (elongated) primary cilia in patient fibroblasts, in contrast to the shorter/absent cilia phenotype seen with partial loss-of-function mutations, suggesting a dosage-dependent mechanism in cilia length regulation. Patient fibroblast analysis, whole genome sequencing, RT-PCR, Western blot, immunofluorescence of cilia NPJ genomic medicine Medium 41073425

Source papers

Stage 0 corpus · 30 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis. Journal of the American Society of Nephrology : JASN 168 18199800
2013 CCDC41 is required for ciliary vesicle docking to the mother centriole. Proceedings of the National Academy of Sciences of the United States of America 131 23530209
2014 Mutations of CEP83 cause infantile nephronophthisis and intellectual disability. American journal of human genetics 93 24882706
2020 Centrosome anchoring regulates progenitor properties and cortical formation. Nature 76 32238932
2008 Mutation analysis in nephronophthisis using a combined approach of homozygosity mapping, CEL I endonuclease cleavage, and direct sequencing. Human mutation 68 18076122
2019 Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation. The Journal of cell biology 67 31455668
2015 Mother Centriole Distal Appendages Mediate Centrosome Docking at the Immunological Synapse and Reveal Mechanistic Parallels with Ciliogenesis. Current biology : CB 62 26670998
2004 A comparative expression analysis of gene transcripts in post-fertilization developmental stages of bovine embryos produced in vitro or in vivo. Reproduction in domestic animals = Zuchthygiene 50 15598228
2020 Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin kinase 2. Molecular biology of the cell 43 32129703
2018 LRRC45 contributes to early steps of axoneme extension. Journal of cell science 42 30131441
2025 A hierarchical pathway for assembly of the distal appendages that organize primary cilia. eLife 25 39882846
2019 RABL2 positively controls localization of GPCRs in mammalian primary cilia. Journal of cell science 25 30578315
2019 The C7orf43/TRAPPC14 component links the TRAPPII complex to Rabin8 for preciliary vesicle tethering at the mother centriole during ciliogenesis. The Journal of biological chemistry 25 31467083
2022 The evolutionary conserved proteins CEP90, FOPNL, and OFD1 recruit centriolar distal appendage proteins to initiate their assembly. PLoS biology 20 36070319
2020 Identification of Aberrantly-Expressed Long Non-Coding RNAs in Osteoblastic Cells from Osteoporotic Patients. Biomedicines 18 32204466
2023 A hierarchical pathway for assembly of the distal appendages that organize primary cilia. bioRxiv : the preprint server for biology 12 36711481
2020 Clinical and pathological features and varied mutational spectra of pathogenic genes in 55 Chinese patients with nephronophthisis. Clinica chimica acta; international journal of clinical chemistry 12 32173348
2022 The centrosomal protein 83 (CEP83) regulates human pluripotent stem cell differentiation toward the kidney lineage. eLife 10 36222666
2021 Beyond nephronophthisis: Retinal dystrophy in the absence of kidney dysfunction in childhood expands the clinical spectrum of CEP83 deficiency. American journal of medical genetics. Part A 7 33938610
2013 Identification of novel tumour-associated antigens in canine mammary gland tumour. Veterinary and comparative oncology 6 23510442
2025 PCM1 coordinates centrosome asymmetry with polarized endosome dynamics to regulate daughter cell fate. Nature communications 3 41315244
2025 Cortex folding by combined progenitor expansion and adhesion-controlled neuronal migration. Nature communications 1 40877293
2025 CCDC41 Drives Oocyte Meiotic Progression by Promoting Rab11a/Rab7-Positive Vesicle Fusion with Target Membranes. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41331237
2026 Expression and regulation of lncRNAs in the testes of Yili geese with high and low sperm motility. BMC genomics 0 41917816
2026 Development of Potent and Cell Active 5-Azaindole-Based Tau Tubulin Kinase Inhibitors. bioRxiv : the preprint server for biology 0 42094407
2025 TTBK2 affects sperm quality by regulating the expression of centrosomal proteins and flagellar transporters during spermiogenesis in mice. Molecular human reproduction 0 40581359
2025 A ciliopathy combining Joubert syndrome and Oro-Facial-Digital syndrome caused by bi-allelic 5'-UTR loss-of-function CEP83 variant. NPJ genomic medicine 0 41073425
2024 Bilateral Perisylvian Polymicrogyria, Intellectual Disability and Nephronophthisis Associated With Compound Heterozygous Pathogenic Variants in the CEP83  Gene. American journal of medical genetics. Part A 0 39219159
2024 Distinct roles of centriole distal appendage proteins in ciliary assembly and disassembly. Cell communication and signaling : CCS 0 39696441
2023 Multi-color live-cell fluorescence imaging of primary ciliary membrane assembly and dynamics. Methods in cell biology 0 37164540

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