Affinage

CEP83

Centrosomal protein of 83 kDa · UniProt Q9Y592

Length
701 aa
Mass
82.9 kDa
Annotated
2026-04-28
28 papers in source corpus 14 papers cited in narrative 14 extracted findings

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 that functions as an essential scaffold for centriole-to-membrane docking and primary ciliogenesis. CEP83 forms a critical functional module with SCLT1 that is required for all four steps of cilium initiation—ciliary vesicle recruitment, IFT recruitment, IFT initiation, and CP110 removal—and acts upstream of LRRC45, RABL2, and FBF1 in the DAP assembly hierarchy, while itself depending on OFD1/FOPNL/CEP90 for centriolar recruitment (PMID:39882846, PMID:30131441, PMID:36070319). CEP83 is phosphorylated by TTBK2 kinase at four sites in a CEP164-dependent manner, and this phosphorylation is required for early ciliogenesis events including ciliary vesicle docking (PMID:31455668, PMID:32129703). Beyond ciliogenesis, CEP83 anchors centrosomes to the apical membrane in neural progenitors, where its loss activates YAP-dependent mechanosignaling leading to cortical overgrowth, and mediates centrosome docking at the immunological synapse in cytotoxic T lymphocytes for secretory lysosome release; biallelic CEP83 mutations cause nephronophthisis-related ciliopathy with renal tubular defects (PMID:32238932, PMID:26670998, PMID:24882706).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2014 High

    Establishing CEP83 as a disease-relevant DAP component resolved the question of whether distal appendage integrity is essential for human ciliogenesis and kidney development, as biallelic CEP83 mutations caused DAP loss, ciliary defects, and nephronophthisis.

    Evidence Targeted exon sequencing, patient fibroblast and renal cell functional analysis, immunofluorescence of DAP composition

    PMID:24882706

    Open questions at the time
    • Precise structural position of CEP83 within DAPs unknown
    • Upstream regulators of CEP83 centriolar recruitment not defined
    • Mechanism by which CEP83 loss causes renal disease not resolved
  2. 2015 Medium

    CEP83's role in non-ciliary centrosome-membrane docking was demonstrated when its knockdown in cytotoxic T lymphocytes impaired secretory lysosome release at the immunological synapse, extending DAP function beyond ciliogenesis.

    Evidence siRNA knockdown in CTLs, high-resolution TEM tomography, secretion assays

    PMID:26670998

    Open questions at the time
    • Single study; independent replication in other non-ciliated docking contexts lacking
    • Molecular mechanism of DAP-mediated membrane docking in CTLs unresolved
  3. 2018 Medium

    Positioning CEP83 in the DAP assembly hierarchy clarified that CEP83 (with SCLT1) acts upstream of LRRC45 recruitment, defining an ordered assembly pathway rather than co-dependent recruitment.

    Evidence siRNA knockdown of CEP83/SCLT1, immunofluorescence of LRRC45 localization

    PMID:30131441

    Open questions at the time
    • Direct physical interaction between CEP83 and LRRC45 not demonstrated
    • Reciprocal dependency not fully tested
  4. 2019 High

    Identification of CEP83 as a direct TTBK2 substrate resolved how kinase signaling initiates ciliogenesis at DAPs: CEP164 recruits TTBK2, which phosphorylates CEP83 at four sites to trigger ciliary vesicle docking and CP110 removal.

    Evidence Biochemical phosphorylation assays, phosphosite mapping, superresolution microscopy, CEP164-dependent recruitment assays

    PMID:31455668 PMID:32129703

    Open questions at the time
    • How phosphorylation alters CEP83 conformation or binding partners is unknown
    • Whether all four phosphosites are equally required was not dissected
  5. 2019 Medium

    CEP83 was linked to preciliary vesicle trafficking through its requirement for RABL2 and Rabin8 centrosomal accumulation and its interaction with TRAPPC14, connecting DAP integrity to vesicular tethering machinery.

    Evidence siRNA knockdown, Co-IP of CEP83-TRAPPC14, fluorescence imaging of Rabin8 and RABL2

    PMID:30578315 PMID:31467083

    Open questions at the time
    • CEP83-TRAPPC14 interaction shown by single Co-IP without reciprocal validation
    • Whether CEP83 directly contacts RABL2 or acts indirectly through DAP structure is unresolved
  6. 2020 High

    Conditional knockout in mouse radial glial progenitors established that CEP83 anchors centrosomes to the apical membrane and thereby constrains YAP-mediated mechanical signaling; loss causes cortical overgrowth reversed by YAP co-deletion, placing CEP83 upstream of tissue-scale mechanosignaling.

    Evidence Conditional Cep83 knockout, Cep83/Yap double KO epistasis, electron microscopy, mechanobiology assays in mouse cortex

    PMID:32238932

    Open questions at the time
    • Whether the phenotype is cilia-dependent or purely docking-dependent is not fully dissected
    • How membrane stiffening activates YAP mechanistically is unclear
  7. 2022 High

    Hierarchical mapping revealed that OFD1/FOPNL/CEP90 act upstream of CEP83 recruitment, defining CEP83 as an intermediate rather than initiating factor in DAP biogenesis.

    Evidence Ultrastructure expansion microscopy, CRISPR/siRNA knockouts in mammalian cells and Paramecium

    PMID:36070319

    Open questions at the time
    • Direct physical contacts between upstream recruiters and CEP83 not biochemically defined
    • Stoichiometry of CEP83 at individual DAPs unknown
  8. 2022 Medium

    CEP83 inactivation in human iPSCs demonstrated that CEP83-dependent ciliogenesis is required for proper mesodermal lineage specification, as knockout shifted differentiation from intermediate mesoderm toward lateral plate mesoderm.

    Evidence CRISPR inactivation of CEP83 in hiPSCs, single-cell transcriptomics, organoid culture

    PMID:36222666

    Open questions at the time
    • Whether lineage defect is solely cilium-dependent or involves non-ciliary CEP83 functions
    • Rescue by CEP83 re-expression not demonstrated
  9. 2025 High

    Systematic CRISPR knockout combined with superresolution microscopy established the CEP83-SCLT1 module as one of two critical DAP units (alongside CEP164-TTBK2) required for structural integrity and all four steps of ciliation, resolving the functional architecture of DAPs.

    Evidence CRISPR-Cas9 knockouts, DNA-PAINT superresolution microscopy, functional ciliogenesis step assays

    PMID:39882846

    Open questions at the time
    • Structural basis for CEP83-SCLT1 interaction not determined at atomic resolution
    • How the CEP83-SCLT1 module communicates with the CEP164-TTBK2 module is not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the structural basis of the CEP83-SCLT1 module at atomic resolution, how TTBK2-mediated phosphorylation of CEP83 changes its interactions to initiate ciliogenesis, and whether CEP83's non-ciliary docking functions in CTLs and neural progenitors use the same or distinct molecular mechanisms.
  • No high-resolution structure of CEP83 or the CEP83-SCLT1 complex
  • Phosphorylation-dependent conformational or interactome changes uncharacterized
  • Relative contributions of ciliary vs. non-ciliary CEP83 functions in disease not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005815 microtubule organizing center 5 GO:0005929 cilium 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 1 R-HSA-168256 Immune System 1
Partners
CEP164CEP90LRRC45OFD1RABL2SCLT1TRAPPC14TTBK2
Complex memberships
distal appendage (CEP83-SCLT1 module)

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 CEP83 is a core component of distal appendages (DAPs) of the mother centriole required for ciliogenesis; biallelic mutations in CEP83 cause altered DAP composition and ciliary defects in patient fibroblasts and tubular renal cells, establishing CEP83 as essential for DAP assembly and cilia initiation. Targeted exon sequencing, patient fibroblast/renal cell functional analysis, immunofluorescence of DAP composition American journal of human genetics High 24882706
2015 CEP83 is required for distal appendage-mediated docking of the mother centriole to the plasma membrane in cytotoxic T lymphocytes (CTLs); siRNA knockdown of CEP83 impairs CTL secretory lysosome release at the immunological synapse, demonstrating a role for CEP83 beyond ciliogenesis in transient centrosome docking. siRNA knockdown, high-resolution TEM tomography, secretion assays in CTLs Current biology : CB Medium 26670998
2019 CEP83 is a bona fide substrate of TTBK2 kinase; TTBK2 phosphorylates CEP83 at four sites in a CEP164-dependent manner (CEP164 recruits TTBK2 to distal appendages), and this phosphorylation is required for early ciliogenesis steps including ciliary vesicle docking and CP110 removal. Biochemical phosphorylation assays, superresolution microscopy, phosphosite mapping, CEP164-dependent recruitment assays The Journal of cell biology High 31455668
2020 CEP83 is phosphorylated by TTBK2 kinase in vitro and in vivo; TTBK2-dependent phosphorylation of CEP83 (along with CEP89, CCDC92, Rabin8, DVL3, and CEP164) contributes to cilia formation control. In vitro kinase assays, phosphosite mapping by mass spectrometry, 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, causing microtubule disorganization, apical membrane stretching/stiffening, YAP activation, and excessive RGP proliferation leading to cortical enlargement and abnormal folding; simultaneous YAP deletion suppresses the CEP83 KO cortical phenotype, placing CEP83 upstream of YAP mechanosignaling. Conditional mouse knockout (Cep83 deletion), genetic epistasis (Cep83/Yap double KO), electron microscopy of distal appendages, mechanobiology assays, cortical morphology analysis Nature High 32238932
2018 CEP83 and SCLT1 (core appendage proteins) recruit LRRC45 to the mother centriole, establishing CEP83 as upstream of LRRC45 in the distal appendage assembly hierarchy. siRNA knockdown of CEP83/SCLT1, immunofluorescence localization of LRRC45 Journal of cell science Medium 30131441
2019 CEP83 is required for RABL2 recruitment to the mother centriole; RABL2 recruitment depends on distal appendage proteins CEP164 and CEP83, linking CEP83-dependent DAP integrity to ciliary GPCR trafficking. siRNA knockdown of CEP83 and CEP164, immunofluorescence of RABL2 localization Journal of cell science Medium 30578315
2019 CEP83 (distal appendage protein) is required for GFP-Rabin8 accumulation at the centrosome, and CEP83 interacts with TRAPPC14 (C7orf43), linking CEP83-dependent DAP function to TRAPPII complex-mediated preciliary vesicle tethering at the mother centriole. Co-immunoprecipitation, siRNA knockdown, fluorescence imaging of Rabin8 centrosomal accumulation The Journal of biological chemistry Medium 31467083
2022 OFD1, FOPNL, and CEP90 (recruited by MNR/Moonraker) act upstream of CEP83, CEP89, and CEP164 to recruit these distal appendage proteins to the centriole, defining a hierarchical assembly pathway where CEP83 occupies a downstream position relative to these early recruiters. Ultrastructure expansion microscopy, CRISPR/siRNA knockouts in mammalian cells and Paramecium, immunofluorescence dependency assays PLoS biology High 36070319
2025 CEP83 forms a functional module with SCLT1 that is critical for structural assembly of distal appendages; CRISPR deletion of CEP83 severely compromises all four key steps of cilium formation (ciliary vesicle recruitment, IFT recruitment/initiation, CP110 removal), with CEP83 and SCLT1 defining one of two critical protein modules (the other being CEP164-TTBK2) required for distal appendage structural integrity. CRISPR-Cas9 knockouts, superresolution microscopy (DNA-PAINT), functional ciliogenesis step assays eLife High 39882846
2023 CEP83-SCLT1 module is critical for distal appendage structural assembly and all four steps of ciliation (ciliary vesicle recruitment, IFT recruitment, IFT initiation, CP110 removal) as shown by CRISPR knockout; CEP83 occupies an early hierarchical position in distal appendage protein recruitment. CRISPR-Cas9 knockouts, immunofluorescence, localization hierarchy mapping bioRxivpreprint Medium 36711481
2022 CEP83 inactivation in human iPSCs disrupts primary cilia formation (absent or elongated cilia) and perturbs differentiation toward intermediate mesoderm (kidney lineage), causing aberrant lateral plate mesoderm specification, demonstrating a role for CEP83-dependent ciliogenesis in mesodermal lineage decisions. CRISPR inactivation of CEP83 in hiPSCs, single-cell and bulk transcriptomics, organoid culture, cilia immunofluorescence eLife Medium 36222666
2024 siRNA knockdown of CEP83 (along with SCLT1 and CEP164) specifically impairs ciliary assembly and centriole docking, placing CEP83 in a functional subgroup of distal appendage proteins responsible for ciliary assembly (distinct from CEP89/FBF1 which regulate disassembly). siRNA knockdown, ciliogenesis kinetics assays, immunofluorescence Cell communication and signaling : CCS Medium 39696441
2025 In zebrafish radial glial progenitors, Pcm1 is asymmetrically associated with Cep83 (used as a mother centrosome marker), and the PARD3-PCM1-CEP83-RAB11 association is conserved in human cortical brain organoids, linking CEP83 at the mother centriole to centrosome asymmetry and fate decisions. In vivo time-lapse imaging, expansion microscopy, Co-IP in human organoids, zebrafish pcm1 loss-of-function Nature communications Low 41315244

Source papers

Stage 0 corpus · 28 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 130 23530209
2014 Mutations of CEP83 cause infantile nephronophthisis and intellectual disability. American journal of human genetics 92 24882706
2020 Centrosome anchoring regulates progenitor properties and cortical formation. Nature 75 32238932
2019 Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation. The Journal of cell biology 67 31455668
2008 Mutation analysis in nephronophthisis using a combined approach of homozygosity mapping, CEL I endonuclease cleavage, and direct sequencing. Human mutation 66 18076122
2015 Mother Centriole Distal Appendages Mediate Centrosome Docking at the Immunological Synapse and Reveal Mechanistic Parallels with Ciliogenesis. Current biology : CB 61 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 42 32129703
2018 LRRC45 contributes to early steps of axoneme extension. Journal of cell science 42 30131441
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
2025 A hierarchical pathway for assembly of the distal appendages that organize primary cilia. eLife 23 39882846
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 2 41315244
2025 CCDC41 Drives Oocyte Meiotic Progression by Promoting Rab11a/Rab7-Positive Vesicle Fusion with Target Membranes. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41331237
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 Cortex folding by combined progenitor expansion and adhesion-controlled neuronal migration. Nature communications 0 40877293
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