Affinage

CEP162

Centrosomal protein of 162 kDa · UniProt Q5TB80

Length
1403 aa
Mass
161.9 kDa
Annotated
2026-04-28
24 papers in source corpus 8 papers cited in narrative 8 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CEP162 is a microtubule-associated ATPase that functions at centriole distal ends to coordinate transition zone assembly during ciliogenesis and to support mitotic spindle integrity. Pre-tethered at the distal tips of centriolar microtubules in a C2CD3-dependent manner, CEP162 recognizes axonemal microtubules and recruits core transition zone components including CEP290; loss of CEP162 arrests ciliogenesis at the transition zone assembly stage, while untethering it causes ectopic transition zone assembly at cilia tips (PMID:23644468, PMID:41364719, PMID:38442096). CEP162 also localizes to spindle poles during mitosis, where its depletion causes chromosome segregation defects and abnormal centrosome separation, and it promotes retinal neurogenesis through a function molecularly separable from its ciliary role (PMID:16302001, PMID:36862503). A truncating CEP162 variant causes late-onset retinitis pigmentosa by selectively abolishing basal-body localization and ciliary transition zone recruitment while preserving spindle and neurogenic functions (PMID:36862503).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2001 Medium

    Establishing that CEP162 participates in neuronal differentiation answered whether this uncharacterized protein has developmental roles: it redistributes to the nucleus in post-mitotic neurons, and its reduction causes ectopic mitosis and retinal dysplasia.

    Evidence Antisense knockdown in chick retina with immunolocalization

    PMID:11287185

    Open questions at the time
    • Molecular targets mediating the neurogenic function were not identified
    • Whether the nuclear relocalization is essential for cell-cycle exit was not tested
  2. 2006 Medium

    Demonstrating that CEP162 is an ATPase at mitotic spindle poles whose depletion causes chromosome segregation defects established a centrosome-associated mitotic function distinct from its later-discovered ciliary role.

    Evidence siRNA knockdown in human cells with spindle pole immunolocalization and viability assays

    PMID:16302001

    Open questions at the time
    • ATPase activity was inferred from sequence but not biochemically measured
    • Whether mitotic and ciliary functions share the same protein domains was unknown
  3. 2013 High

    A landmark study resolved how transition zone assembly is spatially restricted: CEP162 is pre-tethered at centriole distal ends, recognizes axonemal microtubules, and recruits transition zone components; untethering it causes ectopic transition zone assembly at cilia tips, establishing CEP162 as the spatial gatekeeper of transition zone positioning.

    Evidence Quantitative centrosome proteomics, Co-IP, siRNA knockdown, tethering-deficient mutants, and live imaging in mammalian cells

    PMID:23644468

    Open questions at the time
    • The identity of the tethering anchor at the centriole distal end was not determined
    • Direct binding partners among transition zone components were not fully mapped
  4. 2023 High

    Identification of a disease-causing CEP162 truncation that selectively disrupts basal-body but not spindle localization proved that CEP162's ciliary and neurogenic functions are molecularly separable and linked CEP162 to retinitis pigmentosa.

    Evidence Patient variant analysis, shRNA knockdown in mouse retina, rescue experiments with mutant and wild-type constructs

    PMID:36862503

    Open questions at the time
    • The protein domain mediating basal-body targeting specifically was not delineated
    • Whether other ciliopathy phenotypes beyond retinal degeneration arise from CEP162 variants is unexplored
  5. 2024 Medium

    Genetic epistasis in Drosophila placed CEP162 in a Cep131-Cep162 axonemal module that cooperates with a membrane-proximal Cby-Fam92 module to maintain Cep290 at the basal body, defining a two-module architecture for ciliogenesis initiation.

    Evidence Drosophila combinatorial genetic deletions with Cep290 immunolocalization

    PMID:38442096

    Open questions at the time
    • Direct physical interaction between Cep131 and Cep162 was not biochemically demonstrated in this system
    • Whether the two-module architecture is conserved in mammalian ciliogenesis is untested
  6. 2025 Medium

    Identifying C2CD3 as an upstream determinant of CEP162 distal-tip localization resolved how CEP162 is tethered: a C2CD3-organized luminal ring network stabilizes CEP162 at the distal microtubule tip.

    Evidence Ultrastructure expansion microscopy and cryo-ET with C2CD3 depletion in human cells

    PMID:41364719

    Open questions at the time
    • Whether C2CD3 and CEP162 interact directly or through intermediate adaptor proteins is unresolved
    • Structural basis of CEP162 recognition of microtubule distal tips is unknown
  7. 2026 Medium

    Discovery that CEP162 expression is epigenetically controlled by the ASXL2-EZH2-H3K27me3 axis, and that overexpressed CEP162 competes with TUBA3A for TUBB3 binding to destabilize axonemal microtubules, revealed a tubulin-competition mechanism linking CEP162 dosage to cilia structural integrity.

    Evidence ChIP assay on CEP162 promoter, binding competition assay for TUBB3, spermatogenesis phenotype under chronic hypoxia

    PMID:41782374

    Open questions at the time
    • Whether CEP162-TUBB3 binding is direct and stoichiometric has not been confirmed with purified proteins
    • Relevance of this epigenetic regulation outside the spermatogenesis context is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CEP162's axoneme-recognition and transition-zone-recruiting activities, whether its ATPase activity is catalytically required for any of its functions, and the full spectrum of human disease caused by CEP162 variants.
  • No crystal or cryo-EM structure of CEP162 exists
  • ATPase activity has not been biochemically reconstituted or shown to be required
  • Complete interactome mapping of CEP162 at the transition zone is lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0140657 ATP-dependent activity 1
Localization
GO:0005815 microtubule organizing center 4 GO:0005929 cilium 3 GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 1
Partners
C2CD3CEP131CEP290TUBB3

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 CEP162 (KIAA1009) is an axoneme-recognition protein pre-tethered at centriole distal ends that promotes and restricts transition zone assembly specifically at the cilia base. It interacts with core transition zone components and mediates their association with microtubules. Loss of CEP162 arrests ciliogenesis at the transition zone assembly stage. Abolishing its centriolar tethering allows CEP162 to stay on the growing axoneme end and ectopically assemble transition zone components at cilia tips, generating extra-long cilia with swollen tips that release ciliary contents extracellularly. Quantitative centrosome proteomics, Co-IP, loss-of-function (siRNA/KD), tethering mutants, live imaging, fractionation Nature cell biology High 23644468
2006 QN1/KIAA1009 (CEP162) is an ATPase localized at spindle poles and centrosomes during mitosis. siRNA-mediated depletion leads to chromosome segregation defects and abnormal centrosome separation, causing cell death, identifying it as a microtubule-associated ATPase required for cell division. siRNA knockdown, immunofluorescence localization, cell viability assays, sequence conservation analysis Oncogene Medium 16302001
2001 CEP162 (KIAA1009/QN1) protein redistributes from the cytoplasm in proliferating cells to predominantly nuclear localization in post-mitotic neurons during differentiation. Antisense-mediated reduction of QN1 protein causes additional mitosis and retinal dysplasia in vivo, indicating a key role at the onset of neuronal cell cycle withdrawal. Antisense oligonucleotide knockdown in vitro and in vivo, immunofluorescence subcellular localization, retinal developmental assays Mechanisms of development Medium 11287185
2001 KIAA1009 (CEP162) was identified as a nuclear protein co-localizing with GAS41 and NuMA in glioma cells, identified as a binding partner of GAS41 by yeast two-hybrid screening. Yeast two-hybrid screening, immunofluorescence co-localization, polyclonal antibody generation and Western blot Oncogene Low 11521196
2023 A truncating variant in CEP162 (CEP162-E646R*5) causes late-onset retinitis pigmentosa. The mutant protein localizes normally to the mitotic spindle but is absent from the basal body in primary and photoreceptor cilia, impairing transition zone component recruitment and causing delayed dysmorphic cilia formation. In contrast, shRNA knockdown of Cep162 in developing mouse retina increased cell death rescued by the CEP162-E646R*5 mutant, demonstrating that CEP162 has separable ciliary and neurogenic functions. Patient variant analysis, shRNA knockdown in mouse retina, immunolocalization, rescue experiments with mutant construct The Journal of clinical investigation High 36862503
2024 In Drosophila, the Cep131-Cep162 module near the axoneme cooperates with the Cby-Fam92 module near the ciliary membrane to synergistically maintain Cep290 at the basal body and initiate ciliogenesis. Concurrent deletion of components from both modules causes complete loss of Cep290 from the basal body and blocks ciliogenesis initiation. Drosophila genetic deletion, epistasis analysis, immunolocalization PLoS biology Medium 38442096
2025 C2CD3 depletion destabilizes CEP162 at the distal microtubule tip of the centriole, placing CEP162 downstream of C2CD3 in distal centriole organization. CEP162 is identified as a distal microtubule tip protein whose localization depends on the C2CD3-organized luminal ring network. Ultrastructure expansion microscopy (U-ExM), cryo-electron tomography, C2CD3 depletion with immunolocalization readout PLoS biology Medium 41364719
2026 Chronic hypoxia downregulates ASXL2, reducing EZH2 binding to the CEP162 promoter (at bp 3482–3511), decreasing H3K27me3 modification and increasing CEP162 transcription. Overexpressed CEP162 competes with TUBA3A for TUBB3 binding, depleting ciliary TUBB3 and destabilizing axonemal microtubules, causing sperm malformations. ChIP assay, promoter binding analysis, overexpression competition assay (CEP162 vs. TUBA3A for TUBB3), spermatogenesis phenotype analysis Advanced science Medium 41782374

Source papers

Stage 0 corpus · 24 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 New substituted quinoxalines inhibit triple-negative breast cancer by specifically downregulating the c-MYC transcription. Nucleic acids research 85 31584090
2013 CEP162 is an axoneme-recognition protein promoting ciliary transition zone assembly at the cilia base. Nature cell biology 79 23644468
1990 A fusion-defective mutant of the vesicular stomatitis virus glycoprotein. Journal of virology 73 2168975
2014 A genome-wide association study for diabetic retinopathy in a Japanese population: potential association with a long intergenic non-coding RNA. PloS one 67 25364816
2017 Genomewide association studies of suicide attempts in US soldiers. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 50 28902444
2001 Expression, cellular distribution and protein binding of the glioma amplified sequence (GAS41), a highly conserved putative transcription factor. Oncogene 27 11521196
2019 Genetic Associations With Diabetic Retinopathy and Coronary Artery Disease in Emirati Patients With Type-2 Diabetes Mellitus. Frontiers in endocrinology 19 31130920
2006 QN1/KIAA1009: a new essential protein for chromosome segregation and mitotic spindle assembly. Oncogene 16 16302001
2019 A novel water-soluble fluorescence probe based on ICT lighten for detecting hydrogen sulfide and its application in bioimaging. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy 14 30798218
2023 CEP162 deficiency causes human retinal degeneration and reveals a dual role in ciliogenesis and neurogenesis. The Journal of clinical investigation 11 36862503
2020 Genetic determinants of ammonia-induced acute lung injury in mice. American journal of physiology. Lung cellular and molecular physiology 11 33050709
1993 A novel cDNA corresponding to transcripts expressed in retina post-mitotic neurons. Mechanisms of development 10 8297788
2024 Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation. PLoS biology 7 38442096
2015 Design and Synthesis of Nicotinic Acetylcholine Receptor Antagonists and their Effect on Cognitive Impairment. Chemical biology & drug design 7 26235313
2022 Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract. Frontiers in pediatrics 5 35990004
2001 Role of QN1 protein in cell proliferation arrest and differentiation during the neuroretina development. Mechanisms of development 5 11287185
2025 The Luminal Ring Protein C2CD3 Acts as a Radial In-to-Out Organizer of the Distal Centriole and Appendages. bioRxiv : the preprint server for biology 4 40667239
2023 The association of five polymorphisms with diabetic retinopathy in a Chinese population. Ophthalmic genetics 3 37066695
2025 Design, synthesis, characterization, in silico studies, and in vitro anticancer evaluation of novel 7-methoxyquinolone-substituted triazole hybrids. Future medicinal chemistry 2 40667682
2024 Deciphering Estrus Expression in Gilts: The Role of Alternative Polyadenylation and LincRNAs in Reproductive Transcriptomics. Animals : an open access journal from MDPI 2 38473176
2025 The luminal ring protein C2CD3 acts as a radial in-to-out organizer of the distal centriole and appendages. PLoS biology 1 41364719
2026 Chronic Hypoxia Disrupts Spermatogenesis Through ASXL2-EZH2-Mediated Microtubule Destabilization. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41782374
2025 CEP162: A critical regulator of ciliary transition zone assembly and its implications in ciliopathies. Journal of cell communication and signaling 0 40270641
2025 Quinine and Quinidine Derivatives as Photosensitizers for Photodynamic Inactivation of Bacterial Pathogens. Journal of natural products 0 40793874