Affinage

CCDC86

Coiled-coil domain-containing protein 86 · UniProt Q9H6F5

Round 2 corrected
Length
360 aa
Mass
40.2 kDa
Annotated
2026-04-28
47 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCDC86 (Cyclon) is a cytokine-inducible, coiled-coil domain-containing nuclear protein that functions at the interface of ribosome biogenesis, chromosome periphery organization, and mitotic fidelity. During mitosis, CCDC86 localizes to the chromosome periphery where it forms subcomplexes with Ki-67, nucleolin, and NPM1 to regulate spindle length and kinetochore–microtubule attachments; its depletion causes chromosome alignment errors, cytoplasmic aggregation of perichromosomal components, and increased apoptosis (PMID:36695333). In interphase, CCDC86 physically binds mRNA (PMID:22658674, PMID:22681889) and interacts with NPM1 to promote EGFR transcription and PI3K/Akt signaling in cancer cells, and with BHLHE40 to stabilize ATF3 expression and activate ERK-driven glycolysis in glioma (PMID:38247332, PMID:40837407). In T cells, CCDC86 is induced by TCR ligation and promotes activation-induced cell death by upregulating Fas (CD95) expression, as demonstrated by conditional knockout and transgenic rescue of autoimmune pathology in IL-2R-deficient mice (PMID:19528538).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2007 Medium

    Establishing CCDC86 as a cytokine-responsive nuclear protein answered the question of whether the gene encodes a regulated transcription unit and where the product resides, placing it as an immediate-early gene in hematopoietic signaling.

    Evidence Northern blot, nuclear fractionation, promoter-reporter assays in IL-3-stimulated hematopoietic cells

    PMID:17300783

    Open questions at the time
    • No molecular function identified beyond nuclear localization
    • Protein binding partners unknown
    • Relevance beyond IL-3-responsive hematopoietic cells undefined
  2. 2009 High

    Demonstrating that CCDC86 drives Fas upregulation and activation-induced cell death in T cells answered how TCR-stimulated lymphocytes integrate cytokine-inducible gene products into apoptotic control, revealing a physiological function in immune homeostasis.

    Evidence Conditional Ccdc86 heterozygous knockout and transgenic overexpression in mice, flow cytometry for Fas, AICD assays, rescue of autoimmunity in IL-2R-deficient mice

    PMID:19528538

    Open questions at the time
    • Mechanism by which CCDC86 upregulates Fas transcription not resolved
    • Whether CCDC86 directly binds the Fas promoter or acts through intermediaries unknown
    • Homozygous deletion phenotype not reported
  3. 2012 Medium

    Two independent mRNA interactome captures identified CCDC86 as a physical mRNA-binding protein, revealing an unexpected RNA-binding capacity for a coiled-coil protein and expanding its potential functional repertoire beyond transcriptional regulation.

    Evidence UV crosslinking/oligo(dT) capture (HeLa) and PAR-CLIP/oligo(dT) capture (HEK293) with quantitative mass spectrometry

    PMID:22658674 PMID:22681889

    Open questions at the time
    • Identity of bound RNA targets unknown
    • RNA-binding domain not mapped
    • Functional consequence of mRNA binding not tested
  4. 2016 Low

    Identification of CCDC86 as a Ki-67 interactor connected it to the perichromosomal layer and heterochromatin organization, raising the question of whether CCDC86 has a mitotic structural role.

    Evidence Ki-67 immunoaffinity purification with mass spectrometry in proliferating cells

    PMID:26949251

    Open questions at the time
    • Single co-purification without reciprocal validation for CCDC86
    • No functional consequence of the interaction tested
    • Whether CCDC86 is a stoichiometric or transient Ki-67 partner unclear
  5. 2021 Medium

    Demonstrating a physical CCDC86–NPM1 interaction in lymphoma cells placed CCDC86 in the nucleolar/RNA-processing network and linked it to MYC signaling and cell cycle control, bridging its nuclear localization with oncogenic pathways.

    Evidence Co-immunoprecipitation, mass spectrometry interactome, immunohistochemistry in DLBCL cells

    PMID:34885010

    Open questions at the time
    • Direct versus indirect nature of the CCDC86–NPM1 interaction not resolved by structural data
    • Functional consequence of disrupting the interaction not shown
    • Whether NPM1 interaction is required for CCDC86 nucleolar retention unknown
  6. 2023 High

    RNAi depletion of CCDC86 established that it is required for chromosome periphery integrity, correct Ki-67 and nucleolin localization, spindle length control, and proper kinetochore–microtubule attachments, answering the key question of whether its mitotic localization is functionally meaningful.

    Evidence siRNA/shRNA knockdown, live-cell and fixed immunofluorescence, co-immunoprecipitation, biochemical fractionation in human cell lines

    PMID:36695333

    Open questions at the time
    • Whether CCDC86 contributes structural scaffolding or recruits other factors to the periphery is not distinguished
    • No rescue experiment reported to confirm specificity
    • Relationship between mRNA-binding activity and mitotic function unexplored
  7. 2023 Medium

    Showing that CCDC86 acts through NPM1 to upregulate EGFR and activate PI3K/Akt signaling in nasopharyngeal carcinoma resolved how CCDC86 promotes tumor cell invasion and connected its NPM1 interaction to a defined oncogenic pathway.

    Evidence Knockdown/overexpression in NPC cell lines, co-IP for CCDC86–NPM1, xenograft models, Western blotting for EGFR/PI3K/Akt

    PMID:38247332

    Open questions at the time
    • Mechanism by which NPM1 regulates EGFR transcription not delineated
    • Whether CCDC86 stabilizes NPM1 protein or modulates its transcriptional activity not resolved
    • Relevance to non-cancer contexts not tested
  8. 2025 Medium

    Identification of BHLHE40 as a direct CCDC86 interactor and ATF3 as a downstream transcriptional target driving ERK-dependent glycolysis in glioma provided a second interphase signaling axis, revealing that CCDC86 engages distinct transcription factor complexes to activate oncogenic programs.

    Evidence Co-IP for CCDC86–BHLHE40, ChIP and luciferase reporter for ATF3 transcription, knockdown/overexpression in glioma lines and xenografts, glycolysis assays

    PMID:40837407

    Open questions at the time
    • Whether CCDC86 acts as a co-activator or a scaffold for BHLHE40 is unknown
    • Overlap between NPM1- and BHLHE40-dependent CCDC86 functions not investigated
    • Single-lab study; independent replication pending

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how CCDC86's mRNA-binding activity relates to its mitotic and interphase functions, whether it possesses intrinsic enzymatic activity, and what structural features mediate its incorporation into the chromosome periphery versus its engagement with NPM1 and BHLHE40 in transcriptional signaling.
  • No structural model or domain-resolution interaction mapping available
  • mRNA targets and functional consequence of RNA binding uncharacterized
  • Relationship between T-cell AICD function and mitotic/oncogenic roles unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005694 chromosome 1 GO:0005730 nucleolus 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1640170 Cell Cycle 1 R-HSA-168256 Immune System 1
Partners
BHLHE40MKI67NCLNPM1

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 CCDC86 (Cyclon) is a cytokine-inducible immediate-early gene encoding a nuclear protein with repetitive sequences at the amino-terminus and a coiled-coil domain at the carboxyl-terminus; it is induced in hematopoietic cells by IL-3, and its promoter contains redundant elements sufficient for IL-3-driven transcriptional activation. Northern blot/RT-PCR identification of induced gene, subcellular fractionation and immunostaining showing nuclear localization, transient reporter assay mapping promoter elements FEBS letters Medium 17300783
2009 CCDC86 (Cyclon) is induced in T cells upon TCR ligation and promotes activation-induced cell death (AICD) by upregulating Fas (CD95) expression; conditional deletion of one Cyclon allele in activated CD4+ T cells reduced Fas expression and AICD, while transgenic Cyclon expression enhanced AICD and ameliorated autoimmune phenotype in IL-2R-deficient mice. Conditional knockout mice, transgenic overexpression, flow cytometry for Fas surface expression, AICD assay, autoimmune phenotype rescue in vivo Blood High 19528538
2012 CCDC86 was identified as an mRNA-binding protein in human HeLa cells by UV crosslinking and oligo(dT) purification (interactome capture), indicating it physically associates with mRNA. UV crosslinking followed by oligo(dT) purification and quantitative mass spectrometry (interactome capture) Cell Medium 22658674
2012 CCDC86 was independently identified as an mRNA-associated protein in human HEK293 cells using photoactivatable-ribonucleoside-enhanced crosslinking and oligo(dT) purification (PAR-CLIP-based mRNA interactome). PAR-CLIP (photoreactive nucleotide-enhanced UV crosslinking) and oligo(dT) purification coupled to quantitative proteomics Molecular cell Medium 22681889
2013 CCDC86 (Cyclon) protein is expressed in neurons and astrocytes of the adult macaque hippocampus (including CA fields and dentate gyrus), extending its known expression beyond lymphocytes to the central nervous system. Immunohistochemistry and confocal microscopy on adult non-human primate brain sections with cell-type co-labeling Journal of neuroimmunology Low 23528659
2015 CCDC86 was identified as part of conserved metazoan macromolecular complexes by biochemical co-fractionation across multiple species, placing it within ancient protein assemblies. Biochemical fractionation coupled with quantitative mass spectrometry across metazoan species Nature Low 26344197
2016 CCDC86 was identified among Ki-67 interactors in proliferating cells, connecting it to the Ki-67 nuclear protein network involved in heterochromatin organisation. Ki-67 immunoaffinity purification followed by mass spectrometry identification of interacting proteins eLife Low 26949251
2020 CCDC86 was identified as a host protein that physically associates with SARS-CoV-2 Nsp8 by affinity-purification mass spectrometry, placing it in the viral-host protein interaction network. AP-MS (affinity purification coupled to mass spectrometry) in HEK293T cells expressing tagged SARS-CoV-2 proteins Nature Low 32353859
2021 CCDC86 (CYCLON) physically interacts with NPM1 (nucleophosmin) and participates in a protein interaction network connecting it to the nucleolus, RNA processing, MYC signalling, and cell cycle progression in diffuse large B-cell lymphoma cells. Immunoprecipitation/co-IP, mass spectrometry-based interactome mapping, immunohistochemistry for subcellular localization (extra-nucleolar vs. nucleolar) Cancers Medium 34885010
2023 CCDC86 localises to the chromosome periphery during mitosis and physically interacts with Ki-67 (MKI67); RNAi-mediated depletion of CCDC86 causes disorganisation of the chromosome periphery with altered localisation of Ki-67 and nucleolin, formation of cytoplasmic aggregates, chromosome alignment errors, altered spindle length, and increased apoptosis, indicating that CCDC86 is part of subcomplexes with nucleolin and NPM1 (B23) required for mitotic spindle regulation and correct kinetochore-microtubule attachments. RNA interference (siRNA/shRNA), live-cell and fixed immunofluorescence microscopy, co-immunoprecipitation, biochemical fractionation Journal of cell science High 36695333
2023 CCDC86 promotes proliferation, invasion, and migration of nasopharyngeal carcinoma cells by binding NPM1, which positively regulates EGFR transcription/expression; activated EGFR in turn activates downstream PI3K/Akt signalling to drive EMT and MMP upregulation. CCDC86 does not directly bind EGFR but acts through NPM1. siRNA knockdown and overexpression in NPC cell lines, in vivo xenograft assays, co-immunoprecipitation (CCDC86–NPM1 interaction), Western blotting for EGFR/PI3K/Akt pathway components, invasion/migration assays Neoplasma Medium 38247332
2025 CCDC86 promotes glioma cell proliferation and migration and inhibits apoptosis by interacting with the transcription factor BHLHE40, stabilising ATF3 expression; CCDC86 then activates the ERK signalling pathway through ATF3 to enhance aerobic glycolysis and tumour progression. siRNA knockdown and overexpression in glioma cell lines and in vivo xenograft models, co-immunoprecipitation (CCDC86–BHLHE40), chromatin-immunoprecipitation/luciferase reporter for ATF3 transcription, ERK pathway Western blotting, glycolysis assays Genes & diseases Medium 40837407

Source papers

Stage 0 corpus · 47 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 3411 32353859
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 1362 16751776
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2020 Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis. Med (New York, N.Y.) 291 32838362
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 265 26949251
2014 Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. Journal of proteomics 215 25281560
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2020 Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nature cell biology 194 32203420
2013 The protein interaction landscape of the human CMGC kinase group. Cell reports 174 23602568
2014 Global mapping of herpesvirus-host protein complexes reveals a transcription strategy for late genes. Molecular cell 173 25544563
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2012 Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Molecular & cellular proteomics : MCP 145 22586326
2018 Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains. Molecular cell 136 30554943
2013 Association of granulomatosis with polyangiitis (Wegener's) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis. Arthritis and rheumatism 133 23740775
2003 A novel N-terminal cyclic dynorphin A analogue cyclo(N,5)[Trp(3),Trp(4),Glu(5)] dynorphin A-(1-11)NH(2) that lacks the basic N-terminus. Journal of medicinal chemistry 29 12672226
2007 Redundant promoter elements mediate IL-3-induced expression of a novel cytokine-inducible gene, cyclon. FEBS letters 20 17300783
2009 Regulation of Fas-mediated immune homeostasis by an activation-induced protein, Cyclon. Blood 16 19528538
2019 Cgr1, a ripe rot resistance QTL in Vitis amurensis 'Shuang Hong' grapevine. Horticulture research 15 31231525
2023 CCDC86 is a novel Ki-67-interacting protein important for cell division. Journal of cell science 8 36695333
2001 Isolation and expression of a gene (CGR1) regulated during the yeast-hyphal transition in Candida albicans. Biochimica et biophysica acta 7 11342110
2023 CCDC86 promotes the aggressive behavior of nasopharyngeal carcinoma by positively regulating EGFR and activating the PI3K/Akt signaling. Neoplasma 6 38247332
2021 CYCLON and NPM1 Cooperate within an Oncogenic Network Predictive of R-CHOP Response in DLBCL. Cancers 5 34885010
2015 Complete genome sequence of Microbacterium sp. CGR1, bacterium tolerant to wide abiotic conditions isolated from the Atacama Desert. Journal of biotechnology 5 26521698
2013 Expression and differential response to haloperidol treatment of Cyclon/CCDC86 mRNA in schizophrenia patients. Neurochemistry international 5 23439384
2013 Expression of Cyclon/CCDC86, a novel nuclear protein, in the hippocampus of adult non-human primates. Journal of neuroimmunology 5 23528659
2005 The CRAL/TRIO and GOLD domain protein CGR-1 promotes induction of vulval cell fates in Caenorhabditis elegans and interacts genetically with the Ras signaling pathway. Genetics 5 16219793
2001 Molecular cloning of cgrA, the gene encoding the Aspergillus nidulans ortholog of Saccharomyces cerevisiae CGR1. Current microbiology 4 11381331
2025 Establishment of an Assay with Ultrahigh Sensitivity for Detecting sEV-Derived PD-L1 as a Serum Biomarker for Lung Cancer-A Pilot Study Using TN-cyclon™. Current issues in molecular biology 2 40729033
2025 CCDC86-BHLHE40-ATF3 axis promotes aerobic glycolysis and tumor development in glioma. Genes & diseases 2 40837407
2026 Single-cell RNA sequencing unveils CCDC86-driven immune modulation and antigen-presenting cell dynamics in head and neck squamous cell carcinoma. Discover oncology 0 41661401
2025 CCDC86 modulates immune cell infiltration and disease progression in head and neck squamous cell carcinoma. Discover oncology 0 41467918