Affinage

CCDC124

Coiled-coil domain-containing protein 124 · UniProt Q96CT7

Length
223 aa
Mass
25.8 kDa
Annotated
2026-06-09
25 papers in source corpus 9 papers cited in narrative 9 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

CCDC124, with its yeast ortholog Lso2, is a conserved eukaryotic ribosome-binding protein that mediates reversible translational inactivation (ribosome hibernation) and recovery after stress (PMID:30208026, PMID:32687489). On idle ribosomes in the non-rotated state it adopts a bridging conformation that connects the mRNA decoding site of the small subunit with the GTPase activating center of the large subunit, a configuration that — unlike Stm1/SERBP1-bound rotated ribosomes — remains compatible with Dom34-dependent ribosome splitting and recycling (PMID:32687489). This bridging mode is structurally conserved from microsporidia to humans (PMID:33125369), and loss of the protein causes global translation defects during recovery from stationary phase, with ribosomes accumulating at start codons (PMID:30208026). CCDC124 is itself an RNA-binding protein that associates with diverse mRNAs (PMID:33896821). Beyond the ribosome, CCDC124 has discrete subcellular roles: it localizes to the centrosome and cytokinetic midbody, where its depletion produces enlarged multinucleated cells and where it interacts with RasGEF1B, linking it to Rap2 signaling during abscission (PMID:23894443); it localizes to the nucleolus through interaction with NPM1, with its nucleolar residence depending on NPM1 and lost upon stress-induced NPM1 redistribution (PMID:38029384); and it is a component of stress granules (PMID:39009911). The protein is highly disordered, with an N-terminal low-complexity region and a central aggregation motif that drives cytoplasmic dimer/oligomer formation (PMID:34369007).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2018 High

    Established that the Lso2/CCDC124 ortholog physically engages the translating ribosome and is functionally required for translational recovery, defining it as a ribosome-associated factor rather than an uncharacterized coiled-coil protein.

    Evidence CLIP, ribosome profiling, and mass spectrometry in lso2Δ yeast with human ortholog crosslinking

    PMID:30208026

    Open questions at the time
    • Did not resolve the structural basis of ribosome binding
    • Direct mechanism linking start-codon accumulation to Lso2 loss not defined
  2. 2020 High

    Resolved how CCDC124/Lso2 inactivates ribosomes, showing it bridges the small-subunit decoding site to the large-subunit GTPase center on non-rotated ribosomes and distinguishing it functionally from the Stm1/SERBP1 hibernation mode by permitting Dom34-dependent recycling.

    Evidence Cryo-EM of yeast and human hibernating ribosomes with functional comparison to Stm1/SERBP1

    PMID:32687489

    Open questions at the time
    • Trigger and kinetics of CCDC124 loading/release in vivo not defined
    • Relationship between hibernation role and non-ribosomal localizations unaddressed
  3. 2020 High

    Demonstrated cross-kingdom conservation of the bridging mechanism, establishing the reversible ribosome inactivation function as a general eukaryotic property.

    Evidence Cryo-EM of Paranosema locustae (microsporidian) hibernating ribosomes

    PMID:33125369

    Open questions at the time
    • Does not address human-specific regulation or non-ribosomal functions
  4. 2013 Medium

    Linked CCDC124 to cell division, showing it localizes to the centrosome and midbody and is required for cytokinetic abscission via interaction with RasGEF1B/Rap2 signaling.

    Evidence Immunofluorescence, siRNA knockdown with multinucleation readout, and Co-IP in HeLa cells

    PMID:23894443

    Open questions at the time
    • RasGEF1B interaction from single-lab Co-IP without reciprocal validation
    • Mechanistic connection between ribosomal and cytokinetic roles unknown
  5. 2021 Medium

    Identified CCDC124 as an RNA-binding protein associating with cellular mRNAs, consistent with a broader role in RNA metabolism beyond the ribosome.

    Evidence RIP followed by RNA-seq

    PMID:33896821

    Open questions at the time
    • No specific functional mRNA targets validated
    • Binding determinants and sequence specificity unknown
  6. 2021 Medium

    Characterized the biophysical basis of CCDC124 self-association, showing a disordered N-terminus and central aggregation motif drive cytoplasmic dimer/oligomer formation.

    Evidence In silico modeling, Co-IP, BiFC, and immunostaining in live cells

    PMID:34369007

    Open questions at the time
    • Functional consequence of oligomerization not established
    • V153 role inferred from docking rather than mutagenesis in cells
  7. 2023 Medium

    Connected CCDC124 to nucleolar stress sensing by showing its nucleolar localization depends on NPM1 and is lost upon stress-induced NPM1 redistribution.

    Evidence LC-MS/MS interactome, Co-IP, and immunocytochemistry with doxorubicin-induced NPM1 translocation in HEK293/U2OS cells

    PMID:38029384

    Open questions at the time
    • Functional role of CCDC124 in the nucleolus undefined
    • Single lab; NPM1 interaction not reciprocally validated
  8. 2024 Medium

    Placed CCDC124 within stress granules, the membraneless organelles of translational shutdown, consistent with its hibernation and RNA-binding roles.

    Evidence Split-GFP live-cell imaging in U2OS cells with G3BP1 overexpression

    PMID:39009911

    Open questions at the time
    • Single method for stress-granule localization
    • Whether CCDC124 affects stress-granule assembly or dynamics untested
  9. 2025 Low

    Implicated CCDC124 in viral late gene transcription via m6A-modified R-loops in phase-separated viral replication compartments.

    Evidence Split-APEX2 proximity labeling and functional disruption in HSV-infected cells

    PMID:41335005

    Open questions at the time
    • Proximity labeling does not establish direct interaction
    • Limited mechanistic detail; not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CCDC124's ribosome-hibernation role mechanistically integrates with its distinct localizations at the centrosome/midbody, nucleolus, and stress granules — and whether these reflect one coordinated stress-response program or independent functions — remains unresolved.
  • No unifying mechanism linking ribosomal and non-ribosomal pools
  • Regulatory signals controlling CCDC124 partitioning unknown
  • No structural data on non-ribosomal complexes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0045182 translation regulator activity 2
Localization
GO:0005840 ribosome 2 GO:0005730 nucleolus 1 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-8953854 Metabolism of RNA 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
G3BP1NPM1RASGEF1B

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 Lso2 (yeast ortholog of CCDC124) is a ribosome-associated protein that crosslinks to 25S rRNA near the A site overlapping the GTPase activation center, and also crosslinks to most tRNAs. Deletion of LSO2 causes global translation defects during recovery from stationary phase, with ribosomes accumulating at start codons, depleted from stop codons, and showing codon-specific occupancy changes. Quantitative mass spectrometry (ribosome identification), genome-wide crosslinking and immunoprecipitation (CLIP), ribosome profiling of lso2Δ yeast PLoS biology High 30208026
2020 Cryo-EM structures of translationally inactive yeast and human ribosomes show Lso2/CCDC124 accumulates on idle ribosomes in the non-rotated state and bridges the decoding site of the small subunit with the GTPase activating center (GAC) of the large subunit, in contrast to Stm1/SERBP1-bound ribosomes which are in the rotated state. Lso2-containing ribosomes are compatible with Dom34-dependent ribosome recycling (splitting), whereas Stm1-containing ribosomes are not. Cryo-electron microscopy (cryo-EM) structural determination of yeast and human hibernating ribosomes PLoS biology High 32687489
2020 The microsporidian Lso2 homolog adopts a V-shaped conformation to bridge the mRNA decoding site and the large subunit tRNA binding sites in Paranosema locustae ribosomes, providing a conserved reversible ribosome inactivation mechanism consistent with the eukaryotic hibernation function of CCDC124/Lso2. Cryo-electron microscopy (cryo-EM) structural determination of P. locustae hibernating ribosomes PLoS biology High 33125369
2013 Human CCDC124 localizes to the centrosome and cytokinetic midbody. Knockdown of CCDC124 in HeLa cells leads to accumulation of enlarged and multinucleated cells without affecting centrosome maturation. CCDC124 interacts with Ras-guanine nucleotide exchange factor 1B (RasGEF1B), linking CCDC124 to Rap2 signaling at the midbody during cytokinetic abscission. Immunofluorescence/subcellular localization, siRNA knockdown with phenotypic readout (multinucleated cells), co-immunoprecipitation (interaction with RasGEF1B) PloS one Medium 23894443
2021 CCDC124 is an RNA-binding protein (RBP) that interacts with various mRNAs as demonstrated by RNA immunoprecipitation (RIP) and RNA-seq experiments. RNA immunoprecipitation (RIP) followed by RNA-seq Cancer biomarkers : section A of Disease markers Medium 33896821
2021 CCDC124 is a highly disordered protein with low-complexity regions at the N-terminus and an aggregation sequence (151-IAVLSV-156) in the middle region. CCDC124 forms dimers/oligomers predominantly in the cytoplasm, with residue V153 implicated in high-order oligomeric state formation by molecular docking and binding free energy analysis. In silico protein modeling, co-immunoprecipitation (Co-IP), immunostaining, bimolecular fluorescence complementation (BiFC) in live cells Proteins Medium 34369007
2023 CCDC124 interacts with nucleophosmin-1 (Npm1/NPM1) and colocalizes with it in the nucleolus. Nucleolar localization of CCDC124 is impaired when Npm1 translocates from the nucleolus to the nucleoplasm in response to doxorubicin (a DNA-intercalator and Topo2 inhibitor), linking CCDC124 nucleolar localization to Npm1-dependent nucleolar stress-sensing. LC-MS/MS proteomics (unbiased interactome), co-immunoprecipitation, immunocytochemistry with GFP-tagged CCDC124 in HEK293 and U2OS cells, doxorubicin treatment to induce Npm1 translocation Biology of the cell Medium 38029384
2024 CCDC124 is present in G3BP1-overexpression-induced stress granules in living U2OS cells, identifying CCDC124 as a novel component of stress granules, membraneless organelles involved in translational shutdown during cellular stress. Live cell protein imaging using split-GFP (GFP11×4/GFP1-10) tagging and laser scanning confocal microscopy in U2OS cells with G3BP1 overexpression The protein journal Medium 39009911
2025 CCDC124 was identified as an essential regulator of m6A-modified R-loops within phase-separated viral replication compartments during HSV infection; disruption of CCDC124 selectively impairs viral late gene transcription. Proximity proteomics (split-APEX2 proximity labeling) and functional disruption assay in HSV-infected cells Analytical chemistry Low 41335005

Source papers

Stage 0 corpus · 25 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes. PLoS biology 87 32687489
2018 Maternal genome-wide DNA methylation profiling in gestational diabetes shows distinctive disease-associated changes relative to matched healthy pregnancies. Epigenetics 53 27019060
2018 Lso2 is a conserved ribosome-bound protein required for translational recovery in yeast. PLoS biology 41 30208026
2020 FOLFOX treatment response prediction in metastatic or recurrent colorectal cancer patients via machine learning algorithms. Cancer medicine 32 31893575
2008 Milk fatty acid composition of grazing dairy cows when supplemented with linseed oil. Journal of dairy science 26 18218760
2020 Differences in structure and hibernation mechanism highlight diversification of the microsporidian ribosome. PLoS biology 22 33125369
2016 A Pap1-Oxs1 signaling pathway for disulfide stress in Schizosaccharomyces pombe. Nucleic acids research 21 27664222
2014 A chemical potentiator of copper-accumulation used to investigate the iron-regulons of Saccharomyces cerevisiae. Molecular microbiology 19 24895027
2013 Coiled-coil domain containing protein 124 is a novel centrosome and midbody protein that interacts with the Ras-guanine nucleotide exchange factor 1B and is involved in cytokinesis. PloS one 18 23894443
2021 Corn silage-based diet supplemented with increasing amounts of linseed oil: Effects on methane production, rumen fermentation, nutrient digestibility, nitrogen utilization, and milk production of dairy cows. Journal of dairy science 16 33663815
2021 Coiled-coil domain-containing protein-124 (Ccdc124) is a novel RNA binding factor up-regulated in endometrial, ovarian, and urinary bladder cancers. Cancer biomarkers : section A of Disease markers 13 33896821
2022 Nuclear Proteomics of Induced Leukemia Cell Differentiation. Cells 11 36291090
2015 The late-annotated small ORF LSO1 is a target gene of the iron regulon of Saccharomyces cerevisiae. MicrobiologyOpen 11 26450372
2020 Overproduction of plant nuclear export signals enhances diamide tolerance in Schizosaccharomyces pombe. Biochemical and biophysical research communications 4 32800339
2018 Protection from Disulfide Stress by Inhibition of Pap1 Nuclear Export in Schizosaccharomyces pombe. Genetics 4 30181192
2025 Proteomic Profiling Reveals Novel Molecular Insights into Dysregulated Proteins in Established Cases of Rheumatoid Arthritis. Proteomes 3 40700276
2021 Dimerization underlies the aggregation propensity of intrinsically disordered coiled-coil domain-containing 124. Proteins 3 34369007
2015 Silica nanowire conjugated with loop-shaped oligonucleotides: A new structure to silence cysteine proteinase gene in Leishmania tropica. Colloids and surfaces. B, Biointerfaces 3 26432619
2025 Development and validation of a disulfidptosis-related genes signature for predicting outcomes and immunotherapy in acute myeloid leukemia. Frontiers in immunology 2 40255396
2025 Environmental drivers affecting the dormancy of Paranosema locustae. Journal of applied microbiology 1 40275519
2025 Detection and Characterization of the Eukaryotic Vacant Ribosome. International journal of molecular sciences 1 41516182
2024 Live Cell Protein Imaging of Tandem Complemented-GFP11-Tagged Coiled-Coil Domain-Containing Protein-124 Identifies this Factor in G3BP1-Induced Stress-Granules. The protein journal 1 39009911
2023 Proteomics analysis identifies the ribosome associated coiled-coil domain-containing protein-124 as a novel interaction partner of nucleophosmin-1. Biology of the cell 1 38029384
2025 Transcriptomic and Polysomnographic Insights Into Core Signaling Pathways in Obstructive Sleep Apnea. Mediators of inflammation 0 41058921
2025 Spatial Mapping and Interactome Profiling of m6A-Modified R-Loops via Chemically Inducible Split-APEX2 Proximity Labeling. Analytical chemistry 0 41335005

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