Affinage

CCDC102B

Coiled-coil domain-containing protein 102B · UniProt Q68D86

Round 2 corrected
Length
513 aa
Mass
60.4 kDa
Annotated
2026-04-28
43 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCDC102B is a centrosome linker protein that is recruited to the centrosome by C-Nap1 (CEP250), where it physically interacts with rootletin and LRRC45 to facilitate linker filament assembly and maintain centrosome cohesion during interphase; at mitosis onset, Nek2A-mediated phosphorylation causes CCDC102B to dissociate, enabling centrosome separation (PMID:30404835). CCDC102B also interacts with RACK1 and, when overexpressed, competitively reduces RACK1–IKKα association, thereby activating NF-κB signaling and promoting breast cancer metastasis in xenograft models; RACK1 in turn targets CCDC102B for lysosomal degradation via chaperone-mediated autophagy (PMID:35957886).

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2018 High

    Established CCDC102B as a centrosome linker component, resolving how rootletin filaments are assembled and how centrosome cohesion is maintained and then released at mitosis via Nek2A phosphorylation.

    Evidence Co-immunoprecipitation, immunofluorescence, knockdown-induced centrosome splitting, in vitro Nek2A phosphorylation assay, and rootletin filament formation assay in human cells

    PMID:30404835

    Open questions at the time
    • Exact phosphorylation sites on CCDC102B by Nek2A are not mapped at residue resolution
    • No structural model of the CCDC102B–rootletin or CCDC102B–LRRC45 interfaces
    • Whether CCDC102B has linker-independent functions was unexplored
  2. 2022 Medium

    Revealed a non-centrosomal role for CCDC102B in cancer, showing it activates NF-κB by sequestering RACK1 away from IKKα and is itself degraded by RACK1-directed chaperone-mediated autophagy, linking centrosome biology to metastatic signaling.

    Evidence Co-IP, mass spectrometry, RNA-seq pathway analysis, CRISPR screen, xenograft and tail-vein metastasis models in breast cancer cell lines

    PMID:35957886

    Open questions at the time
    • Findings originate from a single laboratory; independent replication is lacking
    • Whether the RACK1–CCDC102B axis operates in non-breast cancer contexts is unknown
    • Relationship between centrosome linker function and NF-κB activation has not been dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how the centrosome-linker and NF-κB-signaling functions of CCDC102B are coordinated, whether CCDC102B possesses intrinsic enzymatic activity, and what post-translational modifications beyond Nek2A phosphorylation regulate its stability and localization.
  • No enzymatic activity has been attributed to CCDC102B
  • No high-resolution structure exists
  • In vivo animal models of CCDC102B loss for centrosome cohesion phenotypes are absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 1 R-HSA-1640170 Cell Cycle 1
Partners
CEP250CROCCLRRC45RACK1

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 CCDC102B is a centrosome linker protein required for centrosome cohesion. It localizes to the centrosome via recruitment by C-Nap1 (CEP250), physically interacts with the centrosome linker components rootletin and LRRC45, and decorates and facilitates the formation of rootletin filaments. At the onset of mitosis, CCDC102B is phosphorylated by Nek2A and dissociates from the centrosome, thereby enabling centrosome separation. Co-immunoprecipitation, immunofluorescence localization, loss-of-function (knockdown) with centrosome cohesion phenotype readout, in vitro phosphorylation assay (Nek2A), rootletin filament formation assay Journal of cell science High 30404835
2022 CCDC102B promotes breast cancer metastasis by interacting with RACK1 and positively regulating the NF-κB pathway. RACK1 promotes lysosomal degradation of CCDC102B via chaperone-mediated autophagy (CMA); loss of RACK1 stabilizes CCDC102B. Overexpression of CCDC102B reduces interaction between RACK1 and IKKα, thereby activating NF-κB signaling and driving metastatic behavior in vitro and in vivo. Co-immunoprecipitation, mass spectrometry, RNA sequencing (pathway enrichment), CRISPR/Cas9 loss-of-function in vivo screen, tail vein and xenograft tumor models, nuclear protein extraction, immunofluorescence, cell migration/invasion assays Frontiers in oncology Medium 35957886

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
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
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2014 Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. Nature communications 111 24722188
2016 Development of a methylation marker set for forensic age estimation using analysis of public methylation data and the Agena Bioscience EpiTYPER system. Forensic science international. Genetics 108 27337627
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2016 Identification and evaluation of age-correlated DNA methylation markers for forensic use. Forensic science international. Genetics 100 27017110
2018 An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders. Nature genetics 61 29892012
2019 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. Nature communications 60 31515488
2019 TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile. Proceedings of the National Academy of Sciences of the United States of America 48 31182584
2018 CCDC102B confers risk of low vision and blindness in high myopia. Nature communications 42 29725004
2022 A common epigenetic clock from childhood to old age. Forensic science international. Genetics 39 35777225
1990 Human aminoacylase-1: cloning, regional assignment to distal chromosome 3p21.1, and identification of a cross-hybridizing sequence on chromosome 18. Genomics 36 1707030
2020 The evaluation of seven age-related CpGs for forensic purpose in blood from Chinese Han population. Forensic science international. Genetics 34 32006895
2018 Estimation of chimpanzee age based on DNA methylation. Scientific reports 31 29968770
2010 A maternally inherited chromosome 18q22.1 deletion in a male with late-presenting diaphragmatic hernia and microphthalmia-evaluation of DSEL as a candidate gene for the diaphragmatic defect. American journal of medical genetics. Part A 29 20358601
2019 Novel multiplex strategy for DNA methylation-based age prediction from small amounts of DNA via Pyrosequencing. Forensic science international. Genetics 21 31648151
2018 CCDC102B functions in centrosome linker assembly and centrosome cohesion. Journal of cell science 20 30404835
2002 Delineation and candidate gene mutation screening of the 18q22 minimal region of deletion in head and neck squamous cell carcinoma. Oncogene 19 12118382
2021 Genome-wide identification of age-related CpG sites for age estimation from blood DNA of Han Chinese individuals. Electrophoresis 16 33978960
2022 Accurate age estimation from blood samples of Han Chinese individuals using eight high-performance age-related CpG sites. International journal of legal medicine 15 35819508
2022 Stabilization of CCDC102B by Loss of RACK1 Through the CMA Pathway Promotes Breast Cancer Metastasis via Activation of the NF-κB Pathway. Frontiers in oncology 11 35957886
2013 Genome-wide association study of liver enzymes in korean children. Genomics & informatics 10 24124411
2023 Pulse-SILAC and Interactomics Reveal Distinct DDB1-CUL4-Associated Factors, Cellular Functions, and Protein Substrates. Molecular & cellular proteomics : MCP 8 37689310
2023 DNA methylation-based age estimation and quantification of the degradation levels of bisulfite-converted DNA. Legal medicine (Tokyo, Japan) 7 37923589
2020 Genetic and environmental factors related to the development of myopic maculopathy in Spanish patients. PloS one 7 32730261
2024 Development and validation of a biomarker-based prediction model for metastasis in patients with colorectal cancer: Application of machine learning algorithms. Heliyon 4 39839508
2025 Enhanced fibrotic potential of COL1A1hiNR4A1low fibroblasts in ischemic heart revealed by transcriptional dynamics heterogeneity analysis at both bulk and single-cell levels. Frontiers in cardiovascular medicine 2 39834736
2024 Epigenetic-based age prediction in blood samples: Model development. Journal of forensic sciences 2 38308398
2024 Exploring legal age estimation using DNA methylation. Forensic science international. Genetics 2 39243524
2026 The 12 o'clock assay: an optimized dodecaplex droplet digital PCR assay for robust DNA methylation quantification and epigenetic clock-based age-predictions. Clinical epigenetics 0 41877244
2026 A targeted epigenetic clock for simultaneous assessment of biological aging and cancer-associated methylation drift. Clinical epigenetics 0 41963974
2025 A new robust AI/ML based model for accurate forensic age estimation using DNA methylation markers. Forensic science, medicine, and pathology 0 40085291
2025 Profiling the TRPV4 ankyrin repeat domain interactome and its disruption by neuromuscular disease-causing mutations. The Journal of biological chemistry 0 41338459