Affinage

CCDC57

Coiled-coil domain-containing protein 57 · UniProt Q2TAC2

Length
915 aa
Mass
103.0 kDa
Annotated
2026-06-09
19 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCDC57 is a centriole- and basal body-associated protein that coordinates ciliary polarity and centrosome duplication across cell types (PMID:32402286, PMID:39592607). At the proximal end of centrioles it interacts with the microcephaly protein CEP63, centriolar satellite proteins, and microtubules; its centrosome-targeting region mediates CEP63 binding and is required for centriole duplication and recruitment of CEP63 and CEP152 to the centrosome, while its microtubule-targeting region supports mitotic functions, and its loss perturbs mitotic progression even in centriole-less cells (PMID:32402286). At basal bodies, CCDC57 is positioned as a rotationally asymmetric punctum that polarizes away from the basal foot, and it couples axonemal orientation to basal foot position during rotational polarization, thereby aligning ciliary beating across the epithelium (PMID:39592607). Loss of CCDC57 disrupts coordinated multiciliary beating and cerebrospinal fluid flow, producing hydrocephalus and scoliosis, with rescue restoring spinal curvature and acting upstream of urotensin neuropeptide signaling (PMID:36862758, PMID:36669737, PMID:39592607).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2020 High

    Established CCDC57 as a centriolar protein required for centriole duplication and for recruiting key centrosomal microcephaly factors, defining its earliest molecular role.

    Evidence Proximity mapping, superresolution imaging, Co-IP, siRNA depletion, and domain mutagenesis in human cells

    PMID:32402286

    Open questions at the time
    • Mechanism by which CCDC57 promotes CEP63/CEP152 recruitment is not resolved
    • Structural basis of microtubule and CEP63 binding undefined
    • Separation of mitotic versus duplication functions only mapped to broad domains
  2. 2023 High

    Showed in vivo that CCDC57 controls planar polarity of ependymal cells and coordinated cilia beating, linking the protein to CSF flow and disease phenotypes (hydrocephalus, scoliosis).

    Evidence Zebrafish mutant analysis, immunofluorescence localization, cilia beat live imaging, CSF flow assay, and genetic/pharmacological rescue

    PMID:36669737 PMID:36862758

    Open questions at the time
    • Molecular link between CCDC57 and microtubule network organization not detailed
    • How CCDC57 connects to downstream urotensin signaling is unresolved
    • Relationship between basal body positioning and planar polarity machinery undefined
  3. 2024 High

    Defined the structural mechanism: CCDC57 acts as a rotationally asymmetric basal body marker that couples axonemal orientation to basal foot position, explaining how it enforces epithelium-wide directional ciliary beating.

    Evidence Mouse Ccdc57 knockout, superresolution imaging of basal body asymmetry, basal foot orientation immunofluorescence, and CSF flow measurement across tissues

    PMID:39592607

    Open questions at the time
    • Molecular partners establishing the asymmetric punctum are unidentified
    • How axonemal orientation signal is mechanically transmitted to the basal foot is unknown
    • Whether centriolar (CEP63/CEP152) functions and basal body polarity functions share a mechanism is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CCDC57's centriole-duplication/mitotic activities mechanistically relate to its basal body rotational-polarity function, and the molecular intermediaries to urotensin signaling, remain open.
  • No structural model of CCDC57 or its complexes
  • No identified effectors bridging basal foot coupling to ciliary orientation
  • Mechanism connecting ciliary defects to urotensin pathway not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005929 cilium 3 GO:0005856 cytoskeleton 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-1640170 Cell Cycle 1
Partners
CEP152CEP63

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 CCDC57 localizes to the proximal end of centrioles and interacts with the microcephaly protein CEP63, centriolar satellite proteins, and microtubules. Loss of CCDC57 causes defects in centriole duplication and failure to localize CEP63 and CEP152 to the centrosome. Its centrosome-targeting region is required for interaction with CEP63 and functions during centriole duplication and cilium assembly, whereas the microtubule-targeting region is required for mitotic functions. CCDC57 depletion also perturbs mitotic progression in both wild-type and centriole-less cells. Proximity mapping, superresolution imaging, Co-IP/pulldown, loss-of-function (siRNA depletion), domain mutagenesis Cell reports High 32402286
2023 In zebrafish, Ccdc57 localizes to ciliary basal bodies and controls the planar polarity of ependymal cells by regulating microtubule network organization and proper positioning of basal bodies. Loss of ccdc57 causes uncoordinated cilia beating in ependymal cells, defective cerebrospinal fluid flow, hydrocephalus, and scoliosis. Mutant spinal cord showed altered expression of Urotensin neuropeptides consistent with spine curvature. Zebrafish mutant analysis, immunofluorescence localization, live imaging of cilia beating, CSF flow assay, in vivo loss-of-function PLoS biology High 36862758
2023 In zebrafish, Ccdc57 colocalizes with acetylated α-tubulin at cilia, and its loss specifically disrupts coordinated cilia beating of multiple cilia bundles in the brain ventricle, leading to impaired cerebrospinal fluid flow and spinal curvature. mRNA rescue or epinephrine treatment reverses spinal curvature and upregulates urotensin signaling, placing Ccdc57 upstream of urotensin in the pathway. Zebrafish mutant analysis (zygotic and maternal-zygotic), immunofluorescence colocalization, mRNA injection rescue, pharmacological rescue, cilia beat imaging Journal of genetics and genomics High 36669737
2024 CCDC57 localizes to basal bodies as a rotationally asymmetric punctum that polarizes away from the basal foot after rotational polarity is achieved. CCDC57 is required for coupling axonemal orientation to basal foot position during rotational polarization of basal bodies. Loss of CCDC57 in mice causes ependymal multicilia to lack basal foot–axonemal orientation coupling, resulting in directional beats only at the single-cell level (not coordinated across the epithelium), impaired CSF flow, severe hydrocephalus, and high mortality. Tracheal multicilia in Ccdc57−/− mice also fail to fully align their basal feet. Mouse knockout (Ccdc57−/−), superresolution imaging of basal body asymmetry, immunofluorescence of basal foot orientation, CSF flow measurement, in vivo loss-of-function phenotyping Nature communications High 39592607

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels: a systematic review and replication in a case-control sample of the Lifelines study. Diabetologia 107 29164275
2012 Genome-wide linkage and association analyses implicate FASN in predisposition to Uterine Leiomyomata. American journal of human genetics 71 23040493
2014 DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis. Oncology reports 31 24737029
2023 Ependymal polarity defects coupled with disorganized ciliary beating drive abnormal cerebrospinal fluid flow and spine curvature in zebrafish. PLoS biology 23 36862758
2020 CCDC57 Cooperates with Microtubules and Microcephaly Protein CEP63 and Regulates Centriole Duplication and Mitotic Progression. Cell reports 21 32402286
2022 Genome-wide associations for heat stress response suggest potential candidate genes underlying milk fatty acid composition in dairy cattle. Journal of dairy science 19 35094857
2013 Fine mapping of a quantitative trait locus for bovine milk fat composition on Bos taurus autosome 19. Journal of dairy science 19 24315323
2020 Transcriptome-wide association study for restless legs syndrome identifies new susceptibility genes. Communications biology 18 32651461
2015 Evaluation of GWAS candidate susceptibility loci for uterine leiomyoma in the multi-ethnic NIEHS uterine fibroid study. Frontiers in genetics 16 26236334
2018 Genome-wide association study and prediction of genomic breeding values for fatty-acid composition in Korean Hanwoo cattle using a high-density single-nucleotide polymorphism array. Journal of animal science 15 30265318
2018 Nuclear factor I X is a recurrent target for HPV16 insertions in anal carcinomas. Genes, chromosomes & cancer 11 30264502
2022 Comparison of the genetic characteristics of directly measured and Fourier-transform mid-infrared-predicted bovine milk fatty acids and proteins. Journal of dairy science 9 36307235
2023 Ccdc57 is required for straightening the body axis by regulating ciliary motility in the brain ventricle of zebrafish. Journal of genetics and genomics = Yi chuan xue bao 6 36669737
2025 Multiple strategies association revealed functional candidate FASN gene for fatty acid composition in cattle. Communications biology 4 39930002
2024 Directional ciliary beats across epithelia require Ccdc57-mediated coupling between axonemal orientation and basal body polarity. Nature communications 4 39592607
2020 Candidate genes for predicting the survival of patients with gastric cancer: a study based on The Cancer Genome Atlas (TCGA) database. Translational cancer research 4 35117619
2019 Haplotypes of CYP1B1 and CCDC57 genes in an Afro-Caribbean female population with uterine leiomyoma. Molecular biology reports 1 30989560
2026 Identification of Short Amino Acid Sequences That Correlate with Cytoplasmic Retention of Human Proteins. Cells 0 41597208
2026 A Novel Mutation of PTCHD3 Identified in a Chinese Family with Basal Cell Nevus Syndrome-associated Odontogenic Keratocysts. The Chinese journal of dental research 0 41848310

Missed literature

Know a paper Affinage missed for CCDC57? Flag it for the maintainers and the community.

No submissions yet.