| 2014 |
CCDC93, together with CCDC22 and C16orf62, forms the CCC (COMMD/CCDC22/CCDC93) complex that localizes to early endosomes and interacts with the WASH complex to regulate endosomal trafficking of the copper transporter ATP7A; the carboxyl-terminal end of CCDC93 interacts with FAM21 (a WASH complex subunit) to recruit the CCC complex to endosomes. |
Co-immunoprecipitation, protein depletion (siRNA knockdown), endosomal localization assays, copper homeostasis functional readouts |
Molecular biology of the cell |
High |
25355947
|
| 2017 |
CCDC93 is a core subunit of the CCC complex (CCDC93, CCDC22, COMMD proteins), which associates with the cargo adaptor SNX17 and the Retriever complex to form a larger assembly that prevents lysosomal degradation and promotes cell surface recycling of α5β1 integrin and over 120 other cell surface proteins. |
Quantitative proteomics, Co-immunoprecipitation, cell surface proteomics, loss-of-function depletion with cargo recycling readouts |
Nature cell biology |
High |
28892079
|
| 2016 |
The CCC complex (including CCDC93) is required for endosomal sorting and recycling of LDLR back to the cell surface; depletion of CCC components leads to LDLR mislocalization and decreased LDL uptake. |
Liver-specific knockout mice, CRISPR/Cas9 somatic gene editing, plasma LDL measurements, LDLR localization assays, LDL uptake assays |
Nature communications |
High |
26965651
|
| 2015 |
The CCC complex (including CCDC93) controls Notch receptor recycling to the cell surface; disruption of the CCC complex causes intracellular accumulation of Notch2 and reduced Notch signaling. |
siRNA depletion of CCC components, Notch2 localization assays, Notch signaling reporter assays, conditional Commd9 knockout mice |
The Journal of cell biology |
High |
26553930
|
| 2019 |
The CCC complex (including CCDC93) maintains normal endosomal levels of phosphatidylinositol-3-phosphate (PI(3)P) by regulating the phosphorylation and endosomal recruitment of the PI(3)P phosphatase MTMR2; CCC depletion elevates endosomal PI(3)P, leading to enhanced WASH recruitment, excess endosomal F-actin, and trapping of internalized receptors. |
siRNA depletion of CCC components, PI(3)P biosensor imaging, F-actin quantification, MTMR2 phosphorylation and localization assays, receptor recycling assays |
Nature communications |
High |
31537807
|
| 2023 |
Cryo-EM structure of the Retriever complex was determined, and biochemical, cellular, and proteomic analyses revealed the structural organization of the entire Retriever-CCC complex; CCDC93 (along with CCDC22) scaffolds the CCC and Retriever subcomplexes together; cancer-associated mutations disrupt complex formation and impair membrane protein homeostasis. |
Cryogenic electron microscopy, AlphaFold structural predictions, biochemical pulldowns, cellular and proteomic analyses, mutagenesis of disease variants |
Nature structural & molecular biology |
High |
37333304 37397996 38062209
|
| 2024 |
Cryo-EM structure of the endogenous human Commander complex shows that CCDC22 and CCDC93 act as a scaffold bridging the stable COMMD1-10 core and the effector module containing DENND10 and Retriever (VPS26C, VPS29, VPS35L); key interaction interfaces between these submodules were identified. |
Cryogenic electron microscopy, mass spectrometry-based proteomics, structural analysis of endogenous complex |
Nature structural & molecular biology |
High |
38459129
|
| 2013 |
CCDC93 (along with CCDC22 and related proteins) contains a divergent N-terminal calponin homology (NN-CH)-like domain adjoined to C-terminal heptad repeats predicted to form a coiled-coil, defining a novel protein family sharing evolutionary ancestry with NDC80/NUF2 kinetochore components. |
Computational profile-to-profile comparisons, structure modeling |
Bioinformatics (Oxford, England) |
Low |
24257188
|
| 2018 |
COMMD protein deficiency destabilizes the core of the CCC complex (CCDC22 and CCDC93 protein levels are reduced), and CCDC22 deletion by CRISPR/Cas9 likewise destabilizes the complete CCC complex, demonstrating that the integrity of COMMD proteins is required for CCC complex stability. |
Liver-specific Commd knockout mice, quantitative targeted proteomics, CRISPR/Cas9 somatic Ccdc22 deletion, western blotting of complex components |
Circulation research |
High |
29545368
|
| 2020 |
A coding variant in CCDC93 (p.Pro228Leu) increases CCDC93 protein stability; overexpression of CCDC93 in mice decreases plasma LDL-c, while CCDC93 ablation reduces LDLR cell surface levels and LDL uptake. |
Population genetics combined with functional cell-based assays (overexpression in mice, CCDC93 ablation), LDLR surface level and LDL uptake assays |
European heart journal |
Medium |
31630160
|
| 2021 |
Deficiency of any of three COMMD genes (Commd1, Commd6, or Commd9) destabilizes the entire CCC complex including CCDC93, and the CCC complex regulates ATP7B endosomal recycling and copper excretion in hepatocytes. |
Enterocyte- and hepatocyte-specific COMMD knockout mice, biochemical analysis of CCC complex integrity, copper level measurements |
Disease models & mechanisms |
Medium |
33262129
|
| 2025 |
The CCC complex (including CCDC93) is essential for phagosome maturation in macrophages; CCC deficiency impairs phagosome-lysosome fusion, leads to excessive PI(3)P accumulation on phagosome membranes, and reduces bacterial clearance. |
Bone marrow-derived macrophage (BMDM) loss-of-function, PI(3)P imaging, phagosome-lysosome fusion assays, bacterial clearance assays |
bioRxiv : the preprint server for biologypreprint |
Medium |
41473320
|
| 2025 |
CCDC93 interacts with WIPI2 (a PROPPIN protein) as part of the CROP2 complex (Retriever-PROPPIN complex), which is required for endosomal exit of β1-Integrin but not for CROP (Retromer-WIPI1)-dependent cargos such as EGFR or GLUT1; WIPI2 uses an FSSS motif to integrate into the Retriever complex via interaction with CCDC93. |
Co-immunoprecipitation, cargo trafficking assays (β1-Integrin, EGFR, GLUT1), mutagenesis of FSSS motif, loss-of-function depletion |
bioRxivpreprint |
Medium |
bio_10.1101_2025.10.08.681146
|
| 2025 |
Mutations in CCDC93 cause Ritscher-Schinzel syndrome (RSS) by disrupting Commander complex assembly, leading to reduced cell surface presentation of integral membrane proteins containing SNX17-recognized ΦxNPxY/F sorting motifs; mouse models of CCDC93 deficiency replicate RSS phenotypes including proteinuria, skeletal malformation, and neurological impairment. |
Interactome analysis of patient mutations, cell surface proteomics, mouse models of CCDC93 deficiency, motif analysis of cargo proteins |
Science translational medicine |
High |
40601774
|
| 2025 |
CCDC22 mutations (p.E208K and p.P172R) that impair CCC complex assembly do so by disrupting a conserved interaction surface required for CCDC22-COMMD4 binding, demonstrating that COMMD binding to CCDC22 is required for CCC complex integrity; CCDC93 remains part of the complex that is disrupted by these mutations. |
Mutagenesis of CCDC22, co-immunoprecipitation of CCC complex components including CCDC93, patient mutation characterization |
BMC medical genomics |
Medium |
40448120
|
| 2024 |
Heterozygous Ccdc93 deletion in mice (homozygous deletion is embryonic lethal by day 10.5) results in elevated systolic blood pressure, impaired acetylcholine-induced arterial relaxation, enhanced phenylephrine-induced contraction, elevated plasma free fatty acids, and aortic mitochondrial dysfunction with aberrant Parkin and Nix expression. |
CRISPR/Cas9 Ccdc93 knockout mice, wire myography, RNA-Seq transcriptome analysis, plasma fatty acid measurements, western blotting for mitochondrial proteins |
PLoS genetics |
Medium |
39250516
|
| 2025 |
Loss of COMMD3 (a CCC complex component) increases release of lysosomal proteins through extracellular vesicles, leading to impaired delivery to endolysosomes and lysosomal dysfunction; COMMD3 was identified as a modifier of lysosomal glucocerebrosidase (GCase) activity through a genome-wide CRISPR interference screen. |
Pooled genome-wide CRISPRi screen, extracellular vesicle proteomics, lysosomal function assays |
Science (New York, N.Y.) |
Medium |
40209002
|