Coiled-coil domain-containing protein 28B (CCDC28B; historically MGC1203) is a small pericentriolar/basal-body-associated protein that acts as an accessory factor and genetic modifier of ciliary trafficking. It is required for normal ciliogenesis and for the control of cilium length, and it physically interacts with multiple Bardet-Biedl syndrome (BBSome) subunits, including BBS1, BBS2, BBS4, BBS5, BBS6, BBS7 and TTC8/BBS8, with which it colocalizes near centrosomes and basal bodies. Functionally, CCDC28B regulates cilium length in part through its interaction with SIN1/MAPKAP1 and acts as a positive regulator of mTOR complex 2 (mTORC2) assembly and activity; its effect on cilium length appears to be largely independent of canonical mTOR signaling. Depletion of the protein causes defective ciliogenesis in cultured cells and ciliopathy-like phenotypes in zebrafish (hydrocephalus, left-right axis defects, renal dysfunction). It is not a numbered structural BBS subunit but a modifier of BBSome-dependent ciliary function; homologous sequences are restricted to ciliated metazoa.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005813 centrosome | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred centrosome localization. Consistent with the experimentally observed pericentriolar/basal-body localization of CCDC28B and with the localization of BBSome-associated proteins. Reason: Localization is supported by direct experimental evidence (PMID:16327777) and is biologically coherent; however it is a subcellular-location annotation rather than the protein's core function (ciliogenesis/cilium-length control). |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation derived from UniProt subcellular-location vocabulary mapping. Redundant with the experimental IDA centrosome annotation from PMID:16327777. Reason: The localization is correct and corroborated experimentally, though this electronic entry is redundant with the IDA evidence and is a non-core localization annotation. |
| GO:0005515 protein binding | IPI PMID:16327777 Dissection of epistasis in oligogenic Bardet-Biedl syndrome. | MARK AS OVER ANNOTATED | Summary: IPI annotation capturing physical interactions with BBSome subunits (WITH includes BBS4/Q96RK4 and other BBS proteins). The underlying interactions are real and central to CCDC28B biology, but "protein binding" is an uninformative molecular-function term that conveys no specific activity. Reason: Per curation guidelines, the bare "protein binding" term should be avoided. The biologically meaningful content (binding to BBSome subunits near the basal body) is better represented by the ciliogenesis process annotation and by localization terms rather than by an uninformative MF term. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: IPI annotation from a proteome-scale binary (Y2H) interactome map, supporting a CCDC28B-ATRIP (Q8WXE1) interaction. This is a single high-throughput binary hit and the term itself is uninformative. Reason: "Protein binding" is discouraged as uninformative, and this is a single high-throughput interactome data point whose biological relevance to CCDC28B function is unestablished. |
| GO:0005813 centrosome | IDA PMID:16327777 Dissection of epistasis in oligogenic Bardet-Biedl syndrome. | ACCEPT | Summary: Direct experimental evidence that CCDC28B is a pericentriolar protein localizing near centrosomes and basal bodies, where it colocalizes with BBS proteins. The falcon deep-research synthesis is consistent with this, describing CCDC28B as concentrating at the ciliary basal body (the microtubule-organizing center from which the primary cilium extends). Reason: Well-supported direct localization evidence. This is a core localization for CCDC28B, consistent with its role at the base of the cilium. Supporting Evidence: file:human/CCDC28B/CCDC28B-deep-research-falcon.md CCDC28B concentrates at the basal body, the microtubule organizing center from which the primary cilium extends |
| GO:0060271 cilium assembly | IMP PMID:23015189 Characterization of CCDC28B reveals its role in ciliogenesis... | ACCEPT | Summary: Loss-of-function (IMP) evidence that CCDC28B is required for ciliogenesis, shown both in cultured cells and in zebrafish, where depletion produces ciliopathy phenotypes (hydrocephalus, left-right axis defects, renal impairment). This is the best-supported functional annotation and reflects the gene's core biological role. Subsequent literature, as synthesized in the falcon deep-research report, reinforces that CCDC28B acts as a positive regulator of ciliogenesis and cilium length rather than a passive structural component. Reason: Strong experimental loss-of-function evidence across cell and animal models; represents the core function of CCDC28B as a ciliogenesis factor. Supporting Evidence: PMID:23015189 show it affects ciliogenesis both in cultured cells and in vivo in zebrafish file:human/CCDC28B/CCDC28B-deep-research-falcon.md CCDC28B positively regulates primary cilium length and promotes ciliogenesis in somatic cells |
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Download this section (compressed HTML)Q: Is CCDC28B a stable, stoichiometric component of the BBSome (GO:0034464), or a transient/peripheral interactor that modulates BBSome function without being part of the core complex?
Q: Does CCDC28B localize within the cilium proper (e.g., transition zone or axoneme) or is it restricted to the pericentriolar/basal-body region?
Q: What is the molecular activity by which CCDC28B controls cilium length, whether primarily through SIN1 scaffolding, through IFT/BBSome trafficking, or both?
Experiment: Determine whether CCDC28B co-fractionates stoichiometrically with the BBSome by size-exclusion chromatography and quantitative mass spectrometry, to test BBSome membership versus accessory association.
Experiment: Use proximity labeling (BioID/TurboID) from CCDC28B in ciliated cells to define its in vivo interaction neighborhood at the basal body, transition zone, and cilium.
Experiment: Perform live-imaging of cilium assembly and length dynamics in CCDC28B-null cells with rescue by separation-of-function mutants (SIN1-binding versus BBSome-binding deficient) to dissect the mechanism of cilium-length control.
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