CEP89 (centrosomal protein of 89 kDa; also Cep123/CCDC123) is a coiled-coil component of the distal appendages (ciliary transition fibers) of the mother centriole and basal body of primary and motile cilia. It is recruited by CEP83 and forms part of the appendage blade backbone, but is not needed to recruit FBF1 or CEP164. CEP89 is required for formation of the ciliary vesicle and for assembly, but not maintenance, of primary cilia; it interacts with the centriolar satellite proteins PCM-1, OFD1 and CEP290. CEP89 binds and recruits the myristoylated calcium sensor NCS1 (and CEP15) to the distal appendages; NCS1 in turn captures RAB34-positive preciliary vesicles, so CEP89 acts as an adaptor that positions the vesicle-capture machinery. Super-resolution imaging shows CEP89 in two layers, at the distal and subdistal appendage levels. A cytosolic pool and a pool in the mitochondrial intermembrane space have been reported, and CEP89 depletion lowered cytochrome c oxidase (complex IV) activity in human cells and flies; a homozygous deletion including CEP89 was found in a patient with complex IV deficiency and intellectual disability.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000922 spindle pole | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | KEEP AS NON CORE | Summary: IDA spindle pole from the Jakobsen et al. centrosome/HPA screen. Reason: The specific image is in supplementary material not in the cache. Distal appendage proteins remain on the mother centriole, which sits at a spindle pole during mitosis, so the observation is plausible but reflects centriole position rather than a mitotic spindle function. Supporting Evidence: PMID:21399614 An antibody screen covering 4000 genes revealed an additional 113 candidates. |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA spindle pole from UniProt subcellular location. Reason: Same reasoning as the IDA row: plausible because centrioles occupy spindle poles, but not a functional location. Supporting Evidence: PMID:21399614 An antibody screen covering 4000 genes revealed an additional 113 candidates. |
| GO:0005515 protein binding | IPI PMID:23789104 Primary ciliogenesis requires the distal appendage component... | REMOVE | Summary: IPI with OFD1 (O75665); Cep123/CEP89 co-immunoprecipitates centriolar satellite proteins PCM-1, OFD1 and CEP290. Reason: Bare protein binding is uninformative and no specific molecular function follows from the co-immunoprecipitation. The interaction itself is not disputed. Supporting Evidence: PMID:23789104 Cep123 interacts with the centriolar satellite proteins PCM-1, Cep290 and OFD1, all of which play a role in primary ciliogenesis. |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:23575228 CEP89 is required for mitochondrial metabolism and neuronal ... | KEEP AS NON CORE | Summary: IDA: fractionation places a pool of CEP89 in the mitochondrial intermembrane space. Reason: Supported by the cited abstract, but Mitochondrial roles rest on a single study (patient with a homozygous deletion that also removes SLC7A9, siRNA knockdown in cultured cells, and Drosophila knockdown); they have not been independently replicated, whereas the distal appendage role is supported by several independent laboratories. Supporting Evidence: PMID:23575228 Immunocytochemistry and cellular fractionation experiments showed that CEP89 is present both in the cytosol and in the mitochondrial intermembrane space. |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA mitochondrial intermembrane space from UniProt subcellular location (derived from the same study). Reason: Mitochondrial roles rest on a single study (patient with a homozygous deletion that also removes SLC7A9, siRNA knockdown in cultured cells, and Drosophila knockdown); they have not been independently replicated, whereas the distal appendage role is supported by several independent laboratories. Supporting Evidence: PMID:23575228 Immunocytochemistry and cellular fractionation experiments showed that CEP89 is present both in the cytosol and in the mitochondrial intermembrane space. |
| GO:0005813 centrosome | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence (GO_REF:0000052): centrosome (HPA grade Supported). Reason: Consistent with CEP89 localization to the distal appendages of the mother centriole. Supporting Evidence: PMID:23789104 showing that Cep123 localizes to the distal appendages of the mother centriole. |
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: IDA centrosome from the Jakobsen et al. centrosome proteome. Reason: CCDC123/CEP89 was one of the confirmed centrosomal candidates; consistent with subsequent distal appendage localization. Supporting Evidence: PMID:21399614 An antibody screen covering 4000 genes revealed an additional 113 candidates. PMID:23789104 showing that Cep123 localizes to the distal appendages of the mother centriole. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: IEA centrosome from UniProt subcellular location. Reason: Consistent with direct evidence. Supporting Evidence: PMID:23789104 showing that Cep123 localizes to the distal appendages of the mother centriole. |
| GO:0005814 centriole | IBA GO_REF:0000033 | ACCEPT | Summary: IBA centriole; CEP89 among the sources. Reason: CEP89 is a distal appendage protein of the mother centriole. Supporting Evidence: PMID:23789104 showing that Cep123 localizes to the distal appendages of the mother centriole. |
| GO:0005814 centriole | IDA PMID:23348840 Centriole distal appendages promote membrane docking, leadin... | ACCEPT | Summary: IDA: CEP89 identified as a distal appendage component. Reason: Direct localization. Supporting Evidence: PMID:23348840 we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins |
| GO:0005814 centriole | IEA GO_REF:0000120 | ACCEPT | Summary: IEA centriole location. Reason: Consistent with direct evidence. Supporting Evidence: PMID:23348840 we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence (GO_REF:0000052): cytosol is the HPA main location for CEP89. Reason: A diffuse cytosolic pool is also reported by fractionation, and overexpressed CEP89 forms cytoplasmic particles co-localizing with centriolar satellites. Plausible but not the functional location. Supporting Evidence: PMID:23575228 Immunocytochemistry and cellular fractionation experiments showed that CEP89 is present both in the cytosol and in the mitochondrial intermembrane space. |
| GO:0005829 cytosol | IDA PMID:23575228 CEP89 is required for mitochondrial metabolism and neuronal ... | KEEP AS NON CORE | Summary: IDA cytosol from fractionation and immunocytochemistry. Reason: Supported by the cited abstract; non-core relative to the distal appendage location. Supporting Evidence: PMID:23575228 Immunocytochemistry and cellular fractionation experiments showed that CEP89 is present both in the cytosol and in the mitochondrial intermembrane space. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA cytosol from UniProt subcellular location. Reason: As for the IDA row. Supporting Evidence: PMID:23575228 Immunocytochemistry and cellular fractionation experiments showed that CEP89 is present both in the cytosol and in the mitochondrial intermembrane space. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626223 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626227 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626228 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626681 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626699 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0007005 mitochondrion organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA mitochondrion organization, propagated from Drosophila Cep89 and human CEP89. Reason: Fly Cep89 knockdown impairs mitochondrial integrity and human CEP89 knockdown lowers complex IV activity. Mitochondrial roles rest on a single study (patient with a homozygous deletion that also removes SLC7A9, siRNA knockdown in cultured cells, and Drosophila knockdown); they have not been independently replicated, whereas the distal appendage role is supported by several independent laboratories. Supporting Evidence: PMID:23575228 Furthermore, Cep89 is required for mitochondrial integrity, membrane depolarization and synaptic transmission of photoreceptor neurons, and for (sub)synaptic organization of the larval neuromuscular junction. PMID:23575228 we ascertained in vitro that downregulation of CEP89 resulted in a severe decrease in complex IV in-gel activity and altered mobility, suggesting that the complex is aberrantly formed. |
| GO:0007005 mitochondrion organization | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: IEA (InterPro2GO, IPR033545) mitochondrion organization. Reason: Family-level mapping that rests on the same fly/human study. Mitochondrial roles rest on a single study (patient with a homozygous deletion that also removes SLC7A9, siRNA knockdown in cultured cells, and Drosophila knockdown); they have not been independently replicated, whereas the distal appendage role is supported by several independent laboratories. Supporting Evidence: PMID:23575228 Furthermore, Cep89 is required for mitochondrial integrity, membrane depolarization and synaptic transmission of photoreceptor neurons, and for (sub)synaptic organization of the larval neuromuscular junction. |
| GO:0007268 chemical synaptic transmission | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: IEA (InterPro2GO) chemical synaptic transmission. Reason: Derived from a Drosophila knockdown phenotype in photoreceptor synaptic transmission that is most simply explained by mitochondrial or ciliary dysfunction. There is no evidence that CEP89 performs a step of synaptic transmission, and the family-wide mapping applies it to all members. Supporting Evidence: PMID:23575228 Furthermore, Cep89 is required for mitochondrial integrity, membrane depolarization and synaptic transmission of photoreceptor neurons, and for (sub)synaptic organization of the larval neuromuscular junction. |
| GO:0031514 motile cilium | IEA GO_REF:0000107 | ACCEPT | Summary: IEA motile cilium from mouse Cep89. Reason: CEP89 localizes to the base of motile ependymal cilia as well as primary cilia, so a location within the motile cilium (at its basal body) is supported; ciliary basal body is more precise. Supporting Evidence: PMID:23789104 Cep123 localized to the base of ependymal cilia confirming that it is a component of both motile and immotile cilia. |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IMP PMID:23575228 CEP89 is required for mitochondrial metabolism and neuronal ... | UNDECIDED | Summary: IMP: CEP89 knockdown reduces complex IV in-gel activity and alters its mobility. Reason: The cited abstract supports an effect on complex IV, but the paper does not establish whether CEP89 acts directly in assembly or affects complex IV indirectly, and the finding has not been replicated. The full text is not cached. Mitochondrial roles rest on a single study (patient with a homozygous deletion that also removes SLC7A9, siRNA knockdown in cultured cells, and Drosophila knockdown); they have not been independently replicated, whereas the distal appendage role is supported by several independent laboratories. Supporting Evidence: PMID:23575228 we ascertained in vitro that downregulation of CEP89 resulted in a severe decrease in complex IV in-gel activity and altered mobility, suggesting that the complex is aberrantly formed. PMID:23575228 We identified a homozygous deletion of CEP89 in a patient with isolated complex IV deficiency, intellectual disability and multisystemic problems. |
| GO:0036064 ciliary basal body | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence (GO_REF:0000052): basal body (HPA grade Supported). Reason: Consistent with distal appendages becoming transition fibers on the basal body. Supporting Evidence: PMID:23789104 Cep123 localized to the base of ependymal cilia confirming that it is a component of both motile and immotile cilia. |
| GO:0045202 synapse | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: IEA synapse, inferred (GO_REF:0000108) from the chemical synaptic transmission IEA. Reason: Derived automatically from an over-annotated process term that itself rests on an indirect fly knockdown phenotype. There is no direct evidence that CEP89 localizes to synapses. Supporting Evidence: PMID:23575228 Furthermore, Cep89 is required for mitochondrial integrity, membrane depolarization and synaptic transmission of photoreceptor neurons, and for (sub)synaptic organization of the larval neuromuscular junction. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cilium assembly; CEP89 among the sources. Reason: CEP89 is required for assembly of primary cilia and acts at the ciliary vesicle formation step. Supporting Evidence: PMID:23789104 Here, we show that the distal appendage protein Cep123 (Cep89/CCDC123) is required for the assembly, but not the maintenance, of a primary cilium. In the absence of Cep123 ciliary vesicle formation fails, suggesting that it functions in the early stages of primary ciliogenesis. |
| GO:0060271 cilium assembly | IEA GO_REF:0000002 | ACCEPT | Summary: IEA (InterPro2GO) cilium assembly. Reason: Consistent with experimental evidence. Supporting Evidence: PMID:23789104 Here, we show that the distal appendage protein Cep123 (Cep89/CCDC123) is required for the assembly, but not the maintenance, of a primary cilium. In the absence of Cep123 ciliary vesicle formation fails, suggesting that it functions in the early stages of primary ciliogenesis. |
| GO:0060271 cilium assembly | IMP PMID:23348840 Centriole distal appendages promote membrane docking, leadin... | ACCEPT | Summary: IMP: CEP89 depletion blocks ciliogenesis (Tanos et al.). Reason: All five distal appendage components are essential for ciliogenesis. Supporting Evidence: PMID:23348840 All five DAP components are essential for ciliogenesis; loss of CEP83 specifically blocks centriole-to-membrane docking. |
| GO:0060271 cilium assembly | IMP PMID:23348840 Centriole distal appendages promote membrane docking, leadin... | ACCEPT | Summary: IMP: CEP89 depletion blocks ciliogenesis (involved_in row). Reason: As above; CEP89 is a distal appendage blade component that acts in ciliary vesicle formation. Supporting Evidence: PMID:23348840 All five DAP components are essential for ciliogenesis; loss of CEP83 specifically blocks centriole-to-membrane docking. PMID:23789104 Nevertheless, depletion of Cep123 with the Cep123 P2 siRNAs significantly reduced primary cilium formation, but did not affect cell cycle progression, thereby supporting a direct role for Cep123 in primary ciliogenesis. |
| GO:0097539 ciliary transition fiber | IBA GO_REF:0000033 | ACCEPT | Summary: IBA ciliary transition fiber; CEP89 among the sources. Reason: CEP89 is a distal appendage blade component. Supporting Evidence: PMID:29789620 CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. |
| GO:0097539 ciliary transition fiber | IDA PMID:23348840 Centriole distal appendages promote membrane docking, leadin... | ACCEPT | Summary: IDA: CEP89 is one of five distal appendage components. Reason: Defining location. Supporting Evidence: PMID:23348840 we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins |
| GO:0097539 ciliary transition fiber | IDA PMID:23789104 Primary ciliogenesis requires the distal appendage component... | ACCEPT | Summary: IDA: immunogold EM places Cep123/CEP89 on the distal appendages of the mother centriole. Reason: Direct ultrastructural localization. Supporting Evidence: PMID:23789104 showing that Cep123 localizes to the distal appendages of the mother centriole. |
| GO:0097539 ciliary transition fiber | IEA GO_REF:0000107 | ACCEPT | Summary: IEA transition fiber from mouse. Reason: Consistent with direct human evidence. Supporting Evidence: PMID:29789620 CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. |
| GO:0097730 non-motile cilium | IDA PMID:23789104 Primary ciliogenesis requires the distal appendage component... | ACCEPT | Summary: IDA: CEP89 localizes to the base of primary (non-motile) cilia. Reason: CEP89 is at the base of primary cilia (at the transition fibers of the basal body); the term is correct but less precise than ciliary transition fiber. Supporting Evidence: PMID:23789104 Cep123 localized to the base of ependymal cilia confirming that it is a component of both motile and immotile cilia. |
| GO:1905515 non-motile cilium assembly | IMP PMID:23789104 Primary ciliogenesis requires the distal appendage component... | ACCEPT | Summary: IMP: Cep123/CEP89 depletion prevents primary cilium assembly and ciliary vesicle formation. Reason: Direct evidence for a role in assembling primary cilia, acting at the ciliary vesicle step. Supporting Evidence: PMID:23789104 Here, we show that the distal appendage protein Cep123 (Cep89/CCDC123) is required for the assembly, but not the maintenance, of a primary cilium. In the absence of Cep123 ciliary vesicle formation fails, suggesting that it functions in the early stages of primary ciliogenesis. PMID:23789104 Nevertheless, depletion of Cep123 with the Cep123 P2 siRNAs significantly reduced primary cilium formation, but did not affect cell cycle progression, thereby supporting a direct role for Cep123 in primary ciliogenesis. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:39882855 Myristoylated Neuronal Calcium Sensor-1 captures the precili... | NEW | Summary: Proposed: CEP89 directly binds NCS1 (via its N-terminal region) and is required to recruit NCS1 to the distal appendage, linking the appendage to the vesicle-capturing calcium sensor. Reason: Kanie et al. 2025 identify NCS1 as a stoichiometric CEP89 interactor, show direct binding and that NCS1 centriolar localization is abolished in CEP89 knockouts and rescued by CEP89 re-expression, while NCS1 loss does not displace CEP89. This is an adaptor activity bridging the distal appendage and NCS1, and is more informative than protein binding. Supporting Evidence: PMID:39882855 This localization was completely abolished in CEP89 knockouts, suggesting that CEP89 recruits NCS1 to the distal appendage. PMID:39882855 The lack of a membrane-binding motif in CEP89 suggests that it may indirectly recruit preciliary vesicles via another binding partner. Here, we identify Neuronal Calcium Sensor-1 (NCS1) as a stoichiometric interactor of CEP89. file:human/CEP89/CEP89-deep-research-falcon.md CEP89 bound NCS1 through its **N-terminal residues 1–343** and bound CEP15 independently |
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Download this section (compressed HTML)Q: Is the reported mitochondrial intermembrane-space pool of CEP89 genuine and functionally linked to complex IV, or does the complex IV defect reflect indirect effects of loss of cilia or of the co-deleted SLC7A9 locus?
Q: What does CEP89 contribute to ciliary vesicle formation that the other distal appendage proteins do not, given that it is dispensable for FBF1 and CEP164 recruitment?
Experiment: Generate CEP89-knockout human cells and rescue with wild-type or centriole-targeting-deficient CEP89, then measure complex IV assembly by BN-PAGE alongside ciliogenesis, to separate centriolar and putative mitochondrial functions.
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