BBS10 is a divergent member of the type II TCP-1/CCT chaperonin family that helps assemble the BBSome, a complex involved in ciliary membrane protein trafficking. It associates with BBS6/MKKS, BBS12 and BBSome proteins and regulates formation of assembly machinery containing CCT/TRiC proteins. These interactions support BBS7 stability and assembly of the BBS7-BBS2-BBS9 intermediate from which the mature BBSome forms. BBS10 associates transiently or substoichiometrically with the assembly machinery and is not a stable subunit of the mature BBSome. It localizes to ciliary basal bodies in human cell models. Biallelic loss-of-function variants cause Bardet-Biedl syndrome type 10, with ciliary dysfunction affecting multiple tissues.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0051131 chaperone-mediated protein complex assembly | IBA GO_REF:0000033 | ACCEPT | Summary: BBS10 participates in chaperone-assisted BBSome assembly. Reason: Human-cell complex-association and assembly experiments in PMID:20080638 and BBS10-specific perturbations in PMID:22500027 support this core process. The phylogenetic annotation agrees with independent evidence on human BBS10. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding remains a sequence-derived annotation rather than a demonstrated BBS10 catalytic mechanism. Reason: Retain the InterPro-based nucleotide-binding inference without promoting it to a defining catalytic core. UniProt labels the folding activity probable; its D81N note explicitly permits disruption of overall conformation rather than selective loss of ATP binding. Neither a binding assay nor ATP hydrolysis was established in the passages read. This uncertainty does not demonstrate that the original ATP-binding IEA is false. |
| GO:0005929 cilium | IEA GO_REF:0000044 | MODIFY | Summary: The source cilium localization can be specified as ciliary basal body. Reason: Endogenous BBS10 localizes to basal bodies in human primary renal proximal tubular epithelial cells and differentiating human preadipocytes (PMID:19190184, Results and Figures 1 and 3). The ciliary basal body is a part of the cilium, so this is a more specific location. The PMID:40914337 abstract reports primary-cilium localization without resolving basal body from axoneme; no exclusive or universal localization is inferred. Proposed replacements: ciliary basal body Supporting Evidence: PMID:19190184 both proteins localized to the basal body of the primary cilium. |
| GO:0051131 chaperone-mediated protein complex assembly | IEA GO_REF:0000002 | ACCEPT | Summary: The BBS10-specific InterPro assembly assignment agrees with the demonstrated assembly role. Reason: BBS10-containing complexes and BBS10-dependent assembly in PMID:20080638 and PMID:22500027 independently support the InterPro process assignment. |
| GO:0005515 protein binding | IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | KEEP AS NON CORE | Summary: The BBS9-scoped source records a supported BBS10 association during BBSome assembly. Reason: BBS9/Q3SYG4 co-immunoprecipitates with BBS10 in the selected PMID:20080638 Results, and UniProt independently records this partner. The association supports assembly context without establishing autonomous folding activity or isolated binary affinity. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: The curated BioPlex source names BBS7/Q8IWZ6 as the BBS10 interaction partner. Reason: The official BioPlex 2.0 filtered directed HEK293T network lists BBS7 (GeneID 55212) as bait and BBS10 (GeneID 79738) as prey. This verifies AP-MS association in the cited network, not purified binary binding, stoichiometry or autonomous BBS10 folding activity. The supported generic interaction remains non-core under the explicit ClinGen project instruction. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: The curated BioPlex source names BBS7/Q8IWZ6 as the BBS10 interaction partner. Reason: The official BioPlex 3.0 filtered directed HEK293T network lists BBS7 (GeneID 55212) as bait and BBS10 (GeneID 79738) as prey. This verifies AP-MS association in the cited network, not purified binary binding, stoichiometry or autonomous BBS10 folding activity. The supported generic interaction remains non-core under the explicit ClinGen project instruction. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:22302990 Direct role of Bardet-Biedl syndrome proteins in transcripti... | MODIFY | Summary: BBS10 association with RNF2 is better represented as ubiquitin protein ligase binding. Reason: Myc-BBS10 co-immunoprecipitates HA-RNF2 in human HEK293 experiments (PMID:22302990, Results and Figure 3C). RNF2 is the PRC1 E3 ubiquitin ligase, so ubiquitin protein ligase binding describes the partner class more accurately than binding a sequence-specific RNA polymerase II transcription factor. This is a tagged-protein association assay; endogenous BBS7 interaction and downstream transcription or turnover mechanisms are not assigned to BBS10. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0043254 regulation of protein-containing complex assembly | IMP PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | ACCEPT | Summary: BBS10 regulates formation of the BBS-chaperonin assembly machinery. Reason: BBS10 knockdown reduces, and BBS10 overexpression promotes, BBS6 association with CCT proteins in human 293T cells. These opposing perturbations establish regulation of the assembly machinery. This complements participation in BBSome assembly: the two process terms describe machinery formation and assembly of its product, respectively. Supporting Evidence: PMID:22500027 BBS10 regulates the formation of the BBS-chaperonin complex. |
| GO:0051131 chaperone-mediated protein complex assembly | IMP PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | ACCEPT | Summary: Chaperone-mediated BBSome assembly is the best-supported central process for BBS10. Reason: The BBS6/BBS10/BBS12-CCT system mediates BBSome assembly in PMID:20080638. BBS10-specific complex-formation experiments and impaired BBSome assembly in patient fibroblasts in PMID:22500027 corroborate this role without establishing autonomous folding activity. Supporting Evidence: PMID:20080638 BBS6, BBS10, and BBS12 are necessary for ... BBSome assembly |
| GO:0045494 photoreceptor cell maintenance | IMP PMID:17980398 Retinal morphology in patients with BBS1 and BBS10 related B... | KEEP AS NON CORE | Summary: The retinal phenotype supports a contextual photoreceptor-maintenance association. Reason: The accessible PMID:17980398 cache describes retinal imaging in BBS1- and BBS10-variant patients with disrupted photoreceptor integrity. This is a human clinical phenotype, not a purified biochemical mechanism. Retain the experimental annotation as non-core while grounding the molecular core in BBSome assembly; do not require the product to be a stable photoreceptor structure for a process association. |
| GO:1905515 non-motile cilium assembly | IMP PMID:17980398 Retinal morphology in patients with BBS1 and BBS10 related B... | KEEP AS NON CORE | Summary: Ciliogenesis effects depend on cell context and are separable from the central assembly role. Reason: PMID:17980398 provides a retinal/connecting-cilium phenotype but the accessible cache lacks a dedicated ciliogenesis assay and complete Methods. Independent original PMID:19190184 Results/Figure 4 report reduced ciliation after two BBS10 RNAi reagents in differentiating human preadipocytes. In contrast, PMID:22500027 reports preserved cilia formation in BBS10 c91fs95 patient fibroblasts despite impaired BBSome assembly. Retain a contextual non-core process assertion, with both conditions stated; neither universal requirement nor curator misattribution follows. Supporting Evidence: PMID:19190184 a significant reduction in the number of ciliated cells |
| GO:0005515 protein binding | IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | KEEP AS NON CORE | Summary: The recovered BBS12-scoped source records a supported BBS10 interaction in assembly machinery. Reason: PMID:20080638 reports BBS10-BBS12 co-immunoprecipitation, including recovery of endogenous BBS10 with low-expressed FLAG-BBS12. This supports the BBS12/Q6ZW61 association as non-core assembly context, without demonstrating direct substrate folding or an isolated binary interaction. |
| GO:0005515 protein binding | IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | KEEP AS NON CORE | Summary: The recovered BBS7-scoped source records a supported BBS10 interaction in assembly machinery. Reason: PMID:20080638 reports BBS10-BBS7 co-immunoprecipitation and recovery of BBS7 with the BBS/CCT machinery. This supports the BBS7/Q8IWZ6 association as non-core assembly context without identifying autonomous BBS10 folding activity. |
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Download this section (compressed HTML)Q: Which physical step does BBS10 perform when promoting the association of BBS6-BBS12-BBS7 with CCT proteins, and does nucleotide binding contribute to that step independently of protein stability?
Q: Which cell-state differences explain impaired ciliogenesis after BBS10 depletion in differentiating preadipocytes but retained cilia formation in the patient fibroblasts studied in PMID:22500027?
Q: What functional consequence does the observed BBS10-RNF2 association have in human cells, beyond the BBS7-specific transcriptional experiments reported in PMID:22302990?
Experiment: Reconstitute BBS10 with BBS6, BBS12, BBS7 and CCT in defined combinations. Measure nucleotide binding and hydrolysis separately from substrate conformation and BBSome assembly, controlling for ATPase activity contributed by CCT and for purified-protein quality.
Hypothesis: BBS10 promotes assembly through a specific recruitment or regulatory interaction that can be separated experimentally from CCT-mediated folding.
Type: in vitro biochemistry and reconstitution
Experiment: Compare wild-type BBS10, engineered D81N and verified patient variants with matched expression, folding and localization controls before interpreting changes in partner association or BBSome assembly.
Hypothesis: Some interaction defects arise from altered BBS10 conformation rather than loss of a nucleotide-dependent catalytic step.
Type: structure-function analysis
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