BBIP1, also called BBIP10 or BBS18, is a small structural subunit of the BBSome, a protein complex that supports ciliary membrane-protein trafficking. In the human BBSome core, BBIP1 contacts BBS4 and BBS8 and helps maintain complex architecture. It localizes to primary cilia and the cytoplasm and contributes to ciliogenesis. BBIP1 depletion also affects cytoplasmic microtubule polymerization and acetylation, and inhibition of the associated deacetylase HDAC6 restores acetylation in depleted cells. The molecular connection between this phenotype and its BBSome role remains unresolved. Loss-of-function variants cause Bardet–Biedl syndrome type 18.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0034464 BBSome | IBA GO_REF:0000033 | ACCEPT | Summary: BBIP1/BBIP10 is a bona fide, experimentally validated core subunit of the BBSome. The phylogenetic (IBA) call agrees with direct experimental evidence. Reason: Retain the positive IBA BBSome assertion: direct discovery evidence and the later human structure agree with complex membership. Local IBD PTN002006313 is positive; the full tree and MSA were not reinterpreted. |
| GO:0097500 receptor localization to non-motile cilium | IBA GO_REF:0000033 | ACCEPT | Summary: The BBSome's central, defining function is trafficking signaling receptors (e.g. ciliary GPCRs) into and out of the primary (non-motile) cilium. As an integral subunit required for BBSome integrity, BBIP1 is appropriately annotated to this process. Reason: The human structure identifies BBIP1 as an integral BBSome scaffold, and the cited Reactome events describe BBSome-dependent receptor cargo targeting to cilia. This structural contribution supports the inherited receptor-localization process without assigning autonomous cargo recognition to BBIP1; no IBA donor-count judgment is made. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt records BBIP1 in the cytoplasm, consistent with its cytoplasmic microtubule role and with BBSome subunits cycling through the cytoplasm before ciliary entry. This IEA call is corroborated by the experimental IDA below. Reason: Correct but generic localization; the informative CC annotations are BBSome, cilium, and ciliary membrane. Retain as supporting context. |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: BBIP1 localizes inside the primary cilium, like other BBSome subunits. The UniProt subcellular-location-derived IEA is consistent with experimental data. Reason: Ciliary localization is well supported experimentally and is central to BBIP1/BBSome function. |
| GO:0034464 BBSome | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR028233, BBIP10 family) maps the BBSome membership. This is redundant with, and corroborated by, the experimental BBSome annotations. Reason: Family-level electronic inference correctly assigns BBSome membership, consistent with direct evidence. |
| GO:0060271 cilium assembly | IEA GO_REF:0000002 | ACCEPT | Summary: BBIP1 is required for primary cilium assembly; the InterPro2GO electronic inference agrees with the experimental IMP from the same depletion study. Reason: Cilium assembly is a core, experimentally supported process for BBIP1; the IEA is corroborated. |
| GO:0005515 protein binding | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | KEEP AS NON CORE | Summary: The BBS4-scoped source records BBIP1 association with BBS4 in the BBSome. Reason: The original GOA record names BBS4/Q96RK4 as its supporting entity. This source is now represented separately from the HDAC6 association reported in the same paper. BBS4 association is consistent with the assembly study and later human BBSome structure, which places BBIP1 against BBS4. Retain this supported interaction as non-core context; the structural scaffold function is represented separately. No histone-deacetylase-binding replacement is applied to the BBS4 source, and a simultaneous BBS4–BBIP1–HDAC6 bridge is not established. |
| GO:0005515 protein binding | IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | KEEP AS NON CORE | Summary: BBIP10 associates with BBS4 in the BBSome assembly study. Reason: Selected primary Results distinguish BBIP10–BBS4 association from PCM1 co-association that requires BBS4; the later human structure independently places BBIP1 against BBS4. Retain the supported BBS4 interaction as non-core under the supplied ActionEnum. These observations do not establish a coordinated HDAC6/BBS4 adaptor mechanism. |
| GO:0005515 protein binding | IPI PMID:29039417 Protein interaction perturbation profiling at amino-acid res... | KEEP AS NON CORE | Summary: The original interaction-profiling study directly examined the BBS4–BBS18 pair. Reason: The publisher supplementary Figure 6 caption reports interaction-disrupting mutations in both BBS4 and BBS18, supporting the curated BBS4/Q96RK4 interaction. The caption describes a 104-residue BBS18 construct; its exact isoform provenance and the complete mutation matrix were not read. Retain the interaction as non-core without assigning it to one of the four recorded products. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617815 | KEEP AS NON CORE | Summary: Reactome places the BBSome (and thus BBIP1) in the cytosol during pathway steps prior to ciliary entry. Consistent with cytoplasmic localization but less specific than the BBSome/ciliary CCs. Reason: Reactome places the BBIP1-containing BBSome in the cytosol for its association with RAB3IP. Retain this pathway-localization context as non-core because BBSome membership and ciliary locations describe its principal role more specifically. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624125 | KEEP AS NON CORE | Summary: Duplicate cytosol localization from the Reactome Formation of the BBSome reaction. Reason: The source records cytosolic BBSome formation. As a constituent of the assembled complex, BBIP1 shares that localization; retain this broad assembly context as non-core alongside the specific BBSome annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624126 | KEEP AS NON CORE | Summary: Duplicate cytosol localization from a Reactome BBSome cargo-binding reaction. Reason: The source places the BBIP1-containing BBSome in the cytosolic and membrane recruitment context of ARL6-dependent cargo binding. Retain the broad cytosol location as non-core alongside its more informative BBSome and ciliary locations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624127 | KEEP AS NON CORE | Summary: Duplicate cytosol localization from a Reactome BBSome cargo-targeting reaction. Reason: The curated event describes trafficking of the BBIP1-containing BBSome and its cargo toward the primary cilium. Retain the associated cytosolic complex location as non-core; the specific ciliary locations remain separately supported. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624129 | KEEP AS NON CORE | Summary: Duplicate cytosol localization from the Reactome LZTFL1-BBSome reaction. Reason: Reactome describes a cytosolic LZTFL1–BBSome complex. BBIP1 is a BBSome constituent, supporting this broad cytosol annotation as non-core. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence places BBIP1 in the cytosol. Consistent with cytoplasmic localization and the cytoplasmic microtubule role, though generic. Reason: The official HPA antibody text reports cytosolic staining in RPTEC/TERT1 and serum-starved hTERT-RPE1 cells (https://www.proteinatlas.org/ENSG00000214413-BBIP1/summary/antibody). Retain this broad localization as non-core. This assessment uses the record text and the original HPA IDA; image pixels were not independently scored and no isoform-specific localization is inferred. |
| GO:0036064 ciliary basal body | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas antibody observations support ciliary basal-body localization. Reason: The official HPA antibody text reports basal-body staining in RPTEC/TERT1 and serum-starved hTERT-RPE1 cells (https://www.proteinatlas.org/ENSG00000214413-BBIP1/summary/antibody). This corroborates the original HPA IDA. Retain the basal-body assignment with deference to the antibody-data curators: image pixels and antibody specificity were not independently reassessed. Basal bodies and centriolar satellites are distinct structures, so the reported satellite-localization caveat does not contradict this term. |
| GO:0034464 BBSome | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: The discovery paper identifies BBIP10 as a component of the BBSome. Reason: Retain direct complex membership, corroborated by later human structural work. The accessible original abstract and Figure 2 caption support membership and ciliogenesis; the complete biochemical Results were not available for independent reanalysis. |
| GO:0060170 ciliary membrane | IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: Retain the curated ciliary-membrane localization in its BBSome context. Reason: The original full localization experiment was unavailable. The annotation is consistent with the established ciliary BBSome location, so defer to the experimental curator; general ciliary localization alone is not claimed as independent proof of membrane localization. |
| GO:0060271 cilium assembly | NAS PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: Non-traceable author statement of the cilium-assembly role from the discovery paper. The same process is independently supported by the IMP annotation below. Reason: Keep NAS cilium-assembly assertion, corroborated by source IMP and primary depletion evidence. |
| GO:0005737 cytoplasm | IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | KEEP AS NON CORE | Summary: Direct experimental observation of cytoplasmic BBIP1, consistent with UniProt subcellular location and with its cytoplasmic microtubule function. Reason: Retain the curated experimental cytoplasmic localization, consistent with the discovery study’s cytoplasmic microtubule phenotype. It provides broad cellular context; BBSome membership and ciliary locations are more specific to the principal function. |
| GO:0034464 BBSome | IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: Direct experimental evidence (UniProt-curated IDA) that BBIP10 is part of the BBSome. Reason: Keep direct BBSome membership; strong independent structural corroboration. |
| GO:0060271 cilium assembly | IMP PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: BBIP10 depletion impairs ciliogenesis (characteristic BBS phenotypes in zebrafish; ciliary defects in cells). Strong mutant-phenotype evidence for a role in cilium assembly. Reason: Keep source IMP cilium assembly: primary cell/zebrafish experiments plus structural BBSome contribution. This existing assertion is not a newly manufactured necessity-only BP. |
| GO:0140378 protein complex scaffold activity | IDA PMID:31951201 Structure of the human BBSome core complex. | NEW | Summary: BBIP1 provides an integral structural scaffold within the human BBSome core. Reason: The human six-subunit structure places BBIP1 between BBS4 and BBS8, maintaining their assembly. This is a subunit-specific structural contribution matching GO:0140378, rather than a complex-wide cargo-adaptor activity or a process inferred only from depletion. The prior broad structural-molecule proposal is replaced, not retained alongside its descendant. Selected original Results and purification Methods were read online, then checked against the exact normal source record already present on signed main. The structural anchor is recorded once in the core function. |
| GO:0005515 protein binding | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | MODIFY | Summary: The HDAC6-scoped source supports histone deacetylase binding by BBIP1. Reason: The source supporting entity is HDAC6/Q9UBN7, and the original abstract explicitly reports physical interaction of BBIP10 with HDAC6. GO:0042826 describes binding to a histone deacetylase and therefore captures this supported partner class more specifically than generic protein binding. This replacement applies only to the separate HDAC6 source. The accessible abstract does not establish isolated binary binding, direct inhibition of HDAC6 catalysis, or a simultaneous HDAC6–BBIP1–BBS4 bridge; none is asserted. Proposed replacements: histone deacetylase binding Supporting Evidence: PMID:19081074 BBIP10 physically interacts with HDAC6. |
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Download this section (compressed HTML)Q: Does BBIP1 directly alter tubulin assembly or HDAC6 catalysis, or are the cytoplasmic microtubule phenotypes mediated through another cellular step?
Suggested experts: Maxence V. Nachury
Q: Are the BBSome scaffold and HDAC6-associated effects separable, and does the latter occur in BBSome-bound or free BBIP1?
Q: Which BBIP1 product was used for the 104-residue BBS18 construct in the 2017 interaction study, and how does it relate to the current UniProt products?
Experiment: Separation-of-function mutagenesis of BBIP1 to uncouple BBSome incorporation (BBS4 binding) from HDAC6 binding/microtubule acetylation, assayed by ciliary GPCR trafficking versus cytoplasmic microtubule acetylation in BBIP1-null cells.
Hypothesis: BBIP1's BBSome-structural role and its microtubule/HDAC6-related role are genetically separable functions of the same small protein.
Experiment: Map the BBIP1-HDAC6 interaction interface and test whether BBIP1 directly inhibits HDAC6 tubulin-deacetylase activity in vitro.
Hypothesis: BBIP1 promotes microtubule acetylation by directly antagonizing HDAC6 rather than by an indirect cellular mechanism.
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