BBIP1 (also known as BBIP10 and BBS18) is the small (92 aa, ~10.5 kDa) eighth core subunit of the BBSome, an octameric, coat-like adaptor complex (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBIP10) that traffics signaling membrane receptors, including ciliary GPCRs, into and out of the primary cilium in conjunction with intraflagellar transport and the small GTPase ARL6/BBS3. BBIP1 is an integral, stably incorporated subunit that joins the complex through BBS4 and is required for BBSome integrity/stability and for primary cilium assembly. It is found inside the primary cilium and in the cytoplasm but not at centriolar satellites. Beyond its structural role in the BBSome, BBIP1 has a distinct activity not shared by other BBSome subunits; it is required for cytoplasmic microtubule polymerization and acetylation, acting in part through physical interaction with the tubulin deacetylase HDAC6. BBIP1 is restricted to ciliated organisms, and loss-of-function mutations cause the ciliopathy 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: BBIP10 was discovered and characterized as the eighth BBSome subunit and is an integral component that binds the complex through BBS4. This is a core cellular-component annotation for the gene. |
| 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: Term definition (a receptor is transported to, or maintained in, a location within a non-motile cilium) matches the established BBSome cargo- trafficking role; this is a core biological process for the gene. |
| 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, ... | MARK AS OVER ANNOTATED | Summary: This IPI (WITH BBS4/Q96RK4) records a real, meaningful interaction (BBIP10 binds the BBSome through BBS4), but the term "protein binding" is uninformative and discouraged. The biological meaning is captured by the BBSome part_of annotations and, separately, by the HDAC6 interaction. Reason: GO:0005515 conveys no specific function; the underlying BBS4 interaction is already represented by BBSome membership. Per curation guidance, avoid bare protein binding. |
| GO:0005515 protein binding | IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | MARK AS OVER ANNOTATED | Summary: Same uninformative term, supported by the BBSome assembly study showing BBIP10 binds the complex via BBS4. Better represented as BBSome membership. Reason: Protein binding is not an informative molecular function; the specific interaction is captured by the BBSome part_of annotations. |
| GO:0005515 protein binding | IPI PMID:29039417 Protein interaction perturbation profiling at amino-acid res... | MARK AS OVER ANNOTATED | Summary: High-throughput Y2H perturbation profiling across the eight BBSome subunits (WITH BBS4/Q96RK4). Confirms BBIP1 PPIs within the BBSome but yields only the generic protein-binding term. Reason: Uninformative MF term; the meaningful content (BBSome subunit interactions) is captured by BBSome membership annotations. |
| 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: Plausible and curator-asserted (TAS), but generic; the informative localizations are BBSome, cilium, ciliary membrane. |
| 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: Correct but generic localization; retain as supporting, non-core. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624126 | KEEP AS NON CORE | Summary: Duplicate cytosol localization from a Reactome BBSome cargo-binding reaction. Reason: Correct but generic localization; retain as supporting, non-core. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624127 | KEEP AS NON CORE | Summary: Duplicate cytosol localization from a Reactome BBSome cargo-targeting reaction. Reason: Correct but generic localization; retain as supporting, non-core. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624129 | KEEP AS NON CORE | Summary: Duplicate cytosol localization from the Reactome LZTFL1-BBSome reaction. Reason: Correct but generic localization; retain as supporting, 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: Experimentally observed but non-specific localization; informative CCs are BBSome, cilium, ciliary membrane. |
| GO:0036064 ciliary basal body | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence localizes BBIP1 to the ciliary basal body. The BBSome traffics through the basal body en route to the cilium, so this is plausible. Note UniProt states BBIP1 localizes inside the cilium but NOT at centriolar satellites; basal body is distinct from satellites. Reason: Experimental (IDA) localization consistent with the BBSome trafficking route through the basal body; defer to the experimental call. Supporting Evidence: file:human/BBIP1/BBIP1-deep-research-falcon.md is present along the ciliary axoneme but not at centriolar satellites |
| GO:0034464 BBSome | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: Direct experimental evidence (mass-spec identification of BBIP10 within the purified BBSome; ComplexPortal CPX-1908) establishes BBIP1 as a BBSome subunit. This is the strongest CC annotation. Reason: Core, experimentally validated cellular-component annotation; defining identity of the gene product. |
| GO:0060170 ciliary membrane | IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: The BBSome acts as a membrane coat at the ciliary membrane and BBIP10 localizes within the cilium. ComplexPortal IDA annotation to ciliary membrane reflects where the complex functions. Reason: Consistent with the BBSome coat function at the ciliary membrane and with BBIP1's ciliary localization; experimentally supported. |
| 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: Correct process; redundant with stronger IMP evidence from the same study. |
| 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: Experimentally observed but generic localization; informative CCs are BBSome, cilium, ciliary membrane. |
| 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: Core, experimentally validated BBSome membership; defining function. |
| 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: Experimental IMP for a core biological process; the gene is required for primary cilium assembly. |
| GO:0005198 structural molecule activity | IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | NEW | Summary: Proposed new molecular-function annotation. BBIP1 is an integral structural subunit that contributes to BBSome integrity/stability; this captures its subunit-level structural role, which is currently only implied by the generic protein-binding IPIs. The falcon deep research summarizes the subunit-specific assembly requirement, noting that BBIP1 depletion prevents BBSome assembly and causes BBS4 to fail to copurify with the other subunits. Reason: Captures BBIP1's structural contribution to the BBSome (required for BBSome stability), a more informative molecular function than protein binding. This is genuinely subunit-specific (a depletion phenotype of BBIP1 itself), not merely inferred from holo-complex function. Proposed replacements: structural molecule activity Supporting Evidence: file:human/BBIP1/BBIP1-deep-research-falcon.md Depletion of BBIP1 by siRNA prevents the assembly of the BBSome, as demonstrated by metabolic labeling experiments showing that BBS4 fails to copurify with other BBSome subunits in BBIP1-depleted cells |
| GO:0046785 microtubule polymerization | IMP PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | NEW | Summary: Proposed new biological-process annotation capturing BBIP1's distinct, non-BBSome-shared role in cytoplasmic microtubule polymerization and acetylation (rescued by HDAC6 inhibition; BBIP1 binds HDAC6). Not currently represented in GOA. The falcon deep research independently emphasizes that this microtubule-acetylation phenotype is specific to the BBIP1 subunit and is not seen on depletion of other BBSome subunits. Reason: BBIP10 depletion abolishes cytoplasmic microtubule polymerization and acetylation, a function explicitly distinguished from its BBSome role. Proposed replacements: microtubule polymerization Supporting Evidence: file:human/BBIP1/BBIP1-deep-research-falcon.md Depletion of BBIP1 results in marked reduction of cytoplasmic microtubule acetylation and dramatically decreased ciliogenesis, phenotypes not observed with depletion of other BBSome subunits |
| GO:0060090 molecular adaptor activity | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | NEW | Summary: Proposed new molecular-function annotation. BBIP1 physically interacts with the tubulin deacetylase HDAC6, and this interaction underlies its promotion of microtubule acetylation; an adaptor activity is a more informative MF than the generic protein-binding IPI from the same paper. Reason: BBIP1 binds HDAC6 (with BBS4/Q96RK4) and couples the BBSome to tubulin acetylation; molecular adaptor activity captures this bridging role. Proposed replacements: molecular adaptor activity Supporting Evidence: file:human/BBIP1/BBIP1-deep-research-falcon.md BBIP1 physically interacts with HDAC6, a tubulin deacetylase, and inhibition of HDAC6 restores microtubule acetylation in BBIP1-depleted cells |
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Download this section (compressed HTML)Q: Is the microtubule-stabilizing/acetylation function of BBIP1 mediated by BBSome-bound BBIP1 or by a free pool of BBIP1, and does it depend on direct HDAC6 inhibition versus an indirect mechanism?
Suggested experts: Maxence V. Nachury
Q: Does BBIP1 contribute specific structural contacts within the cryo-EM BBSome architecture that are required for cargo (GPCR) capture or membrane coating, beyond simply stabilizing the complex?
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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