BBS2 is a structural subunit of the BBSome, an eight-protein complex that supports membrane-protein trafficking at cilia. BBS2 associates with BBS7 through a coiled-coil interface and contacts BBS9 through its C-terminal helical region, linking these subunits within the assembled complex. BBSome function supports ciliary signaling and the maintenance of sensory cells, including retinal photoreceptors. BBS2 is found in cytoplasmic and ciliary compartments. Biallelic pathogenic variants cause Bardet-Biedl syndrome, and some variants are associated with nonsyndromic retinitis pigmentosa.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043005 neuron projection | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: BBS2 has a supported non-core localization to specialized cell projections. Reason: Retain the PAINT localization and its mouse/worm supporting entities. The QuickGO is_a- only ancestor response for stereocilium (GO:0032420) includes neuron projection (GO:0043005), as well as actin-based cell projection. Mouse Bbs2 localization to stereocilia in PMID:25605782 is therefore compatible with this broad location. The relationship was rechecked on 2026-10-09 at https://www.ebi.ac.uk/QuickGO/services/ontology/go/terms/GO%3A0032420/ancestors?relations=is_a. It does not make BBS2 a neuronal structural protein or replace the ancestral PAINT evidence. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: BBS2 supports cilium assembly through the BBSome. Reason: Its integral assembly and trafficking role supports this inherited process. Dependence varies by cell type: Bbs2-null mice can initially form several cilia, so the annotation does not mean BBS2 is universally indispensable for initiation of every cilium. |
| GO:0016020 membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: BBS2 associates with membranes as a BBSome component. Reason: The broad membrane location is compatible with a peripheral coat complex and need not mean a transmembrane protein. It also allows membrane contexts beyond the separately supported ciliary membrane, so retain its breadth as non-core. |
| GO:0034464 BBSome | IBA GO_REF:0000033 | ACCEPT | Summary: BBS2 is an integral BBSome subunit. Reason: Independent purification and assembly studies directly establish BBS2 in this complex, in agreement with the phylogenetic assertion. |
| GO:0036064 ciliary basal body | IBA GO_REF:0000033 | ACCEPT | Summary: BBS2 localizes to the ciliary basal body. Reason: Basal-body localization is concordant with its BBSome assembly and trafficking role and the separately curated direct target annotation. |
| GO:0031514 motile cilium | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: BBS2 can localize to motile cilia. Reason: Airway localization and functional observations support the location. A role in BBSome-dependent maintenance is compatible with motile-cilium localization and does not confer axonemal motor activity. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: BBS2 has a cytoplasmic pool. Reason: The UniProt-derived broad localization is compatible with cytosolic assembly and membrane recruitment of the BBSome; it is not an assertion that BBS2 is restricted to the cytoplasm. |
| GO:0034451 centriolar satellite | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: BBS2 is annotated at centriolar satellites. Reason: Retain the UniProt-derived satellite localization as a trafficking-associated context. Lack of a separately demonstrated satellite-specific molecular function is not evidence against a cellular-component annotation. |
| GO:0034464 BBSome | IEA GO_REF:0000120 | ACCEPT | Summary: BBS2 belongs to the BBSome. Reason: The electronic family and ortholog annotation agrees with direct human complex isolation and assembly evidence. |
| GO:0060170 ciliary membrane | IEA GO_REF:0000044 | ACCEPT | Summary: BBS2 associates with the ciliary membrane through the BBSome. Reason: This is a central location for the BBSome coat. Association does not require BBS2 to span the membrane or independently recognize every cargo. |
| GO:1905515 non-motile cilium assembly | IEA GO_REF:0000002 | ACCEPT | Summary: BBS2 contributes to non-motile cilium assembly. Reason: The family-derived process agrees with BBSome-dependent ciliary membrane biogenesis. Assembly and maintenance requirements are cell-context dependent, not a universal requirement for axoneme initiation. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with PSME3 (P61289). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | MODIFY | Summary: BBS2 binds BBS9 (Q3SYG4) as part of its BBSome scaffold role. Reason: The source row records BBS2 interaction with BBS9 (UniProtKB:Q3SYG4) by IPI from PMID:17574030. PMID:22500027 shows BBS2 bridging BBS7 and BBS9, and PMID:22072986 shows BBSome disintegration after BBS2 depletion. PMID:31530639 places the BBS9 interface on BBS2 and tests a disruptive BBS2 mutation. This integral structural role supports the specific scaffold adaptor GO:0140378: BBS2 organizes distinct protein contacts needed to assemble the complex. This is more informative than an unspecified adaptor or structural-molecule term and does not assign autonomous cargo recognition. Proposed replacements: protein complex scaffold activity |
| GO:0005515 protein binding | IPI PMID:18000879 Novel interaction partners of Bardet-Biedl syndrome proteins... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with ALDOB (P05062). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | MODIFY | Summary: BBS2 binds BBS9 (Q3SYG4) as part of its BBSome scaffold role. Reason: The source row records BBS2 interaction with BBS9 (UniProtKB:Q3SYG4) by IPI from PMID:20080638. PMID:22500027 shows BBS2 bridging BBS7 and BBS9, and PMID:22072986 shows BBSome disintegration after BBS2 depletion. PMID:31530639 places the BBS9 interface on BBS2 and tests a disruptive BBS2 mutation. This integral structural role supports the specific scaffold adaptor GO:0140378: BBS2 organizes distinct protein contacts needed to assemble the complex. This is more informative than an unspecified adaptor or structural-molecule term and does not assign autonomous cargo recognition. Proposed replacements: protein complex scaffold activity |
| GO:0005515 protein binding | IPI PMID:22139371 Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals ... | MODIFY | Summary: BBS2 binds BBS9 (Q3SYG4) as part of its BBSome scaffold role. Reason: The source row records BBS2 interaction with BBS9 (UniProtKB:Q3SYG4) by IPI from PMID:22139371. PMID:22500027 shows BBS2 bridging BBS7 and BBS9, and PMID:22072986 shows BBSome disintegration after BBS2 depletion. PMID:31530639 places the BBS9 interface on BBS2 and tests a disruptive BBS2 mutation. This integral structural role supports the specific scaffold adaptor GO:0140378: BBS2 organizes distinct protein contacts needed to assemble the complex. This is more informative than an unspecified adaptor or structural-molecule term and does not assign autonomous cargo recognition. Proposed replacements: protein complex scaffold activity |
| GO:0005515 protein binding | IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | MODIFY | Summary: BBS2 binds BBS9 (Q3SYG4) as part of its BBSome scaffold role. Reason: The source row records BBS2 interaction with BBS9 (UniProtKB:Q3SYG4) by IPI from PMID:22500027. PMID:22500027 shows BBS2 bridging BBS7 and BBS9, and PMID:22072986 shows BBSome disintegration after BBS2 depletion. PMID:31530639 places the BBS9 interface on BBS2 and tests a disruptive BBS2 mutation. This integral structural role supports the specific scaffold adaptor GO:0140378: BBS2 organizes distinct protein contacts needed to assemble the complex. This is more informative than an unspecified adaptor or structural-molecule term and does not assign autonomous cargo recognition. Proposed replacements: protein complex scaffold activity |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: BBS2 is reported to associate with PSME3 (P61289). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:25552655 Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integ... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with IQCB1/NPHP5 (Q15051). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | MODIFY | Summary: BBS2 binds BBS9 (Q3SYG4) as part of its BBSome scaffold role. Reason: The source row records BBS2 interaction with BBS9 (UniProtKB:Q3SYG4) by IPI from PMID:27173435. PMID:22500027 shows BBS2 bridging BBS7 and BBS9, and PMID:22072986 shows BBSome disintegration after BBS2 depletion. PMID:31530639 places the BBS9 interface on BBS2 and tests a disruptive BBS2 mutation. This integral structural role supports the specific scaffold adaptor GO:0140378: BBS2 organizes distinct protein contacts needed to assemble the complex. This is more informative than an unspecified adaptor or structural-molecule term and does not assign autonomous cargo recognition. Proposed replacements: protein complex scaffold activity |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: BBS2 forms a heterodimer with BBS7 (Q8IWZ6). Reason: Retain the IPI evidence for BBS2 interaction with BBS7 (UniProtKB:Q8IWZ6) from PMID:28514442 and refine the molecular function using independent human BBS2–BBS7 structural evidence in PMID:31530639. The coiled-coil interface forms a tight heterodimer within the BBSome. This independent grounding supports GO:0046982; the original interaction assay is not represented as a structural experiment. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:29039417 Protein interaction perturbation profiling at amino-acid res... | MODIFY | Summary: BBS2 binds BBS9 (Q3SYG4) as part of its BBSome scaffold role. Reason: The source row records BBS2 interaction with BBS9 (UniProtKB:Q3SYG4) by IPI from PMID:29039417. PMID:22500027 shows BBS2 bridging BBS7 and BBS9, and PMID:22072986 shows BBSome disintegration after BBS2 depletion. PMID:31530639 places the BBS9 interface on BBS2 and tests a disruptive BBS2 mutation. This integral structural role supports the specific scaffold adaptor GO:0140378: BBS2 organizes distinct protein contacts needed to assemble the complex. This is more informative than an unspecified adaptor or structural-molecule term and does not assign autonomous cargo recognition. Proposed replacements: protein complex scaffold activity |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: BBS2 is reported to associate with HNRNPF (P52597). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: BBS2 forms a heterodimer with BBS7 (Q8IWZ6). Reason: Retain the IPI evidence for BBS2 interaction with BBS7 (UniProtKB:Q8IWZ6) from PMID:33961781 and refine the molecular function using independent human BBS2–BBS7 structural evidence in PMID:31530639. The coiled-coil interface forms a tight heterodimer within the BBSome. This independent grounding supports GO:0046982; the original interaction assay is not represented as a structural experiment. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: BBS2 forms a heterodimer with BBS7 (Q8IWZ6). Reason: Retain the IPI evidence for BBS2 interaction with BBS7 (UniProtKB:Q8IWZ6) from PMID:40205054 and refine the molecular function using independent human BBS2–BBS7 structural evidence in PMID:31530639. The coiled-coil interface forms a tight heterodimer within the BBSome. This independent grounding supports GO:0046982; the original interaction assay is not represented as a structural experiment. Proposed replacements: protein heterodimerization activity |
| GO:0005902 microvillus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse Bbs2 has been directly localized to microvilli. Reason: The transferred location is supported by PMID:25605782, whose primary Results and Fig. 6 caption explicitly place Bbs2 immunogold signal in epithelial microvilli. The paper title emphasizes Bbs8/Ift20 but the localization experiment assays Bbs2. Keep this contextual location; the inherited cilia-only exclusion is incorrect. Supporting Evidence: PMID:25605782 Bbs2 localized to actin-rich structures in developing hair cells |
| GO:0016020 membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse-derived membrane annotation is compatible with BBSome membrane association. Reason: BBS2 is a peripheral membrane-associated coat component, not necessarily a transmembrane protein. Preserve this broad transferred scope alongside the more specific ciliary-membrane annotation. |
| GO:0031514 motile cilium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse evidence supports BBS2 at motile cilia. Reason: Retain the ortholog-derived location, corroborated by airway-cilium studies. Motile-cilium localization is compatible with a maintenance/trafficking role and does not imply that BBS2 is the beat-generating motor. |
| GO:0032420 stereocilium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse Bbs2 localizes to stereocilia as well as ciliary structures. Reason: PMID:25605782 directly reports Bbs2 immunogold labeling of cochlear stereocilia. Actin-based stereocilia are distinct from microtubule-based cilia, but that distinction does not exclude a protein from localizing to both. Retain this specific ortholog-derived location as non-core. Supporting Evidence: PMID:25605782 particular concentration along stereocilia and microvilli |
| GO:0038108 negative regulation of appetite by leptin-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BBS2 supports leptin-dependent appetite control in a physiological context. Reason: PMID:19150989 includes Bbs2-null mouse leptin-response measurements and separates impaired receptor trafficking from downstream receptor activation machinery. Retain the existing mouse-derived process as a pleiotropic outcome of trafficking, without assigning BBS1’s direct leptin-receptor interaction to BBS2. |
| GO:0045444 fat cell differentiation | IEA GO_REF:0000107 | UNDECIDED | Summary: A direct BBS2 role in adipocyte differentiation remains unresolved. Reason: The traced mouse source, PMID:17379567, reports temporal Bbs2 expression during preadipocyte differentiation. The complete accessible abstract does not demonstrate that Bbs2 performs or regulates a differentiation step. Full primary experimental detail was not inspected, so preserve the assertion as undecided rather than equating expression with participation or declaring it false. |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: BBS2 contributes to ciliary assembly through its BBSome role. Reason: The mouse transfer agrees with human BBSome assembly and trafficking studies. This is a central role, while the normal initial appearance of some cilia in Bbs2-null mice limits any claim of universal ciliogenesis dependence. |
| GO:0060296 regulation of cilium beat frequency involved in ciliary motility | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BBS2 perturbation can alter motile-cilium beat frequency. Reason: The airway study reports impaired ciliary beating in BBS-deficient models. GO:0060296 describes a process that modulates beat frequency and does not require direct motor catalysis. Retain this contextual process, while allowing altered ciliary structure or maintenance to mediate the phenotype. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617815 | KEEP AS NON CORE | Summary: BBS2 occurs in the cytosolic BBSome pool represented by this Reactome event. Reason: Reactome:R-HSA-5617815 places the BBSome in a cytosolic trafficking or recruitment step. Retain the compartment without assigning the catalytic activity of RAB3IP, ARL6 or another event participant to BBS2. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624125 | KEEP AS NON CORE | Summary: BBS2 occurs in the cytosolic BBSome pool represented by this Reactome event. Reason: Reactome:R-HSA-5624125 places the BBSome in a cytosolic trafficking or recruitment step. Retain the compartment without assigning the catalytic activity of RAB3IP, ARL6 or another event participant to BBS2. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624126 | KEEP AS NON CORE | Summary: BBS2 occurs in the cytosolic BBSome pool represented by this Reactome event. Reason: Reactome:R-HSA-5624126 places the BBSome in a cytosolic trafficking or recruitment step. Retain the compartment without assigning the catalytic activity of RAB3IP, ARL6 or another event participant to BBS2. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624127 | KEEP AS NON CORE | Summary: BBS2 occurs in the cytosolic BBSome pool represented by this Reactome event. Reason: Reactome:R-HSA-5624127 places the BBSome in a cytosolic trafficking or recruitment step. Retain the compartment without assigning the catalytic activity of RAB3IP, ARL6 or another event participant to BBS2. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624129 | KEEP AS NON CORE | Summary: BBS2 occurs in the cytosolic BBSome pool represented by this Reactome event. Reason: Reactome:R-HSA-5624129 places the BBSome in a cytosolic trafficking or recruitment step. Retain the compartment without assigning the catalytic activity of RAB3IP, ARL6 or another event participant to BBS2. |
| GO:0035869 ciliary transition zone | IDA GO_REF:0000052 | ACCEPT | Summary: BBS2 has a curated ciliary transition-zone localization. Reason: Retain the direct atlas-derived cellular-component annotation as a relevant ciliary location. The source supports localization; it does not by itself make BBS2 a transition-zone receptor or structural gate. |
| GO:0034464 BBSome | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: BBS2 is a BBSome component in the BBIP1 study. Reason: Retain the curated complex association, consistent with independent BBSome isolation. The focal BBIP1 phenotype does not imply that the study omitted BBS2 or that every BBIP1 activity belongs to BBS2. |
| GO:0060170 ciliary membrane | IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: BBS2 localizes with the BBSome at the ciliary membrane. Reason: The curated direct localization is consistent with the BBSome coat function. Keep the location without inferring autonomous membrane insertion or cargo recognition by BBS2. |
| GO:0060271 cilium assembly | NAS PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: BBS2 contributes to cilium assembly as part of the BBSome. Reason: The non-traceable statement is consistent with independent BBSome/ciliary membrane-biogenesis evidence. The microtubule stability and acetylation effects specifically attributed to BBIP1 are not assigned to BBS2. |
| GO:0034464 BBSome | IMP PMID:19150989 Requirement of Bardet-Biedl syndrome proteins for leptin rec... | ACCEPT | Summary: BBS2 is required for normal BBSome integrity. Reason: Retain the mutant-supported complex annotation. Independent BBS2 depletion and assembly-intermediate experiments provide direct grounding for its integral structural role. |
| GO:0005515 protein binding | IPI PMID:33144677 Dlec1 is required for spermatogenesis and male fertility in ... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with DLEC1 (Q9Y238). Reason: The primary Results directly report co-immunoprecipitation of BBS2 with tagged human DLEC1 in HEK293F cells. This supports an interaction context, not a demonstrated new BBS2 enzyme, motor or cargo-loading activity; co-IP alone does not prove purified binary affinity. |
| GO:0005515 protein binding | IPI PMID:18762586 Recruitment of PCM1 to the centrosome by the cooperative act... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with DISC1 (Q9NRI5). Reason: Retain the curator-supported BBS2–DISC1 interaction as a non-core context. The abstract emphasizes BBS4, but that does not demonstrate absence of a BBS2 experiment. The inspected evidence does not establish a more specific activity for this exact interaction. |
| GO:0007601 visual perception | IMP PMID:25541840 Association between missense mutations in the BBS2 gene and ... | KEEP AS NON CORE | Summary: BBS2 deficiency affects retinal function and visual perception. Reason: Human nonsyndromic retinal disease and mouse photoreceptor-maintenance defects support this tissue-specific process. Retain the existing visual outcome without describing BBS2 as a photopigment or visual-signal transducer. |
| GO:0034464 BBSome | IDA PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | ACCEPT | Summary: BBS2 is a directly supported BBSome subunit. Reason: Retain the experimentally curated complex localization. It agrees with independent purification and assembly studies even though the paper foregrounds BBS4. |
| 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: BBS2 associates with the ubiquitin ligase RNF2. Reason: Retain the curator-assigned BBS2 interaction with RNF2 (UniProtKB:Q99496), recorded as IPI from PMID:22302990. The title foregrounds BBS7, but an abstract-only cache is not grounds for rejecting the curator's BBS2 assay. Refine the partner function: RNF2/RING1B is an E3 ubiquitin ligase, whereas GO:0061629 requires a sequence-specific DNA-binding RNA polymerase II transcription factor partner. GO:0031625 ubiquitin protein ligase binding therefore captures the supported interaction. This reasoning does not require a figure-level claim unavailable in the cached article or imply a core BBS2 transcriptional function. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16327777 Dissection of epistasis in oligogenic Bardet-Biedl syndrome. | KEEP AS NON CORE | Summary: BBS2 is reported to associate with CCDC28B (Q9BUN5). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0038108 negative regulation of appetite by leptin-mediated signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BBS2 supports leptin-dependent appetite control in a physiological context. Reason: PMID:19150989 includes Bbs2-null mouse leptin-response measurements and separates impaired receptor trafficking from downstream receptor activation machinery. Retain the existing mouse-derived process as a pleiotropic outcome of trafficking, without assigning BBS1’s direct leptin-receptor interaction to BBS2. |
| GO:0043001 Golgi to plasma membrane protein transport | IMP PMID:19150989 Requirement of Bardet-Biedl syndrome proteins for leptin rec... | KEEP AS NON CORE | Summary: BBS2 supports receptor trafficking from an intracellular compartment toward the cell surface. Reason: PMID:19150989 directly depleted BBS2 in human ARPE19 cells and observed altered LepRb distribution. Retain the curator’s Golgi-to-plasma-membrane transport assignment as a non-core trafficking context, while preserving the authors’ uncertainty about the precise blocked compartment and avoiding a claim of direct BBS2–LepRb binding. |
| GO:0032402 melanosome transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Bbs2 perturbation alters melanosome transport in zebrafish. Reason: The original donor is zebrafish Q98SP7. PMID:16399798 explicitly reports retrograde melanosome-transport impairment after bbs2 knockdown. This is a supported non-ciliary transport context; its zebrafish origin does not contradict BBS2 function. Retain as non-core without claiming a direct human melanocyte experiment. |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: BBS2 contributes to ciliary assembly through its BBSome role. Reason: The mouse transfer agrees with human BBSome assembly and trafficking studies. This is a central role, while the normal initial appearance of some cilia in Bbs2-null mice limits any claim of universal ciliogenesis dependence. |
| GO:0060296 regulation of cilium beat frequency involved in ciliary motility | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BBS2 perturbation can alter motile-cilium beat frequency. Reason: The airway study reports impaired ciliary beating in BBS-deficient models. GO:0060296 describes a process that modulates beat frequency and does not require direct motor catalysis. Retain this contextual process, while allowing altered ciliary structure or maintenance to mediate the phenotype. |
| GO:0007288 sperm axoneme assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse Bbs2 is required for normal sperm flagellum formation. Reason: The Bbs2-null mouse study reports failed flagellar synthesis in males. Retain the sperm axoneme-assembly transfer as a tissue-specific outcome of BBS2-dependent trafficking and assembly, without assigning DLEC1’s own knockout phenotype or a motor activity to BBS2. |
| GO:0008104 intracellular protein localization | ISS GO_REF:0000024 | MODIFY | Summary: BBS2 supports protein localization to the cilium. Reason: The inherited intracellular-localization term is broad. Human BBS2 depletion disrupts BBSome assembly and ciliary entry in PMID:22072986, while mouse Bbs2 loss causes rhodopsin mislocalization in PMID:15539463. GO:0061512 captures the ciliary localization mechanism without claiming that BBS2 is a transport motor or directly recognizes every cargo. Proposed replacements: protein localization to cilium |
| GO:0021756 striatum development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Bbs2-null mice show abnormal striatum morphology. Reason: PMID:18032602 explicitly includes Bbs2-null mice and reports corresponding striatum abnormalities despite a Bbs1-focused title. Retain the mouse-derived developmental process as non-core; the observations do not resolve a direct BBS2 developmental instruction from secondary consequences of ciliary dysfunction. |
| GO:0021766 hippocampus development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Bbs2-null mice show abnormal hippocampus morphology. Reason: PMID:18032602 explicitly includes Bbs2-null mice and reports corresponding hippocampus abnormalities despite a Bbs1-focused title. Retain the mouse-derived developmental process as non-core; the observations do not resolve a direct BBS2 developmental instruction from secondary consequences of ciliary dysfunction. |
| GO:0021987 cerebral cortex development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Bbs2-null mice show abnormal cerebral cortex morphology. Reason: PMID:18032602 explicitly includes Bbs2-null mice and reports corresponding cerebral cortex abnormalities despite a Bbs1-focused title. Retain the mouse-derived developmental process as non-core; the observations do not resolve a direct BBS2 developmental instruction from secondary consequences of ciliary dysfunction. Supporting Evidence: PMID:18032602 Similar abnormalities were also observed in the brains of Bbs2(-/-), Bbs4(-/-), and Bbs6(-/-) mice |
| GO:0030534 adult behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse Bbs2 loss changes adult social behavior. Reason: PMID:15539463 reports reduced social dominance in Bbs2-null mice, including controls addressing visual impairment. Retain the transferred organismal process as non-core without asserting a specific human behavioral mechanism. |
| GO:0040015 negative regulation of multicellular organism growth | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BBS2 supports normal body-size regulation in a physiological context. Reason: Bbs2-null mice develop excessive weight gain with increased food consumption, while leptin-response defects are documented independently. These observations are consistent with the broad transferred negative regulation of organism growth/body size, but do not establish an autonomous BBS2 growth-control activity. |
| GO:0045444 fat cell differentiation | ISS GO_REF:0000024 | UNDECIDED | Summary: A direct BBS2 role in adipocyte differentiation remains unresolved. Reason: The traced mouse source, PMID:17379567, reports temporal Bbs2 expression during preadipocyte differentiation. The complete accessible abstract does not demonstrate that Bbs2 performs or regulates a differentiation step. Full primary experimental detail was not inspected, so preserve the assertion as undecided rather than equating expression with participation or declaring it false. |
| GO:0045494 photoreceptor cell maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BBS2 supports photoreceptor maintenance. Reason: Bbs2-null mice initially develop photoreceptors but show rhodopsin mislocalization followed by degeneration; human retinal disease provides additional context. Retain maintenance as a tissue-specific consequence of the core ciliary trafficking function. |
| GO:0048854 brain morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Bbs2-null mice show abnormal brain morphology. Reason: PMID:18032602 explicitly includes Bbs2-null mice and reports corresponding brain abnormalities despite a Bbs1-focused title. Retain the mouse-derived developmental process as non-core; the observations do not resolve a direct BBS2 developmental instruction from secondary consequences of ciliary dysfunction. |
| GO:0034464 BBSome | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: BBS2 is an experimentally isolated BBSome subunit. Reason: The founding complex study and later assembly work support this central cellular-component annotation. |
| GO:0031514 motile cilium | IDA PMID:18299575 Loss of Bardet-Biedl syndrome proteins alters the morphology... | KEEP AS NON CORE | Summary: BBS2 localizes to motile cilia in the airway study. Reason: Retain the direct experimental location as a contextual BBSome distribution. Motile-cilium localization does not require BBS2 to be an axonemal motor or a factor dedicated exclusively to motile cilia. |
| GO:0036064 ciliary basal body | IDA PMID:18299575 Loss of Bardet-Biedl syndrome proteins alters the morphology... | ACCEPT | Summary: BBS2 localizes to ciliary basal bodies. Reason: Retain the direct location as a central trafficking-associated site, in agreement with the independently inherited basal-body assertion. |
| GO:0005515 protein binding | IPI PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | MODIFY | Summary: BBS2 forms a heterodimer with BBS7 (Q8IWZ6). Reason: Retain the IPI evidence for BBS2 interaction with BBS7 (UniProtKB:Q8IWZ6) from PMID:17574030 and refine the molecular function using independent human BBS2–BBS7 structural evidence in PMID:31530639. The coiled-coil interface forms a tight heterodimer within the BBSome. This independent grounding supports GO:0046982; the original interaction assay is not represented as a structural experiment. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with BBS1 (Q8NFJ9). Reason: BBS1 and BBS2 are components of the assembled BBSome. Retain this partner-specific association, but co-complex membership alone does not establish a BBS2–BBS1 heterodimer or transfer BBS1 cargo recognition to BBS2. |
| GO:0005515 protein binding | IPI PMID:18000879 Novel interaction partners of Bardet-Biedl syndrome proteins... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with EEF1A1 (P68104). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:18000879 Novel interaction partners of Bardet-Biedl syndrome proteins... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with PCM1 (Q15154). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with BBS12 (Q6ZW61). Reason: This interaction is compatible with BBS2 passing through chaperonin-assisted assembly intermediates. Being a chaperone client or associated assembly substrate does not give BBS2 autonomous folding activity. Retain the reported partner interaction as non-core without assigning the partner’s chaperone mechanism to BBS2. |
| GO:0005515 protein binding | IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | MODIFY | Summary: BBS2 forms a heterodimer with BBS7 (Q8IWZ6). Reason: Retain the IPI evidence for BBS2 interaction with BBS7 (UniProtKB:Q8IWZ6) from PMID:20080638 and refine the molecular function using independent human BBS2–BBS7 structural evidence in PMID:31530639. The coiled-coil interface forms a tight heterodimer within the BBSome. This independent grounding supports GO:0046982; the original interaction assay is not represented as a structural experiment. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with MKKS/BBS6 (Q9NPJ1). Reason: This interaction is compatible with BBS2 passing through chaperonin-assisted assembly intermediates. Being a chaperone client or associated assembly substrate does not give BBS2 autonomous folding activity. Retain the reported partner interaction as non-core without assigning the partner’s chaperone mechanism to BBS2. |
| GO:0005515 protein binding | IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | MODIFY | Summary: BBS2 forms a heterodimer with BBS7 (Q8IWZ6). Reason: Retain the IPI evidence for BBS2 interaction with BBS7 (UniProtKB:Q8IWZ6) from PMID:22500027 and refine the molecular function using independent human BBS2–BBS7 structural evidence in PMID:31530639. The coiled-coil interface forms a tight heterodimer within the BBSome. This independent grounding supports GO:0046982; the original interaction assay is not represented as a structural experiment. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with BBS1 (Q8NFJ9). Reason: BBS1 and BBS2 are components of the assembled BBSome. Retain this partner-specific association, but co-complex membership alone does not establish a BBS2–BBS1 heterodimer or transfer BBS1 cargo recognition to BBS2. |
| GO:0005515 protein binding | IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with MKKS/BBS6 (Q9NPJ1). Reason: This interaction is compatible with BBS2 passing through chaperonin-assisted assembly intermediates. Being a chaperone client or associated assembly substrate does not give BBS2 autonomous folding activity. Retain the reported partner interaction as non-core without assigning the partner’s chaperone mechanism to BBS2. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: BBS2 is reported to associate with RBPMS (Q93062). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: BBS2 is reported to associate with MDFI (Q99750). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | MODIFY | Summary: BBS2 forms a heterodimer with BBS7 (Q8IWZ6). Reason: Retain the IPI evidence for BBS2 interaction with BBS7 (UniProtKB:Q8IWZ6) from PMID:27173435 and refine the molecular function using independent human BBS2–BBS7 structural evidence in PMID:31530639. The coiled-coil interface forms a tight heterodimer within the BBSome. This independent grounding supports GO:0046982; the original interaction assay is not represented as a structural experiment. Proposed replacements: protein heterodimerization activity |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with BBS1 (Q8NFJ9). Reason: BBS1 and BBS2 are components of the assembled BBSome. Retain this partner-specific association, but co-complex membership alone does not establish a BBS2–BBS1 heterodimer or transfer BBS1 cargo recognition to BBS2. |
| GO:0005515 protein binding | IPI PMID:29039417 Protein interaction perturbation profiling at amino-acid res... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with BBS7 isoform 2 (Q8IWZ6-2). Reason: Retain the exact BBS7 isoform-2 interaction as non-core. The independent BBS2–BBS7 structural study supports the canonical interface, but the exact isoform of its construct has not been established here. A heterodimerization replacement for this distinct source tuple would therefore overstate the isoform-specific evidence. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: BBS2 is reported to associate with PSME3 (P61289). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: BBS2 is reported to associate with LMO4 (P61968). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: BBS2 is reported to associate with NRF1 isoform 4 (Q16656-4). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: BBS2 is reported to associate with FNDC3B isoform 3 (Q53EP0-3). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: BBS2 is reported to associate with MDFI (Q99750). Reason: Retain the supported partner-specific interaction as non-core under the explicit ClinGen project instruction. The inspected evidence does not establish a finer BBS2 molecular function for this pair. Generic binding is not used to describe the core mechanism; the standing project instruction permits supported non-core retention despite the generic-binding advisory. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with BBS1 (Q8NFJ9). Reason: BBS1 and BBS2 are components of the assembled BBSome. Retain this partner-specific association, but co-complex membership alone does not establish a BBS2–BBS1 heterodimer or transfer BBS1 cargo recognition to BBS2. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: BBS2 is reported to associate with BBS1 (Q8NFJ9). Reason: BBS1 and BBS2 are components of the assembled BBSome. Retain this partner-specific association, but co-complex membership alone does not establish a BBS2–BBS1 heterodimer or transfer BBS1 cargo recognition to BBS2. |
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Download this section (compressed HTML)Q: Does BBS2 make direct contacts with ciliary cargo, or do its effects on cargo trafficking arise from its contribution to BBSome architecture?
Q: Which consequence of BBS2 association with RNF2 is established in human cells independently of the transcriptional effects measured for BBS7?
Q: How do variants associated with nonsyndromic retinal disease differ from other pathogenic BBS2 variants in complex assembly, abundance and photoreceptor trafficking?
Experiment: Compare independently verified BBS2 variants with matched protein expression and stability, measuring BBS7 association, BBS9 association and assembly of the complete BBSome separately. Relate these measurements to ciliary cargo trafficking in an appropriate human-cell model.
Hypothesis: Distinct BBS2 interfaces can be perturbed separately, with different consequences for BBSome assembly and trafficking.
Type: controlled biochemical and cell-based structure-function analysis
Experiment: Test cargo contact using purified complete BBSome and BBS2 interface variants that retain complex integrity, distinguishing direct cargo contact from loss of other subunits or altered complex stability.
Hypothesis: Effects of some BBS2 variants on cargo handling result from altered complex architecture rather than a direct cargo-binding defect.
Type: biochemical reconstitution and cargo-binding analysis
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