BBS7 is a core subunit of the BBSome, an octameric coat/adaptor-like protein complex (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9, BBIP1) that sorts and traffics specific membrane signaling receptors into and out of the primary cilium in coordination with the small GTPase ARL6/BBS3 and intraflagellar transport. BBS7 carries a beta-propeller, a gamma-adaptin ear (GAE) domain, a platform domain, and a hairpin, structural features it shares with BBS2 and BBS9; together BBS2, BBS7 and BBS9 form the beta-propeller/GAE/platform scaffold core of the BBSome. Newly synthesized BBS7 is a client of the BBS-chaperonin complex (BBS6/BBS10/BBS12 with CCT/TRiC), which stabilizes BBS7 and nucleates assembly of the BBS7-BBS2-BBS9 core before the remaining subunits are added. The BBSome localizes to the ciliary membrane, basal body, centrosome and centriolar satellites, and is required for ciliary membrane biogenesis and for trafficking of cargo such as Smoothened during Hedgehog signaling. Loss of BBS7 function causes Bardet-Biedl syndrome, a pleiotropic ciliopathy featuring retinal degeneration, obesity, polydactyly, renal malformation, hypogenitalism and intellectual disability.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008104 intracellular protein localization | IBA GO_REF:0000033 | MODIFY | Summary: BBSome-mediated trafficking of membrane proteins to the cilium. The generic term is correct in spirit, but a more specific child term capturing ciliary protein localization is preferable. Reason: As part of the BBSome, BBS7 specifically mediates protein localization to the cilium rather than generic intracellular protein localization. GO:0061512 better captures the established BBSome function. Proposed replacements: protein localization to cilium |
| GO:0016020 membrane | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Very high-level cellular component. BBS7 associates with the ciliary membrane; the generic membrane term is uninformative given the more specific ciliary membrane and BBSome annotations. Reason: The root-level membrane term is uninformative and is superseded by the specific GO:0060170 ciliary membrane and GO:0034464 BBSome annotations on this gene. |
| GO:0034464 BBSome | IBA GO_REF:0000033 | ACCEPT | Summary: BBS7 is a core structural subunit of the BBSome. Strongly supported by phylogenetic inference and by direct experimental evidence in human. Reason: BBSome membership is the defining, best-supported feature of BBS7, also supported by IDA annotations from PMID:17574030, PMID:20080638, PMID:24550735 and PMID:19081074. Supporting Evidence: PMID:17574030 Here we identify a complex composed of seven highly conserved BBS proteins. This complex, the BBSome, localizes to nonmembranous centriolar satellites in the cytoplasm but also to the membrane of the cilium. |
| GO:0036064 ciliary basal body | IBA GO_REF:0000033 | ACCEPT | Summary: BBSome subunits, including BBS7, localize at and near the basal body, consistent with UniProt subcellular location and the ciliary trafficking role. Reason: Basal body localization is well established for BBSome subunits and supported by UniProt subcellular location. |
| GO:0043005 neuron projection | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic transfer reflecting BBSome roles at neuronal cilia, such as GPCR trafficking in neuronal cilia. Largely a restatement of ciliary localization in a neuronal context. Reason: Neuron projection localization is a context-specific manifestation of the BBSome ciliary function rather than a core annotation; retained as non-core. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: The BBSome is required for ciliogenesis and ciliary membrane biogenesis; BBS7 loss yields characteristic BBS ciliary phenotypes. Well supported. Reason: Cilium assembly involvement is established for the BBSome (PMID:17574030) and is a core biological process for BBS7. Supporting Evidence: PMID:17574030 the BBSome is required for ciliogenesis but is dispensable for centriolar satellite function. |
| GO:0005930 axoneme | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The BBSome moves along and within cilia, but BBS7 is not an axonemal structural component; localization is principally to the ciliary membrane and base. Reason: Axonemal association is a plausible but non-core, low-specificity location relative to the ciliary membrane and basal body where BBS7 function is established. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: BBS7 has a cytoplasmic pool involved in BBSome assembly and centriolar satellites. Correct but low specificity; the EXP-supported cytoplasm annotation below carries the evidence. Reason: Cytoplasm is correct but generic; retained as non-core given more specific locations (centriolar satellite, centrosome, ciliary membrane). |
| GO:0034451 centriolar satellite | IEA GO_REF:0000044 | ACCEPT | Summary: The BBSome localizes to nonmembranous centriolar satellites in the cytoplasm (PMID:17574030); BBS7 is at centriolar satellites and the centrosome (PMID:22072986). Reason: Centriolar satellite localization is well supported for the BBSome and consistent with UniProt subcellular location. Supporting Evidence: PMID:17574030 the BBSome, localizes to nonmembranous centriolar satellites in the cytoplasm |
| GO:0034464 BBSome | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate of the BBSome membership annotation, here by InterPro mapping of the BBS7 signature. Correct. Reason: BBSome membership is correct and corroborated by experimental IDA annotations. |
| GO:0060170 ciliary membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The BBSome associates with the ciliary membrane; BBS7 ciliary membrane localization is also experimentally annotated (IDA, PMID:19081074). Reason: Ciliary membrane localization is a core, experimentally supported location for the BBSome and BBS7. Supporting Evidence: PMID:17574030 This complex, the BBSome, localizes to nonmembranous centriolar satellites in the cytoplasm but also to the membrane of the cilium. |
| GO:1905515 non-motile cilium assembly | IEA GO_REF:0000002 | ACCEPT | Summary: Primary (non-motile) cilia are the principal site of BBSome function; this is a more specific child of cilium assembly and is appropriate. Reason: BBS7 and the BBSome act in assembly and function of primary non-motile cilia (sensory cilia, retina); the InterPro-based involvement is consistent with established biology. |
| GO:0005515 protein binding | IPI PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from BBSome subunit interactions (e.g. BBS1, BBS2). Uninformative per curation guidelines; the meaningful relationships are captured by BBSome membership. Reason: protein binding is uninformative; the underlying BBS1 and BBS2 interactions are represented by the GO:0034464 BBSome part_of annotation. |
| GO:0005515 protein binding | IPI PMID:18000879 Novel interaction partners of Bardet-Biedl syndrome proteins... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from the BBS7-ALDOB interaction. Uninformative molecular function. Reason: protein binding is uninformative; ALDOB is not a core functional partner of the BBSome. |
| GO:0005515 protein binding | IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (BBS7 with CCT2, BBS10, BBS12, BBS2 chaperonin-assembly partners). Uninformative MF term, though the underlying chaperonin-client biology is real. Reason: protein binding is uninformative; the CCT/chaperonin and BBS2 interactions are better captured by BBSome membership and assembly process annotations. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a high-throughput interaction resource (JUN). Uninformative. Reason: protein binding is uninformative and derives from a large-scale interaction screen. |
| GO:0005515 protein binding | IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (BBS7 with CCT2, BBS12, BBS1, BBS2 during sequential BBSome assembly). Uninformative MF term. Reason: protein binding is uninformative; the assembly interactions are captured by BBSome membership and the assembly literature. |
| GO:0005515 protein binding | IPI PMID:25552655 Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (BBS7-IQCB1/NPHP5). Uninformative MF term. Reason: protein binding is uninformative; NPHP5/CEP290 regulation of the BBSome is process context, not a core molecular function term. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from an organelle-specific proteomic interactome (BBS1, BBS2). Uninformative. Reason: protein binding is uninformative and derives from a large-scale interactome study. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a large-scale interactome (BBS2, BBS10, BBS12). Uninformative. Reason: protein binding is uninformative and derives from a high-throughput interactome. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a proteome-scale interaction network (BBS subunits). Uninformative. Reason: protein binding is uninformative and derives from a high-throughput interactome. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a multimodal cell-map interactome (BBS1, BBS2). Uninformative. Reason: protein binding is uninformative and derives from a high-throughput cell-map study. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617815 | KEEP AS NON CORE | Summary: Reactome places the cytosolic BBSome (binding RAB3IP/Rabin8) in the cytosol. Correct but generic relative to the centriolar satellite and centrosome locations. Reason: Cytosol is correct for the assembled cytoplasmic BBSome but low specificity; retained as non-core. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624125 | KEEP AS NON CORE | Summary: Reactome Formation of the BBSome places BBS7 in the cytosol during assembly. Correct but generic. Reason: Cytosol is correct for BBSome assembly but low specificity; retained as non-core. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624126 | KEEP AS NON CORE | Summary: Reactome (ARL6-GTP and BBSome bind ciliary cargo) places BBS7 in the cytosol. Correct but generic. Reason: Cytosol is correct but low specificity; retained as non-core. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624127 | KEEP AS NON CORE | Summary: Reactome (ARL6-GTP and BBSome target cargo to cilium) places BBS7 in the cytosol. Correct but generic. Reason: Cytosol is correct but low specificity; retained as non-core. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624129 | KEEP AS NON CORE | Summary: Reactome (LZTFL1 binds BBSome and prevents ciliary traffic) places BBS7 in the cytosol. Correct but generic. Reason: Cytosol is correct but low specificity; retained as non-core. |
| GO:0005737 cytoplasm | EXP PMID:22072986 A novel protein LZTFL1 regulates ciliary trafficking of the ... | KEEP AS NON CORE | Summary: Experimentally supported cytoplasmic localization of BBS7 (BBSome assembly, centriolar satellites). Correct, generic but evidence-backed. Reason: Cytoplasm is correct and experimentally supported but low specificity relative to centriolar satellite, centrosome and ciliary membrane; retained as non-core. |
| GO:0034464 BBSome | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: ComplexPortal-curated BBSome membership of BBS7. Correct and directly supported. Reason: BBSome membership is the defining feature of BBS7, here from ComplexPortal curation. |
| GO:0060170 ciliary membrane | IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: Direct experimental ciliary membrane localization of the BBSome, including BBS7. Reason: Ciliary membrane is a core, experimentally supported location for BBS7 and the BBSome. |
| GO:0060271 cilium assembly | NAS PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: Cilium assembly involvement asserted by author statement. Consistent with the stronger experimental and IBA support; redundant but correct. Reason: Cilium assembly is a core BBSome process; the NAS annotation is consistent with better-supported annotations of the same term. |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: ISS transfer of cilium assembly involvement from ortholog. Consistent with established BBSome biology. Reason: Cilium assembly is a core, well-corroborated process for BBS7. |
| GO:0005515 protein binding | IPI PMID:18762586 Recruitment of PCM1 to the centrosome by the cooperative act... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (PCM1, a centriolar satellite protein; via SYSCILIA curation). Uninformative MF term. Reason: protein binding is uninformative; the satellite and centrosome context is captured by the centriolar satellite and centrosome location annotations. |
| GO:0005515 protein binding | IPI PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | MARK AS OVER ANNOTATED | Summary: Generic protein binding (AZI1/CEP131, a centriolar satellite regulator of BBSome trafficking). Uninformative MF term. Reason: protein binding is uninformative; CEP131/AZI1 regulation of BBSome trafficking is process context, not a core MF term. |
| GO:0034464 BBSome | IDA PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | ACCEPT | Summary: BBSome membership of BBS7 directly demonstrated. Correct. Reason: BBSome membership is the defining, experimentally supported feature of BBS7. |
| GO:0006357 regulation of transcription by RNA polymerase II | IPI PMID:22302990 Direct role of Bardet-Biedl syndrome proteins in transcripti... | KEEP AS NON CORE | Summary: Gascue et al. report a nuclear role for BBS7 via interaction with the PcG protein RNF2/RING1B, whose targets are dysregulated upon BBS protein loss. A real but non-canonical secondary activity for a structural ciliary trafficking subunit. Reason: Experimentally supported (do not remove) but a non-core, indirect role relative to the defining ciliary trafficking function of the BBSome; retained as non-core. Supporting Evidence: PMID:22302990 loss of BBS proteins leads to the aberrant expression of endogenous RNF2 targets in vivo, including several genes that are crucial for development |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IPI PMID:22302990 Direct role of Bardet-Biedl syndrome proteins in transcripti... | KEEP AS NON CORE | Summary: BBS7 regulates RNF2 protein levels, probably through a proteasome-mediated mechanism (PMID:22302990). A specific but non-core, indirect downstream effect. Reason: Experimentally supported (do not remove) but a non-core, secondary activity relative to the core ciliary trafficking role of BBS7; retained as non-core. Supporting Evidence: PMID:22302990 BBS7 interacts physically with the polycomb group (PcG) member RNF2 and regulate its protein levels, probably through a proteasome-mediated mechanism |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:22302990 Direct role of Bardet-Biedl syndrome proteins in transcripti... | KEEP AS NON CORE | Summary: Specific physical interaction of BBS7 with the PcG/transcription factor RNF2 (UniProtKB:Q99496). An informative, defined molecular-function partner (unlike generic protein binding) reflecting a non-core nuclear role. Reason: Informative and experimentally supported MF interaction with RNF2, but reflecting a secondary nuclear role rather than the core BBSome function; retained as non-core. Supporting Evidence: PMID:22302990 BBS7 interacts physically with the polycomb group (PcG) member RNF2 |
| GO:0005515 protein binding | IPI PMID:16327777 Dissection of epistasis in oligogenic Bardet-Biedl syndrome. | MARK AS OVER ANNOTATED | Summary: Generic protein binding (CCDC28B, a BBS modifier). Uninformative MF term. Reason: protein binding is uninformative; CCDC28B is a modifier interaction not representing a core function. |
| GO:0034464 BBSome | IDA PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | ACCEPT | Summary: Direct demonstration of BBS7 as a BBSome component. Correct. Reason: BBSome membership is the defining, experimentally supported feature of BBS7. |
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: BBS7 identified as an asymmetrically localizing centrosomal component by proteomics. Consistent with the centriolar satellite and basal body localization. Reason: Centrosome localization is experimentally supported and consistent with the basal body and satellite biology of BBS7. Supporting Evidence: PMID:21399614 Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods. |
| GO:0001947 heart looping | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Pleiotropic developmental process transferred by similarity from a vertebrate ortholog; a downstream consequence of ciliary and left-right signaling defects. Reason: Developmental phenotype secondary to the core ciliary function; retained as non-core. |
| GO:0007368 determination of left/right symmetry | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Left-right patterning depends on node cilia; BBSome dysfunction can perturb this. A pleiotropic, organism-level process transferred by similarity. Reason: Downstream developmental consequence of ciliary dysfunction; retained as non-core. |
| GO:0032402 melanosome transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Reflects zebrafish bbs melanosome transport assays (an intracellular transport role of the BBSome). Transferred by similarity; non-core for human BBS7. Reason: Organism-specific intracellular transport phenotype transferred by similarity; plausibly retained as non-core. |
| GO:0045444 fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Reflects the obesity/adipogenesis phenotype of BBS, transferred by similarity from the mouse ortholog. A downstream physiological consequence, not a molecular activity. Reason: Pleiotropic metabolic phenotype secondary to ciliary signaling dysfunction; retained as non-core. |
| GO:0048546 digestive tract morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Pleiotropic developmental process transferred by similarity from a vertebrate ortholog; a downstream consequence of ciliary dysfunction. Reason: Developmental phenotype secondary to the core ciliary function; retained as non-core. |
| GO:0051877 pigment granule aggregation in cell center | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Reflects zebrafish melanosome/pigment granule transport assays of BBS proteins (an intracellular transport role). Transferred by similarity; non-core for human BBS7. Reason: Organism-specific intracellular transport phenotype transferred by similarity; retained as non-core. |
| GO:0034464 BBSome | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: Foundational direct identification of BBS7 as a BBSome subunit (Nachury 2007). Reason: BBSome membership is the defining, experimentally supported feature of BBS7. Supporting Evidence: PMID:17574030 Here we identify a complex composed of seven highly conserved BBS proteins. This complex, the BBSome |
| GO:0005198 structural molecule activity | IDA PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | NEW | Summary: BBS7 is a structural constituent of the BBSome, contributing the beta-propeller/GAE/platform scaffold (with BBS2 and BBS9) that nucleates and organizes the complex. Not currently present in GOA (GOA records only uninformative protein binding for the MF aspect); proposed as a NEW molecular function annotation better reflecting BBS7's role than protein binding. Reason: BBS7 forms the BBSome core scaffold; structural molecule activity is the appropriate informative MF, replacing uninformative protein binding annotations. Supporting Evidence: PMID:22500027 BBS7 interacts with BBS2 and becomes part of a BBS7-BBS2-BBS9 assembly intermediate referred to as the BBSome core complex because it forms the core of the BBSome. |
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Download this section (compressed HTML)Q: Is the nuclear/transcriptional role of BBS7 (RNF2/PcG interaction; PMID:22302990) a direct, conserved function or an indirect consequence of disturbed ciliary signaling?
Q: What is the precise contribution of the BBS7 GAE and platform domains to cargo selection versus scaffold assembly within the BBSome?
Experiment: Cryo-EM of the human BBSome with bound cargo to map BBS7 domain contributions to cargo recognition and the assembly interface with BBS2 and BBS9.
Experiment: Structure-function analysis of patient BBS7 variants (e.g. T211I, H323R, Y671C) in a BBS7-null cell line to dissect effects on chaperonin-assisted folding, BBSome assembly, and ciliary cargo trafficking.
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