BBS4 is a core subunit of the BBSome, an eight-subunit (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9, BBIP1) coat-like complex that acts as a cargo adaptor for sorting membrane proteins into and out of the primary cilium in conjunction with the small GTPase ARL6/BBS3 and the Rab8 GEF Rabin8/RAB3IP. BBS4 is a tetratricopeptide-repeat (TPR) superhelical protein (about ten TPR repeats) that is added last during chaperonin (BBS6/BBS10/BBS12, CCT/TRiC) assisted assembly of the BBSome onto the BBS7-BBS2-BBS9 core. Beyond its role within the BBSome, BBS4 localizes to centriolar satellites, the pericentriolar material, the centrosome/basal body and the ciliary membrane, and acts as an adaptor for the p150-glued (DCTN1) subunit of the dynein/dynactin motor to recruit PCM1 and associated cargo (e.g. ninein) to the centrosome, cooperating with DISC1; loss of BBS4 mislocalizes PCM1 and de-anchors centrosomal microtubules. The BBSome regulates ciliary trafficking of signalling receptors (e.g. Smoothened, polycystin-1/PKD1) and is regulated by satellite proteins such as CEP131/AZI1 and the CEP290/NPHP5 module. Loss-of-function mutations cause Bardet-Biedl syndrome, a pleiotropic ciliopathy with retinal degeneration, obesity, polydactyly, renal malformation, hypogenitalism and cognitive impairment.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred ciliogenesis role, consistent with the well-established requirement of the BBSome for ciliary membrane biogenesis and ciliary trafficking. BBS4 contributes to ciliogenesis as a BBSome subunit rather than independently. Reason: Supported by experimental data on the BBSome and BBS4 loss-of-function phenotypes; appropriate IBA call. |
| GO:0036064 ciliary basal body | IBA GO_REF:0000033 | ACCEPT | Summary: BBS4 and the BBSome localize at/near the basal body. Experimentally corroborated by IDA annotations below. Reason: Consistent with experimental localization (PMID:15107855, PMID:18299575). |
| GO:0061512 protein localization to cilium | IBA GO_REF:0000033 | ACCEPT | Summary: Core BBSome function: sorting/transport of membrane proteins to the cilium. Well supported and central to BBS4 biology. Reason: Core function; corroborated by experimental IMP annotations (PMID:23943788). |
| GO:0000226 microtubule cytoskeleton organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: BBS4 loss de-anchors centrosomal microtubules, so a microtubule-organization role is plausible, but this is a downstream consequence of PCM1/dynein-adaptor function rather than a distinct core process. The more specific term microtubule anchoring at centrosome (GO:0034454) captures the actual role better. Reason: General term; the specific microtubule-anchoring-at-centrosome annotation is the precise representation of this activity. |
| GO:0005634 nucleus | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Nuclear localization is inferred electronically via inter-ontology links and rests on a weak generalization that BBS proteins have a nuclear/transcriptional role (PMID:22302990 is primarily a BBS7 study). BBS4 is overwhelmingly a cytoplasmic/centrosomal/ciliary protein; a stable nuclear pool is not well established. Reason: Electronic inference; primary localization data place BBS4 at centrosome/satellites/cilium, not nucleus. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: BBS4 is a cytoplasmic protein (centriolar satellites/pericentriolar region). Correct but very general; more specific locations are annotated. Reason: Accurate but general parent term. |
| GO:0005813 centrosome | IEA GO_REF:0000120 | ACCEPT | Summary: BBS4 localizes to the centrosome; experimentally confirmed by IDA below. Reason: Corroborated by IDA (PMID:15107855, PMID:18762586, PMID:22500027, PMID:24550735). |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: BBS4/BBSome localizes to the cilium; experimentally confirmed by IDA below. Reason: Corroborated by IDA (PMID:23943788, PMID:24550735). |
| GO:0007600 sensory perception | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Generic sensory-perception term derived from BBS ciliopathy phenotypes (vision/olfaction). Too general and downstream of the molecular role. Reason: Over-general phenotype-derived term; not a direct BBS4 function. |
| GO:0031514 motile cilium | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: BBS4 localizes to motile cilia of airway epithelia (IDA, PMID:18299575). Most BBS4 biology concerns non-motile primary cilia, but the motile-cilium localization is experimentally supported. Reason: Supported by IDA (PMID:18299575); non-core relative to primary-cilium role. |
| GO:0034451 centriolar satellite | IEA GO_REF:0000120 | ACCEPT | Summary: BBS4 is a hallmark centriolar satellite protein; experimentally confirmed by IDA. Reason: Corroborated by IDA (PMID:15107855, PMID:23943788, PMID:24550735). |
| GO:0035869 ciliary transition zone | IEA GO_REF:0000117 | ACCEPT | Summary: Transition-zone localization is supported by IDA (PMID:23943788). Reason: Corroborated by experimental IDA. |
| GO:0060170 ciliary membrane | IEA GO_REF:0000044 | ACCEPT | Summary: BBSome localizes to the ciliary membrane; confirmed by IDA below. Reason: Corroborated by IDA (PMID:17574030, PMID:19081074). |
| GO:0061512 protein localization to cilium | IEA GO_REF:0000117 | ACCEPT | Summary: Duplicate (electronic) of the core protein-localization-to-cilium function. Reason: Core function; experimentally corroborated (PMID:23943788 IMP). |
| GO:0097730 non-motile cilium | IEA GO_REF:0000117 | ACCEPT | Summary: Primary (non-motile) cilium localization; confirmed by IDA (PMID:17574030). Reason: Corroborated by experimental IDA. |
| GO:0005515 protein binding | IPI PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from the PCM1/DCTN1 interaction study. Per curation guidelines, protein binding is uninformative; the specific adaptor activity and dynactin binding annotations from this paper capture the real function. Reason: Uninformative MF; superseded by specific MF annotations from same reference. |
| GO:0005515 protein binding | IPI PMID:16327777 Dissection of epistasis in oligogenic Bardet-Biedl syndrome. | MARK AS OVER ANNOTATED | Summary: Generic protein binding from the CCDC28B interaction (oligogenic BBS epistasis study). Real interaction but uninformative MF term. Reason: Uninformative 'protein binding'; use specific interactors in notes. |
| 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 identification; uninformative MF. Reason: Uninformative 'protein binding'; BBSome part_of and tubulin binding capture the role. |
| 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 ALDOB interaction; uninformative MF. Reason: Uninformative 'protein binding'. |
| GO:0005515 protein binding | IPI PMID:18772192 CEP290 interacts with the centriolar satellite component PCM... | MARK AS OVER ANNOTATED | Summary: Generic protein binding associated with the CEP290/PCM1 satellite study; uninformative MF. Reason: Uninformative 'protein binding'. |
| GO:0005515 protein binding | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from the BBSome/BBIP10 study; uninformative MF. Reason: Uninformative 'protein binding'; BBSome part_of captures the role. |
| 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 from the chaperonin/BBSome-assembly study; uninformative MF. Reason: Uninformative 'protein binding'. |
| GO:0005515 protein binding | IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from the BBSome sequential-assembly study; uninformative MF. Reason: Uninformative 'protein binding'; BBSome part_of captures the role. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a high-throughput interactome (Rolland et al.); uninformative MF. Reason: Uninformative 'protein binding' from HT interactome. |
| GO:0005515 protein binding | IPI PMID:25552655 Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from the NPHP5/CEP290 BBSome-integrity study; uninformative MF. Reason: Uninformative 'protein binding'. |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a splicing-isoform interactome screen; uninformative MF. Reason: Uninformative 'protein binding' from HT interactome. |
| 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-proteome interactome study; uninformative MF. Reason: Uninformative 'protein binding' from HT interactome. |
| GO:0005515 protein binding | IPI PMID:29039417 Protein interaction perturbation profiling at amino-acid res... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from an interaction-perturbation profiling study; uninformative MF. Reason: Uninformative 'protein binding' from HT interactome. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Generic protein binding from the HuRI binary interactome; uninformative MF. Reason: Uninformative 'protein binding' from HT interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from a neurodegeneration interactome map; uninformative MF. Reason: Uninformative 'protein binding' from HT 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 the BioPlex dual-proteome interactome; uninformative MF. Reason: Uninformative 'protein binding' from HT 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 study; uninformative MF. Reason: Uninformative 'protein binding' from HT interactome. |
| GO:0001750 photoreceptor outer segment | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Inferred from mouse ortholog via Ensembl Compara. Plausible given the connecting-cilium localization in photoreceptors, but no direct human evidence; relevant to retinal ciliopathy phenotype. Reason: Electronic ortholog transfer; relevant to retinal degeneration phenotype, non-core. |
| GO:0001917 photoreceptor inner segment | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Inferred from mouse ortholog; plausible but no direct human evidence. Reason: Electronic ortholog transfer; non-core. |
| GO:0016020 membrane | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Very general membrane term; BBS4 associates with the ciliary membrane via the BBSome but is not itself an integral membrane protein. Subsumed by the specific ciliary membrane annotation. Reason: Over-general; ciliary membrane is the informative term. |
| GO:0032391 photoreceptor connecting cilium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Inferred from mouse ortholog; UniProt notes connecting-cilium localization by similarity. Relevant to retinal phenotype. Reason: Electronic ortholog transfer; relevant but non-core for human. |
| GO:0034464 BBSome | IEA GO_REF:0000120 | ACCEPT | Summary: BBS4 is a core BBSome subunit; experimentally confirmed by multiple IDA/IPI annotations. Reason: Core; corroborated by IDA (PMID:17574030, PMID:20080638, PMID:24550735) and IPI. |
| GO:0038108 negative regulation of appetite by leptin-mediated signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Derived from BBS mouse obesity phenotypes (leptin resistance). A downstream physiological consequence of ciliary dysfunction, not a direct molecular function of BBS4. Reason: Phenotype/physiology-derived; relevant to obesity, non-core. |
| GO:0045444 fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Adipogenesis link reflects BBS obesity biology (cilia regulate adipocyte differentiation). Downstream/physiological, not direct. Reason: Phenotype-derived; non-core. |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Ciliogenesis role inferred from mouse ortholog; consistent with BBSome biology. Reason: Core; corroborated experimentally. |
| GO:0060296 regulation of cilium beat frequency involved in ciliary motility | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Derived from airway motile-cilia phenotypes (PMID:18299575). A motile-cilia function is plausible but peripheral to the core primary-cilium cargo-trafficking role. Reason: Motile-cilia phenotype; non-core relative to primary-cilium function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617815 | KEEP AS NON CORE | Summary: Reactome cytosol annotation for the BBSome-binds-RAB3IP reaction. Cytosolic pool exists but the cilium/centrosome locations are the functionally informative ones. Reason: Pathway-database location; general but not incorrect. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624125 | KEEP AS NON CORE | Summary: Reactome cytosol annotation for BBSome formation reaction. Reason: Pathway-database location; general. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624126 | KEEP AS NON CORE | Summary: Reactome cytosol annotation for ARL6:GTP/BBSome cargo-binding reaction. Reason: Pathway-database location; general. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624127 | KEEP AS NON CORE | Summary: Reactome cytosol annotation for ARL6:GTP/BBSome cargo-targeting reaction. Reason: Pathway-database location; general. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624129 | KEEP AS NON CORE | Summary: Reactome cytosol annotation for the LZTFL1-binds-BBSome reaction. Reason: Pathway-database location; general. |
| GO:0034464 BBSome | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: BBS4 part of the BBSome (BBIP10 study). Core localization/complex assignment. Reason: Core complex membership; experimentally supported. |
| GO:0060170 ciliary membrane | IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: BBSome localizes to the ciliary membrane (IDA). Core localization. Reason: Direct experimental localization. |
| GO:0060271 cilium assembly | NAS PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: Asserted ciliogenesis role for BBSome subunits. Consistent with stronger experimental evidence for the BBSome's ciliogenic function. Reason: Core function, consistent with broader evidence. |
| GO:0001947 heart looping | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from mouse ortholog by sequence-similarity curator judgment; reflects left-right asymmetry defects (node cilia). Downstream developmental phenotype of ciliary dysfunction. Reason: Ortholog-transferred developmental phenotype; non-core. |
| GO:0032402 melanosome transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Classic BBS readout: bbs4 morphant zebrafish show retrograde melanosome transport delay (e.g. PMID:24550735, PMID:16399798). Reflects BBS4's role in dynein-based intracellular transport. Non-core relative to ciliary trafficking. Reason: Supported by zebrafish assays; intracellular-transport readout, non-core. |
| GO:0060271 cilium assembly | ISS PMID:16399798 Bardet-Biedl syndrome genes are important in retrograde intr... | ACCEPT | Summary: Ciliogenesis/retrograde-trafficking role inferred from zebrafish BBS studies. Consistent with core BBSome function. Reason: Core function; supported across species. |
| GO:0005515 protein binding | IPI PMID:33144677 Dlec1 is required for spermatogenesis and male fertility in ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from the DLEC1 interaction (mouse spermatogenesis study). Uninformative MF term. Reason: Uninformative 'protein binding'. |
| GO:0030674 protein-macromolecule adaptor activity | IMP PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | ACCEPT | Summary: Captures BBS4's central molecular function as a cargo adaptor: it bridges the dynein/dynactin p150-glued (DCTN1) subunit to PCM1 and associated cargo, and within the BBSome it functions as part of a cargo-sorting adaptor for ciliary membrane proteins. This is the best available informative MF for BBS4. Reason: Strong experimental support (PMID:15107855); represents the core molecular function of BBS4. |
| 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 from the DISC1/PCM1 centrosome-recruitment study. The functional content (PCM1 recruitment to centrosome) is captured by process annotations. Reason: Uninformative 'protein binding'. |
| GO:0005813 centrosome | IDA PMID:18762586 Recruitment of PCM1 to the centrosome by the cooperative act... | ACCEPT | Summary: BBS4 localizes to the centrosome (DISC1/PCM1 study). Core localization. Reason: Direct experimental localization. |
| GO:0005515 protein binding | IPI PMID:23943788 BBS mutations modify phenotypic expression of CEP290-related... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from the CEP290 interaction study; uninformative MF. Reason: Uninformative 'protein binding'. |
| GO:0005929 cilium | IDA PMID:23943788 BBS mutations modify phenotypic expression of CEP290-related... | ACCEPT | Summary: BBS4 localizes to the cilium (CEP290 study, full text available). Core localization. Reason: Direct experimental localization. Supporting Evidence: PMID:23943788 co-localizes with CEP290 to the transition zone (TZ) of primary cilia and centriolar satellites in ciliated cells |
| GO:0034451 centriolar satellite | IDA PMID:23943788 BBS mutations modify phenotypic expression of CEP290-related... | ACCEPT | Summary: BBS4 localizes to centriolar satellites (CEP290 study). Core localization. Reason: Direct experimental localization. Supporting Evidence: PMID:23943788 co-localizes with CEP290 to the transition zone (TZ) of primary cilia and centriolar satellites in ciliated cells |
| GO:0035869 ciliary transition zone | IDA PMID:23943788 BBS mutations modify phenotypic expression of CEP290-related... | ACCEPT | Summary: Transition-zone localization (CEP290 study). Supported. Reason: Direct experimental localization. Supporting Evidence: PMID:23943788 co-localizes with CEP290 to the transition zone (TZ) of primary cilia and centriolar satellites in ciliated cells |
| GO:0061512 protein localization to cilium | IMP PMID:23943788 BBS mutations modify phenotypic expression of CEP290-related... | ACCEPT | Summary: BBS4 required for protein localization to the cilium (mutant phenotype, CEP290-ciliopathy modifier study). Direct support for the core trafficking function. Reason: Core function with experimental (IMP) support. |
| GO:0005515 protein binding | IPI PMID:24939912 Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from the PKD1 ciliary-trafficking study; uninformative MF. Reason: Uninformative 'protein binding'. |
| GO:0034464 BBSome | IDA PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | ACCEPT | Summary: BBS4 part of the BBSome (AZI1/CEP131 study). Core complex membership. Reason: Direct experimental support. |
| GO:0005515 protein binding | IPI PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from the AZI1/CEP131 interaction; uninformative MF. Reason: Uninformative 'protein binding'. |
| GO:0005813 centrosome | IDA PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | ACCEPT | Summary: BBS4 localizes to the centrosome (AZI1 study). Core localization. Reason: Direct experimental localization. |
| GO:0005929 cilium | IDA PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | ACCEPT | Summary: BBS4/BBSome localizes to the cilium (AZI1 study). Core localization. Reason: Direct experimental localization. |
| GO:0034451 centriolar satellite | IDA PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | ACCEPT | Summary: BBS4 localizes to centriolar satellites (AZI1 study). Core localization. Reason: Direct experimental localization. |
| GO:0000281 mitotic cytokinesis | IMP PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | MARK AS OVER ANNOTATED | Summary: BBS4 silencing causes arrest in cell division and apoptosis (PMID:15107855), but these are downstream secondary consequences of PCM1 mislocalization and microtubule de-anchoring, not a dedicated cytokinesis function of BBS4. BBS is not a cytokinesis disorder. Reason: Secondary RNAi phenotype; not a core/direct BBS4 function. |
| GO:0071539 protein localization to centrosome | IMP PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | ACCEPT | Summary: BBS4 recruits PCM1 (and, with DISC1, ninein) to the centrosome via the dynein/dynactin motor (PMID:15107855, PMID:18762586). A genuine, well supported BBS4 process directly reflecting its adaptor activity. Reason: Strong experimental support; core process tied to adaptor function. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:22302990 Direct role of Bardet-Biedl syndrome proteins in transcripti... | MARK AS OVER ANNOTATED | Summary: Annotation rests on a study primarily of BBS7's nuclear/transcriptional role (interaction with the PcG protein RNF2), with only a generalized suggestion that other BBS proteins behave similarly. Evidence specifically for BBS4 binding an RNA Pol II transcription factor is weak, and BBS4 is not established as a nuclear protein. Reason: Weak generalization from a BBS7-focused study; BBS4-specific transcription-factor-binding role not established. |
| GO:0005813 centrosome | IDA PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | ACCEPT | Summary: BBS4 localizes to the centrosome (BBSome assembly study). Core localization. Reason: Direct experimental localization. |
| GO:0038108 negative regulation of appetite by leptin-mediated signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred from mouse obesity/leptin-resistance phenotypes. Downstream physiological consequence of ciliary dysfunction. Reason: Phenotype-derived; relevant to obesity, non-core. |
| GO:0034464 BBSome | IDA PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | ACCEPT | Summary: BBS4 part of the BBSome (chaperonin assembly study). Core complex membership. Reason: Direct experimental support. |
| GO:0000226 microtubule cytoskeleton organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred microtubule-organization role. Reflects centrosomal microtubule de-anchoring on BBS4 loss; the specific microtubule anchoring at centrosome term is more precise. Reason: General; specific anchoring term preferred. |
| GO:0001843 neural tube closure | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred developmental phenotype (neural tube defects in BBS models). Downstream consequence of ciliary signalling dysfunction. Reason: Developmental phenotype; non-core. |
| GO:0001895 retina homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred; reflects retinal degeneration in BBS. Downstream physiological readout relevant to the disease. Reason: Phenotype-derived; relevant to retinal disease, non-core. |
| GO:0007286 spermatid development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred; reflects flagellum/sperm defects in BBS models (cf. DLEC1 interaction, PMID:33144677). Downstream developmental role. Reason: Developmental phenotype; non-core. |
| GO:0007608 sensory perception of smell | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred; olfactory ciliary dysfunction in BBS models. Downstream sensory phenotype. Reason: Phenotype-derived; non-core. |
| GO:0016358 dendrite development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred neuronal developmental term. Indirect, linked to centrosomal/PCM1 function in neurons (cf. PMID:18762586). Reason: Developmental phenotype; non-core. |
| GO:0019216 regulation of lipid metabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred; reflects metabolic dysregulation in BBS obesity. Downstream physiological consequence. Reason: Phenotype-derived; non-core. |
| GO:0021756 striatum development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred brain-development term; indirect/downstream. Reason: Developmental phenotype; non-core. |
| GO:0021766 hippocampus development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred brain-development term; indirect/downstream. Reason: Developmental phenotype; non-core. |
| GO:0021987 cerebral cortex development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred; consistent with BBS4/DISC1/PCM1 role in cortical neuronal migration (PMID:18762586). Downstream developmental process. Reason: Developmental phenotype; non-core but biologically grounded. |
| GO:0030534 adult behavior | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred behavioral phenotype term; very indirect. Reason: Phenotype-derived; non-core. |
| GO:0045444 fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred adipogenesis term; reflects BBS obesity biology. Reason: Phenotype-derived; non-core. |
| GO:0045494 photoreceptor cell maintenance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred; reflects retinal degeneration in BBS. Downstream physiological role via connecting-cilium trafficking. Reason: Phenotype-derived; relevant to retinal disease, non-core. |
| GO:0045724 positive regulation of cilium assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred; consistent with the BBSome's ciliogenesis-promoting role. A more regulatory framing of the cilium-assembly function. Reason: Consistent with core ciliogenesis function; retained as supporting. |
| GO:0046548 retinal rod cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred retinal-development term; downstream/indirect. Reason: Developmental phenotype; non-core. |
| GO:0048854 brain morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred neurodevelopmental term; indirect. Reason: Developmental phenotype; non-core. |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog-transferred ciliogenesis role; consistent with core BBSome function. Reason: Core function; supported across species. |
| GO:0060296 regulation of cilium beat frequency involved in ciliary motility | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-transferred motile-cilia function (cf. airway phenotype PMID:18299575). Peripheral to the primary-cilium cargo-trafficking role. Reason: Motile-cilia phenotype; non-core. |
| GO:1905515 non-motile cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog-transferred; specifically the primary (non-motile) cilium assembly role, which is BBS4's central biological context. Reason: Specific, core ciliogenesis term; well aligned with BBS4 biology. |
| GO:0034451 centriolar satellite | IDA PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | ACCEPT | Summary: BBS4 localizes to centriolar satellites (original Kim et al. study). Core localization. Reason: Direct experimental localization (foundational paper). Supporting Evidence: PMID:15107855 BBS4 localizes to the centriolar satellites of centrosomes and basal bodies of primary cilia |
| GO:0034452 dynactin binding | IDA PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | ACCEPT | Summary: BBS4 binds the p150-glued (DCTN1) subunit of dynactin, the molecular basis of its adaptor function linking dynein-based transport to PCM1/cargo recruitment. Informative, experimentally supported MF. Reason: Direct experimental evidence; mechanistically central MF. Supporting Evidence: PMID:15107855 it functions as an adaptor of the p150(glued) subunit of the dynein transport machinery |
| GO:0034454 microtubule anchoring at centrosome | IMP PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | ACCEPT | Summary: BBS4 silencing de-anchors centrosomal microtubules (PMID:15107855). A genuine, specific BBS4 process downstream of its PCM1-recruitment role. Reason: Specific, well-supported process directly tied to BBS4 function. Supporting Evidence: PMID:15107855 Silencing of BBS4 induces PCM1 mislocalization and concomitant deanchoring of centrosomal microtubules |
| GO:0034464 BBSome | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: BBS4 part of the BBSome (founding BBSome paper). Core complex membership. Reason: Direct experimental support (BBSome discovery). Supporting Evidence: PMID:17574030 we identify a complex composed of seven highly conserved BBS proteins |
| GO:0000242 pericentriolar material | IDA PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | ACCEPT | Summary: BBS4 localizes to the pericentriolar material (Kim et al.). Core localization. Reason: Direct experimental localization. |
| GO:0005814 centriole | IDA PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | ACCEPT | Summary: BBS4 localizes near centrioles/basal bodies (Kim et al.). Supported. Reason: Direct experimental localization. |
| GO:0031514 motile cilium | IDA PMID:18299575 Loss of Bardet-Biedl syndrome proteins alters the morphology... | KEEP AS NON CORE | Summary: BBS4 localizes to motile cilia of airway epithelia (PMID:18299575). Direct evidence; non-core relative to primary-cilium role. Reason: Supported by IDA; motile-cilium context is non-core. |
| GO:0032465 regulation of cytokinesis | IMP PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | MARK AS OVER ANNOTATED | Summary: As with mitotic cytokinesis, the cell-division defect on BBS4 silencing is a secondary consequence of PCM1/microtubule disruption, not a dedicated cytokinesis-regulatory function. Reason: Secondary RNAi phenotype; not a core/direct BBS4 function. |
| GO:0036064 ciliary basal body | IDA PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | ACCEPT | Summary: BBS4 localizes to the ciliary basal body (Kim et al.). Core localization. Reason: Direct experimental localization. |
| GO:0036064 ciliary basal body | IDA PMID:18299575 Loss of Bardet-Biedl syndrome proteins alters the morphology... | ACCEPT | Summary: BBS4 at the basal body of airway cilia (PMID:18299575). Core localization. Reason: Direct experimental localization. |
| GO:0043014 alpha-tubulin binding | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | KEEP AS NON CORE | Summary: Alpha-tubulin binding reported in the BBSome study. Plausible (BBS4/BBSome associates with microtubules), though this could partly reflect complex-level rather than BBS4-intrinsic binding. Retained as supporting molecular detail. Reason: Experimentally annotated MF; ancillary to the adaptor core function. |
| GO:0048487 beta-tubulin binding | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | KEEP AS NON CORE | Summary: Beta-tubulin binding reported in the BBSome study; same caveats as alpha-tubulin binding. Retained as supporting molecular detail. Reason: Experimentally annotated MF; ancillary to the adaptor core function. |
| GO:0051457 maintenance of protein location in nucleus | IGI PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | MARK AS OVER ANNOTATED | Summary: This term is poorly aligned with the Kim et al. study, which concerns cytoplasmic PCM1 recruitment to centrosomes, not nuclear protein retention. The annotation appears to be an over-interpretation; BBS4 is not established to maintain proteins in the nucleus. Reason: Not supported by a credible nuclear-retention function; inconsistent with BBS4's cytoplasmic/centrosomal localization. |
| GO:0060170 ciliary membrane | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: BBSome at the ciliary membrane (founding paper). Core localization. Reason: Direct experimental localization. Supporting Evidence: PMID:17574030 but also to the membrane of the cilium |
| GO:0097730 non-motile cilium | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: BBS4/BBSome in the primary (non-motile) cilium. Core localization. Reason: Direct experimental localization. |
| GO:0005813 centrosome | IDA PMID:14520415 Basal body dysfunction is a likely cause of pleiotropic Bard... | ACCEPT | Summary: Centrosome localization reported in an early BBS basal-body review/study. Consistent with strong experimental evidence elsewhere. Reason: Corroborated by multiple independent IDA annotations. |
| GO:0050893 sensory processing | TAS PMID:14520415 Basal body dysfunction is a likely cause of pleiotropic Bard... | MARK AS OVER ANNOTATED | Summary: TAS sensory-processing term from an early review framing BBS as a basal-body/cilia sensory disorder. Downstream/phenotypic, not a direct molecular function. Reason: Phenotype-level TAS term; not a direct BBS4 function. |
| GO:0007098 centrosome cycle | IMP PMID:15107855 The Bardet-Biedl protein BBS4 targets cargo to the pericentr... | MARK AS OVER ANNOTATED | Summary: Annotation derives from cell-cycle/centrosome effects of BBS4 silencing (PMID:15107855). These are secondary consequences of PCM1/microtubule disruption rather than a dedicated centrosome-cycle function. Reason: Secondary RNAi phenotype; not a core/direct BBS4 function. |
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Download this section (compressed HTML)Q: Is BBS4's alpha-/beta-tubulin binding an intrinsic property of BBS4 or a complex-level (BBSome) property, and what is its mechanistic role?
Q: Does BBS4 have any direct, stable nuclear/transcriptional function, or are the nucleus and transcription-factor-binding annotations generalizations from BBS7?
Q: To what extent are the cytokinesis/cell-cycle phenotypes of BBS4 loss direct versus secondary to PCM1 mislocalization and microtubule de-anchoring?
Experiment: Use the cryo-EM BBSome structure (PDB 6XT9) and crosslinking-MS to map BBS4's direct binding partners within the BBSome and define its contribution to cargo (e.g. SMO, PKD1) recognition versus a purely structural role.
Experiment: Acute degron-based depletion (vs. chronic RNAi) of BBS4 in ciliated cells with live imaging of PCM1, ninein, microtubule anchoring and cell-cycle progression to separate direct from secondary phenotypes.
Experiment: Reconstitute the BBS4-DCTN1(p150-glued)-PCM1 module in vitro to test whether BBS4 is sufficient as an adaptor bridging dynactin to PCM1 cargo.
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