BBS5 is a subunit of the BBSome, an eight-protein complex involved in ciliary membrane-protein trafficking. It contains two pleckstrin-homology-like domains and binds phosphoinositides in isolated-protein assays. BBS5 occurs in the cytoplasmic BBSome and at ciliary membranes and basal bodies. In human retinal pigment epithelial cells, BBS5 supports cilium formation and entry of the BBSome into cilia. Biallelic pathogenic variants cause Bardet-Biedl syndrome, with variable retinal degeneration, obesity, polydactyly, renal abnormalities and other manifestations.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0034464 BBSome | IBA GO_REF:0000033 | ACCEPT | Summary: BBS5 is a subunit of the BBSome. Reason: The inherited complex membership agrees with direct target purification and interaction studies. Membership does not imply that BBS5 alone nucleates or is indispensable for assembly of the remaining complex. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: BBS5 contributes to cilium assembly in the tested cellular contexts. Reason: Retain the phylogenetically inherited process. Independent human RPE-cell BBS5 RNAi reduces the frequency of ciliated cells. This does not establish a requirement in every cell type or identify lipid binding as the causal step. |
| GO:0032266 phosphatidylinositol-3-phosphate binding | IBA GO_REF:0000033 | ACCEPT | Summary: BBS5 binds phosphatidylinositol-3-phosphate in a protein–lipid overlay assay. Reason: Original experiments show phosphoinositide binding by recombinant full-length BBS5 and the isolated N-terminal PH-like domain. This supports the binding function. Native BBSome liposome preferences differ from isolated BBS5 overlays, and a recombinant BBS4/8/9/18 subcomplex also binds lipids without BBS5; therefore the assay does not establish BBS5 as the exclusive physiological membrane anchor or its in-vivo lipid specificity. |
| GO:0036064 ciliary basal body | IBA GO_REF:0000033 | ACCEPT | Summary: BBS5 localizes to the ciliary basal body. Reason: Retain the inherited localization, consistent with basal-body observations in the original BBS5 study and later mouse photoreceptor imaging. Localization does not require BBS5 to be an exclusive basal-body structural component. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: BBS5 has a cytoplasmic pool. Reason: The broad electronic localization is compatible with BBSome assembly and trafficking pools. It does not exclude ciliary or basal-body localization. |
| GO:0034451 centriolar satellite | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: BBS5 is annotated to centriolar satellites. Reason: Retain the combined ortholog and UniProt localization as non-core. Satellite association does not make BBS5 a satellite scaffold or imply that BBS5 performs the PCM1–dynactin adaptor mechanism established for BBS4. |
| GO:0034464 BBSome | IEA GO_REF:0000120 | ACCEPT | Summary: BBS5 is a BBSome subunit. Reason: Retain complex membership from the original source. In human RPE cells depleted of BBS5, much of the remaining BBSome remains assembled even though ciliary localization is impaired; membership is distinct from being an obligate assembly scaffold. |
| GO:0060170 ciliary membrane | IEA GO_REF:0000044 | ACCEPT | Summary: BBS5 associates with the ciliary membrane as part of the BBSome. Reason: Retain the membrane localization. The BBSome is a peripheral membrane-associated complex; a transmembrane segment or exclusive BBS5-dependent membrane anchoring is not required for this cellular-component annotation. |
| GO:0005515 protein binding | IPI PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with BBS9 (Q3SYG4). Reason: Retain the partner-specific BBS9 association within the BBSome. The source interaction does not by itself establish an autonomous BBS5 cargo-recognition or scaffold activity. BBS5 depletion can leave most of the remaining BBSome assembled, so BBS2/BBS9 assembly mechanisms are not transferred to this pair. |
| GO:0005515 protein binding | IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with BBS9 (Q3SYG4). Reason: Retain the partner-specific BBS9 association within the BBSome. The source interaction does not by itself establish an autonomous BBS5 cargo-recognition or scaffold activity. BBS5 depletion can leave most of the remaining BBSome assembled, so BBS2/BBS9 assembly mechanisms are not transferred to this pair. |
| GO:0005515 protein binding | IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with BBS9 (Q3SYG4). Reason: Retain the partner-specific BBS9 association within the BBSome. The source interaction does not by itself establish an autonomous BBS5 cargo-recognition or scaffold activity. BBS5 depletion can leave most of the remaining BBSome assembled, so BBS2/BBS9 assembly mechanisms are not transferred to this pair. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: BBS5 is reported to associate with CRADD (P78560). Reason: Retain the experimentally supported exact-partner interaction as non-core under the explicit CLINGEN_MENDELIAN project instruction for supported generic protein binding. The inspected evidence does not establish a more specific molecular activity for this pair; limited mechanistic specificity does not make the interaction incorrect. |
| GO:0005515 protein binding | IPI PMID:25552655 Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integ... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with IQCB1/NPHP5 (Q15051). Reason: Retain the NPHP5/IQCB1-associated BBSome interaction. The paper links NPHP5 depletion to BBSome integrity and trafficking, but that perturbation does not establish an autonomous NPHP5-like activity of BBS5. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with BBS9 (Q3SYG4). Reason: Retain the partner-specific BBS9 association within the BBSome. The source interaction does not by itself establish an autonomous BBS5 cargo-recognition or scaffold activity. BBS5 depletion can leave most of the remaining BBSome assembled, so BBS2/BBS9 assembly mechanisms are not transferred to this pair. |
| GO:0005515 protein binding | IPI PMID:29039417 Protein interaction perturbation profiling at amino-acid res... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with BBS9 (Q3SYG4). Reason: Retain the partner-specific BBS9 association within the BBSome. The source interaction does not by itself establish an autonomous BBS5 cargo-recognition or scaffold activity. BBS5 depletion can leave most of the remaining BBSome assembled, so BBS2/BBS9 assembly mechanisms are not transferred to this pair. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with BBS9 (Q3SYG4). Reason: Retain the partner-specific BBS9 association within the BBSome. The source interaction does not by itself establish an autonomous BBS5 cargo-recognition or scaffold activity. BBS5 depletion can leave most of the remaining BBSome assembled, so BBS2/BBS9 assembly mechanisms are not transferred to this pair. |
| GO:0005929 cilium | IEA GO_REF:0000107 | ACCEPT | Summary: BBS5 localizes to cilia. Reason: Retain the localization, independently corroborated by endogenous BBS5 staining in human RPE cilia. This does not assert that BBS5 is an axonemal motor or restrict its distribution to cilia. |
| GO:0005930 axoneme | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse Bbs5 has an axonemal photoreceptor pool. Reason: Retain the transferred specialized localization. Independent mouse photoreceptor imaging places BBS5 along the outer-segment axoneme as well as at other ciliary regions; this does not imply a motility-generating activity or a universal axonemal distribution in human cells. |
| GO:0036064 ciliary basal body | IEA GO_REF:0000107 | ACCEPT | Summary: BBS5 localizes to the ciliary basal body. Reason: The mouse-derived electronic location agrees with the original BBS5 discovery observations and later photoreceptor basal-body localization. Retain the compartment without making it exclusive. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617815 | KEEP AS NON CORE | Summary: BBS5 participates in a cytosolic BBSome pool in this Reactome event. Reason: BBS5 is part of the cytosolic BBSome in the RAB3IP-binding event. The event identifies BBS1 as the RAB3IP-contacting component and RAB3IP as the RAB8A exchange factor; it does not assign either activity to BBS5. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624125 | KEEP AS NON CORE | Summary: BBS5 participates in a cytosolic BBSome pool in this Reactome event. Reason: BBS5 is a constituent of the BBSome assembled in this cytosolic event. This location annotation does not establish that BBS5 autonomously scaffolds the complex or performs the BBS/CCT chaperone-dependent assembly steps. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624126 | KEEP AS NON CORE | Summary: BBS5 participates in a cytosolic BBSome pool in this Reactome event. Reason: Retain the cytosolic BBSome context of the ARL6:GTP cargo-binding event. The summary assigns ARL6 contact to BBS1 and describes cargo recognition by the complex; it does not identify BBS5 as the direct ARL6 or cargo-binding site. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624127 | KEEP AS NON CORE | Summary: BBS5 participates in a cytosolic BBSome pool in this Reactome event. Reason: Retain the source cytosol annotation for BBS5 as a BBSome component in the cargo-targeting pathway. This event describes ARL6/BBSome-dependent ciliary cargo accumulation and its regulation by LZTFL1, without assigning autonomous transport or motor activity to BBS5. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5624129 | KEEP AS NON CORE | Summary: BBS5 participates in a cytosolic BBSome pool in this Reactome event. Reason: This event places the BBSome in a cytosolic complex with LZTFL1 that regulates BBSome entry into cilia without changing its assembly or stability. Retain BBS5 in that complex-level localization context without asserting that BBS5 itself is the direct LZTFL1-binding interface. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: BBS5 has a cytosolic pool in the immunofluorescence annotation. Reason: Retain the broad experimental localization alongside the more specific ciliary locations. A cytosolic annotation does not mean BBS5 is confined to that compartment. |
| GO:0005929 cilium | IDA GO_REF:0000052 | ACCEPT | Summary: BBS5 localizes to cilia. Reason: Retain the localization, independently corroborated by endogenous BBS5 staining in human RPE cilia. This does not assert that BBS5 is an axonemal motor or restrict its distribution to cilia. |
| GO:0034464 BBSome | IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: BBS5 is a BBSome subunit. Reason: Retain complex membership from the original source. In human RPE cells depleted of BBS5, much of the remaining BBSome remains assembled even though ciliary localization is impaired; membership is distinct from being an obligate assembly scaffold. |
| GO:0060170 ciliary membrane | IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: BBS5 associates with the ciliary membrane as part of the BBSome. Reason: Retain the membrane localization. The BBSome is a peripheral membrane-associated complex; a transmembrane segment or exclusive BBS5-dependent membrane anchoring is not required for this cellular-component annotation. |
| GO:0060271 cilium assembly | NAS PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ... | ACCEPT | Summary: BBS5 contributes to cilium assembly as a BBSome subunit. Reason: Retain the cited process, independently supported by BBS5 RNAi in the founding study. The BBIP1-focused source is not used to assign BBIP1-specific HDAC6 regulation or microtubule acetylation to BBS5. |
| GO:0005515 protein binding | IPI PMID:33144677 Dlec1 is required for spermatogenesis and male fertility in ... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with DLEC1 (Q9Y238). Reason: The primary Results explicitly include BBS5 in tagged human DLEC1 co-immunoprecipitation from HEK293F cells. Retain the association as non-core: co-IP is not purified binary affinity, and the mouse Dlec1 knockout phenotype is not a BBS5 perturbation. |
| GO:0005515 protein binding | IPI PMID:18762586 Recruitment of PCM1 to the centrosome by the cooperative act... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with DISC1 (Q9NRI5). Reason: The exact source partner is DISC1, not PCM1. Preserve the curated BBS5–DISC1 interaction as non-core; the abstract foregrounds the BBS4/DISC1/PCM1 mechanism and cannot justify declaring the BBS5 assay mis-attributed or assigning that whole adaptor mechanism to BBS5. |
| GO:0005515 protein binding | IPI PMID:24939912 Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary ... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with TTC8/BBS8 (Q8TAM2). Reason: The exact source partner is TTC8/BBS8, not PKD1. Retain this BBSome association as non-core. Although the paper reports BBS5 interaction with PC1 separately, BBS5 depletion did not impair PC1 ciliary trafficking in the tested kidney epithelial cells; that BBS1-dependent phenotype is not assigned to BBS5. |
| GO:0005515 protein binding | IPI PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | KEEP AS NON CORE | Summary: BBS5 is reported to associate with CEP131/AZI1 (Q9UPN4). Reason: Retain the CEP131/AZI1-associated interaction as non-core in the BBSome trafficking context. The source does not make BBS5 a centriolar-satellite scaffold or a motor, and the separate zebrafish melanosome transfer requires its own donor evidence. |
| GO:0034464 BBSome | IDA PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an... | ACCEPT | Summary: BBS5 is a BBSome subunit. Reason: Retain complex membership from the original source. In human RPE cells depleted of BBS5, much of the remaining BBSome remains assembled even though ciliary localization is impaired; membership is distinct from being an obligate assembly scaffold. |
| 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: BBS5 associates with the E3 ubiquitin ligase RNF2. Reason: Original Fig. 3C and Results explicitly include tagged BBS5–RNF2 co-immunoprecipitation. RNF2 is an E3 ligase rather than the sequence-specific RNA-polymerase-II DNA-binding transcription factor required by GO:0061629. Refine the partner activity to ubiquitin protein ligase binding without assigning RNF2 catalysis to BBS5. The endogenous co-IP and yeast screen in the paper concern BBS7. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0044458 motile cilium assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BBS5 contributes to motile-cilium assembly in the transferred donor context. Reason: Retain the orthology-based motile-cilium process as non-core. The donor is the Chlamydomonas BBS5 protein, and the original discovery work reports a requirement for flagellar formation. This transfer does not establish a direct human motile-cilium assay or make BBS5 an axonemal motor. |
| GO:0005515 protein binding | IPI PMID:16327777 Dissection of epistasis in oligogenic Bardet-Biedl syndrome. | KEEP AS NON CORE | Summary: BBS5 is reported to associate with CCDC28B (Q9BUN5). Reason: Retain the experimentally supported exact-partner interaction as non-core under the explicit CLINGEN_MENDELIAN project instruction for supported generic protein binding. The inspected evidence does not establish a more specific molecular activity for this pair; limited mechanistic specificity does not make the interaction incorrect. |
| GO:0034464 BBSome | IDA PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | ACCEPT | Summary: BBS5 is a BBSome subunit. Reason: Retain complex membership from the original source. In human RPE cells depleted of BBS5, much of the remaining BBSome remains assembled even though ciliary localization is impaired; membership is distinct from being an obligate assembly scaffold. |
| GO:0001947 heart looping | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Bbs5 depletion affects normal heart looping in zebrafish. Reason: The donor Q7ZWB7 is zebrafish Bbs5. Original BBS knockdown work and an independent BBS5 morpholino/rescue study support laterality and heart-looping phenotypes. Retain this transferred developmental context without describing a direct human cardiac mechanism or confusing morpholino depletion with genetic knockout. In PMID:24559376, wild-type mRNA improves composite and organ phenotypes, and the text reports absence of situs inversus among rescue phenotypes. A separately quantified heart-looping rescue series is not provided; these observations are not a direct human cardiac mechanism. |
| GO:0032402 melanosome transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Bbs5 perturbation affects retrograde melanosome transport in zebrafish. Reason: The original zebrafish study explicitly includes bbs5 knockdown and melanosome-transport defects. Retain the transferred physiological context as non-core. It does not demonstrate intrinsic motor activity, and the AZI1 study is not the identity of this Bbs5 donor evidence. |
| GO:0034464 BBSome | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: BBS5 is a BBSome subunit. Reason: Retain complex membership from the original source. In human RPE cells depleted of BBS5, much of the remaining BBSome remains assembled even though ciliary localization is impaired; membership is distinct from being an obligate assembly scaffold. |
| GO:0032266 phosphatidylinositol-3-phosphate binding | IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: BBS5 binds phosphatidylinositol-3-phosphate in a protein–lipid overlay assay. Reason: Original experiments show phosphoinositide binding by recombinant full-length BBS5 and the isolated N-terminal PH-like domain. This supports the binding function. Native BBSome liposome preferences differ from isolated BBS5 overlays, and a recombinant BBS4/8/9/18 subcomplex also binds lipids without BBS5; therefore the assay does not establish BBS5 as the exclusive physiological membrane anchor or its in-vivo lipid specificity. |
| GO:0036064 ciliary basal body | ISS GO_REF:0000024 | ACCEPT | Summary: BBS5 localizes to the ciliary basal body in the donor evidence. Reason: The source Q21626 is C. elegans BBS-5. The original discovery abstract explicitly reports basal-body localization in mouse and C. elegans. Retain the localization without claiming that BBS5 is exclusively a basal-body constituent. |
| GO:0060271 cilium assembly | IMP PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra... | ACCEPT | Summary: BBS5 depletion reduces ciliogenesis in human RPE cells. Reason: The original supplementary experiment measures reduced BBS5 mRNA and fewer ciliated RPE[LAPBBS4] cells after BBS5 siRNA. Retain the perturbation-supported process with its cell context; the accompanying broad PI3-kinase inhibitor experiment does not establish that BBS5 lipid binding is the causal mechanism. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: BBS5 is reported to associate with KLC3 (Q6P597). Reason: Retain this recovered KLC3 interaction as non-core with its exact source and partner. A kinesin-light-chain interaction does not establish that BBS5 generates motor force or selects a particular cargo; the original high-throughput assay remains the evidence scope. |
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Download this section (compressed HTML)Q: Which lipid contacts made by BBS5 contribute to BBSome behavior in living cells, and how do they differ from the interactions detected by recombinant protein-lipid overlays?
Q: How does BBS5 promote ciliary entry of an otherwise largely assembled BBSome, and how is this requirement bypassed by reducing LZTFL1?
Q: For which ciliary cargoes does BBS5 contribute to entry, exit or transport within cilia, separately from its effect on ciliary entry of the BBSome itself?
Experiment: Compare full-length BBS5 and PH-domain mutants in quantitative liposome binding and cellular rescue experiments while measuring protein stability, BBSome assembly, ciliary entry and several defined cargoes independently.
Experiment: Track the remaining BBSome after acute BBS5 depletion with and without LZTFL1 depletion to distinguish effects on entry, retention and transport within cilia.
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