Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0043005 neuron projection	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Phylogenetic (IBA) localization to neuron projection. BBS2 acts in the primary cilium, and neuronal primary cilia are a relevant context, but neuron projection is a broad/imprecise CC for a BBSome subunit whose precise site of action is the ciliary membrane/basal body. Reason: BBSome subunits act at the primary cilium; neuron projection is an over-general localization. The specific ciliary localizations (ciliary membrane, basal body, transition zone) are separately and better annotated.
GO:0060271 cilium assembly	IBA GO_REF:0000033	ACCEPT	Summary: BBSome is required for ciliogenesis; phylogenetic inference is consistent with experimental data across species. Reason: Cilium assembly is a core BBSome process well supported across orthologs and by human experimental data.
GO:0016020 membrane	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Generic membrane localization. The BBSome is a peripheral coat that associates with the ciliary membrane; the specific term ciliary membrane is already annotated. Reason: Uninformative/over-general CC superseded by GO:0060170 ciliary membrane.
GO:0034464 BBSome	IBA GO_REF:0000033	ACCEPT	Summary: BBSome membership inferred phylogenetically; consistent with abundant experimental evidence. Reason: Core defining feature of BBS2 - it is a structural subunit of the BBSome.
GO:0036064 ciliary basal body	IBA GO_REF:0000033	ACCEPT	Summary: Basal-body localization inferred phylogenetically and supported experimentally (IDA PMID:18299575). Reason: Well-supported ciliary localization of BBS2/the BBSome.
GO:0031514 motile cilium	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Motile-cilium localization inferred phylogenetically; supported by airway motile cilia data (IDA PMID:18299575). Reason: The principal site of action of BBS2 is the primary (non-motile sensory) cilium; motile cilium localization is genuine in ciliated epithelia but is not the core context.
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: BBSome assembles and resides in the cytoplasm before/between ciliary entry; consistent with UniProt subcellular location. Reason: Accurate but non-specific background localization; the functionally salient sites are ciliary.
GO:0034451 centriolar satellite	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Centriolar-satellite localization is reported (UniProt SubCell; BBS4-dependent recruitment, PMID:24550735), although BBSome function is dispensable for centriolar satellite function. Reason: Genuine localization but non-core; the defining activity of BBS2 is at the ciliary membrane/basal body, not the satellites.
GO:0034464 BBSome	IEA GO_REF:0000120	ACCEPT	Summary: Electronic BBSome membership annotation; redundant with experimental annotations. Reason: Correct core localization/complex membership.
GO:0060170 ciliary membrane	IEA GO_REF:0000044	ACCEPT	Summary: Ciliary membrane localization; supported experimentally (IDA PMID:19081074). Reason: Core localization where the BBSome acts as a membrane coat.
GO:1905515 non-motile cilium assembly	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO inference. The primary (non-motile) cilium is precisely the context where the BBSome acts, so this is an appropriately specific process term. Reason: BBSome is required for primary (non-motile/sensory) cilium biogenesis and cargo sorting; this is the most precise process term.
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding from a high-throughput interactome (partner PSME3/P61289). Uninformative per curation guidelines. Reason: The protein binding term conveys no specific function; the high-throughput partner is likely non-specific. The relevant molecular role of BBS2 is as a BBSome structural subunit.
GO:0005515 protein binding	IPI PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra...	MARK AS OVER ANNOTATED	Summary: Protein binding to BBSome subunits (BBS9/Q3SYG4, BBS7/Q8IWZ6, BBS1/Q8NFJ9) identified in BBSome purification. Biologically real but captured by the BBSome membership annotation. Reason: The informative annotation is BBSome complex membership; the protein binding term itself is uninformative.
GO:0005515 protein binding	IPI PMID:18000879 Novel interaction partners of Bardet-Biedl syndrome proteins...	MARK AS OVER ANNOTATED	Summary: Protein binding to ALDOB (P05062), tubulin (P68104), KRT8 (Q15154). Generic and likely non-specific. Reason: Uninformative MF term; partners not function-defining for BBS2.
GO:0005515 protein binding	IPI PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c...	MARK AS OVER ANNOTATED	Summary: Protein binding to BBSome/assembly partners (BBS9, BBS12, BBS7, MKKS). Real interactions but uninformative MF. Reason: Captured by BBSome membership/assembly biology; the protein binding term is uninformative.
GO:0005515 protein binding	IPI PMID:22139371 Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals ...	MARK AS OVER ANNOTATED	Summary: Protein binding to BBS9 (Q3SYG4) from a Bbs3 knockout study. Reason: Uninformative MF term; intra-BBSome interaction already represented by complex membership.
GO:0005515 protein binding	IPI PMID:22500027 Intrinsic protein-protein interaction-mediated and chaperoni...	MARK AS OVER ANNOTATED	Summary: Protein binding to BBSome subunits (BBS9, BBS7, BBS1, MKKS) in the BBSome assembly study. Reason: Uninformative MF term; intra-complex interactions captured by BBSome membership.
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 (PSME3, RBPMS, MDFI). Reason: Uninformative; high-throughput partners likely non-specific.
GO:0005515 protein binding	IPI PMID:25552655 Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integ...	MARK AS OVER ANNOTATED	Summary: Protein binding to IQCB1/NPHP5 (Q15051), which regulates BBSome integrity and ciliary cargo delivery. Biologically meaningful interaction but uninformative as an MF term. Reason: The protein binding term is uninformative; the regulatory relationship is better captured at the process level.
GO:0005515 protein binding	IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis...	MARK AS OVER ANNOTATED	Summary: Protein binding to BBSome subunits from organellar proteomics. Reason: Uninformative MF term.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding (BBS7) from a high-throughput AP-MS interactome. Reason: Uninformative MF term.
GO:0005515 protein binding	IPI PMID:29039417 Protein interaction perturbation profiling at amino-acid res...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding (BBS7) from interaction perturbation profiling. Reason: Uninformative MF term.
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 (HNRNPF, PSME3, LMO4, NRF1, RBPMS, FNDC3B). Several partners are likely non-specific. Reason: Uninformative MF term; high-throughput Y2H partners not function-defining.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Generic protein-binding (BBS1, BBS7) from a high-throughput interactome. Reason: Uninformative MF term; intra-BBSome interactions captured by membership.
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 (BBS7, BBS1) from multimodal cell mapping. Reason: Uninformative MF term.
GO:0005902 microvillus	IEA GO_REF:0000107	REMOVE	Summary: Electronic Ensembl-Compara transfer from mouse. There is no robust evidence that BBS2 localizes to or acts at microvilli; BBSome subunits act at cilia, not microvilli. Reason: Over-propagated electronic annotation lacking biological support; likely conflation with ciliary/apical structures. Not supported by primary data.
GO:0016020 membrane	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic membrane localization (electronic transfer). Reason: Over-general; superseded by ciliary membrane (GO:0060170).
GO:0031514 motile cilium	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Motile-cilium localization (electronic transfer); supported by airway motile-cilia data. Reason: Genuine in ciliated epithelia but not the core (primary cilium) context.
GO:0032420 stereocilium	IEA GO_REF:0000107	REMOVE	Summary: Electronic Ensembl transfer from mouse. Evidence for genuine BBS2 localization to stereocilia (actin-based, non-ciliary structures) is weak. Reason: Over-propagated electronic annotation; stereocilia are actin-based hair bundles distinct from cilia, and there is no robust support for BBS2 acting there.
GO:0038108 negative regulation of appetite by leptin-mediated signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic transfer from mouse. Supported by the leptin-resistance phenotype of Bbs2-/- mice and a role for BBS proteins in leptin receptor trafficking/signaling. Reason: Biologically supported organismal/physiological process downstream of BBSome-mediated receptor trafficking, not a direct molecular function of BBS2.
GO:0045444 fat cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic transfer from mouse; BBS proteins are implicated in adipogenesis/obesity. Reason: Plausible but indirect organismal phenotype; not a direct BBS2 molecular function.
GO:0060271 cilium assembly	IEA GO_REF:0000107	ACCEPT	Summary: Electronic transfer of the core ciliogenesis role. Reason: Core BBSome process, also supported experimentally.
GO:0060296 regulation of cilium beat frequency involved in ciliary motility	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Electronic transfer from mouse. Bbs loss alters motile-cilia morphology and function in airway epithelia (PMID:18299575), but a direct role for BBS2 in regulating ciliary beat frequency is weak; the core role of the BBSome is in sensory (non-motile) cilia. Reason: Indirect/over-propagated; motility defects are likely secondary to ciliary trafficking/biogenesis defects rather than direct beat-frequency regulation.
GO:0005829 cytosol	TAS Reactome:R-HSA-5617815	KEEP AS NON CORE	Summary: Reactome cytosolic localization (BBSome binds RAB3IP/Rabin8). Consistent with the cytoplasmic pool of the BBSome. Reason: Accurate background localization; the functionally salient sites are ciliary.
GO:0005829 cytosol	TAS Reactome:R-HSA-5624125	KEEP AS NON CORE	Summary: Reactome cytosolic localization (Formation of the BBSome). Reason: BBSome assembly occurs in the cytoplasm; accurate but non-core.
GO:0005829 cytosol	TAS Reactome:R-HSA-5624126	KEEP AS NON CORE	Summary: Reactome cytosolic localization (ARL6:GTP and the BBSome bind ciliary cargo). Reason: Accurate but non-core background localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-5624127	KEEP AS NON CORE	Summary: Reactome cytosolic localization (ARL6:GTP and the BBSome target cargo to the cilium). Reason: Accurate but non-core background localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-5624129	KEEP AS NON CORE	Summary: Reactome cytosolic localization (LZTFL1 binds the BBSome). Reason: Accurate but non-core background localization.
GO:0035869 ciliary transition zone	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence (HPA) localization to the ciliary transition zone, a gate region at the ciliary base where the BBSome operates. Reason: Experimentally supported ciliary localization consistent with BBSome cargo gating.
GO:0034464 BBSome	IPI PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ...	ACCEPT	Summary: ComplexPortal IPI evidence for BBSome membership. Reason: Core defining feature of BBS2. Supporting Evidence: PMID:19081074 BBS proteins form a stable complex, the BBSome
GO:0060170 ciliary membrane	IDA PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ...	ACCEPT	Summary: Direct-assay ciliary membrane localization. Reason: Core localization of the BBSome coat.
GO:0060271 cilium assembly	NAS PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, ...	ACCEPT	Summary: BBSome subunit role in ciliogenesis (non-traceable author statement), consistent with experimental evidence. Reason: Core BBSome process. Supporting Evidence: PMID:19081074 A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.
GO:0034464 BBSome	IMP PMID:19150989 Requirement of Bardet-Biedl syndrome proteins for leptin rec...	ACCEPT	Summary: MGI IMP-supported BBSome membership; the leptin study uses Bbs2-/- mice and frames BBS2 as a BBSome subunit. Reason: Core defining feature of BBS2. Supporting Evidence: PMID:19150989 form a stable complex known as the BBSome
GO:0005515 protein binding	IPI PMID:33144677 Dlec1 is required for spermatogenesis and male fertility in ...	MARK AS OVER ANNOTATED	Summary: Protein binding to DLEC1 (Q9Y238) from a spermatogenesis study. Real interaction but uninformative MF term. Reason: The protein binding term is uninformative; partner not function-defining for BBS2.
GO:0005515 protein binding	IPI PMID:18762586 Recruitment of PCM1 to the centrosome by the cooperative act...	MARK AS OVER ANNOTATED	Summary: Protein binding to PCM1 (Q9NRI5) from a PCM1/DISC1/BBS4-centric centrosomal-recruitment study. Real interaction but uninformative MF term. Reason: The protein binding term is uninformative; the PCM1 interaction is centrosome/satellite-related and not function-defining for BBS2.
GO:0007601 visual perception	IMP PMID:25541840 Association between missense mutations in the BBS2 gene and ...	KEEP AS NON CORE	Summary: BBS2 missense mutations cause nonsyndromic retinitis pigmentosa (RP74), implicating BBS2 in vision via photoreceptor (connecting cilium) function. Reason: Genuine, experimentally/genetically supported organismal role, but a downstream physiological consequence of the ciliary-trafficking function of BBS2 rather than a direct molecular activity.
GO:0034464 BBSome	IDA PMID:24550735 The centriolar satellite protein AZI1 interacts with BBS4 an...	ACCEPT	Summary: Direct-assay BBSome membership. Reason: Core defining feature of BBS2.
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 derives from a BBS7-centric study reporting interaction with the PcG protein RNF2 (Q99496) and proposing a transcriptional role for BBS proteins generally. For BBS2 specifically this is indirect, and a nuclear transcriptional function is contested against the well-established cytoplasmic/ciliary trafficking role. Reason: Weak, indirect support for BBS2; the proposed transcriptional role is disputed and not a core function. Retained (not removed) as it derives from an experimental interaction annotation, but flagged as over-annotation.
GO:0005515 protein binding	IPI PMID:16327777 Dissection of epistasis in oligogenic Bardet-Biedl syndrome.	MARK AS OVER ANNOTATED	Summary: Protein binding to CCDC28B (Q9BUN5), a BBS modifier. Real interaction but uninformative MF term. Reason: The protein binding term is uninformative; better captured at the complex/process level.
GO:0038108 negative regulation of appetite by leptin-mediated signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from mouse; supported by Bbs2-/- leptin resistance and BBS-mediated leptin receptor trafficking. Reason: Supported physiological role downstream of receptor trafficking; not a direct molecular function.
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 depletion mistraffics the leptin receptor between the Golgi and the plasma/ciliary membrane (large perinuclear vesicles), supporting a role in Golgi-to-surface receptor transport. Reason: Experimentally supported trafficking role, but secondary to / a facet of the core ciliary membrane-protein trafficking activity of the BBSome. Supporting Evidence: PMID:19150989 similar mistrafficking of LepRb when BBS2 protein was depleted
GO:0032402 melanosome transport	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Sequence-similarity transfer (with reference UniProtKB:Q98SP7, a non-mammalian ortholog). Evidence for a genuine melanosome-transport role of human BBS2 is weak. Reason: Over-propagated ISS from a distant ortholog; not supported by mammalian experimental data and inconsistent with the ciliary-trafficking function of BBS2.
GO:0060271 cilium assembly	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity transfer of the core ciliogenesis role. Reason: Core BBSome process, supported by direct evidence.
GO:0060296 regulation of cilium beat frequency involved in ciliary motility	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Sequence-similarity transfer from mouse; same caveats as the IEA version - the core role of BBS2 is in sensory cilia, and motility effects are likely indirect. Reason: Indirect; beat-frequency effects are downstream of trafficking/biogenesis defects rather than a direct BBS2 function.
GO:0007288 sperm axoneme assembly	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from mouse. BBS proteins/BBSome contribute to flagellar/ciliary trafficking, and BBS2 interacts with DLEC1 (a spermatogenesis factor), giving plausible but indirect support. Reason: Plausible flagellar (cilium-related) role but indirect and tissue- specific; not a core function.
GO:0008104 intracellular protein localization	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Broad process term capturing the BBSome's role in localizing membrane-protein cargo. Accurate in essence but too general. Reason: Over-general; the specific trafficking processes (ciliary membrane-protein sorting/cilium assembly) are the informative annotations.
GO:0021756 striatum development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from mouse brain-development phenotypes of Bbs2 loss. Reason: Downstream organismal/developmental consequence of ciliary dysfunction, not a direct BBS2 molecular function.
GO:0021766 hippocampus development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from mouse brain-development phenotypes. Reason: Downstream developmental consequence of ciliary dysfunction.
GO:0021987 cerebral cortex development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from mouse brain-development phenotypes. Reason: Downstream developmental consequence of ciliary dysfunction.
GO:0030534 adult behavior	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from mouse behavioral phenotypes of Bbs2 loss. Reason: Downstream organismal phenotype, not a direct molecular function.
GO:0040015 negative regulation of multicellular organism growth	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from mouse growth phenotypes. Reason: Downstream organismal phenotype; not a direct molecular function.
GO:0045444 fat cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer (duplicate of the IEA version); BBS/adipogenesis link. Reason: Plausible but indirect organismal phenotype.
GO:0045494 photoreceptor cell maintenance	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer; consistent with retinal degeneration in BBS2 and nonsyndromic RP74 (PMID:25541840), reflecting the role of the connecting cilium / BBSome trafficking in photoreceptors. Reason: Genuine tissue-specific role downstream of ciliary trafficking; not a direct molecular function.
GO:0048854 brain morphogenesis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Sequence-similarity transfer from mouse neurodevelopmental phenotypes. Reason: Downstream developmental consequence of ciliary dysfunction.
GO:0034464 BBSome	IDA PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Ra...	ACCEPT	Summary: Direct-assay BBSome membership from the founding BBSome purification. Reason: Core defining feature of BBS2. Supporting Evidence: PMID:17574030 A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.
GO:0031514 motile cilium	IDA PMID:18299575 Loss of Bardet-Biedl syndrome proteins alters the morphology...	KEEP AS NON CORE	Summary: Direct localization to motile cilia of airway epithelia. Reason: Genuine localization in ciliated epithelia but not the core (primary cilium) context. Supporting Evidence: PMID:18299575 BBS2 and BBS4 localized to cellular structures associated with motile cilia
GO:0036064 ciliary basal body	IDA PMID:18299575 Loss of Bardet-Biedl syndrome proteins alters the morphology...	ACCEPT	Summary: Direct localization to the ciliary basal body. Reason: Core ciliary localization of BBS2/the BBSome. Supporting Evidence: PMID:18299575 BBS2 and BBS4 localized to cellular structures associated with motile cilia

Core Functions

BBS2 is a structural subunit of the BBSome octameric coat complex, contributing (with BBS7 and BBS9) the beta-propeller/GAE/platform scaffold that holds the complex together.

In Complex:

BBSome

Supporting Evidence:

PMID:17574030
A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.
PMID:22500027
sequential assembly of the BBSome

As part of the BBSome, BBS2 mediates the sorting and trafficking of specific membrane proteins (signaling receptors such as ciliary GPCRs, Smoothened, and the leptin receptor) into and out of the primary cilium, functioning as a membrane coat recruited by ARL6/BBS3-GTP and cooperating with Rab8/Rabin8.

Directly Involved In:

non-motile cilium assembly

Cellular Locations:

ciliary membrane ciliary basal body ciliary transition zone

In Complex:

BBSome

Supporting Evidence:

PMID:17574030
cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis
PMID:19150989
similar mistrafficking of LepRb when BBS2 protein was depleted

BBS2/the BBSome is required for assembly and maintenance of the primary (non-motile, sensory) cilium.

Directly Involved In:

cilium assembly

In Complex:

BBSome

Supporting Evidence:

PMID:19081074
A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:16189514

Towards a proteome-scale map of the human protein-protein interaction network.

PMID:16327777

Dissection of epistasis in oligogenic Bardet-Biedl syndrome.

PMID:17574030

A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.

PMID:18000879

Novel interaction partners of Bardet-Biedl syndrome proteins.

PMID:18299575

Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia.

PMID:18762586

Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses.

PMID:19081074

A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.

PMID:19150989

Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling.

PMID:20080638

BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly.

PMID:22072986

A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.

PMID:22139371

Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes.

PMID:22302990

Direct role of Bardet-Biedl syndrome proteins in transcriptional regulation.

PMID:22500027

Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential assembly of stable bardet-biedl syndrome protein complex, the BBSome.

PMID:24550735

The centriolar satellite protein AZI1 interacts with BBS4 and regulates ciliary trafficking of the BBSome.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:25541840

Association between missense mutations in the BBS2 gene and nonsyndromic retinitis pigmentosa.

PMID:25552655

Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integrity, ciliary trafficking and cargo delivery.

PMID:27173435

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:29039417

Protein interaction perturbation profiling at amino-acid resolution.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:33144677

Dlec1 is required for spermatogenesis and male fertility in mice.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

Reactome:R-HSA-5617815

BBSome binds RAB3IP

Reactome:R-HSA-5624125

Formation of the BBSome

Reactome:R-HSA-5624126

ARL6:GTP and the BBSome bind ciliary cargo

Reactome:R-HSA-5624127

ARL6:GTP and the BBSome target cargo to the primary cilium

Reactome:R-HSA-5624129

LZTFL1 binds the BBSome and prevents its traffic to the cilium

Suggested Experiments

Experiment: Cryo-EM of the human BBSome with and without BBS2 to define BBS2's structural contacts and the consequences of pathogenic missense variants (e.g. D104A, R632P) on complex integrity.

Hypothesis: BBS2 missense variants destabilize specific scaffold contacts within the BBSome.

Experiment: Quantitative ciliary proteomics (e.g. cilium-APEX) in BBS2-null versus wild-type cells to define the full set of receptor cargoes whose ciliary localization depends on BBS2.

Hypothesis: BBS2 loss selectively depletes a defined set of GPCR/receptor cargoes from the ciliary membrane.

Experiment: Structure-function analysis of BBS2 missense alleles causing syndromic BBS versus nonsyndromic RP74 to determine whether RP-specific alleles selectively impair photoreceptor-relevant cargo trafficking.

Hypothesis: RP74-specific BBS2 alleles retain general BBSome function but impair trafficking of photoreceptor-specific cargo.

📚 Additional Documentation

Notes

(BBS2-notes.md)

BBS2 (Q9BXC9) curation notes

(See BBS2-ai-review.yaml for the structured review.)

Identity and structure

Human BBS2, "BBSome complex member BBS2" / Bardet-Biedl syndrome 2 protein. 721 aa. UniProt Q9BXC9, HGNC:967.
Domain architecture (InterPro/Pfam): N-terminal β-propeller (WD40/YVTN repeat-like, Gene3D 2.130.10.10), middle domain, GAE (γ-adaptin ear) domain, hairpin, platform, and C-terminal helical (CtH) domain. A coiled-coil region (residues 325–369) mediates interaction with MKKS/BBS6. Architecture is coatomer/adaptin-like, consistent with the BBSome being a coat-like complex [UniProt Q9BXC9 FT/DR].
BBS2 together with BBS7 and BBS9 forms the β-propeller/GAE/platform scaffold core of the BBSome.

Core complex membership (BBSome)

BBSome is a stable octameric complex of BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9, and BBIP1/BBIP10 [PMID:17574030 "seven highly conserved BBS proteins form a stable complex, the BBSome"; PMID:19081074 BBIP10 added as eighth subunit].
ComplexPortal CPX-1908 (BBSome complex). TCDB 3.A.33.1.1 "the bbsome complex (bbsome) family".
BBS2 interacts directly via its C-terminus with BBS7, and via its coiled coil with MKKS/BBS6 [UniProt SUBUNIT]. IntAct: strong BBS2–BBS7 (NbExp=17), BBS2–BBS9 (NbExp=14), BBS2–BBS1 (NbExp=10).
BBSome assembly is chaperonin-assisted: BBS6/MKKS, BBS10, BBS12 form a complex with CCT/TRiC chaperonins that mediates BBSome assembly; BBS7 is delivered by the chaperonin to nucleate assembly [PMID:20080638; PMID:22500027].

Function — ciliary membrane protein trafficking

BBSome functions as a coat complex for sorting specific membrane proteins to/from primary cilia. It cooperates with the GTPase Rab8 (via Rabin8/RAB3IP GEF) to promote ciliary membrane biogenesis [PMID:17574030 "A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis"; UniProt FUNCTION].
ARL6/BBS3-GTP recruits the BBSome to the membrane to form a coat that sorts ciliary cargo (Reactome R-HSA-5624126/5624127). LZTFL1 binds the BBSome and regulates its ciliary trafficking and Smoothened/Hedgehog signaling [PMID:22072986; Reactome R-HSA-5624129].
BBSome with LZTFL1 controls SMO ciliary trafficking and contributes to SHH (sonic hedgehog) pathway regulation [UniProt FUNCTION].
Required for ciliogenesis but dispensable for centriolar satellite function [UniProt FUNCTION].
Localizes to cilium membrane, basal body, and cytoplasm; also reported at centriolar satellites and ciliary transition zone [UniProt SUBCELLULAR LOCATION; HPA IDA GO:0035869].

Function — receptor signaling / obesity (cargo trafficking)

BBS proteins are required for leptin receptor (LepR) signaling in the hypothalamus. Bbs2-/-, Bbs4-/-, Bbs6-/- mice are leptin-resistant; leptin-induced STAT3 phosphorylation reduced; Pomc expression reduced PMID:19150989. BBS1 is the direct LepRb interactor, but BBS2 depletion also mistraffics LepRb (large perinuclear vesicles), so BBS2 is functionally required for LepRb trafficking [PMID:19150989 Fig 6 "We found similar mistrafficking of LepRb when BBS2 protein was depleted"]. This supports involvement in leptin-mediated appetite regulation and fat-cell/obesity phenotypes, mechanistically via membrane-receptor trafficking.

Disease

Bardet–Biedl syndrome 2 (BBS2; MIM 615981): pigmentary retinopathy, obesity, polydactyly, hypogenitalism, renal malformation, intellectual disability; autosomal recessive (occasional triallelism) [UniProt DISEASE; PMID:11285252 positional cloning].
Retinitis pigmentosa 74 (RP74; MIM 616562): nonsyndromic RP caused by BBS2 missense mutations (p.A33D, p.P134R, p.D104A, p.R632P) PMID:25541840. Basis for the IMP "visual perception" annotation — supports photoreceptor cilium/role in vision.

Specific annotations evaluated

GO:0034464 BBSome (part_of): strongly supported by multiple experimental sources (IDA PMID:17574030, IDA PMID:24550735, IPI PMID:19081074 ComplexPortal, IMP PMID:19150989, plus IBA/IEA). CORE.
GO:0060170 ciliary membrane (located_in): supported, ComplexPortal IDA PMID:19081074, UniProt SubCell. CORE localization.
GO:0036064 ciliary basal body / GO:0035869 ciliary transition zone: experimentally supported localizations (IDA PMID:18299575; HPA IDA). Accept.
GO:0005829 cytosol / GO:0005737 cytoplasm: BBSome assembles and exists in cytoplasm before ciliary entry; supported. Accept as non-core background localization.
GO:0034451 centriolar satellite: UniProt SubCell SL-0485; also note UniProt FUNCTION explicitly states BBSome is "dispensable for centriolar satellite function" but BBS4 recruits BBSome there. Localization reported. Accept (located_in) but non-core.
GO:0060271 cilium assembly (involved_in): BBSome required for ciliogenesis; well supported. CORE process.
GO:0007601 visual perception (IMP PMID:25541840): supported by RP74 disease (photoreceptor cilium). Keep as non-core (downstream/organismal).
GO:0043001 Golgi to plasma membrane protein transport (IMP PMID:19150989): the leptin paper shows LepRb mistrafficking between Golgi and plasma/ciliary membrane in BBS2-depleted cells. Reasonable; keep (non-core, related to receptor trafficking).
GO:0038108 negative regulation of appetite by leptin-mediated signaling pathway (ISS/IEA from mouse Q9CWF6): supported by Bbs2-/- leptin resistance phenotype PMID:19150989. Keep as non-core.
GO:0045444 fat cell differentiation (ISS/IEA): BBS proteins implicated in adipogenesis/obesity; transfer from mouse. Keep as non-core (organismal phenotype, plausible but indirect).
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding (IPI PMID:22302990, WITH UniProtKB:Q99496=RNF2/RING2): based on a paper foregrounding BBS7 interacting with PcG member RNF2; "our data supports a similar role for other BBS proteins." This is an interaction-based MF annotation. RNF2 (Q99496) is a transcriptional repressor (PRC1). The annotation captures a physical interaction; the broader "direct role in transcription" is contested/indirect. Mark as over-annotated / keep cautiously — interaction is real but functional significance for BBS2 specifically is weak. Use UNDECIDED-leaning; this is an experimental IPI so do not REMOVE — mark non-core / over-annotated.

protein binding (GO:0005515) IPI annotations

Numerous IntAct/IPI GO:0005515 protein binding annotations to BBSome partners (BBS1, BBS7, BBS9, BBS12, MKKS), assembly chaperonins, and to non-BBSome partners (ALDOB P05062, CCDC28B Q9BUN5, DLEC1 Q9Y238, IQCB1/NPHP5 Q15051, PCM1 Q9NRI5, and many high-throughput Y2H/AP-MS hits such as HNRNPF, LMO4, MDFI, NRF1, RBPMS, PSME3, FNDC3B, TUBA P68104, KRT8 Q15154, etc.).
Per curation guidelines, GO:0005515 "protein binding" is uninformative and should be marked over-annotated; the informative MF is the structural/adaptor role within the BBSome (no good specific MF term beyond complex membership — BBS2 has no catalytic activity; it is a scaffolding subunit). Many HT-interactome hits (HNRNPF, NRF1, RBPMS, KRT8, TUBA) are likely non-specific.

Mouse/ISS-transferred BP terms (GO_REF:0000024, from mouse Q9CWF6)

Brain/CNS development terms (striatum, hippocampus, cerebral cortex development, brain morphogenesis, adult behavior), photoreceptor cell maintenance, negative regulation of multicellular organism growth, sperm axoneme assembly, melanosome transport, intracellular protein localization, regulation of cilium beat frequency.
These are organismal/tissue phenotypes of Bbs2 loss in mouse, transferred by ISS. Most are downstream consequences of ciliary dysfunction rather than direct BBS2 molecular functions. Keep developmental/behavioral ones as non-core; melanosome transport and regulation of cilium beat frequency are weakly supported (motile-cilia term applies more to airway; BBS2 loss alters motile cilia morphology per PMID:18299575). sperm axoneme assembly relates to flagellar/cilium role.

Key references verified

PMID:17574030 — BBSome definition + Rab8/ciliary membrane biogenesis (HIGH).
PMID:19081074 — BBIP10/eighth subunit; ciliogenesis, MT stability (HIGH for complex membership/localization).
PMID:19150989 — leptin receptor signaling/trafficking, Bbs2-/- (HIGH).
PMID:25541840 — BBS2 missense → nonsyndromic RP74 (HIGH for vision).
PMID:22302990 — BBS7 (and "other BBS proteins") interaction with RNF2, transcriptional role (MEDIUM, BBS7-centric).
PMID:18299575 — Bbs loss alters motile cilia in airway (MEDIUM; supports motile cilium localization/cilium beat).
PMID:33144677 — DLEC1 interaction (spermatogenesis paper) (LOW-MEDIUM, interaction only).

📄 View Raw YAML

id: Q9BXC9
gene_symbol: BBS2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  BBS2 is a core scaffolding subunit of the BBSome, a stable octameric, coat-like
  adaptor complex (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP1/BBIP10)
  that traffics specific membrane proteins, especially signaling receptors such as
  ciliary G-protein-coupled receptors and Hedgehog-pathway components (e.g.
  Smoothened), into and out of the primary cilium. BBS2 is a ~721-residue protein
  built from a coatomer/adaptin-like architecture: an N-terminal beta-propeller,
  followed by middle, GAE (gamma-adaptin ear), platform and C-terminal helical
  domains, plus a coiled-coil region; together with BBS7 and BBS9 it forms the
  beta-propeller/GAE/platform scaffold core of the complex. The BBSome is recruited
  to the ciliary membrane by the small GTPase ARL6/BBS3-GTP and cooperates with the
  Rab8 GEF Rabin8 (RAB3IP) and Rab8 to promote ciliary membrane biogenesis and
  cargo sorting; LZTFL1 regulates its ciliary entry. BBSome-mediated trafficking is
  required for proper localization and signaling of receptors including the leptin
  receptor, linking BBS2 to energy homeostasis. BBS2 itself has no catalytic
  activity; it acts as a structural/adaptor module. The protein localizes to the
  ciliary membrane, basal body, ciliary transition zone, centriolar satellites and
  the cytoplasm. Loss-of-function mutations cause autosomal-recessive Bardet-Biedl
  syndrome (retinal degeneration, obesity, polydactyly, renal anomalies,
  hypogenitalism, cognitive impairment) and, for certain missense alleles,
  nonsyndromic retinitis pigmentosa.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput yeast two-hybrid interactome screen; source of a
      generic protein-binding (IPI) annotation, not function-defining for BBS2.
- id: PMID:16327777
  title: Dissection of epistasis in oligogenic Bardet-Biedl syndrome.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Establishes BBS2 interaction with CCDC28B (Q9BUN5) and oligogenic
      modifier effects; physical interaction, supports protein binding only.
- id: PMID:17574030
  title: A core complex of BBS proteins cooperates with the GTPase Rab8 to promote
    ciliary membrane biogenesis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Defines the BBSome (BBS1/2/4/5/7/8/9) and its role with Rab8 in
      ciliary membrane biogenesis; primary evidence for BBSome membership and
      ciliary membrane localization of BBS2.
- id: PMID:18000879
  title: Novel interaction partners of Bardet-Biedl syndrome proteins.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Reports BBS2 interactions (ALDOB, tubulin, KRT8); physical
      interactions only, not function-defining.
- id: PMID:18299575
  title: Loss of Bardet-Biedl syndrome proteins alters the morphology and function
    of motile cilia in airway epithelia.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Supports BBS2 localization to motile cilium and basal body and a
      role in motile cilia of airway epithelia.
- id: PMID:18762586
  title: 'Recruitment of PCM1 to the centrosome by the cooperative action of DISC1
    and BBS4: a candidate for psychiatric illnesses.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PCM1/DISC1/BBS4-centric; source of a BBS2-PCM1 (Q9NRI5) interaction
      annotation only.
- id: PMID:19081074
  title: A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Adds BBIP10 as the eighth BBSome subunit; supports BBSome
      membership, ciliary membrane localization and role in ciliogenesis.
- id: PMID:19150989
  title: Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Bbs2-/- mice are leptin-resistant; BBS2 depletion mistraffics
      LepRb. Supports leptin-mediated appetite regulation and Golgi-to-membrane
      receptor transport involvement.
- id: PMID:20080638
  title: BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and
    mediate BBSome assembly.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Chaperonin-assisted BBSome assembly; BBS2 interactions with
      BBS7/MKKS documented.
- id: PMID:22072986
  title: A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: LZTFL1 regulates BBSome ciliary trafficking and Smoothened/Hedgehog
      signaling; supports BBSome function in receptor trafficking to cilium.
- id: PMID:22139371
  title: Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated
    phenotypes and Bbs3 unique phenotypes.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: BBS3/ARL6-centric mouse phenotyping; source of a BBS2-BBS9
      interaction annotation.
- id: PMID:22302990
  title: Direct role of Bardet-Biedl syndrome proteins in transcriptional regulation.
  findings: []
  reference_review:
    relevance: LOW
    correctness: DISPUTED
    review_notes: Primarily BBS7-centric; shows BBS7 interaction with PcG member
      RNF2 (Q99496) and proposes a nuclear/transcriptional role for BBS proteins
      generally. The transcriptional role for BBS2 specifically is indirect and
      contested versus the well-established cytoplasmic/ciliary trafficking function.
- id: PMID:22500027
  title: Intrinsic protein-protein interaction-mediated and chaperonin-assisted sequential
    assembly of stable bardet-biedl syndrome protein complex, the BBSome.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Maps the sequential, chaperonin-assisted assembly of the BBSome;
      documents BBS2 interactions with BBS1/7/9/MKKS.
- id: PMID:24550735
  title: The centriolar satellite protein AZI1 interacts with BBS4 and regulates ciliary
    trafficking of the BBSome.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Supports BBSome (containing BBS2) integrity/ciliary trafficking;
      BBS4/AZI1-centric.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of generic protein-binding
      annotations.
- id: PMID:25541840
  title: Association between missense mutations in the BBS2 gene and nonsyndromic
    retinitis pigmentosa.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: BBS2 missense mutations cause nonsyndromic retinitis pigmentosa
      (RP74); basis for involvement in visual perception/photoreceptor maintenance.
- id: PMID:25552655
  title: Nephrocystin proteins NPHP5 and Cep290 regulate BBSome integrity, ciliary
    trafficking and cargo delivery.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: NPHP5(IQCB1)/CEP290 regulate BBSome integrity and ciliary cargo
      delivery; documents BBS2-IQCB1 interaction.
- id: PMID:27173435
  title: An organelle-specific protein landscape identifies novel diseases and molecular
    mechanisms.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput organellar proteomics; source of generic
      protein-binding annotations.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput AP-MS interactome; generic protein-binding only.
- id: PMID:29039417
  title: Protein interaction perturbation profiling at amino-acid resolution.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interaction profiling; generic protein-binding
      only.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput binary interactome (HuRI); many partners are
      likely non-specific (e.g. HNRNPF, NRF1, LMO4).
- id: PMID:33144677
  title: Dlec1 is required for spermatogenesis and male fertility in mice.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Reports BBS2-DLEC1 (Q9Y238) interaction; DLEC1/spermatogenesis-
      centric, physical interaction only.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; generic protein-binding only.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput multimodal cell mapping; generic protein-binding
      only.
- id: Reactome:R-HSA-5617815
  title: BBSome binds RAB3IP
  findings: []
- id: Reactome:R-HSA-5624125
  title: Formation of the BBSome
  findings: []
- id: Reactome:R-HSA-5624126
  title: ARL6:GTP and the BBSome bind ciliary cargo
  findings: []
- id: Reactome:R-HSA-5624127
  title: ARL6:GTP and the BBSome target cargo to the primary cilium
  findings: []
- id: Reactome:R-HSA-5624129
  title: LZTFL1 binds the BBSome and prevents its traffic to the cilium
  findings: []
existing_annotations:
- term:
    id: GO:0043005
    label: neuron projection
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) localization to neuron projection. BBS2 acts in the
      primary cilium, and neuronal primary cilia are a relevant context, but neuron
      projection is a broad/imprecise CC for a BBSome subunit whose precise site of
      action is the ciliary membrane/basal body.
    action: MARK_AS_OVER_ANNOTATED
    reason: BBSome subunits act at the primary cilium; neuron projection is an
      over-general localization. The specific ciliary localizations (ciliary
      membrane, basal body, transition zone) are separately and better annotated.
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: BBSome is required for ciliogenesis; phylogenetic inference is
      consistent with experimental data across species.
    action: ACCEPT
    reason: Cilium assembly is a core BBSome process well supported across orthologs
      and by human experimental data.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Generic membrane localization. The BBSome is a peripheral coat that
      associates with the ciliary membrane; the specific term ciliary membrane is
      already annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative/over-general CC superseded by GO:0060170 ciliary membrane.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: BBSome membership inferred phylogenetically; consistent with abundant
      experimental evidence.
    action: ACCEPT
    reason: Core defining feature of BBS2 - it is a structural subunit of the BBSome.
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Basal-body localization inferred phylogenetically and supported
      experimentally (IDA PMID:18299575).
    action: ACCEPT
    reason: Well-supported ciliary localization of BBS2/the BBSome.
- term:
    id: GO:0031514
    label: motile cilium
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Motile-cilium localization inferred phylogenetically; supported by
      airway motile cilia data (IDA PMID:18299575).
    action: KEEP_AS_NON_CORE
    reason: The principal site of action of BBS2 is the primary (non-motile sensory)
      cilium; motile cilium localization is genuine in ciliated epithelia but is not
      the core context.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: BBSome assembles and resides in the cytoplasm before/between ciliary
      entry; consistent with UniProt subcellular location.
    action: KEEP_AS_NON_CORE
    reason: Accurate but non-specific background localization; the functionally
      salient sites are ciliary.
- term:
    id: GO:0034451
    label: centriolar satellite
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Centriolar-satellite localization is reported (UniProt SubCell;
      BBS4-dependent recruitment, PMID:24550735), although BBSome function is
      dispensable for centriolar satellite function.
    action: KEEP_AS_NON_CORE
    reason: Genuine localization but non-core; the defining activity of BBS2 is at
      the ciliary membrane/basal body, not the satellites.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: Electronic BBSome membership annotation; redundant with experimental
      annotations.
    action: ACCEPT
    reason: Correct core localization/complex membership.
- term:
    id: GO:0060170
    label: ciliary membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Ciliary membrane localization; supported experimentally (IDA
      PMID:19081074).
    action: ACCEPT
    reason: Core localization where the BBSome acts as a membrane coat.
- term:
    id: GO:1905515
    label: non-motile cilium assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro2GO inference. The primary (non-motile) cilium is precisely the
      context where the BBSome acts, so this is an appropriately specific process
      term.
    action: ACCEPT
    reason: BBSome is required for primary (non-motile/sensory) cilium biogenesis and
      cargo sorting; this is the most precise process term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: Generic protein-binding from a high-throughput interactome (partner
      PSME3/P61289). Uninformative per curation guidelines.
    action: MARK_AS_OVER_ANNOTATED
    reason: The protein binding term conveys no specific function; the high-throughput
      partner is likely non-specific. The relevant molecular role of BBS2 is as a
      BBSome structural subunit.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17574030
  qualifier: enables
  review:
    summary: Protein binding to BBSome subunits (BBS9/Q3SYG4, BBS7/Q8IWZ6,
      BBS1/Q8NFJ9) identified in BBSome purification. Biologically real but captured
      by the BBSome membership annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: The informative annotation is BBSome complex membership; the protein
      binding term itself is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18000879
  qualifier: enables
  review:
    summary: Protein binding to ALDOB (P05062), tubulin (P68104), KRT8 (Q15154).
      Generic and likely non-specific.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; partners not function-defining for BBS2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20080638
  qualifier: enables
  review:
    summary: Protein binding to BBSome/assembly partners (BBS9, BBS12, BBS7, MKKS).
      Real interactions but uninformative MF.
    action: MARK_AS_OVER_ANNOTATED
    reason: Captured by BBSome membership/assembly biology; the protein binding term
      is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22139371
  qualifier: enables
  review:
    summary: Protein binding to BBS9 (Q3SYG4) from a Bbs3 knockout study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; intra-BBSome interaction already represented by
      complex membership.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22500027
  qualifier: enables
  review:
    summary: Protein binding to BBSome subunits (BBS9, BBS7, BBS1, MKKS) in the
      BBSome assembly study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; intra-complex interactions captured by BBSome
      membership.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Generic protein-binding from a high-throughput interactome (PSME3,
      RBPMS, MDFI).
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative; high-throughput partners likely non-specific.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25552655
  qualifier: enables
  review:
    summary: Protein binding to IQCB1/NPHP5 (Q15051), which regulates BBSome
      integrity and ciliary cargo delivery. Biologically meaningful interaction but
      uninformative as an MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: The protein binding term is uninformative; the regulatory relationship is
      better captured at the process level.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27173435
  qualifier: enables
  review:
    summary: Protein binding to BBSome subunits from organellar proteomics.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Generic protein-binding (BBS7) from a high-throughput AP-MS interactome.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29039417
  qualifier: enables
  review:
    summary: Generic protein-binding (BBS7) from interaction perturbation profiling.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Generic protein-binding from the HuRI binary interactome (HNRNPF, PSME3,
      LMO4, NRF1, RBPMS, FNDC3B). Several partners are likely non-specific.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; high-throughput Y2H partners not function-defining.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic protein-binding (BBS1, BBS7) from a high-throughput interactome.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; intra-BBSome interactions captured by membership.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Generic protein-binding (BBS7, BBS1) from multimodal cell mapping.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term.
- term:
    id: GO:0005902
    label: microvillus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Electronic Ensembl-Compara transfer from mouse. There is no robust
      evidence that BBS2 localizes to or acts at microvilli; BBSome subunits act at
      cilia, not microvilli.
    action: REMOVE
    reason: Over-propagated electronic annotation lacking biological support; likely
      conflation with ciliary/apical structures. Not supported by primary data.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Generic membrane localization (electronic transfer).
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-general; superseded by ciliary membrane (GO:0060170).
- term:
    id: GO:0031514
    label: motile cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Motile-cilium localization (electronic transfer); supported by airway
      motile-cilia data.
    action: KEEP_AS_NON_CORE
    reason: Genuine in ciliated epithelia but not the core (primary cilium) context.
- term:
    id: GO:0032420
    label: stereocilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Electronic Ensembl transfer from mouse. Evidence for genuine BBS2
      localization to stereocilia (actin-based, non-ciliary structures) is weak.
    action: REMOVE
    reason: Over-propagated electronic annotation; stereocilia are actin-based hair
      bundles distinct from cilia, and there is no robust support for BBS2 acting
      there.
- term:
    id: GO:0038108
    label: negative regulation of appetite by leptin-mediated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from mouse. Supported by the leptin-resistance
      phenotype of Bbs2-/- mice and a role for BBS proteins in leptin receptor
      trafficking/signaling.
    action: KEEP_AS_NON_CORE
    reason: Biologically supported organismal/physiological process downstream of
      BBSome-mediated receptor trafficking, not a direct molecular function of BBS2.
- term:
    id: GO:0045444
    label: fat cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from mouse; BBS proteins are implicated in
      adipogenesis/obesity.
    action: KEEP_AS_NON_CORE
    reason: Plausible but indirect organismal phenotype; not a direct BBS2 molecular
      function.
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer of the core ciliogenesis role.
    action: ACCEPT
    reason: Core BBSome process, also supported experimentally.
- term:
    id: GO:0060296
    label: regulation of cilium beat frequency involved in ciliary motility
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Electronic transfer from mouse. Bbs loss alters motile-cilia morphology
      and function in airway epithelia (PMID:18299575), but a direct role for BBS2
      in regulating ciliary beat frequency is weak; the core role of the BBSome is in
      sensory (non-motile) cilia.
    action: MARK_AS_OVER_ANNOTATED
    reason: Indirect/over-propagated; motility defects are likely secondary to
      ciliary trafficking/biogenesis defects rather than direct beat-frequency
      regulation.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5617815
  qualifier: located_in
  review:
    summary: Reactome cytosolic localization (BBSome binds RAB3IP/Rabin8). Consistent
      with the cytoplasmic pool of the BBSome.
    action: KEEP_AS_NON_CORE
    reason: Accurate background localization; the functionally salient sites are
      ciliary.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624125
  qualifier: located_in
  review:
    summary: Reactome cytosolic localization (Formation of the BBSome).
    action: KEEP_AS_NON_CORE
    reason: BBSome assembly occurs in the cytoplasm; accurate but non-core.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624126
  qualifier: located_in
  review:
    summary: Reactome cytosolic localization (ARL6:GTP and the BBSome bind ciliary
      cargo).
    action: KEEP_AS_NON_CORE
    reason: Accurate but non-core background localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624127
  qualifier: located_in
  review:
    summary: Reactome cytosolic localization (ARL6:GTP and the BBSome target cargo to
      the cilium).
    action: KEEP_AS_NON_CORE
    reason: Accurate but non-core background localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624129
  qualifier: located_in
  review:
    summary: Reactome cytosolic localization (LZTFL1 binds the BBSome).
    action: KEEP_AS_NON_CORE
    reason: Accurate but non-core background localization.
- term:
    id: GO:0035869
    label: ciliary transition zone
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Immunofluorescence (HPA) localization to the ciliary transition zone, a
      gate region at the ciliary base where the BBSome operates.
    action: ACCEPT
    reason: Experimentally supported ciliary localization consistent with BBSome
      cargo gating.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IPI
  original_reference_id: PMID:19081074
  qualifier: part_of
  review:
    summary: ComplexPortal IPI evidence for BBSome membership.
    action: ACCEPT
    reason: Core defining feature of BBS2.
    supported_by:
    - reference_id: PMID:19081074
      supporting_text: BBS proteins form a stable complex, the BBSome
- term:
    id: GO:0060170
    label: ciliary membrane
  evidence_type: IDA
  original_reference_id: PMID:19081074
  qualifier: located_in
  review:
    summary: Direct-assay ciliary membrane localization.
    action: ACCEPT
    reason: Core localization of the BBSome coat.
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: NAS
  original_reference_id: PMID:19081074
  qualifier: involved_in
  review:
    summary: BBSome subunit role in ciliogenesis (non-traceable author statement),
      consistent with experimental evidence.
    action: ACCEPT
    reason: Core BBSome process.
    supported_by:
    - reference_id: PMID:19081074
      supporting_text: A BBSome subunit links ciliogenesis, microtubule stability,
        and acetylation.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IMP
  original_reference_id: PMID:19150989
  qualifier: part_of
  review:
    summary: MGI IMP-supported BBSome membership; the leptin study uses Bbs2-/- mice
      and frames BBS2 as a BBSome subunit.
    action: ACCEPT
    reason: Core defining feature of BBS2.
    supported_by:
    - reference_id: PMID:19150989
      supporting_text: form a stable complex known as the BBSome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33144677
  qualifier: enables
  review:
    summary: Protein binding to DLEC1 (Q9Y238) from a spermatogenesis study. Real
      interaction but uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: The protein binding term is uninformative; partner not function-defining
      for BBS2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18762586
  qualifier: enables
  review:
    summary: Protein binding to PCM1 (Q9NRI5) from a PCM1/DISC1/BBS4-centric
      centrosomal-recruitment study. Real interaction but uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: The protein binding term is uninformative; the PCM1 interaction is
      centrosome/satellite-related and not function-defining for BBS2.
- term:
    id: GO:0007601
    label: visual perception
  evidence_type: IMP
  original_reference_id: PMID:25541840
  qualifier: involved_in
  review:
    summary: BBS2 missense mutations cause nonsyndromic retinitis pigmentosa (RP74),
      implicating BBS2 in vision via photoreceptor (connecting cilium) function.
    action: KEEP_AS_NON_CORE
    reason: Genuine, experimentally/genetically supported organismal role, but a
      downstream physiological consequence of the ciliary-trafficking function of
      BBS2 rather than a direct molecular activity.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:24550735
  qualifier: part_of
  review:
    summary: Direct-assay BBSome membership.
    action: ACCEPT
    reason: Core defining feature of BBS2.
- term:
    id: GO:0061629
    label: RNA polymerase II-specific DNA-binding transcription factor binding
  evidence_type: IPI
  original_reference_id: PMID:22302990
  qualifier: enables
  review:
    summary: Annotation derives from a BBS7-centric study reporting interaction with
      the PcG protein RNF2 (Q99496) and proposing a transcriptional role for BBS
      proteins generally. For BBS2 specifically this is indirect, and a nuclear
      transcriptional function is contested against the well-established
      cytoplasmic/ciliary trafficking role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Weak, indirect support for BBS2; the proposed transcriptional role is
      disputed and not a core function. Retained (not removed) as it derives from an
      experimental interaction annotation, but flagged as over-annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16327777
  qualifier: enables
  review:
    summary: Protein binding to CCDC28B (Q9BUN5), a BBS modifier. Real interaction
      but uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: The protein binding term is uninformative; better captured at the
      complex/process level.
- term:
    id: GO:0038108
    label: negative regulation of appetite by leptin-mediated signaling pathway
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer from mouse; supported by Bbs2-/- leptin
      resistance and BBS-mediated leptin receptor trafficking.
    action: KEEP_AS_NON_CORE
    reason: Supported physiological role downstream of receptor trafficking; not a
      direct molecular function.
- term:
    id: GO:0043001
    label: Golgi to plasma membrane protein transport
  evidence_type: IMP
  original_reference_id: PMID:19150989
  qualifier: acts_upstream_of_or_within
  review:
    summary: BBS2 depletion mistraffics the leptin receptor between the Golgi and the
      plasma/ciliary membrane (large perinuclear vesicles), supporting a role in
      Golgi-to-surface receptor transport.
    action: KEEP_AS_NON_CORE
    reason: Experimentally supported trafficking role, but secondary to / a facet of
      the core ciliary membrane-protein trafficking activity of the BBSome.
    supported_by:
    - reference_id: PMID:19150989
      supporting_text: similar mistrafficking of LepRb when BBS2 protein was depleted
- term:
    id: GO:0032402
    label: melanosome transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer (with reference UniProtKB:Q98SP7, a
      non-mammalian ortholog). Evidence for a genuine melanosome-transport role of
      human BBS2 is weak.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated ISS from a distant ortholog; not supported by mammalian
      experimental data and inconsistent with the ciliary-trafficking function of
      BBS2.
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer of the core ciliogenesis role.
    action: ACCEPT
    reason: Core BBSome process, supported by direct evidence.
- term:
    id: GO:0060296
    label: regulation of cilium beat frequency involved in ciliary motility
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer from mouse; same caveats as the IEA version
      - the core role of BBS2 is in sensory cilia, and motility effects are likely
      indirect.
    action: MARK_AS_OVER_ANNOTATED
    reason: Indirect; beat-frequency effects are downstream of trafficking/biogenesis
      defects rather than a direct BBS2 function.
- term:
    id: GO:0007288
    label: sperm axoneme assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer from mouse. BBS proteins/BBSome contribute
      to flagellar/ciliary trafficking, and BBS2 interacts with DLEC1 (a
      spermatogenesis factor), giving plausible but indirect support.
    action: KEEP_AS_NON_CORE
    reason: Plausible flagellar (cilium-related) role but indirect and tissue-
      specific; not a core function.
- term:
    id: GO:0008104
    label: intracellular protein localization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Broad process term capturing the BBSome's role in localizing
      membrane-protein cargo. Accurate in essence but too general.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-general; the specific trafficking processes (ciliary membrane-protein
      sorting/cilium assembly) are the informative annotations.
- term:
    id: GO:0021756
    label: striatum development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer from mouse brain-development phenotypes of
      Bbs2 loss.
    action: KEEP_AS_NON_CORE
    reason: Downstream organismal/developmental consequence of ciliary dysfunction,
      not a direct BBS2 molecular function.
- term:
    id: GO:0021766
    label: hippocampus development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer from mouse brain-development phenotypes.
    action: KEEP_AS_NON_CORE
    reason: Downstream developmental consequence of ciliary dysfunction.
- term:
    id: GO:0021987
    label: cerebral cortex development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer from mouse brain-development phenotypes.
    action: KEEP_AS_NON_CORE
    reason: Downstream developmental consequence of ciliary dysfunction.
- term:
    id: GO:0030534
    label: adult behavior
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer from mouse behavioral phenotypes of Bbs2
      loss.
    action: KEEP_AS_NON_CORE
    reason: Downstream organismal phenotype, not a direct molecular function.
- term:
    id: GO:0040015
    label: negative regulation of multicellular organism growth
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer from mouse growth phenotypes.
    action: KEEP_AS_NON_CORE
    reason: Downstream organismal phenotype; not a direct molecular function.
- term:
    id: GO:0045444
    label: fat cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer (duplicate of the IEA version);
      BBS/adipogenesis link.
    action: KEEP_AS_NON_CORE
    reason: Plausible but indirect organismal phenotype.
- term:
    id: GO:0045494
    label: photoreceptor cell maintenance
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer; consistent with retinal degeneration in
      BBS2 and nonsyndromic RP74 (PMID:25541840), reflecting the role of the
      connecting cilium / BBSome trafficking in photoreceptors.
    action: KEEP_AS_NON_CORE
    reason: Genuine tissue-specific role downstream of ciliary trafficking; not a
      direct molecular function.
- term:
    id: GO:0048854
    label: brain morphogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity transfer from mouse neurodevelopmental phenotypes.
    action: KEEP_AS_NON_CORE
    reason: Downstream developmental consequence of ciliary dysfunction.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:17574030
  qualifier: part_of
  review:
    summary: Direct-assay BBSome membership from the founding BBSome purification.
    action: ACCEPT
    reason: Core defining feature of BBS2.
    supported_by:
    - reference_id: PMID:17574030
      supporting_text: A core complex of BBS proteins cooperates with the GTPase
        Rab8 to promote ciliary membrane biogenesis.
- term:
    id: GO:0031514
    label: motile cilium
  evidence_type: IDA
  original_reference_id: PMID:18299575
  qualifier: located_in
  review:
    summary: Direct localization to motile cilia of airway epithelia.
    action: KEEP_AS_NON_CORE
    reason: Genuine localization in ciliated epithelia but not the core (primary
      cilium) context.
    supported_by:
    - reference_id: PMID:18299575
      supporting_text: BBS2 and BBS4 localized to cellular structures associated with
        motile cilia
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IDA
  original_reference_id: PMID:18299575
  qualifier: located_in
  review:
    summary: Direct localization to the ciliary basal body.
    action: ACCEPT
    reason: Core ciliary localization of BBS2/the BBSome.
    supported_by:
    - reference_id: PMID:18299575
      supporting_text: BBS2 and BBS4 localized to cellular structures associated with
        motile cilia
core_functions:
- description: BBS2 is a structural subunit of the BBSome octameric coat complex,
    contributing (with BBS7 and BBS9) the beta-propeller/GAE/platform scaffold that
    holds the complex together.
  supported_by:
  - reference_id: PMID:17574030
    supporting_text: A core complex of BBS proteins cooperates with the GTPase Rab8
      to promote ciliary membrane biogenesis.
  - reference_id: PMID:22500027
    supporting_text: sequential assembly of the BBSome
  in_complex:
    id: GO:0034464
    label: BBSome
- description: As part of the BBSome, BBS2 mediates the sorting and trafficking of
    specific membrane proteins (signaling receptors such as ciliary GPCRs,
    Smoothened, and the leptin receptor) into and out of the primary cilium,
    functioning as a membrane coat recruited by ARL6/BBS3-GTP and cooperating with
    Rab8/Rabin8.
  supported_by:
  - reference_id: PMID:17574030
    supporting_text: cooperates with the GTPase Rab8 to promote ciliary membrane
      biogenesis
  - reference_id: PMID:19150989
    supporting_text: similar mistrafficking of LepRb when BBS2 protein was depleted
  directly_involved_in:
  - id: GO:1905515
    label: non-motile cilium assembly
  locations:
  - id: GO:0060170
    label: ciliary membrane
  - id: GO:0036064
    label: ciliary basal body
  - id: GO:0035869
    label: ciliary transition zone
  in_complex:
    id: GO:0034464
    label: BBSome
- description: BBS2/the BBSome is required for assembly and maintenance of the
    primary (non-motile, sensory) cilium.
  supported_by:
  - reference_id: PMID:19081074
    supporting_text: A BBSome subunit links ciliogenesis, microtubule stability, and
      acetylation.
  directly_involved_in:
  - id: GO:0060271
    label: cilium assembly
  in_complex:
    id: GO:0034464
    label: BBSome
proposed_new_terms: []
suggested_questions:
- question: Does BBS2 have any cargo-recognition role distinct from its scaffolding
    function, or is cargo selectivity entirely conferred by other subunits (e.g.
    BBS1, BBS5, BBS9)?
- question: Is the reported nuclear/transcriptional role of BBS proteins (RNF2
    interaction) biologically significant for BBS2 specifically, or restricted to
    BBS7?
- question: To what extent are the brain-development, behavior and growth phenotypes
    of Bbs2 loss direct, versus secondary to systemic ciliary signaling defects?
suggested_experiments:
- description: Cryo-EM of the human BBSome with and without BBS2 to define BBS2's
    structural contacts and the consequences of pathogenic missense variants (e.g.
    D104A, R632P) on complex integrity.
  hypothesis: BBS2 missense variants destabilize specific scaffold contacts within
    the BBSome.
- description: Quantitative ciliary proteomics (e.g. cilium-APEX) in BBS2-null versus
    wild-type cells to define the full set of receptor cargoes whose ciliary
    localization depends on BBS2.
  hypothesis: BBS2 loss selectively depletes a defined set of GPCR/receptor cargoes
    from the ciliary membrane.
- description: Structure-function analysis of BBS2 missense alleles causing syndromic
    BBS versus nonsyndromic RP74 to determine whether RP-specific alleles selectively
    impair photoreceptor-relevant cargo trafficking.
  hypothesis: RP74-specific BBS2 alleles retain general BBSome function but impair
    trafficking of photoreceptor-specific cargo.

BBS2

Gene Description

Existing Annotations Review

Core Functions

BBS2 is a structural subunit of the BBSome octameric coat complex, contributing (with BBS7 and BBS9) the beta-propeller/GAE/platform scaffold that holds the complex together.

BBS2/the BBSome is required for assembly and maintenance of the primary (non-motile, sensory) cilium.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

BBS2 (Q9BXC9) curation notes

Identity and structure

Core complex membership (BBSome)

Function — ciliary membrane protein trafficking

Function — receptor signaling / obesity (cargo trafficking)

Disease

Specific annotations evaluated

protein binding (GO:0005515) IPI annotations

Mouse/ISS-transferred BP terms (GO_REF:0000024, from mouse Q9CWF6)

Key references verified

📄 View Raw YAML