id: Q8N3I7
gene_symbol: BBS5
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: BBS5 is a core subunit of the BBSome, an eight-protein complex (BBS1, BBS2, BBS4, BBS5, BBS7,
  BBS8/TTC8, BBS9 and BBIP1/BBIP10) that functions as a membrane coat-like adaptor in selective protein
  trafficking to and from the primary cilium. The 341-residue protein contains two pleckstrin-homology
  (PH)-like domains and binds phosphoinositides (including phosphatidylinositol-3-phosphate), a property
  that contributes to the membrane association of the BBSome at the ciliary membrane and basal body. Within
  the cilium the BBSome works with the intraflagellar transport (IFT) machinery and the small GTPase ARL6/BBS3
  to recognize ciliary membrane cargo (such as GPCRs including Smoothened) and mediate their import and
  export. The complex assembles in the cytoplasm (assisted by the BBS6/BBS10/BBS12-CCT chaperonin module)
  and is recruited to the basal body and ciliary membrane; it is required for ciliogenesis but dispensable
  for centriolar satellite function. Loss-of-function variants in BBS5 cause Bardet-Biedl syndrome, an
  autosomal-recessive ciliopathy characterized by retinal degeneration, obesity, polydactyly, hypogenitalism,
  renal anomalies and cognitive impairment.
alternative_products:
- name: '1'
  id: Q8N3I7-1
- name: '2'
  id: Q8N3I7-2
  sequence_note: VSP_017240
existing_annotations:
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: BBS5 is a well-established core subunit of the BBSome. The phylogenetic (IBA) assignment
      of the BBSome cellular component is correct and is the central, defining localization for this protein.
    action: ACCEPT
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: The BBSome is required for ciliogenesis; involvement of BBS5 in cilium assembly is supported
      both phylogenetically and by experimental perturbation. Accept as a core biological process.
    action: ACCEPT
- term:
    id: GO:0032266
    label: phosphatidylinositol-3-phosphate binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: BBS5 binds phosphoinositides via its PH-like domains, contributing to BBSome membrane association.
      This IBA assignment mirrors the experimental IDA from PMID:17574030 and is the most informative
      molecular function for BBS5. Accept as a core molecular function.
    action: ACCEPT
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: BBS5/BBSome localizes to the basal body, where it assembles cargo for ciliary import. Consistent
      with UniProt subcellular location and the experimental localization of the BBSome. Accept.
    action: ACCEPT
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Generic cytoplasmic localization derived from UniProt subcellular-location mapping. The BBSome
      assembles in the cytoplasm prior to ciliary entry, so this is correct but non-core relative to the
      cilium-associated terms.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0034451
    label: centriolar satellite
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: The BBSome localizes to nonmembranous centriolar satellites (PMID:17574030); UniProt also
      lists centriolar satellite. Correct localization, though it is a satellite/peripheral site rather
      than the core ciliary trafficking compartment.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: Electronic (IEA) duplicate of the BBSome membership that is also supported experimentally
      (IDA/IPI) and phylogenetically (IBA). Correct; redundant with the higher-evidence annotations.
    action: ACCEPT
- term:
    id: GO:0060170
    label: ciliary membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: The BBSome associates with the ciliary membrane (PMID:17574030, PMID:19081074). This IEA
      mapping agrees with the experimental IDA and is a core localization.
    action: ACCEPT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17574030
  qualifier: enables
  review:
    summary: IntAct IPI capturing the BBS5-BBS9 intra-BBSome interaction. The interaction is real and
      experimentally supported, but the generic 'protein binding' term conveys no specific molecular function
      and per curation guidelines should be avoided in favor of more informative terms; the relationship
      is already captured by BBSome membership.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF; the underlying interaction (with BBS9) is already represented by the BBSome
      part_of annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20080638
  qualifier: enables
  review:
    summary: IPI capturing a BBS5 interaction with another BBSome/assembly-pathway subunit (BBS9). Valid
      interaction evidence but uninformative as a molecular function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding'; relationship captured by BBSome membership.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22500027
  qualifier: enables
  review:
    summary: IPI from a BBSome assembly study (BBS5-BBS9). Real interaction, but the generic 'protein
      binding' term should be avoided as a molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding'; relationship captured by BBSome membership.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: High-throughput interactome IPI (interactions with CRADD and KLC3). These are screen-derived
      binary interactions of uncertain biological relevance, annotated only to the uninformative 'protein
      binding' term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding' from a high-throughput interactome screen.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25552655
  qualifier: enables
  review:
    summary: IPI capturing the interaction with NPHP5/IQCB1, a transition-zone protein that regulates
      BBSome integrity and ciliary trafficking; depletion of NPHP5 selectively dissociates BBS2 and BBS5
      from the BBSome. The interaction is biologically meaningful but the GO term itself ('protein binding')
      is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative MF term; the NPHP5 interaction informs ciliary trafficking regulation but 'protein
      binding' does not capture a specific function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27173435
  qualifier: enables
  review:
    summary: Organelle-proteomics IPI (BBS5-BBS9). Real interaction but annotated to the uninformative
      'protein binding' term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding'; relationship captured by BBSome membership.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29039417
  qualifier: enables
  review:
    summary: Interaction-perturbation profiling IPI (BBS5-BBS9). Valid interaction evidence, uninformative
      MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding'; relationship captured by BBSome membership.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Proteome-scale interaction network IPI (BBS5-BBS9). Valid interaction evidence, uninformative
      MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding'; relationship captured by BBSome membership.
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Cilium localization projected from mouse ortholog by Ensembl Compara, also supported by HPA
      IDA. Correct but a general parent of the more specific ciliary membrane localization.
    action: ACCEPT
- term:
    id: GO:0005930
    label: axoneme
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Axoneme localization projected electronically from the mouse ortholog. The BBSome traffics
      within the ciliary compartment along the axoneme via IFT, so the term is plausible, but it is a
      weaker, ortholog-projected localization not directly demonstrated for human BBS5.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Electronic (Ensembl) duplicate of the basal body localization that is also supported by the
      IBA and UniProt curation. Accept.
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5617815
  qualifier: located_in
  review:
    summary: Reactome-asserted cytosolic localization within the BBSome cargo-targeting pathway. The BBSome
      cycles through the cytosol; correct but non-core relative to the ciliary localizations.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624125
  qualifier: located_in
  review:
    summary: Reactome cytosol localization (BBSome formation). Redundant with the other cytosol annotations;
      correct but non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624126
  qualifier: located_in
  review:
    summary: Reactome cytosol localization (ARL6:GTP/BBSome cargo binding). Redundant; correct but non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624127
  qualifier: located_in
  review:
    summary: Reactome cytosol localization (cargo targeting to cilium). Redundant; correct but non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5624129
  qualifier: located_in
  review:
    summary: Reactome cytosol localization (LZTFL1/BBSome). Redundant; correct but non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Human Protein Atlas immunofluorescence (IDA) cytosolic localization. The BBSome assembles
      and cycles through the cytosol; accept but non-core relative to the ciliary/basal body terms.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Human Protein Atlas immunofluorescence (IDA) cilium localization, consistent with the established
      ciliary role of the BBSome. Accept.
    action: ACCEPT
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IPI
  original_reference_id: PMID:19081074
  qualifier: part_of
  review:
    summary: ComplexPortal IPI documenting BBS5 as a constituent of the BBSome (CPX-1908). Strong evidence
      for the defining localization. Accept.
    action: ACCEPT
- term:
    id: GO:0060170
    label: ciliary membrane
  evidence_type: IDA
  original_reference_id: PMID:19081074
  qualifier: located_in
  review:
    summary: Experimental (IDA) ciliary membrane localization of the BBSome. Core localization. Accept.
    action: ACCEPT
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: NAS
  original_reference_id: PMID:19081074
  qualifier: involved_in
  review:
    summary: Non-traceable author statement that the BBSome functions in ciliogenesis. The underlying
      claim is well supported by stronger evidence (IMP from PMID:17574030 and IBA). Accept as a core
      process.
    action: ACCEPT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33144677
  qualifier: enables
  review:
    summary: IPI capturing an interaction with DLEC1 (Q9Y238), shown in mouse to interact with BBS complex
      subunits and TRiC during spermatogenesis. Valid interaction record but annotated to the uninformative
      'protein binding' term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding' MF term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18762586
  qualifier: enables
  review:
    summary: IPI to PCM1 (Q9NRI5) from a centriolar-satellite interactome (SYSCILIA). Consistent with
      BBSome centriolar-satellite localization, but annotated only to the uninformative 'protein binding'
      term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding' MF term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24939912
  qualifier: enables
  review:
    summary: IPI capturing the interaction with PKD1 (Q8TAM2), a BBSome cargo whose ciliary trafficking
      is regulated by BBS proteins. Biologically meaningful but the GO term ('protein binding') is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding' MF term; PKD1 is a trafficking cargo.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24550735
  qualifier: enables
  review:
    summary: IPI capturing the interaction with AZI1/CEP131 (Q9UPN4), a centriolar satellite protein that
      regulates BBSome ciliary trafficking. Real interaction but uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding' MF term.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:24550735
  qualifier: part_of
  review:
    summary: Experimental (IDA) evidence that BBS5 is part of the BBSome. Strong support for the defining
      localization. Accept.
    action: ACCEPT
- 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 derived from a study whose primary finding is a nuclear role for BBS7 interacting
      with the polycomb protein RNF2/RING2 (Q99496); the paper only states that 'a similar role' may apply
      to other BBS proteins. Evidence specific to BBS5 is indirect, and a nuclear transcription-factor
      binding function is inconsistent with the well-established cytoplasmic and ciliary biology of BBS5.
      Not removing outright because the full text was not read, but it should be flagged as an over-annotation
      rather than treated as a core function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Weakly supported, isolated nuclear MF that conflicts with the consensus cytoplasmic/ciliary
      role; primary evidence concerns BBS7, with BBS5 only inferred ('a similar role for other BBS proteins').
- term:
    id: GO:0044458
    label: motile cilium assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity (ISS) projection of a motile cilium assembly role. BBS5/the BBSome acts
      predominantly in primary (sensory, non-motile) cilia; the more general and better-supported cilium
      assembly term (GO:0060271) already captures the core function. Keep as a non-core, lineage-specific
      possibility.
    action: KEEP_AS_NON_CORE
    reason: Motile-cilium specificity is ISS-projected and not the core BBS5 role; GO:0060271 cilium assembly
      is the better-supported term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16327777
  qualifier: enables
  review:
    summary: IPI capturing the interaction with CCDC28B (Q9BUN5), an epistatic BBS modifier that colocalizes
      with BBS proteins, documented in UniProt. Real interaction but uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative 'protein binding' MF term.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:20080638
  qualifier: part_of
  review:
    summary: Experimental (IDA) evidence that BBS5 is part of the BBSome, from the BBSome-assembly study.
      Strong support for the defining localization. Accept.
    action: ACCEPT
- term:
    id: GO:0001947
    label: heart looping
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity projection from a lower-vertebrate ortholog. Laterality defects are a
      recognized ciliopathy phenotype reflecting nodal/Kupffer's vesicle cilium dysfunction, but heart
      looping is a downstream developmental consequence of impaired ciliary function rather than a core
      molecular role of BBS5. Keep as non-core.
    action: KEEP_AS_NON_CORE
    reason: Downstream developmental phenotype, ISS-projected; not a core BBS5 function.
- term:
    id: GO:0032402
    label: melanosome transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Sequence-similarity projection. BBS knockdown causes melanosome transport delay in zebrafish
      (a classic BBS assay; PMID:24550735), reflecting disrupted intracellular/retrograde transport, but
      in human cells this is a phenotypic readout rather than a direct core molecular function of BBS5.
      Keep as non-core.
    action: KEEP_AS_NON_CORE
    reason: Ortholog-based phenotypic readout; not a core human BBS5 function.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:17574030
  qualifier: part_of
  review:
    summary: Foundational experimental (IDA) identification of BBS5 within the BBSome by tandem affinity
      purification and mass spectrometry. This is the central, defining annotation for BBS5. Accept as
      a core component annotation.
    action: ACCEPT
- term:
    id: GO:0032266
    label: phosphatidylinositol-3-phosphate binding
  evidence_type: IDA
  original_reference_id: PMID:17574030
  qualifier: enables
  review:
    summary: Experimental (IDA) demonstration that BBS5 binds phosphoinositides, consistent with its two
      PH-like domains. This is the most informative molecular function for BBS5 and underlies BBSome membrane
      association. Accept as a core molecular function.
    action: ACCEPT
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Sequence-similarity projection of basal body localization, consistent with experimental and
      IBA evidence and with UniProt subcellular location. Accept.
    action: ACCEPT
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: IMP
  original_reference_id: PMID:17574030
  qualifier: involved_in
  review:
    summary: Experimental (IMP) evidence that BBSome/BBS5 function is required for ciliogenesis (the BBSome
      is required for ciliogenesis but dispensable for centriolar satellite function). This is the best-supported
      biological process annotation for BBS5. Accept as core.
    action: ACCEPT
references:
- 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:16327777
  title: Dissection of epistasis in oligogenic Bardet-Biedl syndrome.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified. Establishes CCDC28B (MGC1203) as an epistatic BBS modifier that interacts
      and colocalizes with BBS proteins; supports the BBS5-CCDC28B interaction recorded in UniProt.
- 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: Foundational BBSome paper. Identifies BBS5 in the BBSome, demonstrates phosphoinositide
      binding, ciliary membrane and centriolar satellite localization, and the requirement of the BBSome
      for ciliogenesis.
- 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: Centriolar-satellite/PCM1 interactome context; the BBS5-PCM1 interaction is annotated
      only to the uninformative protein binding term.
- id: PMID:19081074
  title: A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Identifies BBIP10/BBIP1 as a BBSome subunit; supports BBSome membership and ciliary
      membrane localization annotations (ComplexPortal CPX-1908).
- 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: Describes chaperonin-assisted BBSome assembly; supports BBS5 as a BBSome subunit. The
      associated GO:0005515 IPI is uninformative.
- id: PMID:22302990
  title: Direct role of Bardet-Biedl syndrome proteins in transcriptional regulation.
  findings: []
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: Primary evidence concerns BBS7 interacting with the polycomb protein RNF2/RING2; a transcription-factor
      binding role for BBS5 is only inferred ("a similar role for other BBS proteins"). The GO:0061629
      annotation to BBS5 is weakly supported and conflicts with the consensus cytoplasmic/ciliary localization.
- 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: BBSome sequential assembly study supporting BBS5 membership; the GO:0005515 IPI (BBS5-BBS9)
      is uninformative.
- 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: Shows AZI1/CEP131 regulates BBSome ciliary trafficking; in BBS5-depleted cells the BBSome
      fails to enter cilia. Supports BBSome membership and ciliary-trafficking role; also documents the
      zebrafish melanosome-transport assay relevant to GO:0032402.
- id: PMID:24939912
  title: Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of polycystic kidney
    disease 1 protein.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Documents the BBS5-PKD1 interaction (UniProt) and BBSome-mediated ciliary trafficking
      of PKD1 cargo; the GO:0005515 term is uninformative.
- 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 screen (interactions with CRADD, KLC3) annotated only to
      protein binding; biological relevance uncertain.
- 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: Shows NPHP5/IQCB1 interacts with the BBSome and that its depletion dissociates BBS2
      and BBS5 from the complex; biologically meaningful, but the GO:0005515 term is uninformative.
- id: PMID:27173435
  title: An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Organelle-proteomics interactome (BBS5-BBS9) annotated to uninformative protein binding.
- id: PMID:29039417
  title: Protein interaction perturbation profiling at amino-acid resolution.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Interaction-perturbation profiling (BBS5-BBS9) annotated to uninformative protein binding.
- id: PMID:33144677
  title: Dlec1 is required for spermatogenesis and male fertility in mice.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Mouse study; DLEC1 interacts with TRiC and BBS complex subunits during spermatogenesis.
      Supports an interaction record but the GO:0005515 term is uninformative and the context is IFT/manchette
      in sperm.
- 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: Proteome-scale interactome (BBS5-BBS9) annotated to uninformative protein binding.
- 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: []
core_functions:
- description: Phosphoinositide binding (including phosphatidylinositol-3-phosphate) via the two PH-like
    domains, mediating membrane association of the BBSome.
  supported_by:
  - reference_id: PMID:17574030
    supporting_text_fulltext: BBS5 binds to phosphoinositides via its two PH-like domains
    full_text_unavailable: true
  molecular_function:
    id: GO:0032266
    label: phosphatidylinositol-3-phosphate binding
- description: Structural subunit of the BBSome, the coat-like adaptor complex that acts at the ciliary
    membrane and basal body.
  supported_by:
  - reference_id: PMID:17574030
    supporting_text: we identify a complex composed of seven highly conserved BBS proteins. This complex,
      the BBSome
  in_complex:
    id: GO:0034464
    label: BBSome
  locations:
  - id: GO:0060170
    label: ciliary membrane
- description: As part of the BBSome, required for cilium assembly and for BBSome-mediated trafficking
    of membrane proteins into and out of the primary cilium.
  supported_by:
  - reference_id: PMID:17574030
    supporting_text: the BBSome is required for ciliogenesis but is dispensable for centriolar satellite
      function
  directly_involved_in:
  - id: GO:0060271
    label: cilium assembly
suggested_questions:
- question: Which specific phosphoinositide species does BBS5 bind with highest affinity, and how does
    lipid binding by the PH-like domains contribute quantitatively to BBSome recruitment to the ciliary
    membrane relative to other membrane-anchoring subunits?
- question: Does BBS5 have any direct cargo-recognition role within the BBSome, or is its contribution
    primarily structural and membrane-associative?
- question: Is the reported nuclear/transcriptional association (via the BBS7-RNF2 study) a genuine BBS5
    function or a complex-level or indirect effect?
suggested_experiments:
- description: Structure-guided mutagenesis of the BBS5 PH-like lipid-binding pockets followed by liposome
    flotation and quantitative measurement of BBSome recruitment to ciliary membranes, to test the contribution
    of BBS5 phosphoinositide binding to BBSome membrane association.
- description: BBS5 knockout and rescue (with wild-type versus lipid-binding-deficient BBS5) in ciliated
    cells, measuring ciliary trafficking of defined BBSome cargos (e.g. Smoothened, GPCRs, PKD1) by quantitative
    ciliary immunofluorescence.
- description: Cryo-EM of the human BBSome focused on BBS5 to define its interaction surfaces with membrane
    lipids and neighboring subunits (BBS9, BBS8) and how disease-associated variants perturb these interfaces.