id: Q8IWZ6
gene_symbol: BBS7
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  BBS7 is a core subunit of the BBSome, an octameric coat/adaptor-like protein complex
  (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9, BBIP1) that sorts and traffics specific
  membrane signaling receptors into and out of the primary cilium in coordination with the
  small GTPase ARL6/BBS3 and intraflagellar transport. BBS7 carries a beta-propeller, a
  gamma-adaptin ear (GAE) domain, a platform domain, and a hairpin, structural features it
  shares with BBS2 and BBS9; together BBS2, BBS7 and BBS9 form the beta-propeller/GAE/platform
  scaffold core of the BBSome. Newly synthesized BBS7 is a client of the BBS-chaperonin
  complex (BBS6/BBS10/BBS12 with CCT/TRiC), which stabilizes BBS7 and nucleates assembly of
  the BBS7-BBS2-BBS9 core before the remaining subunits are added. The BBSome localizes to the
  ciliary membrane, basal body, centrosome and centriolar satellites, and is required for
  ciliary membrane biogenesis and for trafficking of cargo such as Smoothened during Hedgehog
  signaling. Loss of BBS7 function causes Bardet-Biedl syndrome, a pleiotropic ciliopathy
  featuring retinal degeneration, obesity, polydactyly, renal malformation, hypogenitalism and
  intellectual disability.
alternative_products:
- name: 1 (Long, lBBS2L1)
  id: Q8IWZ6-1
- name: 2 (Short, sBBS2L1)
  id: Q8IWZ6-2
  sequence_note: VSP_008850
existing_annotations:
- term:
    id: GO:0008104
    label: intracellular protein localization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      BBSome-mediated trafficking of membrane proteins to the cilium. The generic term is
      correct in spirit, but a more specific child term capturing ciliary protein localization
      is preferable.
    action: MODIFY
    reason: >-
      As part of the BBSome, BBS7 specifically mediates protein localization to the cilium
      rather than generic intracellular protein localization. GO:0061512 better captures the
      established BBSome function.
    proposed_replacement_terms:
    - id: GO:0061512
      label: protein localization to cilium
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Very high-level cellular component. BBS7 associates with the ciliary membrane; the
      generic membrane term is uninformative given the more specific ciliary membrane and
      BBSome annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The root-level membrane term is uninformative and is superseded by the specific
      GO:0060170 ciliary membrane and GO:0034464 BBSome annotations on this gene.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      BBS7 is a core structural subunit of the BBSome. Strongly supported by phylogenetic
      inference and by direct experimental evidence in human.
    action: ACCEPT
    reason: >-
      BBSome membership is the defining, best-supported feature of BBS7, also supported by IDA
      annotations from PMID:17574030, PMID:20080638, PMID:24550735 and PMID:19081074.
    supported_by:
    - reference_id: PMID:17574030
      supporting_text: >-
        Here we identify a complex composed of seven highly conserved BBS proteins. This complex,
        the BBSome, localizes to nonmembranous centriolar satellites in the cytoplasm but also to
        the membrane of the cilium.
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      BBSome subunits, including BBS7, localize at and near the basal body, consistent with
      UniProt subcellular location and the ciliary trafficking role.
    action: ACCEPT
    reason: >-
      Basal body localization is well established for BBSome subunits and supported by UniProt
      subcellular location.
- term:
    id: GO:0043005
    label: neuron projection
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic transfer reflecting BBSome roles at neuronal cilia, such as GPCR trafficking
      in neuronal cilia. Largely a restatement of ciliary localization in a neuronal context.
    action: KEEP_AS_NON_CORE
    reason: >-
      Neuron projection localization is a context-specific manifestation of the BBSome ciliary
      function rather than a core annotation; retained as non-core.
- 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 and ciliary membrane biogenesis; BBS7 loss yields
      characteristic BBS ciliary phenotypes. Well supported.
    action: ACCEPT
    reason: >-
      Cilium assembly involvement is established for the BBSome (PMID:17574030) and is a core
      biological process for BBS7.
    supported_by:
    - reference_id: PMID:17574030
      supporting_text: >-
        the BBSome is required for ciliogenesis but is dispensable for centriolar satellite
        function.
- term:
    id: GO:0005930
    label: axoneme
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      The BBSome moves along and within cilia, but BBS7 is not an axonemal structural
      component; localization is principally to the ciliary membrane and base.
    action: KEEP_AS_NON_CORE
    reason: >-
      Axonemal association is a plausible but non-core, low-specificity location relative to the
      ciliary membrane and basal body where BBS7 function is established.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      BBS7 has a cytoplasmic pool involved in BBSome assembly and centriolar satellites. Correct
      but low specificity; the EXP-supported cytoplasm annotation below carries the evidence.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cytoplasm is correct but generic; retained as non-core given more specific locations
      (centriolar satellite, centrosome, ciliary membrane).
- term:
    id: GO:0034451
    label: centriolar satellite
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      The BBSome localizes to nonmembranous centriolar satellites in the cytoplasm
      (PMID:17574030); BBS7 is at centriolar satellites and the centrosome (PMID:22072986).
    action: ACCEPT
    reason: >-
      Centriolar satellite localization is well supported for the BBSome and consistent with
      UniProt subcellular location.
    supported_by:
    - reference_id: PMID:17574030
      supporting_text: >-
        the BBSome, localizes to nonmembranous centriolar satellites in the cytoplasm
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: part_of
  review:
    summary: >-
      Duplicate of the BBSome membership annotation, here by InterPro mapping of the BBS7
      signature. Correct.
    action: ACCEPT
    reason: BBSome membership is correct and corroborated by experimental IDA annotations.
- 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; BBS7 ciliary membrane localization is
      also experimentally annotated (IDA, PMID:19081074).
    action: ACCEPT
    reason: Ciliary membrane localization is a core, experimentally supported location for the BBSome and BBS7.
    supported_by:
    - reference_id: PMID:17574030
      supporting_text: >-
        This complex, the BBSome, localizes to nonmembranous centriolar satellites in the
        cytoplasm but also to the membrane of the cilium.
- term:
    id: GO:1905515
    label: non-motile cilium assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Primary (non-motile) cilia are the principal site of BBSome function; this is a more
      specific child of cilium assembly and is appropriate.
    action: ACCEPT
    reason: >-
      BBS7 and the BBSome act in assembly and function of primary non-motile cilia (sensory
      cilia, retina); the InterPro-based involvement is consistent with established biology.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17574030
  qualifier: enables
  review:
    summary: >-
      Generic protein binding from BBSome subunit interactions (e.g. BBS1, BBS2). Uninformative
      per curation guidelines; the meaningful relationships are captured by BBSome membership.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      protein binding is uninformative; the underlying BBS1 and BBS2 interactions are
      represented by the GO:0034464 BBSome part_of annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18000879
  qualifier: enables
  review:
    summary: Generic protein binding from the BBS7-ALDOB interaction. Uninformative molecular function.
    action: MARK_AS_OVER_ANNOTATED
    reason: protein binding is uninformative; ALDOB is not a core functional partner of the BBSome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20080638
  qualifier: enables
  review:
    summary: >-
      Generic protein binding (BBS7 with CCT2, BBS10, BBS12, BBS2 chaperonin-assembly partners).
      Uninformative MF term, though the underlying chaperonin-client biology is real.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      protein binding is uninformative; the CCT/chaperonin and BBS2 interactions are better
      captured by BBSome membership and assembly process annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20195357
  qualifier: enables
  review:
    summary: Generic protein binding from a high-throughput interaction resource (JUN). Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: protein binding is uninformative and derives from a large-scale interaction screen.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22500027
  qualifier: enables
  review:
    summary: >-
      Generic protein binding (BBS7 with CCT2, BBS12, BBS1, BBS2 during sequential BBSome
      assembly). Uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      protein binding is uninformative; the assembly interactions are captured by BBSome
      membership and the assembly literature.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25552655
  qualifier: enables
  review:
    summary: Generic protein binding (BBS7-IQCB1/NPHP5). Uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      protein binding is uninformative; NPHP5/CEP290 regulation of the BBSome is process
      context, not a core molecular function term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27173435
  qualifier: enables
  review:
    summary: >-
      Generic protein binding from an organelle-specific proteomic interactome (BBS1, BBS2).
      Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: protein binding is uninformative and derives from a large-scale interactome study.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Generic protein binding from a large-scale interactome (BBS2, BBS10, BBS12). Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: protein binding is uninformative and derives from a high-throughput interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic protein binding from a proteome-scale interaction network (BBS subunits). Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: protein binding is uninformative and derives from a high-throughput interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Generic protein binding from a multimodal cell-map interactome (BBS1, BBS2). Uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: protein binding is uninformative and derives from a high-throughput cell-map study.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5617815
  qualifier: located_in
  review:
    summary: >-
      Reactome places the cytosolic BBSome (binding RAB3IP/Rabin8) in the cytosol. Correct but
      generic relative to the centriolar satellite and centrosome locations.
    action: KEEP_AS_NON_CORE
    reason: Cytosol is correct for the assembled cytoplasmic BBSome but low specificity; retained 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 Formation of the BBSome places BBS7 in the cytosol during assembly. Correct but generic.
    action: KEEP_AS_NON_CORE
    reason: Cytosol is correct for BBSome assembly but low specificity; retained 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 (ARL6-GTP and BBSome bind ciliary cargo) places BBS7 in the cytosol. Correct but generic.
    action: KEEP_AS_NON_CORE
    reason: Cytosol is correct but low specificity; retained 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 (ARL6-GTP and BBSome target cargo to cilium) places BBS7 in the cytosol. Correct but generic.
    action: KEEP_AS_NON_CORE
    reason: Cytosol is correct but low specificity; retained 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 (LZTFL1 binds BBSome and prevents ciliary traffic) places BBS7 in the cytosol. Correct but generic.
    action: KEEP_AS_NON_CORE
    reason: Cytosol is correct but low specificity; retained as non-core.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:22072986
  qualifier: located_in
  review:
    summary: >-
      Experimentally supported cytoplasmic localization of BBS7 (BBSome assembly, centriolar
      satellites). Correct, generic but evidence-backed.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cytoplasm is correct and experimentally supported but low specificity relative to
      centriolar satellite, centrosome and ciliary membrane; retained as non-core.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IPI
  original_reference_id: PMID:19081074
  qualifier: part_of
  review:
    summary: ComplexPortal-curated BBSome membership of BBS7. Correct and directly supported.
    action: ACCEPT
    reason: BBSome membership is the defining feature of BBS7, here from ComplexPortal curation.
- term:
    id: GO:0060170
    label: ciliary membrane
  evidence_type: IDA
  original_reference_id: PMID:19081074
  qualifier: located_in
  review:
    summary: Direct experimental ciliary membrane localization of the BBSome, including BBS7.
    action: ACCEPT
    reason: Ciliary membrane is a core, experimentally supported location for BBS7 and the BBSome.
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: NAS
  original_reference_id: PMID:19081074
  qualifier: involved_in
  review:
    summary: >-
      Cilium assembly involvement asserted by author statement. Consistent with the stronger
      experimental and IBA support; redundant but correct.
    action: ACCEPT
    reason: >-
      Cilium assembly is a core BBSome process; the NAS annotation is consistent with
      better-supported annotations of the same term.
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: ISS transfer of cilium assembly involvement from ortholog. Consistent with established BBSome biology.
    action: ACCEPT
    reason: Cilium assembly is a core, well-corroborated process for BBS7.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18762586
  qualifier: enables
  review:
    summary: >-
      Generic protein binding (PCM1, a centriolar satellite protein; via SYSCILIA curation).
      Uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      protein binding is uninformative; the satellite and centrosome context is captured by the
      centriolar satellite and centrosome location annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24550735
  qualifier: enables
  review:
    summary: >-
      Generic protein binding (AZI1/CEP131, a centriolar satellite regulator of BBSome
      trafficking). Uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      protein binding is uninformative; CEP131/AZI1 regulation of BBSome trafficking is process
      context, not a core MF term.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:24550735
  qualifier: part_of
  review:
    summary: BBSome membership of BBS7 directly demonstrated. Correct.
    action: ACCEPT
    reason: BBSome membership is the defining, experimentally supported feature of BBS7.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IPI
  original_reference_id: PMID:22302990
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Gascue et al. report a nuclear role for BBS7 via interaction with the PcG protein
      RNF2/RING1B, whose targets are dysregulated upon BBS protein loss. A real but
      non-canonical secondary activity for a structural ciliary trafficking subunit.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally supported (do not remove) but a non-core, indirect role relative to the
      defining ciliary trafficking function of the BBSome; retained as non-core.
    supported_by:
    - reference_id: PMID:22302990
      supporting_text: >-
        loss of BBS proteins leads to the aberrant expression of endogenous RNF2 targets in
        vivo, including several genes that are crucial for development
- term:
    id: GO:0032436
    label: positive regulation of proteasomal ubiquitin-dependent protein catabolic process
  evidence_type: IPI
  original_reference_id: PMID:22302990
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      BBS7 regulates RNF2 protein levels, probably through a proteasome-mediated mechanism
      (PMID:22302990). A specific but non-core, indirect downstream effect.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally supported (do not remove) but a non-core, secondary activity relative to
      the core ciliary trafficking role of BBS7; retained as non-core.
    supported_by:
    - reference_id: PMID:22302990
      supporting_text: >-
        BBS7 interacts physically with the polycomb group (PcG) member RNF2 and regulate its
        protein levels, probably through a proteasome-mediated mechanism
- 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: >-
      Specific physical interaction of BBS7 with the PcG/transcription factor RNF2
      (UniProtKB:Q99496). An informative, defined molecular-function partner (unlike generic
      protein binding) reflecting a non-core nuclear role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Informative and experimentally supported MF interaction with RNF2, but reflecting a
      secondary nuclear role rather than the core BBSome function; retained as non-core.
    supported_by:
    - reference_id: PMID:22302990
      supporting_text: >-
        BBS7 interacts physically with the polycomb group (PcG) member RNF2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16327777
  qualifier: enables
  review:
    summary: Generic protein binding (CCDC28B, a BBS modifier). Uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: protein binding is uninformative; CCDC28B is a modifier interaction not representing a core function.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:20080638
  qualifier: part_of
  review:
    summary: Direct demonstration of BBS7 as a BBSome component. Correct.
    action: ACCEPT
    reason: BBSome membership is the defining, experimentally supported feature of BBS7.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:21399614
  qualifier: located_in
  review:
    summary: >-
      BBS7 identified as an asymmetrically localizing centrosomal component by proteomics.
      Consistent with the centriolar satellite and basal body localization.
    action: ACCEPT
    reason: >-
      Centrosome localization is experimentally supported and consistent with the basal body
      and satellite biology of BBS7.
    supported_by:
    - reference_id: PMID:21399614
      supporting_text: >-
        Novel asymmetrically localizing components of human centrosomes identified by
        complementary proteomics methods.
- term:
    id: GO:0001947
    label: heart looping
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Pleiotropic developmental process transferred by similarity from a vertebrate ortholog;
      a downstream consequence of ciliary and left-right signaling defects.
    action: KEEP_AS_NON_CORE
    reason: Developmental phenotype secondary to the core ciliary function; retained as non-core.
- term:
    id: GO:0007368
    label: determination of left/right symmetry
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Left-right patterning depends on node cilia; BBSome dysfunction can perturb this. A
      pleiotropic, organism-level process transferred by similarity.
    action: KEEP_AS_NON_CORE
    reason: Downstream developmental consequence of ciliary dysfunction; retained as non-core.
- term:
    id: GO:0032402
    label: melanosome transport
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Reflects zebrafish bbs melanosome transport assays (an intracellular transport role of the
      BBSome). Transferred by similarity; non-core for human BBS7.
    action: KEEP_AS_NON_CORE
    reason: >-
      Organism-specific intracellular transport phenotype transferred by similarity; plausibly
      retained as non-core.
- term:
    id: GO:0045444
    label: fat cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Reflects the obesity/adipogenesis phenotype of BBS, transferred by similarity from the
      mouse ortholog. A downstream physiological consequence, not a molecular activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Pleiotropic metabolic phenotype secondary to ciliary signaling dysfunction; retained as
      non-core.
- term:
    id: GO:0048546
    label: digestive tract morphogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Pleiotropic developmental process transferred by similarity from a vertebrate ortholog; a
      downstream consequence of ciliary dysfunction.
    action: KEEP_AS_NON_CORE
    reason: Developmental phenotype secondary to the core ciliary function; retained as non-core.
- term:
    id: GO:0051877
    label: pigment granule aggregation in cell center
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Reflects zebrafish melanosome/pigment granule transport assays of BBS proteins (an
      intracellular transport role). Transferred by similarity; non-core for human BBS7.
    action: KEEP_AS_NON_CORE
    reason: Organism-specific intracellular transport phenotype transferred by similarity; retained as non-core.
- term:
    id: GO:0034464
    label: BBSome
  evidence_type: IDA
  original_reference_id: PMID:17574030
  qualifier: part_of
  review:
    summary: Foundational direct identification of BBS7 as a BBSome subunit (Nachury 2007).
    action: ACCEPT
    reason: BBSome membership is the defining, experimentally supported feature of BBS7.
    supported_by:
    - reference_id: PMID:17574030
      supporting_text: >-
        Here we identify a complex composed of seven highly conserved BBS proteins. This complex,
        the BBSome
- term:
    id: GO:0005198
    label: structural molecule activity
  evidence_type: IDA
  original_reference_id: PMID:22500027
  qualifier: enables
  review:
    summary: >-
      BBS7 is a structural constituent of the BBSome, contributing the beta-propeller/GAE/platform
      scaffold (with BBS2 and BBS9) that nucleates and organizes the complex. Not currently present
      in GOA (GOA records only uninformative protein binding for the MF aspect); proposed as a NEW
      molecular function annotation better reflecting BBS7's role than protein binding.
    action: NEW
    reason: >-
      BBS7 forms the BBSome core scaffold; structural molecule activity is the appropriate
      informative MF, replacing uninformative protein binding annotations.
    supported_by:
    - reference_id: PMID:22500027
      supporting_text: >-
        BBS7 interacts with BBS2 and becomes part of a BBS7-BBS2-BBS9 assembly intermediate
        referred to as the BBSome core complex because it forms the core of the BBSome.
core_functions:
- description: >-
    Structural core subunit of the BBSome, contributing the beta-propeller/GAE/platform scaffold
    (with BBS2 and BBS9) that nucleates and organizes the octameric coat complex.
  supported_by:
  - reference_id: PMID:22500027
    supporting_text: >-
      BBS7 interacts with BBS2 and becomes part of a BBS7-BBS2-BBS9 assembly intermediate
      referred to as the BBSome core complex because it forms the core of the BBSome.
  molecular_function:
    id: GO:0005198
    label: structural molecule activity
- description: >-
    Acts within the BBSome as a coat/adaptor that sorts and traffics specific membrane signaling
    receptors (e.g. Smoothened) to and from the ciliary membrane, mediating protein localization
    to the cilium and ciliary membrane biogenesis.
  supported_by:
  - reference_id: PMID:17574030
    supporting_text: >-
      This complex, the BBSome, localizes to nonmembranous centriolar satellites in the cytoplasm
      but also to the membrane of the cilium.
  - reference_id: PMID:22072986
    supporting_text: >-
      BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer,
      Smoothened.
  molecular_function:
    id: GO:0005198
    label: structural molecule activity
  directly_involved_in:
  - id: GO:0061512
    label: protein localization to cilium
  - id: GO:0060271
    label: cilium assembly
  locations:
  - id: GO:0060170
    label: ciliary membrane
  - id: GO:0036064
    label: ciliary basal body
- description: >-
    Client of the BBS-chaperonin complex (BBS6/BBS10/BBS12 with CCT/TRiC); chaperonin assistance
    stabilizes BBS7 and promotes formation of the BBS7-BBS2-BBS9 BBSome core required for assembly
    of the complete BBSome.
  supported_by:
  - reference_id: PMID:22500027
    supporting_text: >-
      the BBS-chaperonin complex plays a role in BBS7 stability.
  - reference_id: PMID:20080638
    supporting_text: >-
      BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome
      assembly.
  molecular_function:
    id: GO:0005198
    label: structural molecule activity
proposed_new_terms: []
suggested_questions:
- question: >-
    Is the nuclear/transcriptional role of BBS7 (RNF2/PcG interaction; PMID:22302990) a direct,
    conserved function or an indirect consequence of disturbed ciliary signaling?
- question: >-
    What is the precise contribution of the BBS7 GAE and platform domains to cargo selection
    versus scaffold assembly within the BBSome?
suggested_experiments:
- description: >-
    Cryo-EM of the human BBSome with bound cargo to map BBS7 domain contributions to cargo
    recognition and the assembly interface with BBS2 and BBS9.
- description: >-
    Structure-function analysis of patient BBS7 variants (e.g. T211I, H323R, Y671C) in a BBS7-null
    cell line to dissect effects on chaperonin-assisted folding, BBSome assembly, and ciliary cargo
    trafficking.
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: PMID:16327777
  title: Dissection of epistasis in oligogenic Bardet-Biedl syndrome.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Identifies the BBS7-CCDC28B interaction; supports a modifier interaction, not a core
      molecular function. PubMed-verified.
- 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 paper defining the BBSome and its ciliary membrane biogenesis role; directly
      establishes BBS7 BBSome membership and ciliary/satellite localization.
- id: PMID:18000879
  title: Novel interaction partners of Bardet-Biedl syndrome proteins.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Reports the BBS7-ALDOB interaction; peripheral to core BBS7 function.
- 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: Centrosomal/satellite context (PCM1); supports a protein interaction only.
- id: PMID:19081074
  title: A BBSome subunit links ciliogenesis, microtubule stability, and acetylation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Discovery of BBIP10/BBIP1 as a BBSome subunit; source of ComplexPortal BBSome membership
      and ciliary membrane localization annotations for BBS7.
- id: PMID:20080638
  title: BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and
    mediate BBSome assembly.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Establishes the BBS-chaperonin complex and its role in BBSome assembly; BBS7 is a
      chaperonin client. Supports BBSome membership (IDA).
- id: PMID:20195357
  title: A comprehensive resource of interacting protein regions for refining human
    transcription factor networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interaction resource (JUN); supports generic protein binding only.
- id: PMID:21399614
  title: Novel asymmetrically localizing components of human centrosomes identified
    by complementary proteomics methods.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Proteomic identification of BBS7 as an asymmetric centrosomal component; supports
      centrosome localization (IDA).
- 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: >-
      Full text available; establishes BBSome (and BBS7-SMO) ciliary trafficking and Hedgehog
      signaling role, and experimental cytoplasmic localization of BBS7.
- id: PMID:22302990
  title: Direct role of Bardet-Biedl syndrome proteins in transcriptional regulation.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reports a non-canonical nuclear role for BBS7 via RNF2/PcG interaction and regulation of
      RNF2 levels; supports the transcription/proteasome/TF-binding annotations as non-core.
      Abstract-only in cache.
- 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: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full text available; defines the BBS7-BBS2-BBS9 BBSome core and the ordered,
      chaperonin-assisted assembly pathway in which BBS7 stability is chaperonin-dependent.
- 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: >-
      AZI1/CEP131 regulates BBSome ciliary trafficking; supports BBSome membership (IDA) and a
      regulatory interaction.
- 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 and CEP290 regulate BBSome integrity and cargo delivery; supports a regulatory
      interaction (BBS7-IQCB1).
- 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-specific interactome; supports generic protein binding to BBS subunits.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Large-scale interactome (BioPlex); supports generic protein binding 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: Proteome-scale interactome; supports 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: Multimodal cell-map interactome; supports 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: []