BBSome ciliary trafficking complex module

The BBSome is a conserved octameric protein complex that acts as a coat-like adaptor for ciliary membrane-protein trafficking. It is built from eight core subunits (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9, and BBIP1/BBS18), assembled with the help of a dedicated chaperonin-like module (BBS6/MKKS, BBS10, BBS12 acting with the CCT/TRiC chaperonin). Once assembled, the BBSome is recruited to the ciliary membrane by the GTP-bound Arf-like GTPase ARL6/BBS3, where it polymerizes into a coat that recognizes signaling-receptor cargo (ciliary GPCRs and Hedgehog-pathway components) and couples them to the intraflagellar transport (IFT) machinery, mediating ciliary import and export of receptors out of the cilium. LZTFL1/BBS17 regulates BBSome ciliary trafficking, and CCDC28B is a BBSome-associated accessory factor. Loss of BBSome function causes Bardet-Biedl syndrome. This module models the BBSome as a cellular component / protein complex grounded in GO:0034464, capturing its composition, assembly, membrane recruitment, cargo trafficking, and regulation.

MODULE:bbsomeCOMPLETEProtein Complexmodules/bbsome.yaml

BBSomeGO:0034464 intraciliary transportGO:0042073

PMID:17574030

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

Identifies the BBSome as a stable complex of seven BBS proteins plus BBIP10 that associates with the ciliary membrane and promotes ciliary membrane trafficking.

PMID:19081074

A BBSome subunit links ciliogenesis, microtubule stability, and acetylation

Establishes BBIP10 (BBIP1) as an integral eighth BBSome subunit required for complex integrity and links the BBSome to microtubule stability and acetylation.

PMID:20603001

The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia

Shows the BBSome forms a planar coat on membranes whose assembly is nucleated by ARL6/BBS3-GTP, supporting the coat-adaptor model for ciliary cargo trafficking.

PMID:25402481

Structural basis for membrane targeting of the BBSome by ARL6

Provides the structural basis for GTP-dependent recruitment of the BBSome to membranes by ARL6/BBS3 via the BBS1 beta-propeller.

PMID:20080638

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

Demonstrates that the chaperonin-like BBS proteins (MKKS/BBS6, BBS10, BBS12) act with the CCT/TRiC chaperonin to assemble the BBSome core, supporting a dedicated assembly module distinct from the mature complex.

PMID:22072986

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

Shows LZTFL1/BBS17 regulates ciliary entry and retrieval of the BBSome and of Smoothened, supporting a trafficking-regulation interface to the complex.

PMID:25443296

The intraflagellar transport protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3.

Shows that IFT27 acts through nucleotide-free ARL6 to drive ciliary exit of the BBSome; loss of IFT27 slows BBSome exit and causes ciliary accumulation of ARL6, the BBSome, and the Hedgehog-pathway GPCR GPR161.

PMID:22922713

The BBSome controls IFT assembly and turnaround in cilia.

Shows in C. elegans that the BBSome is required for IFT assembly and turnaround at the ciliary tip, coupling it to retrograde IFT.

PMID:22139371

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

Loss of ARL6/BBS3 leaves BBSome formation intact but disrupts localization of MCHR1 to ciliary membranes and retrograde transport of Smoothened inside cilia.

PMID:31939736

Structure and activation mechanism of the BBSome membrane protein trafficking complex.

Cryo-EM structures of the mammalian BBSome alone and bound to ARL6-GTP, defining subunit architecture and the ARL6-induced conformational change.

PMID:31951201

Structure of the human BBSome core complex.

Cryo-EM structure of the human BBSome core, placing the beta-propeller, GAE, platform, and TPR-superhelix domains and the BBS5 PH domains.

PMID:16327777

Dissection of epistasis in oligogenic Bardet-Biedl syndrome.

Identifies CCDC28B (MGC1203) as a pericentriolar protein that interacts and colocalizes with BBS proteins and acts as a BBS modifier.

This module is intentionally BBSome-centric: it represents the eight-subunit core complex, its dedicated chaperonin-like assembly module, its ARL6/BBS3 membrane recruiter, and its LZTFL1/CCDC28B trafficking regulators. Broader ciliary machinery that the BBSome cooperates with (the IFT-A/IFT-B trains, the transition-zone MKS/NPHP modules, and Rab8/Rab23 membrane-trafficking regulators) is treated as an interface rather than part of the complex. Several proteins carry "BBS" disease-locus numbers but belong primarily to other ciliary modules (e.g. IFT27/BBS19, IFT172/BBS20, MKS1/BBS13, CEP290/BBS14, SDCCAG8/BBS16, WDPCP/BBS15) and are out of scope here. Subunit architecture follows the cryo-EM structures of the mammalian BBSome (PMID:31939736, PMID:31951201) and the biochemical definition of the complex (PMID:17574030, PMID:19081074); where a precise GO molecular function is uncertain, only a preferred_term and description are given.

7Nodes

6Parts

0Variant Sets

0Variants

6Annotons

4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:bbsome deep-research report alongside the module YAML.

Leaf nodes lacking representative members

1 leaf node(s) with no concrete protein grounding:

BBSome cargo recognition and ciliary import/retrieval PROTEIN_COMPLEX

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

bbsome_assembly → bbsome_core_octamer [NOT_CHECKED]

Gene-review completeness (14/14 grounded genes reviewed)

14 complete review(s) · 8 with deep research · 0 missing review · 6 reviewed but lacking deep research

Gene	Review	Complete	Deep research
ARL6 Q9H0F7	✓	✓	✓
BBIP1 A8MTZ0	✓	✓	✓
BBS1 Q8NFJ9	✓	✓	✗
BBS10 Q8TAM1	✓	✓	✓
BBS12 Q6ZW61	✓	✓	✓
BBS2 Q9BXC9	✓	✓	✗
BBS4 Q96RK4	✓	✓	✗
BBS5 Q8N3I7	✓	✓	✗
BBS7 Q8IWZ6	✓	✓	✗
BBS9 Q3SYG4	✓	✓	✗
CCDC28B Q9BUN5	✓	✓	✓
LZTFL1 Q9NQ48	✓	✓	✓
MKKS Q9NPJ1	✓	✓	✓
TTC8 Q8TAM2	✓	✓	✓

Tree

BBSome ciliary trafficking complexProtein Complexbbsome

Parts
1. 1. assembly of the BBSome core by chaperonin-like factors
2. Chaperonin-mediated BBSome assemblyProtein Complexbbsome_assembly
  
  Annotons
  - BBS chaperonin-like assembly module (BBS6/BBS10/BBS12 + CCT) Protein Complex: BBS chaperonin-like assembly complex with CCT/TRiC
3. 2. mature BBSome core complex
4. BBSome core octamerProtein Complexbbsome_core_octamer
  
  Annotons
  - BBSome octamer subunits Protein Complex: BBSome octamer
5. 3. GTP-dependent membrane recruitment
6. ARL6/BBS3 membrane recruitment of the BBSomeRegulatory Steparl6_membrane_recruitment
  
  Annotons
  - ARL6/BBS3 GTP-dependent BBSome recruitment Gene Product: ARL6 (BBS3)
7. 4. cargo recognition and ciliary trafficking
8. BBSome cargo recognition and ciliary import/retrievalTransport Stepbbsome_cargo_trafficking
  
  Annotons
  - BBSome ciliary cargo adaptor activity Protein Complex: membrane-bound BBSome coat
9. 5. regulation of BBSome ciliary trafficking optional
10. Regulation of BBSome ciliary traffickingRegulatory Stepbbsome_trafficking_regulation
  
  Annotons
  - LZTFL1/BBS17 regulation of BBSome ciliary trafficking Gene Product: LZTFL1 (BBS17)
11. 6. BBSome-associated accessory factor optional
12. CCDC28B BBSome-associated accessory factorBiological Processccdc28b_accessory
  
  Annotons
  - CCDC28B accessory modifier of BBSome ciliary localization Gene Product: CCDC28B

Details

Context

ciliated eukaryotes

ciliumGO:0005929 ciliary membraneGO:0060170 ciliary basal bodyGO:0036064 ciliary tipGO:0097542

BBSome ciliary trafficking complexProtein Complexbbsome

BBSomeGO:0034464 intraciliary transportGO:0042073

Context

ciliated eukaryotes

ciliumGO:0005929 ciliary membraneGO:0060170 ciliary basal bodyGO:0036064 ciliary tipGO:0097542

Connections

bbsome_assembly -> bbsome_core_octamer Precedes

Chaperonin-mediated assembly produces the mature BBSome octamer.

bbsome_core_octamer -> arl6_membrane_recruitment Provides Input For

The assembled octamer is the substrate recruited to the ciliary membrane by ARL6/BBS3.

arl6_membrane_recruitment -> bbsome_cargo_trafficking Provides Input For

Membrane recruitment positions the BBSome coat to capture cargo and couple it to IFT.

bbsome_trafficking_regulation -> bbsome_cargo_trafficking Negatively Regulates

LZTFL1 restrains BBSome ciliary entry and thereby BBSome-dependent cargo trafficking.

Part 1: assembly of the BBSome core by chaperonin-like factors

Chaperonin-mediated BBSome assemblyProtein Complexbbsome_assembly

The chaperonin-like BBS proteins MKKS/BBS6, BBS10, and BBS12 form a complex with the CCT/TRiC chaperonin that folds BBS7 and nucleates assembly of the eight-subunit BBSome core. These factors are required to build the complex but are not stable subunits of the mature BBSome.

chaperone-mediated protein complex assemblyGO:0051131

Annotons

BBS chaperonin-like assembly module (BBS6/BBS10/BBS12 + CCT)

bbs_chaperonin_assembly_module

Participant: Protein Complex: BBS chaperonin-like assembly complex with CCT/TRiC

Protein Complex:

BBS chaperonin-like assembly complex with CCT/TRiC Chaperonin-like BBS proteins acting with the cytosolic CCT/TRiC chaperonin to assemble the BBSome core.

Active units:

MKKS/BBS6 chaperonin-like unit

Participant: Gene Product: MKKS (BBS6)

Gene Product:

MKKS (BBS6)UniProtKB:Q9NPJ1

Role: chaperonin-like assembly factor

Function:

protein folding chaperoneGO:0044183

BBS10 chaperonin-like unit

Participant: Gene Product: BBS10

Gene Product:

BBS10UniProtKB:Q8TAM1

Role: chaperonin-like assembly factor

Function:

protein folding chaperoneGO:0044183

BBS12 chaperonin-like unit

Participant: Gene Product: BBS12

Gene Product:

BBS12UniProtKB:Q6ZW61

Role: chaperonin-like assembly factor

Function:

protein folding chaperoneGO:0044183

CCT/TRiC chaperonin

Participant: Protein Complex: CCT/TRiC chaperonin

Protein Complex:

CCT/TRiC chaperonin Cytosolic chaperonin containing TCP-1 (TRiC) that cooperates with the BBS chaperonins.

Role: cytosolic chaperonin that folds BBSome subunits

Function

chaperonin-like BBSome core assembly factor Assembly-factor role for the BBS6/BBS10/BBS12-CCT module; no exact GO molecular-function term is asserted here.

Targets: BBSome core subunits

Processes

chaperone-mediated protein complex assemblyGO:0051131

PMID:20080638

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

Part 2: mature BBSome core complex

BBSome core octamerProtein Complexbbsome_core_octamer

The mature eight-subunit BBSome. BBS2, BBS7, and BBS9 form an interlocking beta-propeller/GAE/platform scaffold; BBS1 is the principal cargo- and ARL6/BBS3-interaction subunit; BBS4 and BBS8/TTC8 are TPR-superhelix adaptors; BBS5 contributes phosphoinositide-binding pleckstrin-homology domains for membrane association; and the small BBIP1/BBS18 subunit is required for complex integrity.

BBSomeGO:0034464

Annotons

BBSome octamer subunits

bbsome_octamer_units

Participant: Protein Complex: BBSome octamer

Protein Complex:

BBSome octamerGO:0034464

Active units:

BBS1 subunit1

Participant: Gene Product: BBS1

Gene Product:

BBS1UniProtKB:Q8NFJ9

Role: beta-propeller subunit; principal cargo recognition and ARL6/BBS3-GTP binding interface

BBS2 subunit1

Participant: Gene Product: BBS2

Gene Product:

BBS2UniProtKB:Q9BXC9

Role: beta-propeller/GAE/platform scaffold subunit

BBS4 subunit1

Participant: Gene Product: BBS4

Gene Product:

BBS4UniProtKB:Q96RK4

Role: TPR-superhelix adaptor subunit

BBS5 subunit1

Participant: Gene Product: BBS5

Gene Product:

BBS5UniProtKB:Q8N3I7

Role: pleckstrin-homology subunit; phosphoinositide-dependent membrane association

Function:

phosphatidylinositol-3-phosphate bindingGO:0032266

BBS7 subunit1

Participant: Gene Product: BBS7

Gene Product:

BBS7UniProtKB:Q8IWZ6

Role: beta-propeller/GAE/platform scaffold subunit; CCT/chaperonin client during assembly

BBS8/TTC8 subunit1

Participant: Gene Product: TTC8 (BBS8)

Gene Product:

TTC8 (BBS8)UniProtKB:Q8TAM2

Role: TPR-superhelix adaptor subunit

BBS9 subunit1

Participant: Gene Product: BBS9

Gene Product:

BBS9UniProtKB:Q3SYG4

Role: central beta-propeller/GAE/platform/alpha-helical scaffold subunit

BBIP1/BBS18 subunit1

Participant: Gene Product: BBIP1 (BBIP10, BBS18)

Gene Product:

BBIP1 (BBIP10, BBS18)UniProtKB:A8MTZ0

Role: small subunit required for BBSome integrity; links to microtubule stability/acetylation

Function

ciliary membrane-protein cargo adaptor The assembled octamer functions as a coat-like adaptor that selects membrane-protein cargo for intraflagellar transport.

Locations

ciliary membraneGO:0060170 ciliary basal bodyGO:0036064

PMID:17574030

Defines the seven-subunit BBSome plus BBIP10 associated with the ciliary membrane.

PMID:19081074

Establishes BBIP10/BBIP1 as the integral eighth subunit required for complex integrity.

PMID:31939736

Cryo-EM structure of the mammalian BBSome defining subunit domain architecture.

PMID:31951201

Cryo-EM structure of the human BBSome core placing the beta-propeller, GAE/platform, TPR, and PH domains.

Part 3: GTP-dependent membrane recruitment

ARL6/BBS3 membrane recruitment of the BBSomeRegulatory Steparl6_membrane_recruitment

The Arf-like GTPase ARL6/BBS3, in its GTP-bound state, binds the BBS1 beta-propeller and recruits the BBSome to the ciliary membrane, where BBSome coat polymerization is nucleated. This is the membrane-targeting switch for BBSome function.

Annotons

ARL6/BBS3 GTP-dependent BBSome recruitment

arl6_gtpase_recruitment

Participant: Gene Product: ARL6 (BBS3)

Gene Product:

ARL6 (BBS3)UniProtKB:Q9H0F7

Function

GTP-dependent recruitment of the BBSome to the ciliary membraneGO:0005525 GTP-bound ARL6 binds the BBS1 beta-propeller of the BBSome and recruits it to the membrane; GTP hydrolysis (GTPase activity, GO:0003924) and IFT27-assisted nucleotide release gate the cycle.

Locations

ciliary membraneGO:0060170

PMID:20603001

ARL6/BBS3-GTP nucleates BBSome coat assembly on membranes.

PMID:25402481

Structural basis for ARL6-GTP recruitment of the BBSome via the BBS1 beta-propeller.

PMID:25443296

IFT27 stabilizes nucleotide-free ARL6 to promote BBSome exit from cilia.

Part 4: cargo recognition and ciliary trafficking

BBSome cargo recognition and ciliary import/retrievalTransport Stepbbsome_cargo_trafficking

The membrane-bound BBSome recognizes signaling-receptor cargo (ciliary GPCRs such as SSTR3 and MCHR1, and Hedgehog-pathway components such as Smoothened and GPR161) and couples them to the IFT trains. The BBSome is required for ciliary exit of the BBSome and associated receptor cargo such as GPR161, driven through ARL6 and IFT27, and for IFT turnaround at the ciliary tip.

protein localization to ciliumGO:0061512

Annotons

BBSome ciliary cargo adaptor activity

bbsome_cargo_adaptor

Participant: Protein Complex: membrane-bound BBSome coat

Protein Complex:

membrane-bound BBSome coatGO:0034464

Function

ciliary membrane-protein cargo adaptor coupling to intraflagellar transport Cargo adaptor role coupling ciliary membrane proteins to IFT; no exact GO molecular-function term is asserted here.

Cargo: ciliary GPCR cargo (e.g. SSTR3, MCHR1) Hedgehog signaling components (Smoothened, GPR161)

Processes

intraciliary transportGO:0042073

Locations

ciliary membraneGO:0060170 ciliary tipGO:0097542

PMID:20603001

The BBSome coat traffics membrane proteins to and within cilia (SSTR3, Smoothened).

PMID:25443296

IFT27 and ARL6 drive ciliary exit of the BBSome and the GPCR GPR161.

PMID:22922713

The BBSome controls IFT assembly and turnaround at the ciliary tip.

PMID:22139371

Loss of ARL6/BBS3 disrupts MCHR1 ciliary membrane localization and retrograde Smoothened transport.

Part 5: regulation of BBSome ciliary trafficking (optional)

Regulation of BBSome ciliary traffickingRegulatory Stepbbsome_trafficking_regulation

LZTFL1/BBS17 negatively regulates BBSome ciliary entry. LZTFL1 associates with the BBSome in the cytoplasm, and its depletion increases ciliary trafficking of the BBSome and Smoothened.

Annotons

LZTFL1/BBS17 regulation of BBSome ciliary trafficking

lztfl1_regulation

Participant: Gene Product: LZTFL1 (BBS17)

Gene Product:

LZTFL1 (BBS17)UniProtKB:Q9NQ48

Function

BBSome binding (protein-containing complex binding)GO:0044877 Binds the BBSome and restrains its ciliary entry, thereby controlling BBSome and Smoothened ciliary localization.

Targets: BBSomeGO:0034464 Smoothened

Processes

negative regulation of protein localization to ciliumGO:1903565

PMID:22072986

LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.

Part 6: BBSome-associated accessory factor (optional)

CCDC28B BBSome-associated accessory factorBiological Processccdc28b_accessory

CCDC28B is a pericentriolar BBS-interacting protein and genetic modifier of Bardet-Biedl syndrome that is required for normal ciliogenesis. It associates with BBSome subunits but is not a core subunit, and its effect on BBSome trafficking is not directional enough to model as positive or negative regulation.

Annotons

CCDC28B accessory modifier of BBSome ciliary localization

ccdc28b_modifier

Participant: Gene Product: CCDC28B

Gene Product:

CCDC28BUniProtKB:Q9BUN5

Function

modifier of BBSome ciliary localization Accessory factor that influences BBSome ciliary localization; acts as a genetic modifier of Bardet-Biedl syndrome rather than a core subunit. No precise GO molecular function is asserted here.

Accessory modifier of BBSome ciliary trafficking.

PMID:16327777

CCDC28B (MGC1203) is a pericentriolar protein that interacts and colocalizes with BBS proteins.