id: MODULE:primary_cilium_life_cycle title: Primary cilium life cycle module description: >- The primary cilium is a microtubule-based sensory organelle templated by the mother centriole. Its life cycle runs from licensing of the mother centriole as a basal body, through ciliary vesicle formation, transition zone assembly and IFT-driven axoneme extension, to maintenance of a distinct ciliary membrane, control of cilium length, and disassembly when the cell re-enters the cell cycle. This module captures the ordered stages and the protein roles that carry out each stage, using human proteins as concrete members. status: DRAFT scope: CONCRETE evidence: - source_id: PMID:41005307 title: Intrinsic heterogeneity of primary cilia revealed through spatial proteomics. statement: >- HPA primary-cilium atlas: antibody-based sub-ciliary localization of 715 proteins in three cell lines. Used here as localization evidence for module members; most calls are graded Approved or Uncertain. - &id001 source_id: PMID:23348840 title: Centriole distal appendages promote membrane docking, leading to cilia initiation. statement: >- Identifies CEP83, CEP89, SCLT1, FBF1 and CEP164 as distal appendage components, defines their assembly hierarchy, and shows that undocked centrioles fail to recruit TTBK2 or release CP110. - &id002 source_id: PMID:23141541 title: >- The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis. statement: >- TTBK2 acts at the distal end of the basal body, promotes removal of the CP110 cap and recruitment of IFT proteins, and is required to initiate ciliogenesis. - &id005 source_id: PMID:25686250 title: Early steps in primary cilium assembly require EHD1/EHD3-dependent ciliary vesicle formation. statement: >- EHD1 and EHD3 tubulate membranes to fuse distal appendage vesicles into the ciliary vesicle, acting with the Rab11-Rab8 cascade; Rab8 is activated only after ciliary vesicle assembly. - &id008 source_id: PMID:21725307 title: A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition. statement: >- TCTN1 forms a transition zone complex with MKS1, TMEM216, TMEM67, CEP290, B9D1, TCTN2 and CC2D2A that controls ciliogenesis and ciliary membrane composition in a tissue-specific manner. - &id011 source_id: PMID:31451806 title: Structure of the dynein-2 complex and its assembly with intraflagellar transport trains. statement: Structure of the dynein-2 complex and its assembly onto IFT trains for retrograde transport. - &id024 source_id: PMID:17604723 title: HEF1-dependent Aurora A activation induces disassembly of the primary cilium. statement: >- NEDD9/HEF1 activates Aurora A at the basal body, which phosphorylates and activates the tubulin deacetylase HDAC6 to drive ciliary disassembly. - &id025 source_id: PMID:25660017 title: >- The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation. statement: >- PLK1-activated KIF2A depolymerizes microtubules at the basal body to drive primary cilium disassembly. notes: >- Revised 2026-10-03 after gene reviews of all 60 members (genes/human//). Draft built in the HUMAN_PROTEIN_ATLAS project. Members and UniProt accessions come from projects/HUMAN_PROTEIN_ATLAS/cilium_life_cycle/candidate_members.yaml (UniProt REST). Several roles have no GO molecular-function term (distal appendage scaffold, transition zone barrier, IFT adaptor, microtubule depolymerase) and carry preferred_term only. BBSome cargo export is a separate module (modules/bbsome.yaml). Motile cilia, centriole duplication and the ciliary pocket are outside this boundary. Ontology gaps: GO has no term for regulation of cilium length (negative regulation of non-motile cilium assembly is used), no cytoplasmic dynein-2 complex term (the generic cytoplasmic dynein complex is used) and no microtubule depolymerase activity term (KIF2A, KIF24); these are candidate GO term requests. Curation note: many members have only Approved or Uncertain HPA cilium-atlas calls, which are not exported to GOA; whether those calls should become annotations is tracked in the HUMAN_PROTEIN_ATLAS project. module: id: primary_cilium_life_cycle label: Primary cilium life cycle module_type: ORGANELLE_LIFECYCLE concepts: - preferred_term: cilium organization term: id: GO:0044782 label: cilium organization description: Assembly, arrangement and disassembly of a cilium. - preferred_term: non-motile cilium term: id: GO:0097730 label: non-motile cilium context: taxa: - preferred_term: Homo sapiens term: id: NCBITaxon:9606 label: Homo sapiens conditions: - preferred_term: quiescent or differentiated cells that form a primary cilium description: Cilia assemble in G0/G1 and are resorbed before mitosis. parts: - order: 1 role: mother centriole licensing node: id: mother_centriole_licensing label: Mother centriole licensing and basal body conversion module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: non-motile cilium assembly term: id: GO:1905515 label: non-motile cilium assembly description: >- The mother centriole becomes competent to template a cilium. Distal appendages, assembled in the order CEP83 then SCLT1 and CEP89 then FBF1 and CEP164, dock the centriole to membrane. CEP164 recruits TTBK2, which triggers removal of the CP110-CEP97 cap by phosphorylating cap-anchoring proteins (MPHOSPH9, CEP83); CP110 itself is not a known TTBK2 substrate. KIF24 recruits the cap and depolymerizes centriolar microtubules, restraining ciliogenesis in cycling cells. CEP89 also positions NCS1 to capture preciliary vesicles, linking this stage to ciliary vesicle formation. FBF1 is not needed for licensing itself (cap removal and TTBK2 recruitment are normal without it) but gates IFT and membrane-protein entry at the ciliary base. evidence: - *id001 - *id002 - &id004 source_id: PMID:21620453 title: Centriolar kinesin Kif24 interacts with CP110 to remodel microtubules and regulate ciliogenesis. statement: >- KIF24 binds CP110 and CEP97 at the mother centriole, depolymerizes microtubules in vitro, and restrains cilia assembly in cycling cells. - &id003 source_id: PMID:39882855 statement: >- CEP89 positions myristoylated NCS1 at the distal appendages, where it captures preciliary vesicles for ciliary vesicle formation. annotons: - id: distal_appendage_assembly label: Distal appendage (transition fiber) complex participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: centriole distal appendage complex description: Distal appendage proteins assembled hierarchically on the mother centriole. active_units: - id: cep83_unit label: CEP83 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: CEP83 term: id: UniProtKB:Q9Y592 label: Centrosomal protein of 83 kDa role: distal appendage component - id: sclt1_unit label: SCLT1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: SCLT1 term: id: UniProtKB:Q96NL6 label: Sodium channel and clathrin linker 1 role: distal appendage component - id: cep89_unit label: CEP89 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: CEP89 term: id: UniProtKB:Q96ST8 label: Centrosomal protein of 89 kDa role: distal appendage component - id: fbf1_unit label: FBF1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: FBF1 term: id: UniProtKB:Q8TES7 label: Fas-binding factor 1 role: distal appendage component - id: cep164_unit label: CEP164 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: CEP164 term: id: UniProtKB:Q9UPV0 label: Centrosomal protein of 164 kDa role: distal appendage component function: preferred_term: distal appendage scaffold description: >- Structural scaffold role; no specific GO molecular-function term is asserted. CEP89 additionally acts as an adaptor for NCS1-mediated vesicle capture. processes: - preferred_term: non-motile cilium assembly term: id: GO:1905515 label: non-motile cilium assembly locations: - preferred_term: ciliary basal body term: id: GO:0036064 label: ciliary basal body role_description: Docks the mother centriole to vesicles and membrane and recruits TTBK2. evidence: - *id001 - *id003 - id: ttbk2_cap_removal label: TTBK2 triggers CP110 cap removal participant: selector_type: GENE_PRODUCT gene_product: preferred_term: TTBK2 term: id: UniProtKB:Q6IQ55 label: Tau-tubulin kinase 2 function: preferred_term: protein serine/threonine kinase activity term: id: GO:0004674 label: protein serine/threonine kinase activity processes: - preferred_term: non-motile cilium assembly term: id: GO:1905515 label: non-motile cilium assembly locations: - preferred_term: ciliary basal body term: id: GO:0036064 label: ciliary basal body role_description: >- Kinase recruited by CEP164 that triggers CP110-CEP97 cap removal and IFT recruitment, and restrains KIF2A during cilium growth. evidence: - *id002 - &id026 source_id: PMID:39930500 statement: >- TTBK2 restrains the microtubule depolymerizer KIF2A at the mother centriole to support primary cilia growth. - id: cp110_cep97_cap label: CP110-CEP97 distal cap suppresses ciliogenesis participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: CP110-CEP97 distal centriole cap description: Cap on the distal end of the mother centriole that blocks axoneme extension until removed. active_units: - id: ccp110_unit label: CCP110 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: CCP110 term: id: UniProtKB:O43303 label: Centriolar coiled-coil protein of 110 kDa role: distal cap component - id: cep97_unit label: CEP97 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: CEP97 term: id: UniProtKB:Q8IW35 label: Centrosomal protein of 97 kDa role: distal cap component function: preferred_term: ciliogenesis suppressor cap description: CP110 caps microtubule plus ends; CEP97 acts as a protein-macromolecule adaptor. processes: - preferred_term: negative regulation of cilium assembly term: id: GO:1902018 label: negative regulation of cilium assembly locations: - preferred_term: centriole term: id: GO:0005814 label: centriole role_description: Inhibitory cap; its removal licenses axoneme growth. CEP97 is the adaptor that stabilizes CP110. evidence: - *id004 - *id002 - id: kif24_cap_recruitment label: KIF24 recruits the cap and remodels centriolar microtubules participant: selector_type: GENE_PRODUCT gene_product: preferred_term: KIF24 term: id: UniProtKB:Q5T7B8 label: Kinesin-like protein KIF24 function: preferred_term: microtubule depolymerase description: No GO MF term for microtubule depolymerase activity. processes: - preferred_term: negative regulation of cilium assembly term: id: GO:1902018 label: negative regulation of cilium assembly locations: - preferred_term: centriole term: id: GO:0005814 label: centriole role_description: >- Kinesin-13 that recruits MPHOSPH9 and the CP110-CEP97 cap to the mother centriole and depolymerizes centriolar microtubules, suppressing ciliogenesis in cycling cells. evidence: - *id004 connections: - source: distal_appendage_assembly target: ttbk2_cap_removal connection_type: PROVIDES_INPUT_FOR description: CEP164 at the distal appendages recruits TTBK2 to the mother centriole. - source: ttbk2_cap_removal target: cp110_cep97_cap connection_type: NEGATIVELY_REGULATES description: TTBK2 triggers removal of the CP110-CEP97 cap. - source: kif24_cap_recruitment target: cp110_cep97_cap connection_type: POSITIVELY_REGULATES description: KIF24 recruits and maintains the cap at the mother centriole. - order: 2 role: ciliary vesicle formation node: id: ciliary_vesicle_formation label: Ciliary vesicle formation at the distal appendages module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: ciliary vesicle assembly term: id: GO:1905556 label: ciliary vesicle assembly description: >- Myosin-Va delivers preciliary vesicles to the distal appendages, upstream of ciliary vesicle formation. EHD1 and EHD3 tubulate the docked distal appendage vesicles so they fuse into a single ciliary vesicle; EHD1 is the dominant paralog in RPE1 cells. CEP290 also acts here, at centriolar satellites, in ciliary vesicle maturation and RAB8A recruitment. evidence: - &id006 source_id: PMID:29335527 title: >- Myosin-Va is required for preciliary vesicle transportation to the mother centriole during ciliogenesis. statement: >- Myosin-Va transports preciliary vesicles to the mother centriole, the earliest known step of ciliary vesicle formation. - *id005 annotons: - id: myo5a_vesicle_delivery label: Myosin-Va preciliary vesicle delivery participant: selector_type: GENE_PRODUCT gene_product: preferred_term: MYO5A term: id: UniProtKB:Q9Y4I1 label: Unconventional myosin-Va function: preferred_term: microfilament motor activity term: id: GO:0000146 label: microfilament motor activity processes: - preferred_term: vesicle transport along actin filament term: id: GO:0030050 label: vesicle transport along actin filament - preferred_term: cilium assembly term: id: GO:0060271 label: cilium assembly role_description: >- Processive actin motor that carries preciliary vesicles to the mother centriole; its dominant roles (melanosome and secretory vesicle transport) lie outside cilia. evidence: - *id006 - id: ehd_vesicle_tubulation label: EHD1/EHD3 membrane tubulation participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: EHD1/EHD3 membrane-shaping proteins description: Membrane-tubulating EH-domain ATPases acting on distal appendage vesicles. active_units: - id: ehd1_unit label: EHD1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: EHD1 term: id: UniProtKB:Q9H4M9 label: EH domain-containing protein 1 role: membrane-shaping ATPase - id: ehd3_unit label: EHD3 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: EHD3 term: id: UniProtKB:Q9NZN3 label: EH domain-containing protein 3 role: membrane-shaping ATPase function: preferred_term: ATP hydrolysis activity term: id: GO:0016887 label: ATP hydrolysis activity processes: - preferred_term: ciliary vesicle assembly term: id: GO:1905556 label: ciliary vesicle assembly locations: - preferred_term: ciliary vesicle term: id: GO:0097721 label: ciliary vesicle role_description: Tubulate distal appendage vesicles to form the ciliary vesicle. evidence: - *id005 connections: - source: myo5a_vesicle_delivery target: ehd_vesicle_tubulation connection_type: PRECEDES description: Delivered vesicles are remodeled by EHD1/EHD3 into the ciliary vesicle. - order: 3 role: ciliary membrane extension node: id: ciliary_membrane_extension label: Ciliary membrane supply and extension module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: cilium assembly term: id: GO:0060271 label: cilium assembly description: >- Once the ciliary vesicle has formed, the RAB11-Rabin8-RAB8 cascade supplies membrane for the growing ciliary sheath; RAB8 is activated only after ciliary vesicle assembly. RAB8A is pleiotropic and also acts in exocytosis and endocytic recycling. evidence: - &id007 source_id: PMID:17574030 title: >- A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. statement: >- Rab8-GTP, produced by the Rab8 GEF Rabin8 at the basal body, enters the cilium and promotes ciliary membrane extension. - *id005 annotons: - id: rabin8_rab8_gef label: Rabin8 activates Rab8 participant: selector_type: GENE_PRODUCT gene_product: preferred_term: RAB3IP term: id: UniProtKB:Q96QF0 label: Rab-3A-interacting protein function: preferred_term: guanyl-nucleotide exchange factor activity term: id: GO:0005085 label: guanyl-nucleotide exchange factor activity processes: - preferred_term: cilium assembly term: id: GO:0060271 label: cilium assembly role_description: RAB8 guanine nucleotide exchange factor, delivered to the mother centriole downstream of RAB11. evidence: - *id007 - id: rab8_membrane_supply label: Rab8 ciliary membrane delivery participant: selector_type: GENE_PRODUCT gene_product: preferred_term: RAB8A term: id: UniProtKB:P61006 label: Ras-related protein Rab-8A function: preferred_term: GTPase activity term: id: GO:0003924 label: GTPase activity processes: - preferred_term: cilium assembly term: id: GO:0060271 label: cilium assembly locations: - preferred_term: ciliary membrane term: id: GO:0060170 label: ciliary membrane role_description: GTP-bound RAB8A enters the cilium and promotes ciliary membrane extension. evidence: - *id007 - *id005 connections: - source: rabin8_rab8_gef target: rab8_membrane_supply connection_type: POSITIVELY_REGULATES description: Rabin8 loads RAB8A with GTP. - order: 4 role: transition zone assembly node: id: transition_zone_assembly label: Transition zone assembly module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: ciliary transition zone assembly term: id: GO:1905349 label: ciliary transition zone assembly description: >- The transition zone forms between basal body and axoneme and gates ciliary membrane composition. RPGRIP1L acts upstream as the foundational assembly factor for both the MKS and NPHP modules and CEP290. In the NPHP module, NPHP4 is the adaptor hub bridging RPGRIP1L and NPHP1; NPHP1 depends on both to reach the transition zone. MKS1-B9D2-B9D1 form a linear core of the MKS module. CEP290 is its own transition zone component, not an MKS subunit. GO has merged the former basal body-plasma membrane docking and transition fiber assembly terms into this process. evidence: - *id008 - &id009 source_id: PMID:26392567 statement: Mks5/RPGRIP1L is required to form the transition zone and its ciliary zone of exclusion. - &id010 source_id: PMID:21422230 statement: >- MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function. annotons: - id: rpgrip1l_tz_foundation label: RPGRIP1L founds the transition zone participant: selector_type: GENE_PRODUCT gene_product: preferred_term: RPGRIP1L term: id: UniProtKB:Q68CZ1 label: Protein fantom function: preferred_term: transition zone scaffold processes: - preferred_term: ciliary transition zone assembly term: id: GO:1905349 label: ciliary transition zone assembly locations: - preferred_term: ciliary transition zone term: id: GO:0035869 label: ciliary transition zone role_description: Foundational transition zone assembly factor upstream of the MKS and NPHP modules and CEP290. evidence: - *id009 - id: mks_module label: MKS module participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: MKS complex term: id: GO:0036038 label: MKS complex description: Tectonic/MKS ciliopathy protein complex at the transition zone. active_units: - id: mks1_unit label: MKS1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: MKS1 term: id: UniProtKB:Q9NXB0 label: Tectonic-like complex member MKS1 role: MKS module component - id: tmem67_unit label: TMEM67 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: TMEM67 term: id: UniProtKB:Q5HYA8 label: Meckelin role: MKS module component - id: cc2d2a_unit label: CC2D2A subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: CC2D2A term: id: UniProtKB:Q9P2K1 label: Coiled-coil and C2 domain-containing protein 2A role: MKS module component - id: b9d1_unit label: B9D1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: B9D1 term: id: UniProtKB:Q9UPM9 label: B9 domain-containing protein 1 role: MKS module component - id: b9d2_unit label: B9D2 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: B9D2 term: id: UniProtKB:Q9BPU9 label: B9 domain-containing protein 2 role: MKS module component - id: tctn1_unit label: TCTN1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: TCTN1 term: id: UniProtKB:Q2MV58 label: Tectonic-1 role: MKS module component - id: tctn2_unit label: TCTN2 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: TCTN2 term: id: UniProtKB:Q96GX1 label: Tectonic-2 role: MKS module component - id: tmem216_unit label: TMEM216 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: TMEM216 term: id: UniProtKB:Q9P0N5 label: Transmembrane protein 216 role: MKS module component - id: tmem231_unit label: TMEM231 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: TMEM231 term: id: UniProtKB:Q9H6L2 label: Transmembrane protein 231 role: MKS module component function: preferred_term: ciliary diffusion barrier description: Barrier/gating role; no GO MF term asserted. processes: - preferred_term: ciliary transition zone assembly term: id: GO:1905349 label: ciliary transition zone assembly locations: - preferred_term: ciliary transition zone term: id: GO:0035869 label: ciliary transition zone role_description: Transition zone gate that controls entry of ciliary membrane proteins. evidence: - *id008 - id: nphp_module label: NPHP module participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: NPHP module description: Nephronophthisis proteins at the transition zone; NPHP4 is the hub. active_units: - id: nphp4_unit label: NPHP4 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: NPHP4 term: id: UniProtKB:O75161 label: Nephrocystin-4 role: NPHP module component - id: nphp1_unit label: NPHP1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: NPHP1 term: id: UniProtKB:O15259 label: Nephrocystin-1 role: NPHP module component function: preferred_term: protein-macromolecule adaptor activity term: id: GO:0030674 label: protein-macromolecule adaptor activity processes: - preferred_term: ciliary transition zone assembly term: id: GO:1905349 label: ciliary transition zone assembly locations: - preferred_term: ciliary transition zone term: id: GO:0035869 label: ciliary transition zone role_description: Second transition zone module, partly redundant with the MKS module. evidence: - *id010 - id: cep290_tz_scaffold label: CEP290 transition zone scaffold participant: selector_type: GENE_PRODUCT gene_product: preferred_term: CEP290 term: id: UniProtKB:O15078 label: Centrosomal protein of 290 kDa function: preferred_term: transition zone scaffold processes: - preferred_term: ciliary transition zone assembly term: id: GO:1905349 label: ciliary transition zone assembly locations: - preferred_term: ciliary transition zone term: id: GO:0035869 label: ciliary transition zone role_description: >- Builds the microtubule-to-membrane Y-links of the transition zone; also acts at centriolar satellites in ciliary vesicle maturation. evidence: - *id008 connections: - source: rpgrip1l_tz_foundation target: mks_module connection_type: PRECEDES description: RPGRIP1L is required to assemble the MKS module. - source: rpgrip1l_tz_foundation target: nphp_module connection_type: PRECEDES description: RPGRIP1L is required to recruit the NPHP module. - source: rpgrip1l_tz_foundation target: cep290_tz_scaffold connection_type: PRECEDES description: RPGRIP1L is required for CEP290 localization. - order: 5 role: axoneme extension by IFT node: id: axoneme_extension_ift label: Axoneme extension by intraflagellar transport module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: intraciliary transport term: id: GO:0042073 label: intraciliary transport description: >- IFT trains carry axoneme precursors and membrane proteins to the ciliary tip and back. Kinesin-2 (KIF3A/KIF3B motors with the KIFAP3 cargo adaptor) drives anterograde trains carrying IFT-B. Within IFT-B, IFT81-IFT74 bind tubulin cargo, and IFT88, IFT52 and IFT172 are scaffolds. Dynein-2 drives retrograde trains. IFT-A acts in retrograde transport and, with TULP3, imports membrane proteins; loss of IFT-A subunits other than IFT122 has only mild effects on ciliogenesis. evidence: - &id012 source_id: PMID:11062270 title: >- Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. statement: IFT88 and its mouse homologue Tg737 are required for cilium and flagellum assembly. - &id013 source_id: PMID:36354106 title: Biochemically validated structural model of the 15-subunit intraflagellar transport complex IFT-B. statement: Biochemically validated structural model of the 15-subunit IFT-B complex. - &id014 source_id: PMID:36775821 title: Human IFT-A complex structures provide molecular insights into ciliary transport. statement: Structures of the human IFT-A complex provide the molecular basis of IFT-A in ciliary transport. - *id011 annotons: - id: ift_b_scaffold label: IFT-B scaffold subunits participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: IFT-B complex (scaffold subunits) term: id: GO:0030992 label: intraciliary transport particle B description: Structural core and peripheral IFT-B subunits. active_units: - id: ift88_unit label: IFT88 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: IFT88 term: id: UniProtKB:Q13099 label: Intraflagellar transport protein 88 homolog role: IFT-B subunit - id: ift52_unit label: IFT52 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: IFT52 term: id: UniProtKB:Q9Y366 label: Intraflagellar transport protein 52 homolog role: IFT-B subunit - id: ift172_unit label: IFT172 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: IFT172 term: id: UniProtKB:Q9UG01 label: Intraflagellar transport protein 172 homolog role: IFT-B subunit function: preferred_term: IFT-B structural scaffold description: No GO MF term asserted; cargo binding is shown only for IFT81-IFT74. processes: - preferred_term: intraciliary anterograde transport term: id: GO:0035720 label: intraciliary anterograde transport - preferred_term: cilium assembly term: id: GO:0060271 label: cilium assembly locations: - preferred_term: non-motile cilium term: id: GO:0097730 label: non-motile cilium role_description: Backbone of anterograde IFT trains. evidence: - *id012 - *id013 - id: ift81_ift74_tubulin label: IFT81-IFT74 tubulin module participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: IFT81-IFT74 tubulin-binding module term: id: GO:0030992 label: intraciliary transport particle B description: IFT-B subcomplex that binds tubulin cargo. active_units: - id: ift81_unit label: IFT81 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: IFT81 term: id: UniProtKB:Q8WYA0 label: Intraflagellar transport protein 81 homolog role: tubulin-binding IFT-B subunit - id: ift74_unit label: IFT74 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: IFT74 term: id: UniProtKB:Q96LB3 label: Intraflagellar transport protein 74 homolog role: tubulin-binding IFT-B subunit function: preferred_term: tubulin binding term: id: GO:0015631 label: tubulin binding processes: - preferred_term: intraciliary anterograde transport term: id: GO:0035720 label: intraciliary anterograde transport - preferred_term: cilium assembly term: id: GO:0060271 label: cilium assembly locations: - preferred_term: non-motile cilium term: id: GO:0097730 label: non-motile cilium role_description: Binds tubulin for delivery to the growing axoneme tip. evidence: - *id013 - id: ift_a_complex label: IFT-A complex participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: IFT-A complex term: id: GO:0030991 label: intraciliary transport particle A description: Retrograde IFT and membrane-protein import complex. active_units: - id: ift140_unit label: IFT140 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: IFT140 term: id: UniProtKB:Q96RY7 label: Intraflagellar transport protein 140 homolog role: IFT-A subunit - id: ift122_unit label: IFT122 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: IFT122 term: id: UniProtKB:Q9HBG6 label: Intraflagellar transport protein 122 homolog role: IFT-A subunit - id: wdr35_unit label: WDR35 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: WDR35 term: id: UniProtKB:Q9P2L0 label: WD repeat-containing protein 35 role: IFT-A subunit - id: ttc21b_unit label: TTC21B subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: TTC21B term: id: UniProtKB:Q7Z4L5 label: Tetratricopeptide repeat protein 21B role: IFT-A subunit function: preferred_term: protein carrier activity term: id: GO:0140597 label: protein carrier activity processes: - preferred_term: intraciliary retrograde transport term: id: GO:0035721 label: intraciliary retrograde transport - preferred_term: protein localization to cilium term: id: GO:0061512 label: protein localization to cilium locations: - preferred_term: non-motile cilium term: id: GO:0097730 label: non-motile cilium role_description: Retrograde train component and, with TULP3, carrier for membrane-protein entry into cilia. evidence: - *id014 - &id015 source_id: PMID:20889716 title: >- TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia. statement: >- TULP3 bridges the IFT-A complex and membrane phosphoinositides to traffic G protein-coupled receptors into cilia. - id: kinesin2_anterograde label: Heterotrimeric kinesin-2 participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: kinesin-2 (KIF3A/KIF3B/KIFAP3) term: id: GO:0016939 label: kinesin II complex description: Heterotrimeric kinesin II motor. active_units: - id: kif3a_unit label: KIF3A subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: KIF3A term: id: UniProtKB:Q9Y496 label: Kinesin-like protein KIF3A role: kinesin-2 motor subunit - id: kif3b_unit label: KIF3B subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: KIF3B term: id: UniProtKB:O15066 label: Kinesin-like protein KIF3B role: kinesin-2 motor subunit - id: kifap3_unit label: KIFAP3 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: KIFAP3 term: id: UniProtKB:Q92845 label: Kinesin-associated protein 3 role: non-motor cargo adaptor subunit function: preferred_term: protein-macromolecule adaptor activity term: id: GO:0030674 label: protein-macromolecule adaptor activity function: preferred_term: plus-end-directed microtubule motor activity term: id: GO:0008574 label: plus-end-directed microtubule motor activity processes: - preferred_term: intraciliary anterograde transport term: id: GO:0035720 label: intraciliary anterograde transport locations: - preferred_term: axoneme term: id: GO:0005930 label: axoneme role_description: >- Anterograde IFT motor. KIF3A and KIF3B carry the motor activity; KIFAP3 contributes to it as the non-motor cargo adaptor (protein-macromolecule adaptor activity). - id: dynein2_retrograde label: Dynein-2 participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: cytoplasmic dynein-2 term: id: GO:0005868 label: cytoplasmic dynein complex description: >- Retrograde IFT motor complex; DYNC2H1 is the motor, the intermediate and light intermediate chains contribute. active_units: - id: dync2h1_unit label: DYNC2H1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: DYNC2H1 term: id: UniProtKB:Q8NCM8 label: Cytoplasmic dynein 2 heavy chain 1 role: dynein-2 subunit - id: dync2li1_unit label: DYNC2LI1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: DYNC2LI1 term: id: UniProtKB:Q8TCX1 label: Cytoplasmic dynein 2 light intermediate chain 1 role: dynein-2 subunit - id: dync2i1_unit label: DYNC2I1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: DYNC2I1 term: id: UniProtKB:Q8WVS4 label: Cytoplasmic dynein 2 intermediate chain 1 role: dynein-2 subunit - id: dync2i2_unit label: DYNC2I2 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: DYNC2I2 term: id: UniProtKB:Q96EX3 label: Cytoplasmic dynein 2 intermediate chain 2 role: dynein-2 subunit function: preferred_term: minus-end-directed microtubule motor activity term: id: GO:0008569 label: minus-end-directed microtubule motor activity processes: - preferred_term: intraciliary retrograde transport term: id: GO:0035721 label: intraciliary retrograde transport locations: - preferred_term: axoneme term: id: GO:0005930 label: axoneme role_description: Retrograde IFT motor, carried to the tip in an autoinhibited state on anterograde trains. evidence: - *id011 connections: - source: kinesin2_anterograde target: ift_b_scaffold connection_type: PROVIDES_INPUT_FOR description: Kinesin-2 moves IFT-B trains toward the ciliary tip. - source: dynein2_retrograde target: ift_a_complex connection_type: PROVIDES_INPUT_FOR description: Dynein-2 returns IFT-A trains to the base. - order: 6 role: ciliary membrane composition node: id: ciliary_membrane_composition label: Ciliary membrane identity and protein targeting module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: protein localization to cilium term: id: GO:0061512 label: protein localization to cilium description: >- Mature cilia keep a distinct membrane. ARL13B activates ARL3, a GTP-dependent switch whose GTP-bound form releases lipidated cargo from PDE6D (farnesylated/prenylated cargo) and UNC119B (myristoylated cargo) inside the cilium; RP2 inactivates ARL3. INPP5E keeps PI(4,5)P2 low in the ciliary membrane, and TULP3 couples IFT-A to phosphoinositides to import GPCRs. PDE6D also solubilizes farnesylated RAS outside cilia. BBSome-mediated export is modeled in modules/bbsome.yaml. evidence: - &id016 source_id: PMID:26551564 title: >- A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins. statement: >- ARL13B is the guanine nucleotide exchange factor for ARL3, creating a G-protein cascade that releases lipidated cargo from PDE6D and UNC119 inside the cilium. - *id015 - &id019 source_id: PMID:19668215 title: >- INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. statement: INPP5E localizes to cilia; its loss causes ciliary signaling defects and ciliary instability. - &id017 source_id: PMID:22002721 statement: >- PDE6D is a GDI-like carrier for farnesylated cargo whose release is triggered by ARL2-GTP or ARL3-GTP. - &id018 source_id: PMID:22085962 statement: An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. annotons: - id: arl13b_arl3_gef label: ARL13B activates ARL3 participant: selector_type: GENE_PRODUCT gene_product: preferred_term: ARL13B term: id: UniProtKB:Q3SXY8 label: ADP-ribosylation factor-like protein 13B function: preferred_term: guanyl-nucleotide exchange factor activity term: id: GO:0005085 label: guanyl-nucleotide exchange factor activity processes: - preferred_term: protein localization to cilium term: id: GO:0061512 label: protein localization to cilium locations: - preferred_term: ciliary membrane term: id: GO:0060170 label: ciliary membrane role_description: Ciliary membrane GTPase that acts as GEF for ARL3. evidence: - *id016 - id: arl3_cargo_release label: ARL3 releases lipidated cargo participant: selector_type: GENE_PRODUCT gene_product: preferred_term: ARL3 term: id: UniProtKB:P36405 label: ADP-ribosylation factor-like protein 3 function: preferred_term: G protein activity term: id: GO:0003925 label: G protein activity processes: - preferred_term: protein localization to ciliary membrane term: id: GO:1903441 label: protein localization to ciliary membrane role_description: >- ARL3-GTP binds PDE6D and UNC119B and displaces their lipidated cargo inside the cilium; its intrinsic GTP hydrolysis is negligible without RP2. evidence: - *id016 - id: pde6d_prenyl_carrier label: PDE6D carries farnesylated cargo participant: selector_type: GENE_PRODUCT gene_product: preferred_term: PDE6D term: id: UniProtKB:O43924 label: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta function: preferred_term: farnesylated protein binding term: id: GO:0001918 label: farnesylated protein binding processes: - preferred_term: protein localization to cilium term: id: GO:0061512 label: protein localization to cilium role_description: GDI-like carrier for farnesylated and prenylated cargo such as INPP5E and PDE6 subunits. evidence: - *id017 - id: unc119b_myristoyl_carrier label: UNC119B carries myristoylated cargo participant: selector_type: GENE_PRODUCT gene_product: preferred_term: UNC119B term: id: UniProtKB:A6NIH7 label: Protein unc-119 homolog B function: preferred_term: lipid binding term: id: GO:0008289 label: lipid binding processes: - preferred_term: protein localization to ciliary membrane term: id: GO:1903441 label: protein localization to ciliary membrane role_description: Binds the myristoyl group of cargo such as NPHP3 and delivers it to the ciliary membrane. evidence: - *id018 - id: rp2_arl3_gap label: RP2 inactivates ARL3 participant: selector_type: GENE_PRODUCT gene_product: preferred_term: RP2 term: id: UniProtKB:O75695 label: Protein XRP2 function: preferred_term: GTPase activator activity term: id: GO:0005096 label: GTPase activator activity processes: - preferred_term: protein localization to ciliary membrane term: id: GO:1903441 label: protein localization to ciliary membrane role_description: GTPase-activating protein for ARL3; a regulator, not a cargo carrier. evidence: - *id018 - id: inpp5e_pip2_hydrolysis label: INPP5E sets ciliary phosphoinositides participant: selector_type: GENE_PRODUCT gene_product: preferred_term: INPP5E term: id: UniProtKB:Q9NRR6 label: Phosphatidylinositol polyphosphate 5-phosphatase type IV function: preferred_term: phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity term: id: GO:0004439 label: phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity locations: - preferred_term: ciliary membrane term: id: GO:0060170 label: ciliary membrane role_description: Hydrolyzes PI(4,5)P2 (and PI(3,4,5)P3) in the ciliary membrane. evidence: - *id019 - id: tulp3_gpcr_import label: TULP3 links IFT-A to membrane cargo participant: selector_type: GENE_PRODUCT gene_product: preferred_term: TULP3 term: id: UniProtKB:O75386 label: Tubby-related protein 3 function: preferred_term: protein-macromolecule adaptor activity term: id: GO:0030674 label: protein-macromolecule adaptor activity processes: - preferred_term: protein localization to cilium term: id: GO:0061512 label: protein localization to cilium role_description: Adaptor bridging IFT-A and phosphoinositides for GPCR import. evidence: - *id015 connections: - source: arl13b_arl3_gef target: arl3_cargo_release connection_type: POSITIVELY_REGULATES description: ARL13B loads ARL3 with GTP. - source: rp2_arl3_gap target: arl3_cargo_release connection_type: NEGATIVELY_REGULATES description: RP2 stimulates ARL3 GTP hydrolysis. - source: pde6d_prenyl_carrier target: arl3_cargo_release connection_type: PROVIDES_INPUT_FOR description: PDE6D-bound cargo is released by ARL3-GTP. - source: unc119b_myristoyl_carrier target: arl3_cargo_release connection_type: PROVIDES_INPUT_FOR description: UNC119B-bound cargo is released by ARL3-GTP. - order: 7 role: length control node: id: cilium_length_control label: Cilium length control module_type: REGULATORY_STEP concepts: - preferred_term: negative regulation of non-motile cilium assembly term: id: GO:1902856 label: negative regulation of non-motile cilium assembly description: >- Steady-state length reflects the balance of assembly and turnover at the tip. The RCK kinases CILK1 and MAK limit length by regulating IFT turnaround; CILK1 is the better-supported length kinase in most cells, while MAK evidence comes mainly from the photoreceptor connecting cilium. KIF7, a non-motile kinesin-4, binds growing microtubule plus ends and slows their growth at the tip. GO has no cilium-length term, so negative regulation of non-motile cilium assembly is used. evidence: - &id020 source_id: PMID:24853502 title: >- Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling. statement: Intestinal cell kinase (CILK1) is a key regulator of cilia length and signaling. - &id021 source_id: PMID:25243405 title: >- Regulation of cilium length and intraflagellar transport by the RCK-kinases ICK and MOK in renal epithelial cells. statement: >- The RCK kinases ICK and MOK regulate cilium length and intraflagellar transport in renal epithelial cells. - &id022 source_id: PMID:39293864 statement: >- Ccrk-Mak/Ick signaling regulates ciliary transport and is essential for retinal photoreceptor survival. - &id023 source_id: PMID:24952464 statement: KIF7 organizes the cilium tip compartment by limiting microtubule growth at the tip. annotons: - id: rck_kinases label: RCK kinases restrict cilium length participant: selector_type: PROTEIN_COMPLEX protein_complex: preferred_term: RCK kinases description: Ciliary length-control kinases (not a stable complex). active_units: - id: cilk1_unit label: CILK1 subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: CILK1 term: id: UniProtKB:Q9UPZ9 label: Serine/threonine-protein kinase ICK role: length-control kinase - id: mak_unit label: MAK subunit participant: selector_type: GENE_PRODUCT gene_product: preferred_term: MAK term: id: UniProtKB:P20794 label: Serine/threonine-protein kinase MAK role: length-control kinase function: preferred_term: protein serine/threonine kinase activity term: id: GO:0004674 label: protein serine/threonine kinase activity processes: - preferred_term: negative regulation of non-motile cilium assembly term: id: GO:1902856 label: negative regulation of non-motile cilium assembly locations: - preferred_term: ciliary tip term: id: GO:0097542 label: ciliary tip role_description: Phosphorylate kinesin-2 and IFT components to control IFT turnaround and length. evidence: - *id020 - *id021 - *id022 - id: kif7_tip_organizer label: KIF7 limits microtubule growth at the tip participant: selector_type: GENE_PRODUCT gene_product: preferred_term: KIF7 term: id: UniProtKB:Q2M1P5 label: Kinesin-like protein KIF7 function: preferred_term: microtubule plus-end binding term: id: GO:0051010 label: microtubule plus-end binding processes: - preferred_term: negative regulation of microtubule polymerization term: id: GO:0031115 label: negative regulation of microtubule polymerization - preferred_term: negative regulation of non-motile cilium assembly term: id: GO:1902856 label: negative regulation of non-motile cilium assembly locations: - preferred_term: ciliary tip term: id: GO:0097542 label: ciliary tip role_description: >- Non-motile kinesin-4 that binds microtubule plus ends at the ciliary tip and slows their growth; also a core Hedgehog-pathway regulator. evidence: - *id023 - order: 8 role: cilium disassembly node: id: cilium_disassembly label: Cilium disassembly before cell-cycle re-entry module_type: BIOLOGICAL_PROCESS concepts: - preferred_term: cilium disassembly term: id: GO:0061523 label: cilium disassembly description: >- On cell-cycle re-entry the cilium is resorbed so the centrioles can act at the spindle poles. NEDD9 and Pitchfork (CIMAP3) activate Aurora A at the basal body; Aurora A activates the tubulin deacetylase HDAC6. PLK1 activates KIF2A, which depolymerizes microtubules at the base and is held back by TTBK2 while the cilium grows. Phosphorylated Tctex-1 (DYNLT1) at the transition zone promotes resorption independently of dynein. AURKA, PLK1, KIF2A and NEDD9 are pleiotropic: their dominant roles are mitotic or adhesion-related, and ciliary disassembly is a secondary function. evidence: - *id024 - *id025 - &id028 source_id: PMID:20643351 title: Pitchfork regulates primary cilia disassembly and left-right asymmetry. statement: Pitchfork (CIMAP3) activates Aurora A at the basal body to regulate primary cilia disassembly. - &id029 source_id: PMID:21394082 title: >- Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors. statement: >- Phosphorylated Tctex-1 (DYNLT1) at the transition zone controls ciliary resorption before S-phase entry. - &id027 source_id: PMID:16184168 statement: HEF1/NEDD9 activates Aurora A in vitro and is required for its activation at the centrosome. - *id026 annotons: - id: aurka_disassembly_kinase label: Aurora A drives disassembly participant: selector_type: GENE_PRODUCT gene_product: preferred_term: AURKA term: id: UniProtKB:O14965 label: Aurora kinase A function: preferred_term: protein serine/threonine kinase activity term: id: GO:0004674 label: protein serine/threonine kinase activity processes: - preferred_term: cilium disassembly term: id: GO:0061523 label: cilium disassembly locations: - preferred_term: ciliary basal body term: id: GO:0036064 label: ciliary basal body role_description: Basal body kinase activated by NEDD9 and Pitchfork; phosphorylates HDAC6. evidence: - *id024 - id: nedd9_aurka_activation label: NEDD9 activates Aurora A participant: selector_type: GENE_PRODUCT gene_product: preferred_term: NEDD9 term: id: UniProtKB:Q14511 label: Enhancer of filamentation 1 function: preferred_term: protein serine/threonine kinase activator activity term: id: GO:0043539 label: protein serine/threonine kinase activator activity processes: - preferred_term: cilium disassembly term: id: GO:0061523 label: cilium disassembly role_description: Cas-family scaffold that activates Aurora A at the basal body. evidence: - *id024 - *id027 - id: pitchfork_aurka_activation label: Pitchfork activates Aurora A participant: selector_type: GENE_PRODUCT gene_product: preferred_term: CIMAP3 term: id: UniProtKB:Q8TCI5 label: Ciliary microtubule-associated protein 3 function: preferred_term: protein kinase activator activity term: id: GO:0030295 label: protein kinase activator activity processes: - preferred_term: cilium disassembly term: id: GO:0061523 label: cilium disassembly role_description: Activates Aurora A at the basal body to drive cilium disassembly. evidence: - *id028 - id: hdac6_deacetylation label: HDAC6 deacetylates axonemal tubulin participant: selector_type: GENE_PRODUCT gene_product: preferred_term: HDAC6 term: id: UniProtKB:Q9UBN7 label: Protein deacetylase HDAC6 function: preferred_term: tubulin deacetylase activity term: id: GO:0042903 label: tubulin deacetylase activity processes: - preferred_term: cilium disassembly term: id: GO:0061523 label: cilium disassembly role_description: Tubulin deacetylase activated by Aurora A. evidence: - *id024 - id: plk1_kinase label: PLK1 activates KIF2A participant: selector_type: GENE_PRODUCT gene_product: preferred_term: PLK1 term: id: UniProtKB:P53350 label: Serine/threonine-protein kinase PLK1 function: preferred_term: protein serine/threonine kinase activity term: id: GO:0004674 label: protein serine/threonine kinase activity processes: - preferred_term: cilium disassembly term: id: GO:0061523 label: cilium disassembly role_description: Kinase that activates KIF2A at the basal body. evidence: - *id025 - id: kif2a_depolymerization label: KIF2A depolymerizes microtubules participant: selector_type: GENE_PRODUCT gene_product: preferred_term: KIF2A term: id: UniProtKB:O00139 label: Kinesin-like protein KIF2A function: preferred_term: ATP-dependent microtubule depolymerase activity description: No GO MF term exists; proposed as a new term in the KIF2A review. processes: - preferred_term: microtubule depolymerization term: id: GO:0007019 label: microtubule depolymerization - preferred_term: cilium disassembly term: id: GO:0061523 label: cilium disassembly locations: - preferred_term: ciliary basal body term: id: GO:0036064 label: ciliary basal body role_description: Kinesin-13 ATP-dependent microtubule depolymerase acting at the mother centriole. evidence: - *id025 - *id026 - id: tctex1_resorption label: Phosphorylated Tctex-1 promotes resorption participant: selector_type: GENE_PRODUCT gene_product: preferred_term: DYNLT1 term: id: UniProtKB:P63172 label: Dynein light chain Tctex-type 1 function: preferred_term: resorption promoter processes: - preferred_term: cilium disassembly term: id: GO:0061523 label: cilium disassembly locations: - preferred_term: ciliary transition zone term: id: GO:0035869 label: ciliary transition zone role_description: Phospho-Tctex-1 at the transition zone promotes ciliary resorption, independently of dynein. evidence: - *id029 connections: - source: nedd9_aurka_activation target: aurka_disassembly_kinase connection_type: POSITIVELY_REGULATES description: NEDD9 activates Aurora A. - source: pitchfork_aurka_activation target: aurka_disassembly_kinase connection_type: POSITIVELY_REGULATES description: Pitchfork activates Aurora A. - source: aurka_disassembly_kinase target: hdac6_deacetylation connection_type: POSITIVELY_REGULATES description: Aurora A phosphorylates and activates HDAC6. - source: plk1_kinase target: kif2a_depolymerization connection_type: POSITIVELY_REGULATES description: PLK1 activates KIF2A. connections: - source: mother_centriole_licensing target: ciliary_vesicle_formation connection_type: PRECEDES - source: ciliary_vesicle_formation target: ciliary_membrane_extension connection_type: PRECEDES description: RAB8 is activated only after the ciliary vesicle has formed. - source: ciliary_vesicle_formation target: transition_zone_assembly connection_type: PRECEDES - source: transition_zone_assembly target: axoneme_extension_ift connection_type: PRECEDES - source: axoneme_extension_ift target: ciliary_membrane_composition connection_type: PRECEDES - source: ciliary_membrane_composition target: cilium_disassembly connection_type: PRECEDES description: A mature cilium is resorbed when the cell re-enters the cell cycle. - source: cilium_length_control target: axoneme_extension_ift connection_type: NEGATIVELY_REGULATES description: RCK kinases and KIF7 limit axoneme length. knowledge_gaps: - gap_statement: >- The molecular activities of the distal appendage proteins (CEP83, SCLT1, FBF1, CEP164), the transition zone MKS-module proteins and the IFT-B scaffold subunits (IFT88, IFT52, IFT172) are unknown beyond 'structural scaffold'. boundary: >- Their requirement for ciliogenesis and their positions are well established; what each protein does mechanistically (binding partners, membrane contacts, gating chemistry) is not. gap_kind: - BIOLOGY status: OPEN significance: >- Most structural ciliogenesis proteins have no defined molecular function, so the module can say where they act but not how. resolution: >- Reconstitution and structure-function work, for example in vitro membrane-binding and barrier assays with purified MKS-module and distal appendage subcomplexes.