Primary cilium life cycle module

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.

MODULE:primary_cilium_life_cycleDRAFTCONCRETEOrganelle Lifecyclemodules/primary_cilium_life_cycle.yaml
cilium organizationGO:0044782 non-motile ciliumGO:0097730
PMID:41005307
Intrinsic heterogeneity of primary cilia revealed through spatial proteomics.
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.
PMID:23348840
Centriole distal appendages promote membrane docking, leading to cilia initiation.
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.
PMID:23141541
The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis.
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.
PMID:25686250
Early steps in primary cilium assembly require EHD1/EHD3-dependent ciliary vesicle formation.
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.
PMID:21725307
A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition.
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.
PMID:31451806
Structure of the dynein-2 complex and its assembly with intraflagellar transport trains.
Structure of the dynein-2 complex and its assembly onto IFT trains for retrograde transport.
PMID:17604723
HEF1-dependent Aurora A activation induces disassembly of the primary cilium.
NEDD9/HEF1 activates Aurora A at the basal body, which phosphorylates and activates the tubulin deacetylase HDAC6 to drive ciliary disassembly.
PMID:25660017
The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation.
PLK1-activated KIF2A depolymerizes microtubules at the basal body to drive primary cilium disassembly.

Revised 2026-10-03 after gene reviews of all 60 members (genes/human/<GENE>/). 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.

9Nodes
8Parts
0Variant Sets
0Variants
33Annotons
25Connections

Derived QC

Recommended-field compliance

80.0% recommended fields populated
  • knowledge_gaps[0] · provenance (0/1)

Module deep research

✗ none found

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

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

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.

  • mother_centriole_licensing → ciliary_vesicle_formation [NOT_CHECKED]
  • ciliary_vesicle_formation → ciliary_membrane_extension [NOT_CHECKED]
  • ciliary_vesicle_formation → transition_zone_assembly [NOT_CHECKED]
  • transition_zone_assembly → axoneme_extension_ift [NOT_CHECKED]
  • axoneme_extension_ift → ciliary_membrane_composition [NOT_CHECKED]
  • ciliary_membrane_composition → cilium_disassembly [NOT_CHECKED]

Function consistency and core coverage

18 gene-function check(s) reflected in core functions · 0 conflict(s) · 5 evidence or coverage gap(s) (34 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
distal_appendage_assembly PROTEIN_COMPLEX
Gene 		distal appendage scaffold
No function ID 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
ttbk2_cap_removal TTBK2
UniProtKB:Q6IQ55
Gene 		protein serine/threonine kinase activity
GO:0004674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cp110_cep97_cap PROTEIN_COMPLEX
Gene 		ciliogenesis suppressor cap
No function ID 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
kif24_cap_recruitment KIF24
UniProtKB:Q5T7B8
Gene 		microtubule depolymerase
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
myo5a_vesicle_delivery MYO5A
UniProtKB:Q9Y4I1
Gene 		microfilament motor activity
GO:0000146 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ehd_vesicle_tubulation PROTEIN_COMPLEX
Gene 		ATP hydrolysis activity
GO:0016887 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
rabin8_rab8_gef RAB3IP
UniProtKB:Q96QF0
Gene 		guanyl-nucleotide exchange factor activity
GO:0005085 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rab8_membrane_supply RAB8A
UniProtKB:P61006
Gene 		GTPase activity
GO:0003924 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rpgrip1l_tz_foundation RPGRIP1L
UniProtKB:Q68CZ1
Gene 		transition zone scaffold
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
mks_module PROTEIN_COMPLEX
Gene 		ciliary diffusion barrier
No function ID 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
nphp_module PROTEIN_COMPLEX
Gene 		protein-macromolecule adaptor activity
GO:0030674 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
cep290_tz_scaffold CEP290
UniProtKB:O15078
Gene 		transition zone scaffold
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
ift_b_scaffold PROTEIN_COMPLEX
Gene 		IFT-B structural scaffold
No function ID 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
ift81_ift74_tubulin PROTEIN_COMPLEX
Gene 		tubulin binding
GO:0015631 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
ift_a_complex PROTEIN_COMPLEX
Gene 		protein carrier activity
GO:0140597 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
kinesin2_anterograde PROTEIN_COMPLEX
Gene 		plus-end-directed microtubule motor activity
GO:0008574 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
kinesin2_anterograde/kifap3_unit KIFAP3
UniProtKB:Q92845
Complex Unit 		protein-macromolecule adaptor activity
GO:0030674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dynein2_retrograde PROTEIN_COMPLEX
Gene 		minus-end-directed microtubule motor activity
GO:0008569 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
arl13b_arl3_gef ARL13B
UniProtKB:Q3SXY8
Gene 		guanyl-nucleotide exchange factor activity
GO:0005085 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
arl3_cargo_release ARL3
UniProtKB:P36405
Gene 		G protein activity
GO:0003925 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pde6d_prenyl_carrier PDE6D
UniProtKB:O43924
Gene 		farnesylated protein binding
GO:0001918 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
unc119b_myristoyl_carrier UNC119B
UniProtKB:A6NIH7
Gene 		lipid binding
GO:0008289 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rp2_arl3_gap RP2
UniProtKB:O75695
Gene 		GTPase activator activity
GO:0005096 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
inpp5e_pip2_hydrolysis INPP5E
UniProtKB:Q9NRR6
Gene 		phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity
GO:0004439 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tulp3_gpcr_import TULP3
UniProtKB:O75386
Gene 		protein-macromolecule adaptor activity
GO:0030674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
rck_kinases PROTEIN_COMPLEX
Gene 		protein serine/threonine kinase activity
GO:0004674 		Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews.
kif7_tip_organizer KIF7
UniProtKB:Q2M1P5
Gene 		microtubule plus-end binding
GO:0051010 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aurka_disassembly_kinase AURKA
UniProtKB:O14965
Gene 		protein serine/threonine kinase activity
GO:0004674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
nedd9_aurka_activation NEDD9
UniProtKB:Q14511
Gene 		protein serine/threonine kinase activator activity
GO:0043539 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pitchfork_aurka_activation CIMAP3
UniProtKB:Q8TCI5
Gene 		protein kinase activator activity
GO:0030295 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hdac6_deacetylation HDAC6
UniProtKB:Q9UBN7
Gene 		tubulin deacetylase activity
GO:0042903 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
plk1_kinase PLK1
UniProtKB:P53350
Gene 		protein serine/threonine kinase activity
GO:0004674 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
kif2a_depolymerization KIF2A
UniProtKB:O00139
Gene 		ATP-dependent microtubule depolymerase activity
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
tctex1_resorption DYNLT1
UniProtKB:P63172
Gene 		resorption promoter
No function ID 		No Function Id
A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.

Feedback loops (advisory, prose-driven: a regulator counts as "feedback" when its own description says so)

✓ every negative regulator described as feedback has an upstream edge closing the loop.

  • cilium_length_control ⊣ axoneme_extension_ift [input]
    cilium_length_control is a negative regulator with no upstream edge (not described as feedback)
  • ttbk2_cap_removal ⊣ cp110_cep97_cap [closed]
    ttbk2_cap_removal is regulated by distal_appendage_assembly: feedback loop closed
  • rp2_arl3_gap ⊣ arl3_cargo_release [input]
    rp2_arl3_gap is a negative regulator with no upstream edge (not described as feedback)

Gene-review completeness (60/60 grounded genes reviewed)

46 complete review(s) · 58 with deep research · 0 missing review · 2 reviewed but lacking deep research

Gene Review Complete Deep research
ARL13B Q3SXY8 ✓ 46/178 ✗
ARL3 P36405 ✓ ✓ ✓
AURKA O14965 ✓ 153/154 ✓
B9D1 Q9UPM9 ✓ ✓ ✗
B9D2 Q9BPU9 ✓ ✓ ✓
CC2D2A Q9P2K1 ✓ ✓ ✓
CCP110 O43303 ✓ ✓ ✓
CEP164 Q9UPV0 ✓ 46/48 ✓
CEP290 O15078 ✓ 99/101 ✓
CEP83 Q9Y592 ✓ ✓ ✓
CEP89 Q96ST8 ✓ 38/39 ✓
CEP97 Q8IW35 ✓ ✓ ✓
CILK1 Q9UPZ9 ✓ ✓ ✓
CIMAP3 Q8TCI5 ✓ ✓ ✓
DYNC2H1 Q8NCM8 ✓ 44/46 ✓
DYNC2I1 Q8WVS4 ✓ ✓ ✓
DYNC2I2 Q96EX3 ✓ 56/57 ✓
DYNC2LI1 Q8TCX1 ✓ ✓ ✓
DYNLT1 P63172 ✓ 66/68 ✓
EHD1 Q9H4M9 ✓ ✓ ✓
EHD3 Q9NZN3 ✓ ✓ ✓
FBF1 Q8TES7 ✓ ✓ ✓
HDAC6 Q9UBN7 ✓ 173/175 ✓
IFT122 Q9HBG6 ✓ ✓ ✓
IFT140 Q96RY7 ✓ ✓ ✓
IFT172 Q9UG01 ✓ ✓ ✓
IFT52 Q9Y366 ✓ ✓ ✓
IFT74 Q96LB3 ✓ ✓ ✓
IFT81 Q8WYA0 ✓ ✓ ✓
IFT88 Q13099 ✓ ✓ ✓
INPP5E Q9NRR6 ✓ ✓ ✓
KIF24 Q5T7B8 ✓ ✓ ✓
KIF2A O00139 ✓ ✓ ✓
KIF3A Q9Y496 ✓ ✓ ✓
KIF3B O15066 ✓ 73/74 ✓
KIF7 Q2M1P5 ✓ ✓ ✓
KIFAP3 Q92845 ✓ ✓ ✓
MAK P20794 ✓ ✓ ✓
MKS1 Q9NXB0 ✓ ✓ ✓
MYO5A Q9Y4I1 ✓ ✓ ✓
NEDD9 Q14511 ✓ 77/78 ✓
NPHP1 O15259 ✓ ✓ ✓
NPHP4 O75161 ✓ ✓ ✓
PDE6D O43924 ✓ ✓ ✓
PLK1 P53350 ✓ 326/328 ✓
RAB3IP Q96QF0 ✓ ✓ ✓
RAB8A P61006 ✓ ✓ ✓
RP2 O75695 ✓ 43/44 ✓
RPGRIP1L Q68CZ1 ✓ ✓ ✓
SCLT1 Q96NL6 ✓ ✓ ✓
TCTN1 Q2MV58 ✓ ✓ ✓
TCTN2 Q96GX1 ✓ ✓ ✓
TMEM216 Q9P0N5 ✓ ✓ ✓
TMEM231 Q9H6L2 ✓ ✓ ✓
TMEM67 Q5HYA8 ✓ ✓ ✓
TTBK2 Q6IQ55 ✓ ✓ ✓
TTC21B Q7Z4L5 ✓ 28/29 ✓
TULP3 O75386 ✓ ✓ ✓
UNC119B A6NIH7 ✓ ✓ ✓
WDR35 Q9P2L0 ✓ ✓ ✓

Details

Context
Homo sapiensNCBITaxon:9606
quiescent or differentiated cells that form a primary cilium
Primary cilium life cycleOrganelle Lifecycleprimary_cilium_life_cycle
cilium organizationGO:0044782 non-motile ciliumGO:0097730
Context
Homo sapiensNCBITaxon:9606
quiescent or differentiated cells that form a primary cilium

Connections

RAB8 is activated only after the ciliary vesicle has formed.
A mature cilium is resorbed when the cell re-enters the cell cycle.
RCK kinases and KIF7 limit axoneme length.
Part 1: mother centriole licensing
Mother centriole licensing and basal body conversionBiological Processmother_centriole_licensing

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.

non-motile cilium assemblyGO:1905515
PMID:23348840
Centriole distal appendages promote membrane docking, leading to cilia initiation.
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.
PMID:23141541
The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis.
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.
PMID:21620453
Centriolar kinesin Kif24 interacts with CP110 to remodel microtubules and regulate ciliogenesis.
KIF24 binds CP110 and CEP97 at the mother centriole, depolymerizes microtubules in vitro, and restrains cilia assembly in cycling cells.
PMID:39882855
CEP89 positions myristoylated NCS1 at the distal appendages, where it captures preciliary vesicles for ciliary vesicle formation.

Annotons

Distal appendage (transition fiber) complex
distal_appendage_assembly
Participant: Protein Complex: centriole distal appendage complex
Protein Complex:
centriole distal appendage complex Distal appendage proteins assembled hierarchically on the mother centriole.
Active units:
CEP83 subunit
Participant: Gene Product: CEP83
Gene Product:
CEP83UniProtKB:Q9Y592
Role: distal appendage component
SCLT1 subunit
Participant: Gene Product: SCLT1
Gene Product:
SCLT1UniProtKB:Q96NL6
Role: distal appendage component
CEP89 subunit
Participant: Gene Product: CEP89
Gene Product:
CEP89UniProtKB:Q96ST8
Role: distal appendage component
FBF1 subunit
Participant: Gene Product: FBF1
Gene Product:
FBF1UniProtKB:Q8TES7
Role: distal appendage component
CEP164 subunit
Participant: Gene Product: CEP164
Gene Product:
CEP164UniProtKB:Q9UPV0
Role: distal appendage component

Function

distal appendage scaffold Structural scaffold role; no specific GO molecular-function term is asserted. CEP89 additionally acts as an adaptor for NCS1-mediated vesicle capture.

Processes

non-motile cilium assemblyGO:1905515

Locations

ciliary basal bodyGO:0036064

Docks the mother centriole to vesicles and membrane and recruits TTBK2.

PMID:23348840
Centriole distal appendages promote membrane docking, leading to cilia initiation.
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.
PMID:39882855
CEP89 positions myristoylated NCS1 at the distal appendages, where it captures preciliary vesicles for ciliary vesicle formation.
TTBK2 triggers CP110 cap removal
ttbk2_cap_removal
Participant: Gene Product: TTBK2
Gene Product:
TTBK2UniProtKB:Q6IQ55

Function

protein serine/threonine kinase activityGO:0004674

Processes

non-motile cilium assemblyGO:1905515

Locations

ciliary basal bodyGO:0036064

Kinase recruited by CEP164 that triggers CP110-CEP97 cap removal and IFT recruitment, and restrains KIF2A during cilium growth.

PMID:23141541
The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis.
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.
PMID:39930500
TTBK2 restrains the microtubule depolymerizer KIF2A at the mother centriole to support primary cilia growth.
CP110-CEP97 distal cap suppresses ciliogenesis
cp110_cep97_cap
Participant: Protein Complex: CP110-CEP97 distal centriole cap
Protein Complex:
CP110-CEP97 distal centriole cap Cap on the distal end of the mother centriole that blocks axoneme extension until removed.
Active units:
CCP110 subunit
Participant: Gene Product: CCP110
Gene Product:
CCP110UniProtKB:O43303
Role: distal cap component
CEP97 subunit
Participant: Gene Product: CEP97
Gene Product:
CEP97UniProtKB:Q8IW35
Role: distal cap component

Function

ciliogenesis suppressor cap CP110 caps microtubule plus ends; CEP97 acts as a protein-macromolecule adaptor.

Processes

negative regulation of cilium assemblyGO:1902018

Locations

centrioleGO:0005814

Inhibitory cap; its removal licenses axoneme growth. CEP97 is the adaptor that stabilizes CP110.

PMID:21620453
Centriolar kinesin Kif24 interacts with CP110 to remodel microtubules and regulate ciliogenesis.
KIF24 binds CP110 and CEP97 at the mother centriole, depolymerizes microtubules in vitro, and restrains cilia assembly in cycling cells.
PMID:23141541
The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis.
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.
KIF24 recruits the cap and remodels centriolar microtubules
kif24_cap_recruitment
Participant: Gene Product: KIF24
Gene Product:
KIF24UniProtKB:Q5T7B8

Function

microtubule depolymerase No GO MF term for microtubule depolymerase activity.

Processes

negative regulation of cilium assemblyGO:1902018

Locations

centrioleGO:0005814

Kinesin-13 that recruits MPHOSPH9 and the CP110-CEP97 cap to the mother centriole and depolymerizes centriolar microtubules, suppressing ciliogenesis in cycling cells.

PMID:21620453
Centriolar kinesin Kif24 interacts with CP110 to remodel microtubules and regulate ciliogenesis.
KIF24 binds CP110 and CEP97 at the mother centriole, depolymerizes microtubules in vitro, and restrains cilia assembly in cycling cells.

Connections

CEP164 at the distal appendages recruits TTBK2 to the mother centriole.
ttbk2_cap_removal -> cp110_cep97_cap Negatively Regulates
TTBK2 triggers removal of the CP110-CEP97 cap.
kif24_cap_recruitment -> cp110_cep97_cap Positively Regulates
KIF24 recruits and maintains the cap at the mother centriole.
Part 2: ciliary vesicle formation
Ciliary vesicle formation at the distal appendagesBiological Processciliary_vesicle_formation

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.

ciliary vesicle assemblyGO:1905556
PMID:29335527
Myosin-Va is required for preciliary vesicle transportation to the mother centriole during ciliogenesis.
Myosin-Va transports preciliary vesicles to the mother centriole, the earliest known step of ciliary vesicle formation.
PMID:25686250
Early steps in primary cilium assembly require EHD1/EHD3-dependent ciliary vesicle formation.
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.

Annotons

Myosin-Va preciliary vesicle delivery
myo5a_vesicle_delivery
Participant: Gene Product: MYO5A
Gene Product:
MYO5AUniProtKB:Q9Y4I1

Function

microfilament motor activityGO:0000146

Processes

vesicle transport along actin filamentGO:0030050 cilium assemblyGO:0060271

Processive actin motor that carries preciliary vesicles to the mother centriole; its dominant roles (melanosome and secretory vesicle transport) lie outside cilia.

PMID:29335527
Myosin-Va is required for preciliary vesicle transportation to the mother centriole during ciliogenesis.
Myosin-Va transports preciliary vesicles to the mother centriole, the earliest known step of ciliary vesicle formation.
EHD1/EHD3 membrane tubulation
ehd_vesicle_tubulation
Participant: Protein Complex: EHD1/EHD3 membrane-shaping proteins
Protein Complex:
EHD1/EHD3 membrane-shaping proteins Membrane-tubulating EH-domain ATPases acting on distal appendage vesicles.
Active units:
EHD1 subunit
Participant: Gene Product: EHD1
Gene Product:
EHD1UniProtKB:Q9H4M9
Role: membrane-shaping ATPase
EHD3 subunit
Participant: Gene Product: EHD3
Gene Product:
EHD3UniProtKB:Q9NZN3
Role: membrane-shaping ATPase

Function

ATP hydrolysis activityGO:0016887

Processes

ciliary vesicle assemblyGO:1905556

Locations

ciliary vesicleGO:0097721

Tubulate distal appendage vesicles to form the ciliary vesicle.

PMID:25686250
Early steps in primary cilium assembly require EHD1/EHD3-dependent ciliary vesicle formation.
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.

Connections

Delivered vesicles are remodeled by EHD1/EHD3 into the ciliary vesicle.
Part 3: ciliary membrane extension
Ciliary membrane supply and extensionBiological Processciliary_membrane_extension

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.

cilium assemblyGO:0060271
PMID:17574030
A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.
Rab8-GTP, produced by the Rab8 GEF Rabin8 at the basal body, enters the cilium and promotes ciliary membrane extension.
PMID:25686250
Early steps in primary cilium assembly require EHD1/EHD3-dependent ciliary vesicle formation.
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.

Annotons

Rabin8 activates Rab8
rabin8_rab8_gef
Participant: Gene Product: RAB3IP
Gene Product:
RAB3IPUniProtKB:Q96QF0

Function

guanyl-nucleotide exchange factor activityGO:0005085

Processes

cilium assemblyGO:0060271

RAB8 guanine nucleotide exchange factor, delivered to the mother centriole downstream of RAB11.

PMID:17574030
A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.
Rab8-GTP, produced by the Rab8 GEF Rabin8 at the basal body, enters the cilium and promotes ciliary membrane extension.
Rab8 ciliary membrane delivery
rab8_membrane_supply
Participant: Gene Product: RAB8A
Gene Product:
RAB8AUniProtKB:P61006

Function

GTPase activityGO:0003924

Processes

cilium assemblyGO:0060271

Locations

ciliary membraneGO:0060170

GTP-bound RAB8A enters the cilium and promotes ciliary membrane extension.

PMID:17574030
A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis.
Rab8-GTP, produced by the Rab8 GEF Rabin8 at the basal body, enters the cilium and promotes ciliary membrane extension.
PMID:25686250
Early steps in primary cilium assembly require EHD1/EHD3-dependent ciliary vesicle formation.
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.

Connections

rabin8_rab8_gef -> rab8_membrane_supply Positively Regulates
Rabin8 loads RAB8A with GTP.
Part 4: transition zone assembly
Transition zone assemblyBiological Processtransition_zone_assembly

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.

ciliary transition zone assemblyGO:1905349
PMID:21725307
A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition.
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.
PMID:26392567
Mks5/RPGRIP1L is required to form the transition zone and its ciliary zone of exclusion.
PMID:21422230
MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function.

Annotons

RPGRIP1L founds the transition zone
rpgrip1l_tz_foundation
Participant: Gene Product: RPGRIP1L
Gene Product:
RPGRIP1LUniProtKB:Q68CZ1

Function

transition zone scaffold

Processes

ciliary transition zone assemblyGO:1905349

Locations

ciliary transition zoneGO:0035869

Foundational transition zone assembly factor upstream of the MKS and NPHP modules and CEP290.

PMID:26392567
Mks5/RPGRIP1L is required to form the transition zone and its ciliary zone of exclusion.
MKS module
mks_module
Participant: Protein Complex: MKS complex
Protein Complex:
MKS complexGO:0036038 Tectonic/MKS ciliopathy protein complex at the transition zone.
Active units:
MKS1 subunit
Participant: Gene Product: MKS1
Gene Product:
MKS1UniProtKB:Q9NXB0
Role: MKS module component
TMEM67 subunit
Participant: Gene Product: TMEM67
Gene Product:
TMEM67UniProtKB:Q5HYA8
Role: MKS module component
CC2D2A subunit
Participant: Gene Product: CC2D2A
Gene Product:
CC2D2AUniProtKB:Q9P2K1
Role: MKS module component
B9D1 subunit
Participant: Gene Product: B9D1
Gene Product:
B9D1UniProtKB:Q9UPM9
Role: MKS module component
B9D2 subunit
Participant: Gene Product: B9D2
Gene Product:
B9D2UniProtKB:Q9BPU9
Role: MKS module component
TCTN1 subunit
Participant: Gene Product: TCTN1
Gene Product:
TCTN1UniProtKB:Q2MV58
Role: MKS module component
TCTN2 subunit
Participant: Gene Product: TCTN2
Gene Product:
TCTN2UniProtKB:Q96GX1
Role: MKS module component
TMEM216 subunit
Participant: Gene Product: TMEM216
Gene Product:
TMEM216UniProtKB:Q9P0N5
Role: MKS module component
TMEM231 subunit
Participant: Gene Product: TMEM231
Gene Product:
TMEM231UniProtKB:Q9H6L2
Role: MKS module component

Function

ciliary diffusion barrier Barrier/gating role; no GO MF term asserted.

Processes

ciliary transition zone assemblyGO:1905349

Locations

ciliary transition zoneGO:0035869

Transition zone gate that controls entry of ciliary membrane proteins.

PMID:21725307
A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition.
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.
NPHP module
nphp_module
Participant: Protein Complex: NPHP module
Protein Complex:
NPHP module Nephronophthisis proteins at the transition zone; NPHP4 is the hub.
Active units:
NPHP4 subunit
Participant: Gene Product: NPHP4
Gene Product:
NPHP4UniProtKB:O75161
Role: NPHP module component
NPHP1 subunit
Participant: Gene Product: NPHP1
Gene Product:
NPHP1UniProtKB:O15259
Role: NPHP module component

Function

protein-macromolecule adaptor activityGO:0030674

Processes

ciliary transition zone assemblyGO:1905349

Locations

ciliary transition zoneGO:0035869

Second transition zone module, partly redundant with the MKS module.

PMID:21422230
MKS and NPHP modules cooperate to establish basal body/transition zone membrane associations and ciliary gate function.
CEP290 transition zone scaffold
cep290_tz_scaffold
Participant: Gene Product: CEP290
Gene Product:
CEP290UniProtKB:O15078

Function

transition zone scaffold

Processes

ciliary transition zone assemblyGO:1905349

Locations

ciliary transition zoneGO:0035869

Builds the microtubule-to-membrane Y-links of the transition zone; also acts at centriolar satellites in ciliary vesicle maturation.

PMID:21725307
A transition zone complex regulates mammalian ciliogenesis and ciliary membrane composition.
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.

Connections

RPGRIP1L is required to assemble the MKS module.
RPGRIP1L is required to recruit the NPHP module.
RPGRIP1L is required for CEP290 localization.
Part 5: axoneme extension by IFT
Axoneme extension by intraflagellar transportBiological Processaxoneme_extension_ift

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.

intraciliary transportGO:0042073
PMID:11062270
Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella.
IFT88 and its mouse homologue Tg737 are required for cilium and flagellum assembly.
PMID:36354106
Biochemically validated structural model of the 15-subunit intraflagellar transport complex IFT-B.
Biochemically validated structural model of the 15-subunit IFT-B complex.
PMID:36775821
Human IFT-A complex structures provide molecular insights into ciliary transport.
Structures of the human IFT-A complex provide the molecular basis of IFT-A in ciliary transport.
PMID:31451806
Structure of the dynein-2 complex and its assembly with intraflagellar transport trains.
Structure of the dynein-2 complex and its assembly onto IFT trains for retrograde transport.

Annotons

IFT-B scaffold subunits
ift_b_scaffold
Participant: Protein Complex: IFT-B complex (scaffold subunits)
Protein Complex:
IFT-B complex (scaffold subunits)GO:0030992 Structural core and peripheral IFT-B subunits.
Active units:
IFT88 subunit
Participant: Gene Product: IFT88
Gene Product:
IFT88UniProtKB:Q13099
Role: IFT-B subunit
IFT52 subunit
Participant: Gene Product: IFT52
Gene Product:
IFT52UniProtKB:Q9Y366
Role: IFT-B subunit
IFT172 subunit
Participant: Gene Product: IFT172
Gene Product:
IFT172UniProtKB:Q9UG01
Role: IFT-B subunit

Function

IFT-B structural scaffold No GO MF term asserted; cargo binding is shown only for IFT81-IFT74.

Processes

intraciliary anterograde transportGO:0035720 cilium assemblyGO:0060271

Locations

non-motile ciliumGO:0097730

Backbone of anterograde IFT trains.

PMID:11062270
Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella.
IFT88 and its mouse homologue Tg737 are required for cilium and flagellum assembly.
PMID:36354106
Biochemically validated structural model of the 15-subunit intraflagellar transport complex IFT-B.
Biochemically validated structural model of the 15-subunit IFT-B complex.
IFT81-IFT74 tubulin module
ift81_ift74_tubulin
Participant: Protein Complex: IFT81-IFT74 tubulin-binding module
Protein Complex:
IFT81-IFT74 tubulin-binding moduleGO:0030992 IFT-B subcomplex that binds tubulin cargo.
Active units:
IFT81 subunit
Participant: Gene Product: IFT81
Gene Product:
IFT81UniProtKB:Q8WYA0
Role: tubulin-binding IFT-B subunit
IFT74 subunit
Participant: Gene Product: IFT74
Gene Product:
IFT74UniProtKB:Q96LB3
Role: tubulin-binding IFT-B subunit

Function

tubulin bindingGO:0015631

Processes

intraciliary anterograde transportGO:0035720 cilium assemblyGO:0060271

Locations

non-motile ciliumGO:0097730

Binds tubulin for delivery to the growing axoneme tip.

PMID:36354106
Biochemically validated structural model of the 15-subunit intraflagellar transport complex IFT-B.
Biochemically validated structural model of the 15-subunit IFT-B complex.
IFT-A complex
ift_a_complex
Participant: Protein Complex: IFT-A complex
Protein Complex:
IFT-A complexGO:0030991 Retrograde IFT and membrane-protein import complex.
Active units:
IFT140 subunit
Participant: Gene Product: IFT140
Gene Product:
IFT140UniProtKB:Q96RY7
Role: IFT-A subunit
IFT122 subunit
Participant: Gene Product: IFT122
Gene Product:
IFT122UniProtKB:Q9HBG6
Role: IFT-A subunit
WDR35 subunit
Participant: Gene Product: WDR35
Gene Product:
WDR35UniProtKB:Q9P2L0
Role: IFT-A subunit
TTC21B subunit
Participant: Gene Product: TTC21B
Gene Product:
TTC21BUniProtKB:Q7Z4L5
Role: IFT-A subunit

Function

protein carrier activityGO:0140597

Processes

intraciliary retrograde transportGO:0035721 protein localization to ciliumGO:0061512

Locations

non-motile ciliumGO:0097730

Retrograde train component and, with TULP3, carrier for membrane-protein entry into cilia.

PMID:36775821
Human IFT-A complex structures provide molecular insights into ciliary transport.
Structures of the human IFT-A complex provide the molecular basis of IFT-A in ciliary transport.
PMID:20889716
TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia.
TULP3 bridges the IFT-A complex and membrane phosphoinositides to traffic G protein-coupled receptors into cilia.
Heterotrimeric kinesin-2
kinesin2_anterograde
Participant: Protein Complex: kinesin-2 (KIF3A/KIF3B/KIFAP3)
Protein Complex:
kinesin-2 (KIF3A/KIF3B/KIFAP3)GO:0016939 Heterotrimeric kinesin II motor.
Active units:
KIF3A subunit
Participant: Gene Product: KIF3A
Gene Product:
KIF3AUniProtKB:Q9Y496
Role: kinesin-2 motor subunit
KIF3B subunit
Participant: Gene Product: KIF3B
Gene Product:
KIF3BUniProtKB:O15066
Role: kinesin-2 motor subunit
KIFAP3 subunit
Participant: Gene Product: KIFAP3
Gene Product:
KIFAP3UniProtKB:Q92845
Role: non-motor cargo adaptor subunit
Function:
protein-macromolecule adaptor activityGO:0030674

Function

plus-end-directed microtubule motor activityGO:0008574

Processes

intraciliary anterograde transportGO:0035720

Locations

axonemeGO:0005930

Anterograde IFT motor. KIF3A and KIF3B carry the motor activity; KIFAP3 contributes to it as the non-motor cargo adaptor (protein-macromolecule adaptor activity).

Dynein-2
dynein2_retrograde
Participant: Protein Complex: cytoplasmic dynein-2
Protein Complex:
cytoplasmic dynein-2GO:0005868 Retrograde IFT motor complex; DYNC2H1 is the motor, the intermediate and light intermediate chains contribute.
Active units:
DYNC2H1 subunit
Participant: Gene Product: DYNC2H1
Gene Product:
DYNC2H1UniProtKB:Q8NCM8
Role: dynein-2 subunit
DYNC2LI1 subunit
Participant: Gene Product: DYNC2LI1
Gene Product:
DYNC2LI1UniProtKB:Q8TCX1
Role: dynein-2 subunit
DYNC2I1 subunit
Participant: Gene Product: DYNC2I1
Gene Product:
DYNC2I1UniProtKB:Q8WVS4
Role: dynein-2 subunit
DYNC2I2 subunit
Participant: Gene Product: DYNC2I2
Gene Product:
DYNC2I2UniProtKB:Q96EX3
Role: dynein-2 subunit

Function

minus-end-directed microtubule motor activityGO:0008569

Processes

intraciliary retrograde transportGO:0035721

Locations

axonemeGO:0005930

Retrograde IFT motor, carried to the tip in an autoinhibited state on anterograde trains.

PMID:31451806
Structure of the dynein-2 complex and its assembly with intraflagellar transport trains.
Structure of the dynein-2 complex and its assembly onto IFT trains for retrograde transport.

Connections

kinesin2_anterograde -> ift_b_scaffold Provides Input For
Kinesin-2 moves IFT-B trains toward the ciliary tip.
dynein2_retrograde -> ift_a_complex Provides Input For
Dynein-2 returns IFT-A trains to the base.
Part 6: ciliary membrane composition
Ciliary membrane identity and protein targetingBiological Processciliary_membrane_composition

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.

protein localization to ciliumGO:0061512
PMID:26551564
A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins.
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.
PMID:20889716
TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia.
TULP3 bridges the IFT-A complex and membrane phosphoinositides to traffic G protein-coupled receptors into cilia.
PMID:19668215
INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse.
INPP5E localizes to cilia; its loss causes ciliary signaling defects and ciliary instability.
PMID:22002721
PDE6D is a GDI-like carrier for farnesylated cargo whose release is triggered by ARL2-GTP or ARL3-GTP.
PMID:22085962
An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium.

Annotons

ARL13B activates ARL3
arl13b_arl3_gef
Participant: Gene Product: ARL13B
Gene Product:
ARL13BUniProtKB:Q3SXY8

Function

guanyl-nucleotide exchange factor activityGO:0005085

Processes

protein localization to ciliumGO:0061512

Locations

ciliary membraneGO:0060170

Ciliary membrane GTPase that acts as GEF for ARL3.

PMID:26551564
A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins.
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.
ARL3 releases lipidated cargo
arl3_cargo_release
Participant: Gene Product: ARL3
Gene Product:
ARL3UniProtKB:P36405

Function

G protein activityGO:0003925

Processes

protein localization to ciliary membraneGO:1903441

ARL3-GTP binds PDE6D and UNC119B and displaces their lipidated cargo inside the cilium; its intrinsic GTP hydrolysis is negligible without RP2.

PMID:26551564
A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins.
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.
PDE6D carries farnesylated cargo
pde6d_prenyl_carrier
Participant: Gene Product: PDE6D
Gene Product:
PDE6DUniProtKB:O43924

Function

farnesylated protein bindingGO:0001918

Processes

protein localization to ciliumGO:0061512

GDI-like carrier for farnesylated and prenylated cargo such as INPP5E and PDE6 subunits.

PMID:22002721
PDE6D is a GDI-like carrier for farnesylated cargo whose release is triggered by ARL2-GTP or ARL3-GTP.
UNC119B carries myristoylated cargo
unc119b_myristoyl_carrier
Participant: Gene Product: UNC119B
Gene Product:
UNC119BUniProtKB:A6NIH7

Function

lipid bindingGO:0008289

Processes

protein localization to ciliary membraneGO:1903441

Binds the myristoyl group of cargo such as NPHP3 and delivers it to the ciliary membrane.

PMID:22085962
An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium.
RP2 inactivates ARL3
rp2_arl3_gap
Participant: Gene Product: RP2
Gene Product:
RP2UniProtKB:O75695

Function

GTPase activator activityGO:0005096

Processes

protein localization to ciliary membraneGO:1903441

GTPase-activating protein for ARL3; a regulator, not a cargo carrier.

PMID:22085962
An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium.
INPP5E sets ciliary phosphoinositides
inpp5e_pip2_hydrolysis
Participant: Gene Product: INPP5E
Gene Product:
INPP5EUniProtKB:Q9NRR6

Function

phosphatidylinositol-4,5-bisphosphate 5-phosphatase activityGO:0004439

Locations

ciliary membraneGO:0060170

Hydrolyzes PI(4,5)P2 (and PI(3,4,5)P3) in the ciliary membrane.

PMID:19668215
INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse.
INPP5E localizes to cilia; its loss causes ciliary signaling defects and ciliary instability.
TULP3 links IFT-A to membrane cargo
tulp3_gpcr_import
Participant: Gene Product: TULP3
Gene Product:
TULP3UniProtKB:O75386

Function

protein-macromolecule adaptor activityGO:0030674

Processes

protein localization to ciliumGO:0061512

Adaptor bridging IFT-A and phosphoinositides for GPCR import.

PMID:20889716
TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote trafficking of G protein-coupled receptors into primary cilia.
TULP3 bridges the IFT-A complex and membrane phosphoinositides to traffic G protein-coupled receptors into cilia.

Connections

arl13b_arl3_gef -> arl3_cargo_release Positively Regulates
ARL13B loads ARL3 with GTP.
rp2_arl3_gap -> arl3_cargo_release Negatively Regulates
RP2 stimulates ARL3 GTP hydrolysis.
PDE6D-bound cargo is released by ARL3-GTP.
UNC119B-bound cargo is released by ARL3-GTP.
Part 7: length control
Cilium length controlRegulatory Stepcilium_length_control

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.

negative regulation of non-motile cilium assemblyGO:1902856
PMID:24853502
Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling.
Intestinal cell kinase (CILK1) is a key regulator of cilia length and signaling.
PMID:25243405
Regulation of cilium length and intraflagellar transport by the RCK-kinases ICK and MOK in renal epithelial cells.
The RCK kinases ICK and MOK regulate cilium length and intraflagellar transport in renal epithelial cells.
PMID:39293864
Ccrk-Mak/Ick signaling regulates ciliary transport and is essential for retinal photoreceptor survival.
PMID:24952464
KIF7 organizes the cilium tip compartment by limiting microtubule growth at the tip.

Annotons

RCK kinases restrict cilium length
rck_kinases
Participant: Protein Complex: RCK kinases
Protein Complex:
RCK kinases Ciliary length-control kinases (not a stable complex).
Active units:
CILK1 subunit
Participant: Gene Product: CILK1
Gene Product:
CILK1UniProtKB:Q9UPZ9
Role: length-control kinase
MAK subunit
Participant: Gene Product: MAK
Gene Product:
MAKUniProtKB:P20794
Role: length-control kinase

Function

protein serine/threonine kinase activityGO:0004674

Processes

negative regulation of non-motile cilium assemblyGO:1902856

Locations

ciliary tipGO:0097542

Phosphorylate kinesin-2 and IFT components to control IFT turnaround and length.

PMID:24853502
Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling.
Intestinal cell kinase (CILK1) is a key regulator of cilia length and signaling.
PMID:25243405
Regulation of cilium length and intraflagellar transport by the RCK-kinases ICK and MOK in renal epithelial cells.
The RCK kinases ICK and MOK regulate cilium length and intraflagellar transport in renal epithelial cells.
PMID:39293864
Ccrk-Mak/Ick signaling regulates ciliary transport and is essential for retinal photoreceptor survival.
KIF7 limits microtubule growth at the tip
kif7_tip_organizer
Participant: Gene Product: KIF7
Gene Product:
KIF7UniProtKB:Q2M1P5

Function

microtubule plus-end bindingGO:0051010

Processes

negative regulation of microtubule polymerizationGO:0031115 negative regulation of non-motile cilium assemblyGO:1902856

Locations

ciliary tipGO:0097542

Non-motile kinesin-4 that binds microtubule plus ends at the ciliary tip and slows their growth; also a core Hedgehog-pathway regulator.

PMID:24952464
KIF7 organizes the cilium tip compartment by limiting microtubule growth at the tip.
Part 8: cilium disassembly
Cilium disassembly before cell-cycle re-entryBiological Processcilium_disassembly

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.

cilium disassemblyGO:0061523
PMID:17604723
HEF1-dependent Aurora A activation induces disassembly of the primary cilium.
NEDD9/HEF1 activates Aurora A at the basal body, which phosphorylates and activates the tubulin deacetylase HDAC6 to drive ciliary disassembly.
PMID:25660017
The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation.
PLK1-activated KIF2A depolymerizes microtubules at the basal body to drive primary cilium disassembly.
PMID:20643351
Pitchfork regulates primary cilia disassembly and left-right asymmetry.
Pitchfork (CIMAP3) activates Aurora A at the basal body to regulate primary cilia disassembly.
PMID:21394082
Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors.
Phosphorylated Tctex-1 (DYNLT1) at the transition zone controls ciliary resorption before S-phase entry.
PMID:16184168
HEF1/NEDD9 activates Aurora A in vitro and is required for its activation at the centrosome.
PMID:39930500
TTBK2 restrains the microtubule depolymerizer KIF2A at the mother centriole to support primary cilia growth.

Annotons

Aurora A drives disassembly
aurka_disassembly_kinase
Participant: Gene Product: AURKA
Gene Product:
AURKAUniProtKB:O14965

Function

protein serine/threonine kinase activityGO:0004674

Processes

cilium disassemblyGO:0061523

Locations

ciliary basal bodyGO:0036064

Basal body kinase activated by NEDD9 and Pitchfork; phosphorylates HDAC6.

PMID:17604723
HEF1-dependent Aurora A activation induces disassembly of the primary cilium.
NEDD9/HEF1 activates Aurora A at the basal body, which phosphorylates and activates the tubulin deacetylase HDAC6 to drive ciliary disassembly.
NEDD9 activates Aurora A
nedd9_aurka_activation
Participant: Gene Product: NEDD9
Gene Product:
NEDD9UniProtKB:Q14511

Function

protein serine/threonine kinase activator activityGO:0043539

Processes

cilium disassemblyGO:0061523

Cas-family scaffold that activates Aurora A at the basal body.

PMID:17604723
HEF1-dependent Aurora A activation induces disassembly of the primary cilium.
NEDD9/HEF1 activates Aurora A at the basal body, which phosphorylates and activates the tubulin deacetylase HDAC6 to drive ciliary disassembly.
PMID:16184168
HEF1/NEDD9 activates Aurora A in vitro and is required for its activation at the centrosome.
Pitchfork activates Aurora A
pitchfork_aurka_activation
Participant: Gene Product: CIMAP3
Gene Product:
CIMAP3UniProtKB:Q8TCI5

Function

protein kinase activator activityGO:0030295

Processes

cilium disassemblyGO:0061523

Activates Aurora A at the basal body to drive cilium disassembly.

PMID:20643351
Pitchfork regulates primary cilia disassembly and left-right asymmetry.
Pitchfork (CIMAP3) activates Aurora A at the basal body to regulate primary cilia disassembly.
HDAC6 deacetylates axonemal tubulin
hdac6_deacetylation
Participant: Gene Product: HDAC6
Gene Product:
HDAC6UniProtKB:Q9UBN7

Function

tubulin deacetylase activityGO:0042903

Processes

cilium disassemblyGO:0061523

Tubulin deacetylase activated by Aurora A.

PMID:17604723
HEF1-dependent Aurora A activation induces disassembly of the primary cilium.
NEDD9/HEF1 activates Aurora A at the basal body, which phosphorylates and activates the tubulin deacetylase HDAC6 to drive ciliary disassembly.
PLK1 activates KIF2A
plk1_kinase
Participant: Gene Product: PLK1
Gene Product:
PLK1UniProtKB:P53350

Function

protein serine/threonine kinase activityGO:0004674

Processes

cilium disassemblyGO:0061523

Kinase that activates KIF2A at the basal body.

PMID:25660017
The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation.
PLK1-activated KIF2A depolymerizes microtubules at the basal body to drive primary cilium disassembly.
KIF2A depolymerizes microtubules
kif2a_depolymerization
Participant: Gene Product: KIF2A
Gene Product:
KIF2AUniProtKB:O00139

Function

ATP-dependent microtubule depolymerase activity No GO MF term exists; proposed as a new term in the KIF2A review.

Processes

microtubule depolymerizationGO:0007019 cilium disassemblyGO:0061523

Locations

ciliary basal bodyGO:0036064

Kinesin-13 ATP-dependent microtubule depolymerase acting at the mother centriole.

PMID:25660017
The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation.
PLK1-activated KIF2A depolymerizes microtubules at the basal body to drive primary cilium disassembly.
PMID:39930500
TTBK2 restrains the microtubule depolymerizer KIF2A at the mother centriole to support primary cilia growth.
Phosphorylated Tctex-1 promotes resorption
tctex1_resorption
Participant: Gene Product: DYNLT1
Gene Product:
DYNLT1UniProtKB:P63172

Function

resorption promoter

Processes

cilium disassemblyGO:0061523

Locations

ciliary transition zoneGO:0035869

Phospho-Tctex-1 at the transition zone promotes ciliary resorption, independently of dynein.

PMID:21394082
Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors.
Phosphorylated Tctex-1 (DYNLT1) at the transition zone controls ciliary resorption before S-phase entry.

Connections

NEDD9 activates Aurora A.
Pitchfork activates Aurora A.
Aurora A phosphorylates and activates HDAC6.
plk1_kinase -> kif2a_depolymerization Positively Regulates
PLK1 activates KIF2A.