Function
Processes
Locations
The train complex that anterograde motors carry and that is required to extend the axoneme.
Intraflagellar transport (IFT) is the bidirectional, motor-driven movement of large protein trains along the ciliary axoneme that builds and maintains cilia. It is ancestral in ciliated eukaryotes and has been lost along with cilia in lineages such as most fungi, flowering plants and Dictyostelium. IFT trains are polymers of two multisubunit complexes. IFT-B (including IFT88, IFT52, IFT57, IFT80, IFT70, IFT38, IFT46, IFT54, IFT56, IFT172, IFT20 and the IFT74/IFT81 tubulin-binding module) is needed to extend the axoneme and carries tubulin and other axonemal precursors. IFT-A (IFT140, IFT122, IFT144, IFT139, IFT121 and IFT43) is needed for retrograde transport and for ciliary import of membrane proteins. Heterotrimeric kinesin-II (two kinesin-2 motor subunits and a non-motor KAP subunit) carries trains from the ciliary base through the transition zone toward the tip. Some lineages add a homodimeric kinesin-2 accessory motor. In Caenorhabditis elegans sensory cilia, OSM-3 takes trains over from kinesin-II in a handover zone and alone builds the distal singlet segment, and the IFT-B subunit DYF-1 is required for OSM-3 to dock onto trains. At the tip trains turn around and are returned to the base by IFT-dynein (cytoplasmic dynein-2), whose heavy chain is DYNC2H1 (worm CHE-3). Ciliary kinases of the MAK/CILK1 family (worm DYF-5, human CILK1) regulate motor behaviour, train turnaround and cilium length; DYF-5 phosphorylates the tubulin-binding module of IFT-74 to promote tubulin unloading, and CILK1 phosphorylates the kinesin-II subunit KIF3A. The BBSome couples IFT-A and IFT-B and regulates IFT assembly at the base and turnaround at the tip. Loss of IFT-B, IFT-A, kinesin-II or dynein-2 function causes absent, truncated or malformed cilia; in worms this prevents dye uptake by sensory neurons, and in humans IFT gene mutations cause skeletal and renal ciliopathies.
Boundary. This module covers the IFT machine itself: the IFT-B and IFT-A train complexes, the anterograde kinesin-2 motors, the retrograde IFT-dynein, and the MAK/CILK1-family kinases that regulate motor behaviour and cargo release. The ciliary transition zone (MODULE:ciliary_transition_zone) is a separate module; IFT trains pass through it, and IFT and transition-zone proteins act at different steps of ciliogenesis. Transcriptional control of ciliary genes (RFX factors such as worm DAF-19) is regulatory context, not a part. Taxon scope. The module is set at Eukaryota because the IFT-A, IFT-B, kinesin-II and dynein-2 families were present in the last eukaryotic common ancestor and the IFT cycle has been characterised in green algae, nematodes and vertebrates. It does not apply to lineages that lost cilia, and some ciliated lineages build flagella without IFT (for example, Plasmodium gametes assemble their axonemes in the cytoplasm). Representatives here are from C. elegans and human only. No Chlamydomonas IFT protein has a gene review in this repository, so Chlamydomonas is used as evidence, not as a representative. Lineage-variable motor. The homodimeric kinesin-2 accessory motor is modelled as an optional part with a variant set. Only the nematode OSM-3 variant is grounded. Vertebrate KIF17 is the OSM-3 homolog and acts as an accessory or cell-type-specific motor (for example, in photoreceptor outer segments), but it has no gene review here, so it is mentioned in these notes and not modelled as a variant. Chlamydomonas flagella are built by heterotrimeric kinesin-II (FLA10/FLA8/KAP) without a homodimeric kinesin-2. Relation to MODULE:bbsome. The BBSome is modelled separately. In worms BBS-7 and BBS-8 hold IFT-A and IFT-B together so that both motors move the same train (in bbs-7/bbs-8 mutants IFT-A is moved by kinesin-II and IFT-B by OSM-3 separately; PMID:16049494), and the BBSome binds anterograde trains in a DYF-2- and BBS-1-dependent manner and is needed for turnaround at the tip (PMID:22922713). Those interactions are recorded as an interface in the IFT-A part and the turnaround connection, not as BBSome membership. Members and molecular functions. Each subunit or motor role is an ortholog family, with the worm protein and, where a gene review exists, a human representative (IFT88, IFT140, KIF3A, DYNC2H1, CILK1). Human orthologs of the other worm subunits (for example KIF3B, KIFAP3, DYNC2LI1, IFT122, WDR19, WDR35) have no gene reviews here and are named in text only. Molecular functions follow the gene reviews' core functions. Several worm reviews (OSM-6, CHE-13, CHE-11, DAF-10, DYF-2) give structural molecule activity for scaffold subunits; this module does not use that term, and those subunits, like the ones whose reviews assert no MF (CHE-2, DYF-3, DYF-6, OSM-1, IFT-20, IFT-139, IFT-43, IFTA-1, human IFT88 and IFT140), carry only a role description. IFT20 has a Golgi-associated role in mammalian cells that is not seen in worms; this module covers only its ciliary IFT-B role. Where the worm and human reviews differ, the annoton description says which review asserts the MF. No PANTHER family ids are asserted for these roles. IFT25, IFT27 and IFT22 are intentionally not in the IFT-B roster. IFT25 and IFT27 are absent from several ciliated lineages (PMID:31951201), and no C. elegans ortholog is modelled here. Worm IFTA-2, the IFT22/RABL5 homolog, co-purifies with IFT-74/81 (PMID:35969738), but its loss does not cause overt cilia assembly defects (PMID:16968739), and it has no gene review here, so it is named in text only. Kinase regulation. DYF-5 and CILK1 are modelled as regulators of IFT, not as transport machinery. Worm has a single MAK/CILK1-family ciliary kinase (DYF-5); mammals have both CILK1 and MAK, and only CILK1 is reviewed here. Ciliary segments. Worm amphid channel cilia have a transition zone, a middle segment of doublet microtubules and a distal segment of singlet microtubules. Segment-level anatomy is described in prose because GO has no terms for ciliary middle or distal segments.
knowledge_gaps[0].provenance[0] · reference_section_type
(0/1)knowledge_gaps[1].provenance[0] · reference_section_type
(0/1)✗ none found
No MODULE:intraflagellar_transport deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.
16 gene-function check(s) reflected in core functions · 0 conflict(s) · 13 evidence or coverage gap(s) (32 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.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| ift_b_subunits | PROTEIN_COMPLEX Gene |
IFT train scaffold carrying axonemal precursors 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. |
| ift_b_subunits/ift88_unit | OSM-5 (worm) UniProtKB:G5ED37 Family Representative |
kinesin binding GO:0019894 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ift_b_subunits/ift88_unit | IFT88 (human) UniProtKB:Q13099 Family Representative |
kinesin binding GO:0019894 |
Annotation Supported
A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it. |
| ift_b_subunits/ift70_unit | DYF-1 (worm) UniProtKB:Q8I7G4 Family Representative |
intraciliary transport particle B binding GO:0120170 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ift_b_subunits/ift54_unit | DYF-11 (worm) UniProtKB:Q17595 Family Representative |
microtubule binding GO:0008017 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ift_b_subunits/ift56_unit | DYF-13 (worm) UniProtKB:Q95QT8 Family Representative |
intraciliary transport particle B binding GO:0120170 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ift_b_subunits/ift74_unit | IFT-74 (worm) UniProtKB:A0A2C9C2L6 Family Representative |
beta-tubulin binding GO:0048487 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ift_b_subunits/ift81_unit | IFT-81 (worm) UniProtKB:A8DYR7 Family Representative |
tubulin binding GO:0015631 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ift_a_subunits | PROTEIN_COMPLEX Gene |
IFT train scaffold for retrograde transport and membrane-cargo import 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. |
| kinesin_ii_motor | 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. |
| kinesin_ii_motor/kif3a_unit | KLP-20 (worm) UniProtKB:Q965T6 Family Representative |
plus-end-directed microtubule motor activity GO:0008574 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| kinesin_ii_motor/kif3a_unit | KIF3A (human) UniProtKB:Q9Y496 Family Representative |
plus-end-directed microtubule motor activity GO:0008574 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| kinesin_ii_motor/kif3b_unit | KLP-11 (worm) UniProtKB:Q19633 Family Representative |
microtubule motor activity GO:0003777 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| kinesin_ii_motor/kap_unit | KAP-1 (worm) UniProtKB:G5EEE6 Family Representative |
kinesin binding GO:0019894 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| osm3_motor | OSM-3 UniProtKB:P46873 Gene |
plus-end-directed microtubule motor activity GO:0008574 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| che3_heavy_chain | CHE-3 (worm) UniProtKB:Q19542 Family Representative |
minus-end-directed microtubule motor activity GO:0008569 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| che3_heavy_chain | DYNC2H1 (human) UniProtKB:Q8NCM8 Family Representative |
minus-end-directed microtubule motor activity GO:0008569 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| xbx1_light_intermediate_chain | XBX-1 (worm) UniProtKB:Q19119 Family Representative |
dynein heavy chain binding GO:0045504 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dyf5_kinase | DYF-5 (worm) UniProtKB:B3WFY8 Family Representative |
protein serine/threonine kinase activity GO:0004674 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| dyf5_kinase | CILK1 (human) UniProtKB:Q9UPZ9 Family Representative |
protein serine/threonine kinase activity GO:0004674 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| ift88_unit | IFT88 orthologs Family |
kinesin binding GO:0019894 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| ift70_unit | IFT70/TTC30 orthologs Family |
intraciliary transport particle B binding GO:0120170 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| ift54_unit | IFT54/TRAF3IP1 orthologs Family |
microtubule binding GO:0008017 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| ift56_unit | IFT56/TTC26 orthologs Family |
intraciliary transport particle B binding GO:0120170 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| ift74_unit | IFT74 orthologs Family |
beta-tubulin binding GO:0048487 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| ift81_unit | IFT81 orthologs Family |
tubulin binding GO:0015631 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| kif3a_unit | KIF3A orthologs Family |
plus-end-directed microtubule motor activity GO:0008574 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| kif3b_unit | KIF3B/KIF3C orthologs Family |
microtubule motor activity GO:0003777 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| kap_unit | kinesin-associated protein (KAP3/KIFAP3) orthologs Family |
kinesin binding GO:0019894 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| che3_heavy_chain | cytoplasmic dynein-2 heavy chain (DYNC2H1) orthologs Family |
minus-end-directed microtubule motor activity GO:0008569 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| xbx1_light_intermediate_chain | cytoplasmic dynein-2 light intermediate chain (DYNC2LI1) orthologs Family |
dynein heavy chain binding GO:0045504 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
| dyf5_kinase | MAK/CILK1 (RCK) ciliary kinase family Family |
protein serine/threonine kinase activity GO:0004674 |
Family Id Missing
The family has no identifier linking it to a curated family review. |
✓ every negative regulator described as feedback has an upstream edge closing the loop.
28 complete review(s) · 29 with deep research · 0 missing review · 2 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| che-11 P90757 | ✓ | ✓ | ✓ |
| che-13 Q93833 | ✓ | ✓ | ✓ |
| che-2 G5EGF0 | ✓ | ✓ | ✓ |
| che-3 Q19542 | ✓ | ✓ | ✓ |
| CILK1 Q9UPZ9 | ✓ | ✓ | ✓ |
| daf-10 G5EFW7 | ✓ | ✓ | ✓ |
| dyf-1 Q8I7G4 | ✓ | 15/16 | ✓ |
| dyf-11 Q17595 | ✓ | ✓ | ✓ |
| dyf-13 Q95QT8 | ✓ | ✓ | ✓ |
| dyf-2 G5ECZ4 | ✓ | ✓ | ✓ |
| dyf-3 Q6I6D4 | ✓ | ✓ | ✓ |
| dyf-5 B3WFY8 | ✓ | ✓ | ✓ |
| dyf-6 Q0G838 | ✓ | ✓ | ✓ |
| DYNC2H1 Q8NCM8 | ✓ | 44/46 | ✓ |
| ift-139 Q20255 | ✓ | ✓ | ✗ |
| ift-20 Q8TA52 | ✓ | ✓ | ✓ |
| ift-43 Q9BIA4 | ✓ | ✓ | ✗ |
| ift-74 A0A2C9C2L6 | ✓ | ✓ | ✓ |
| ift-81 A8DYR7 | ✓ | ✓ | ✓ |
| IFT140 Q96RY7 | ✓ | ✓ | ✓ |
| IFT88 Q13099 | ✓ | ✓ | ✓ |
| ifta-1 Q18859 | ✓ | ✓ | ✓ |
| kap-1 G5EEE6 | ✓ | ✓ | ✓ |
| KIF3A Q9Y496 | ✓ | ✓ | ✓ |
| klp-11 Q19633 | ✓ | ✓ | ✓ |
| klp-20 Q965T6 | ✓ | ✓ | ✓ |
| osm-1 Q22830 | ✓ | ✓ | ✓ |
| osm-3 P46873 | ✓ | 46/47 | ✓ |
| osm-5 G5ED37 | ✓ | ✓ | ✓ |
| osm-6 G5EDF6 | ✓ | ✓ | ✓ |
| xbx-1 Q19119 | ✓ | ✓ | ✓ |
IFT-B and IFT-A trains carried to the ciliary tip by kinesin-2 motors and returned to the base by IFT-dynein, with motor behaviour and cargo release tuned by MAK/CILK1-family ciliary kinases.
IFT-B is the larger of the two IFT train subcomplexes. It is needed to build the axoneme and carries tubulin through the IFT74/IFT81 tubulin-binding module. Mammalian interaction mapping divides it into a core (IFT-B1) and a peripheral (IFT-B2) subcomplex. In worms IFT-B is the subcomplex that OSM-3 moves when trains are split in bbs mutants; worm IFT-B subunits concentrate at the ciliary base and move bidirectionally along the axoneme, and mutants lacking them have short or absent axonemes and fail to take up dyes.
The train complex that anterograde motors carry and that is required to extend the axoneme.
IFT-A is the smaller train subcomplex, with a core of IFT140, IFT122 and IFT144 and peripheral subunits IFT139, IFT121 and IFT43. It is needed for retrograde transport and, with its adaptor TULP3 in mammals, for ciliary import of membrane proteins. In worms IFT-A is moved by kinesin-II when trains are split in bbs mutants; IFT-139 and IFT-43 act redundantly to promote dynein-2 motility; and DYF-2/IFT144 is required, together with BBS-1, for the BBSome to bind anterograde trains.
Kinesin-2 motors move IFT trains toward the ciliary tip. Heterotrimeric kinesin-II is the conserved anterograde IFT motor. Some lineages add a homodimeric kinesin-2. In C. elegans, kinesin-II imports trains through the ciliary base and transition zone and hands them over to OSM-3 on the proximal axoneme; in the middle segment the two motors act together and partly redundantly, OSM-3 alone moves trains along the distal singlets, and the BBSome (BBS-7, BBS-8) is needed to keep both motors on the same train.
Heterotrimeric kinesin-II is made of two different kinesin-2 motor subunits (human KIF3A/KIF3B; worm KLP-20/KLP-11) and a non-motor armadillo-repeat subunit (human KAP3; worm KAP-1) that links the motor to IFT cargo. In worms it is the slower, less processive motor: it carries trains through the base and transition zone into a handover zone on the proximal axoneme and then turns around and recycles to the base. KLP-11 is unprocessive as a homodimer and gains processivity by heterodimerizing with KLP-20; heterodimerization is also needed to bind KAP-1, which co-recognizes the folded pair of motor tails.
Carries IFT trains from the ciliary base through the transition zone toward the tip; in worms it imports trains and carries them along the middle-segment doublets.
A homodimeric kinesin-2 of the OSM-3/KIF17 family adds a fast, processive anterograde motor in some lineages. It is absent from Chlamydomonas flagellar IFT. Only the nematode implementation is modelled; vertebrate KIF17 is described in the module notes.
Only the nematode OSM-3 variant is grounded. Vertebrate KIF17 has no gene review in this repository and is left to the module notes rather than modelled as a variant.
Homodimeric OSM-3 gradually replaces kinesin-II in the handover zone and drives trains to the ciliary tip; it is the only motor on the distal singlets. OSM-3 is autoinhibited in solution, and attachment to IFT cargo is proposed to relieve autoinhibition. Docking of OSM-3 onto trains requires the IFT-B subunit DYF-1.
Fast, processive anterograde motor for long-range transport and the sole motor that builds the distal segment.
Cytoplasmic dynein-2 returns IFT trains, kinesin-II and their cargo from the tip to the base. Dynein-2 is itself carried to the tip on anterograde trains in an inhibited state. In worm che-3 mutants retrograde IFT in cilia is blocked while anterograde IFT continues, and IFT proteins accumulate in bulbous cilia. In worms the ciliary entry of dynein-2 needs its tail, the light intermediate chain XBX-1 and IFT-B.
Motor subunit of IFT-dynein.
Non-catalytic subunit of IFT-dynein that binds the heavy chain.
Ciliary serine/threonine kinases of the MAK/CILK1 family (worm DYF-5, human CILK1, Chlamydomonas LF4) travel into the cilium and regulate IFT and cilium length; loss of their function generally gives long cilia. In worm dyf-5 mutants IFT proteins accumulate distally, kinesin-II is no longer confined to the middle segment and OSM-3 moves slowly without attached IFT particles. DYF-5 phosphorylates the tubulin-binding module of IFT-74, lowering IFT-74/81 affinity for tubulin and promoting tubulin unloading at the tip. Human CILK1 concentrates at the ciliary tip and phosphorylates KIF3A, and its loss causes IFT-A, IFT-B and BBSome components to accumulate at ciliary tips. These kinases regulate IFT rather than form part of the transport machinery.
Regulates motor docking and undocking and train turnaround, and phosphorylates IFT components to release cargo and limit cilium length.