IFT-139 is the Caenorhabditis elegans ortholog of human TTC21B (IFT139), a subunit of intraflagellar transport complex A (IFT-A). It is a large (1324 aa) tetratricopeptide-repeat (TPR)/armadillo-like alpha-solenoid protein with no catalytic domain. ift-139 is expressed only in ciliated sensory neurons, and GFP-tagged IFT-139 concentrates at the ciliary base, is present at lower levels in dendrites, and moves bidirectionally along the axoneme at IFT rates. Genetic analysis places IFT-139 in IFT-A and in retrograde (tip-to-base) intraflagellar transport: ift-139 deletion mutants have short, irregular cilia that phenocopy dynein-2 (che-3) and ifta-1 mutants rather than kinesin-II mutants, and are defective in dye filling, dauer formation and male mating. IFT-139 acts partially redundantly with the small IFT-A subunit IFT-43 to promote dynein-2 motility, and with IFT-43 and IFTA-1 it is needed to remove periciliary membrane proteins from the cilium (transition-zone gating). A ciliopathy missense mutation modelled in the worm protein disrupts its function; human TTC21B mutations cause nephronophthisis and short-rib thoracic dysplasia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping placing IFT-139 in the cilium, based on GFP-tagged IFT-139 imaging in sensory cilia. Reason: Correct. Translational IFT-139::GFP localizes to the ciliary base and along the cilium and moves bidirectionally in it. The broad term is consistent with the more specific complex and basal body localizations. Supporting Evidence: PMID:27515926 Many IFT-139::GFP-positive particles were bidirectionally moving in the cilia |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal (IFT-A complex) assertion that IFT-139 localizes to the cilium. Reason: Correct and consistent with direct imaging of IFT-139::GFP in cilia (PMID:27515926). Supporting Evidence: PMID:27515926 the IFT-139::GFP signal was localised to the base of cilia and in the cilia of PHA neuron |
| GO:0030425 dendrite | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping to dendrite, from the diffuse IFT-139::GFP signal seen in amphid dendrites. Reason: The observation is real (a translational fusion gave a diffuse dendritic signal, weaker than the ciliary signal), but the dendrite is the route by which IFT components reach the ciliary base, not a site where IFT-139 acts. Retained as a non-core location. Supporting Evidence: PMID:27515926 In the amphid neurons, the GFP signal was diffuse in dendrites and concentrated to the base of cilia |
| GO:0030991 intraciliary transport particle A | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that IFT-139, as a TTC21B/IFT139 family member, is a subunit of IFT-A. Reason: Core complex membership. IFT139 is an IFT-A subunit across ciliated eukaryotes, and worm genetics place IFT-139 with IFT-A (it phenocopies the IFT-A gene ifta-1 and the retrograde motor che-3). Affinity purification also associates IFT-139 with IFT-A in C. elegans (PMID:28479320). Supporting Evidence: PMID:27515926 Thus, genetic data suggest that IFT-139 is a component of the IFT-A subcomplex in C. |
| GO:0030991 intraciliary transport particle A | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal complex-membership assertion that IFT-139 is part of IFT-A. Reason: Core complex membership, supported by phylogeny and by the affinity purification reported in this paper. Supporting Evidence: PMID:28479320 our affinity purification and genetic analyses show that IFT-A subunits IFT-139 and IFT-43 function redundantly to promote dynein-2 motility |
| GO:0035721 intraciliary retrograde transport | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that IFT-139 acts in retrograde intraflagellar transport. Reason: Core process. ift-139 mutants phenocopy the retrograde dynein-2 mutant che-3 and not the anterograde kinesin-II mutant klp-11, and IFT-139 with IFT-43 promotes dynein-2 motility. Supporting Evidence: PMID:27515926 ift-139 mutations phenocopied che-3 but not klp-11 mutations PMID:27515926 These genetic data suggested that IFT-139 is involved in retrograde IFT. |
| GO:0035721 intraciliary retrograde transport | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal assertion that IFT-A, including IFT-139, mediates retrograde IFT. Reason: Core process; the paper shows IFT-139 and IFT-43 redundantly promote dynein-2 motility. Supporting Evidence: PMID:28479320 our affinity purification and genetic analyses show that IFT-A subunits IFT-139 and IFT-43 function redundantly to promote dynein-2 motility |
| GO:0060271 cilium assembly | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal assertion that IFT-A, including IFT-139, is needed for cilium assembly. Reason: Supported directly by the short, irregular cilia of ift-139 deletion mutants. Cilium assembly follows from the IFT activity that IFT-A subunits carry out. Supporting Evidence: PMID:27515926 ift-139 plays a role in retrograde intraflagellar transport and is required for cilia formation |
| GO:0061512 protein localization to cilium | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that IFT-139 acts in protein localization to the cilium, the cargo-delivery role of IFT-A. Reason: IFT-A trains carry ciliary proteins, and in C. elegans IFT-43, IFTA-1 and IFT-139 are needed to clear periciliary membrane proteins from the cilium. This fits a role in setting ciliary protein composition. The node placement is sound and there is no evidence the worm protein has lost this role. Supporting Evidence: PMID:30293716 with IFT-140 controlling their ciliary entry and IFT-43/121/139 controlling their ciliary removal |
| GO:0036064 ciliary basal body | IDA PMID:27515926 The nephronophthisis-related gene ift-139 is required for ci... | NEW | Summary: New annotation: IFT-139::GFP concentrates at the ciliary base (basal body / transition zone region) of amphid and phasmid cilia. Reason: Directly observed with a translational fusion in this paper, and recorded by UniProt as a basal body location, but missing from GOA. IFT trains assemble at the ciliary base, so this is a core location for an IFT-A subunit. Supporting Evidence: PMID:27515926 IFT-139 is expressed in ciliated neurons and localises to basal bodies and cilia |
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Download this section (compressed HTML)Q: Does IFT-139 bind dynein-2 directly, or does it promote dynein-2 motility only by stabilizing the IFT-A2 lobe (with IFT-43 and IFTA-1)?
Experiment: In ift-139 single and ift-139; ift-43 double mutants, image endogenously tagged dynein-2 (CHE-3) and IFT-A subunits at single-molecule resolution to measure train coupling at the tip and the frequency of retrograde starts.
Hypothesis: IFT-139 is needed for dynein-2 to couple to trains at the ciliary tip, and IFT-43 partly compensates for its loss.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: How IFT-139 contributes to dynein-2 engagement is unknown. It acts redundantly with IFT-43 to promote dynein-2 motility, but which IFT-A interface it supplies, and whether it contacts dynein-2 directly, has not been shown in the worm.
OPEN BIOLOGY
What is known: Established: IFT-A membership, retrograde IFT role, and redundancy with IFT-43 for dynein-2 motility. Unknown: the direct binding partners of IFT-139 within IFT-A and on dynein-2, and why loss of IFT-139 alone is stronger than loss of IFT-43 alone.
Significance: Would explain how the peripheral IFT-A subunits (IFT-A2 lobe) help license retrograde transport and why TTC21B ciliopathy alleles are pathogenic.
What would resolve it: Structure-guided separation-of-function alleles of ift-139 in ift-43 and wild-type backgrounds, with single-molecule dynein-2 imaging.
Provenance (the field's own admissions):
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