DYF-1 is a tetratricopeptide-repeat (TPR) protein and a subunit of intraflagellar transport (IFT) complex B, the anterograde IFT module that builds and maintains cilia. It is the Caenorhabditis elegans ortholog of human TTC30A/TTC30B and of the ciliate/algal IFT70, and its name reflects the abnormal dye-filling (Dyf) phenotype of its mutants. DYF-1 is expressed in ciliated sensory neurons and localizes to the ciliary basal body and the axoneme, moving processively along the axoneme as part of IFT trains. Its central role is to act as an obligatory activator/adaptor for the homodimeric kinesin-2 motor OSM-3 (the KIF17 ortholog): DYF-1 is specifically required for OSM-3 to dock onto and move IFT particles, and in its absence OSM-3 is inactive so that IFT trains are carried by heterotrimeric kinesin-II alone and the distal singlet segments of amphid and phasmid cilia fail to form. As an IFT-B component DYF-1 is required for normal ciliogenesis and for delivery of ciliary cargo, and DYF-1/IFT70 is additionally required for polyglutamylation of the axonemal tubulin of sensory cilia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030992 intraciliary transport particle B | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-1 is a subunit of intraflagellar transport complex B (IFT-B). This IBA transfer is strongly corroborated experimentally: DYF-1 was identified in the C. elegans IFT-B complex by mass spectrometry (PMID:28479320; ComplexPortal CPX-1290). Reason: Core cellular-component identity of DYF-1. Phylogenetically inferred and independently confirmed by biochemical identification of DYF-1 in worm IFT-B. Supporting Evidence: PMID:28479320 intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary localization |
| GO:0042073 intraciliary transport | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-1 functions in intraflagellar (intraciliary) transport as an IFT-B subunit and OSM-3 kinesin activator. IBA is well supported by the C. elegans experimental data. Reason: Core biological process. Confirmed experimentally in worm (PMID:16049494): DYF-1 is required for OSM-3 to move IFT particles. Supporting Evidence: PMID:16049494 specifically required for OSM-3 kinesin to dock onto and move IFT particles |
| GO:0005879 axonemal microtubule | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-1 acts along axonemal microtubules, where IFT trains move. The is_active_in qualifier is appropriate for an IFT motor-associated protein that translocates along the axoneme; corroborated by the experimental IDA localization (PMID:16049494). Reason: Consistent with DYF-1's role as an axoneme-associated IFT-B component that undergoes IFT along ciliary microtubules. |
| GO:0120170 intraciliary transport particle B binding | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-1 binds the IFT-B particle as one of its subunits. This is the most informative molecular-function term available for DYF-1 and is preferable to generic protein binding. Reason: Captures DYF-1's molecular function as an IFT-B-associated protein. Note this binding term does not express DYF-1's distinctive OSM-3-kinesin-activation activity, which has no dedicated GO MF term (see knowledge_gaps). Supporting Evidence: PMID:28479320 intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary localization |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: DYF-1 localizes to the cilium. Electronic mapping from the UniProt Cilium subcellular keyword; redundant with the experimental IDA cilium annotation. Reason: Correct location, independently supported by experimental evidence (PMID:16049494). |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: DYF-1 localizes to the cilium as an IFT-B component (ComplexPortal NAS from PMID:28479320). Reason: Correct ciliary localization; consistent with IFT-B membership and IDA evidence. |
| GO:0030992 intraciliary transport particle B | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: DYF-1 is part of IFT complex B, identified by mass spectrometry in C. elegans (PMID:28479320) and curated by ComplexPortal (CPX-1290). Reason: Direct experimental/curated support for IFT-B membership; the strongest evidence for this core cellular-component identity. Supporting Evidence: PMID:28479320 intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary localization |
| GO:0042073 intraciliary transport | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: DYF-1 participates in intraciliary transport as an IFT-B subunit (ComplexPortal NAS from PMID:28479320). Reason: Core biological process; concordant with the IBA and IMP intraciliary-transport rows. |
| GO:0060271 cilium assembly | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: As an IFT-B component required for anterograde transport, DYF-1 is required for cilium assembly; the distal singlet segments of amphid/phasmid cilia fail to form in dyf-1 mutants (via loss of OSM-3 activity). Reason: IFT-B is essential for ciliogenesis; this NAS annotation is well grounded in DYF-1's role in building the distal ciliary segment. Supporting Evidence: PMID:28479320 essential for cilium formation and maintenance |
| GO:0072659 protein localization to plasma membrane | IMP PMID:16049494 Functional coordination of intraflagellar transport motors. | UNDECIDED | Summary: This IMP is attributed to PMID:16049494 (Ou et al. 2005), whose cached abstract is entirely about coordination of the kinesin-II and OSM-3 IFT motors and does not address localization of any plasma-membrane/ciliary-membrane protein. The generic term protein localization to plasma membrane is also imprecise for a ciliary IFT role (ciliary membrane rather than bulk plasma membrane). Reason: Cannot verify the supporting evidence: the cached publication is abstract-only and the abstract does not mention membrane-protein localization, and no specific mislocalized cargo can be identified from the accessible text. Per review guidelines, marked UNDECIDED rather than removed, since the curator may have used full-text/supplementary data not available here. |
| GO:0036064 ciliary basal body | IDA PMID:22922713 The BBSome controls IFT assembly and turnaround in cilia. | ACCEPT | Summary: DYF-1 localizes to the ciliary basal body (ciliary base), the docking/loading zone where IFT trains assemble. Basal-body localization is a defining feature of IFT-B proteins, which build and load onto IFT trains at the ciliary base. Reason: Experimental IDA (assigned_by MGI) consistent with DYF-1's role as an IFT-B subunit that docks at the ciliary base. DYF-1 is not named in the cached main text of PMID:22922713 (which foregrounds dyf-2/bbs-1); per review guidelines the experimental annotation is retained and deferred to the curator rather than removed, and the citation is flagged UNVERIFIED in reference_review. |
| GO:0005879 axonemal microtubule | IDA PMID:16049494 Functional coordination of intraflagellar transport motors. | ACCEPT | Summary: DYF-1::GFP localizes along the ciliary axoneme and undergoes IFT (Ou et al. 2005), consistent with an axonemal-microtubule location. Reason: Experimental localization supporting DYF-1's presence along axonemal microtubules; concordant with the IBA is_active_in axonemal-microtubule row. |
| GO:0005929 cilium | IDA PMID:16049494 Functional coordination of intraflagellar transport motors. | ACCEPT | Summary: DYF-1 is directly observed in the cilium (Ou et al. 2005). UniProt records the subcellular location Cell projection, cilium from this study. Reason: Experimental (IDA) ciliary localization; the best-supported location annotation. |
| GO:0018095 protein polyglutamylation | IMP PMID:16049494 Functional coordination of intraflagellar transport motors. | KEEP AS NON CORE | Summary: DYF-1/IFT70 is required for tubulin polyglutamylation of the ciliary axoneme. This is a genuine, literature-established function of dyf-1 shown directly in C. elegans by Pathak et al. 2007 (PMID:17761526), although GOA cites it here to PMID:16049494, whose abstract does not address polyglutamylation. It is a downstream/indirect role, not DYF-1's core molecular activity. Reason: Real but non-core: DYF-1 is not itself a glutamylase; polyglutamylation loss is a consequence of DYF-1 dysfunction (whether via failed IFT-delivery of a glutamylase or via the B-tubule/axoneme structural defect is unresolved; see knowledge_gaps). Retained because the function is well supported; supporting text drawn from the definitive paper (PMID:17761526) rather than the GOA-cited PMID:16049494. Supporting Evidence: PMID:17761526 dyf-1, is also required for tubulin polyglutamylation in sensory neuron cilia |
| GO:0042073 intraciliary transport | IMP PMID:16049494 Functional coordination of intraflagellar transport motors. | ACCEPT | Summary: Direct experimental evidence (IMP): in dyf-1 mutants OSM-3 is inactive and IFT particles are moved by kinesin-II alone, so distal singlet ciliary segments are not built. This is the primary experimental support for DYF-1's role in intraciliary transport. Reason: Strongest experimental evidence for DYF-1's core function in anterograde IFT via OSM-3 activation. Supporting Evidence: PMID:16049494 specifically required for OSM-3 kinesin to dock onto and move IFT particles PMID:16049494 an OSM-3 kinesin activator in the formation of two IFT pathways |
| GO:0035720 intraciliary anterograde transport | IMP PMID:16049494 Functional coordination of intraflagellar transport motors. | NEW | Summary: NEW (proposed, more specific). DYF-1 acts specifically in ANTEROGRADE intraciliary transport: it is required for the anterograde kinesin-2 motor OSM-3 to dock onto and move IFT particles, building the distal singlet segment of amphid/phasmid cilia. The current GOA rows use the generic parent term intraciliary transport (GO:0042073); the anterograde-specific child term more precisely captures DYF-1's role. Reason: DYF-1's function is anterograde-specific (OSM-3 activation), so intraciliary anterograde transport (GO:0035720) is more informative than the generic GO:0042073 already annotated by GOA. Supporting Evidence: PMID:16049494 specifically required for OSM-3 kinesin to dock onto and move IFT particles |
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Download this section (compressed HTML)Q: Does DYF-1 bind OSM-3 directly, and does it activate the motor by relieving OSM-3 autoinhibition or by tethering OSM-3 to the IFT-B core?
Q: Is the polyglutamylation defect in dyf-1 mutants a direct consequence of failed IFT delivery of a tubulin glutamylase, or an indirect result of the B-tubule structural defect?
Experiment: Reconstitute purified OSM-3 with DYF-1 and IFT-B and measure single-molecule motility and ATPase activity +/- DYF-1; map the DYF-1-OSM-3 interaction by crosslinking/MS or cryo-EM, and test separation-of-function dyf-1 alleles in vivo for IFT-B binding vs OSM-3 activation.
Hypothesis: DYF-1 activates OSM-3 by direct binding that relieves OSM-3 motor autoinhibition and docks it onto IFT-B.
Type: in vitro reconstitution / single-molecule motility / structural biology
Experiment: Image candidate TTLL glutamylases for IFT-dependent ciliary transport and co-movement with DYF-1/IFT-B; test whether glutamylase ciliary entry and axonemal polyglutamylation are lost in dyf-1 mutants while scoring axonemal ultrastructure across an allelic series.
Hypothesis: DYF-1/IFT-B is required to transport a tubulin polyglutamylase (or its substrate) into the cilium.
Type: live-cell IFT imaging / genetics
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: How DYF-1 activates OSM-3 kinesin at the molecular level is unknown: whether it binds the motor directly, relieves OSM-3 autoinhibition, or bridges OSM-3 to the IFT-B core, and which OSM-3 surface it engages, are undetermined. There is also no GO molecular-function term that expresses a kinesin-2 docking/activation-factor activity, so the gene reads as MF-dark despite a well-defined cellular role.
OPEN BIOLOGYONTOLOGY MF_DARK
What is known: DYF-1 is an IFT complex B subunit localizing to the ciliary base and axoneme that is genetically and specifically required for OSM-3 to dock onto and move IFT particles; loss inactivates OSM-3 and prevents assembly of the distal singlet ciliary segment. Its only informative MF term is intraciliary transport particle B binding (GO:0120170).
Significance: This is the step that selectively couples the OSM-3/KIF17 motor to anterograde IFT and builds the distal ciliary segment; the mechanism is conserved to human TTC30A/TTC30B and the ciliate/algal IFT70, and is central to how two anterograde kinesins are coordinated on a shared IFT train.
What would resolve it: Reconstitute OSM-3 motility with purified DYF-1 and IFT-B in vitro; determine a DYF-1-OSM-3 structure/interface; isolate separation-of-function dyf-1 alleles that uncouple IFT-B binding from OSM-3 activation; propose a molecular-function term for kinesin docking/activation-factor activity.
Provenance (the field's own admissions):
Gap: Whether DYF-1/IFT70 promotes axonemal tubulin polyglutamylation directly (for example by IFT-dependent delivery of a TTLL glutamylase or its tubulin substrate) or indirectly as a downstream consequence of the B-tubule/axoneme structural defect is unresolved, and the responsible glutamylase in the dyf-1 pathway is not identified.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Loss of the DYF-1/fleer ortholog dramatically reduces ciliary polyglutamylated tubulin and causes B-tubule ultrastructural defects, and C. elegans dyf-1 is likewise required for tubulin polyglutamylation in sensory-neuron cilia; the mechanistic link between IFT-B function and the polyglutamylation machinery has not been defined.
Significance: Tubulin polyglutamylation is required for cilium structure and, in motile cilia, motility across species; distinguishing a direct IFT-transport role from an indirect structural consequence would clarify how IFT-B controls axonemal post-translational modification.
What would resolve it: Test whether a TTLL glutamylase or its substrate is an IFT-B/DYF-1 cargo (IFT co-transport imaging, proximity proteomics); quantify polyglutamylation vs axonemal ultrastructure across a dyf-1 allelic series to separate cause from consequence.
Provenance (the field's own admissions):
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