DYF-3 is the C. elegans ortholog of clusterin-associated protein 1 (CLUAP1), also known as IFT38 or qilin, a conserved component of the intraflagellar transport (IFT) complex B. IFT-B, together with kinesin-2 and cytoplasmic dynein-2 motors, drives the bidirectional movement of ciliary cargo between the ciliary base and tip that builds and maintains cilia. DYF-3 is not an enzyme; it is a structural/scaffold subunit of the peripheral (IFT-B2) portion of the complex, contributing to complex architecture through protein-protein interactions rather than catalytic activity. It is expressed in ciliated sensory neurons — including eight pairs of amphid neurons, six IL2 inner labial neurons, and two pairs of phasmid neurons — where its expression is controlled by the RFX-type transcription factor DAF-19 via an X-box promoter motif. The protein is distributed through the neuronal cell body, dendrite and axon, and functions at the sensory cilium and its base. Loss of dyf-3 produces stunted, structurally abnormal sensory cilia, a dye-filling-defective (Dyf) phenotype, and impaired cilia-dependent sensory behaviors. The orthologous protein is essential for ciliogenesis across metazoa: zebrafish qilin mutants develop pronephric cysts, and mouse Cluap1 knockouts lack primary cilia, fail Hedgehog signaling, and die at mid-gestation.
Definition: A structural molecule activity of a protein that is an integral subunit of an intraflagellar transport (IFT) particle (IFT-A or IFT-B), contributing to the assembly and architectural integrity of the complex through protein-protein interactions, without itself catalyzing a biochemical reaction or acting as a motor.
Justification: Non-motor, non-catalytic IFT subunits such as DYF-3/CLUAP1/IFT38 have no adequate GO molecular function term and currently read as MF-dark despite well-defined roles as complex subunits.
Parent term: structural molecule activity
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-3/CLUAP1 is required for sensory cilium formation, directly demonstrated in C. elegans and conserved across metazoa. The IBA call from the CLUAP1/IFT38 orthology group is corroborated by direct experimental evidence in the worm. Reason: Core biological process. Phylogenetic inference agrees with the primary experimental finding that dyf-3 mutants have stunted, structurally abnormal cilia, and with the conserved requirement of the ortholog for ciliogenesis in zebrafish and mouse. Supporting Evidence: PMID:15713455 we analyzed dyf-3 mutants that are defective in uptake of a fluorescent dye and abnormal in sensory cilium structure PMID:15713455 the mutant has stunted cilia and abnormal posterior projections in some sensory neurons |
| GO:0005929 cilium | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-3 acts as an IFT-B component within the cilium. UniProt records cilium as a subcellular location (IDA, PMID:15713455), consistent with this phylogenetic call. Reason: The cilium is the functional site of the IFT machinery. is_active_in is appropriate for an IFT-B subunit that moves along and functions within the cilium. Supporting Evidence: PMID:28479320 Cytoplasmic dynein-2 powers retrograde intraflagellar transport that is essential for cilium formation and maintenance |
| GO:0005815 microtubule organizing center | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IFT trains dock and are assembled at the ciliary base (basal body region), which is a microtubule-organizing center. In vertebrates CLUAP1/IFT38 is recruited to the mother centriole/basal body prior to ciliogenesis. Reason: The basal-body/MTOC association reflects the docking and assembly site of the IFT machinery rather than DYF-3's core functional compartment, which is the cilium and the IFT-B complex. Real but accessory; retained as non-core. (The more specific ciliary basal body, GO:0036064, would be preferable to the broad MTOC term.) |
| GO:0030992 intraciliary transport particle B | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-3 is an integral subunit of IFT complex B. UniProt lists it as a component of the worm IFT-B complex, and the vertebrate ortholog CLUAP1/IFT38 is an integral component of the IFT-B peripheral subcomplex. Reason: Core cellular-component / complex membership, strongly supported by biochemistry of the ortholog and by the worm IFT-B subunit list. Supporting Evidence: PMID:26980730 we identified TTC26/IFT56 and Cluap1/IFT38, neither of which was included with certainty in previous models of the IFT-B complex, as integral components of the core and peripheral subcomplexes, respectively PMID:25443296 all IFT-B subunits, including the suspected subunit CLUAP1/DYF-3/qilin (Ou et al., 2005b), co-purified with IFT27[K68A] and with IFT27 |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt Subcellular Location keyword mapping places DYF-3 in the cilium, consistent with the experimental IDA cilium localization from PMID:15713455. Reason: Electronic subcellular-location mapping agrees with experimental evidence; the cilium is the functional site. |
| GO:0030424 axon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Axon localization derives from UniProt Subcellular Location mapping and mirrors the experimental IDA annotation (PMID:15713455). DYF-3 is distributed through the neuron, but the axon is not its functional site. Reason: Reflects the pan-neuronal distribution of an IFT protein en route to the cilium; accessory to the core ciliary function. |
| GO:0030425 dendrite | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Dendrite localization from UniProt Subcellular Location mapping, mirroring the experimental IDA annotation (PMID:15713455). Reason: The sensory cilium in C. elegans sits at the distal dendrite; DYF-3 is present along the dendrite in transit but its functional compartment is the cilium/ciliary base. Retained as non-core. |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal NAS annotation placing the IFT-B complex (and DYF-3) in the cilium. Reason: Consistent with experimental and phylogenetic evidence that DYF-3 localizes to and functions within the cilium. Supporting Evidence: PMID:28479320 Disruption of the dynein-2 tail domain, light intermediate chain, or intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary localization, revealing their important roles in ciliary entry of dynein-2 |
| GO:0030992 intraciliary transport particle B | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal NAS annotation for DYF-3 membership in IFT particle B, corresponding to ComplexPortal CPX-1290 (Intraflagellar transport complex B). Reason: Core complex membership; agrees with the UniProt IFT-B subunit list and with biochemistry of the CLUAP1/IFT38 ortholog. |
| GO:0042073 intraciliary transport | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: As an IFT-B subunit, DYF-3 participates in intraflagellar transport, the motor-driven bidirectional movement of ciliary cargo along the axoneme. Reason: Core biological process for an IFT-B complex component. Supporting Evidence: PMID:28479320 Disruption of the dynein-2 tail domain, light intermediate chain, or intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary localization, revealing their important roles in ciliary entry of dynein-2 |
| GO:0060271 cilium assembly | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: DYF-3 (as an IFT-B subunit) is required for cilium assembly. This NAS annotation restates the well-supported core process also captured by IDA/IBA. Reason: Core biological process, redundant with but consistent with the IDA annotation from PMID:15713455. |
| GO:0006935 chemotaxis | IMP PMID:23664973 Environmental alkalinity sensing mediated by the transmembra... | KEEP AS NON CORE | Summary: dyf-3 was assayed in this study as a dye-filling-/cilium-defective strain; disrupting the sensory cilium impairs amphid-mediated chemotaxis. This is a downstream consequence of loss of functional cilia, not a distinct molecular activity of DYF-3. Reason: Experimental IMP annotation made by curators with access to the full text (the cached abstract foregrounds the guanylyl cyclase GCY-14 and does not name dyf-3); per curation guidance this is retained, not removed. It reflects the indirect, cilia-dependent behavioral requirement rather than DYF-3's core ciliary function. |
| GO:0007635 chemosensory behavior | IMP PMID:23664973 Environmental alkalinity sensing mediated by the transmembra... | KEEP AS NON CORE | Summary: dyf-3 mutants are defective in chemosensory behavior because their sensory cilia are structurally abnormal, compromising the sensory apparatus. Reason: Downstream, cilia-dependent behavioral phenotype. Experimental IMP; retained as a non-core process consequence of DYF-3's ciliary role. |
| GO:0010446 response to alkaline pH | IMP PMID:23664973 Environmental alkalinity sensing mediated by the transmembra... | KEEP AS NON CORE | Summary: In the alkalinity-sensing study, dyf-3 (cilium-defective) animals fail the ASE-mediated alkaline-pH response, because functional amphid cilia are required to house the sensory transduction machinery (e.g. GCY-14). Reason: Indirect requirement: the behavior fails because the cilium is disrupted, not because DYF-3 has a molecular role in pH transduction. Experimental IMP; retained as non-core. |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: No molecular function is annotated for DYF-3. This is an accurate reflection of a genuine knowledge/ontology gap: DYF-3/CLUAP1 has no catalytic activity and acts as a structural/scaffold IFT-B subunit, a role for which no adequate GO molecular function term currently exists. Reason: The ND molecular_function annotation should be retained rather than replaced with an invented activity. See knowledge_gaps and proposed_new_terms for the associated ontology gap. |
| GO:0030424 axon | IDA PMID:15713455 The dyf-3 gene encodes a novel protein required for sensory ... | KEEP AS NON CORE | Summary: Direct observation of DYF-3::GFP in the axon of ciliated sensory neurons. Reason: Genuine experimental localization, but reflects distribution of the protein through the neuron rather than its functional site (the cilium/ciliary base). Retained as non-core. |
| GO:0030425 dendrite | IDA PMID:15713455 The dyf-3 gene encodes a novel protein required for sensory ... | KEEP AS NON CORE | Summary: Direct observation of DYF-3::GFP in the dendrite of ciliated sensory neurons. Reason: Experimental localization along the dendrite that leads to the sensory cilium; accessory to the core ciliary function. Retained as non-core. |
| GO:0042995 cell projection | IDA PMID:15713455 The dyf-3 gene encodes a novel protein required for sensory ... | KEEP AS NON CORE | Summary: DYF-3::GFP is present in cell projections (cilium, axon, dendrite are all cell projections). This is a broad parent term subsumed by the more specific cilium, axon and dendrite annotations. Reason: Correct but very general; the informative specific children (cilium/axon/dendrite) are separately annotated. Retained as non-core rather than removed, since the experimental IDA is valid. |
| GO:0043025 neuronal cell body | IDA PMID:15713455 The dyf-3 gene encodes a novel protein required for sensory ... | KEEP AS NON CORE | Summary: Direct observation of DYF-3::GFP in the neuronal cell body. Reason: The protein is synthesized in and present throughout the cell body, but its functional compartment is the cilium/ciliary base. Retained as non-core. |
| GO:0060271 cilium assembly | IDA PMID:15713455 The dyf-3 gene encodes a novel protein required for sensory ... | ACCEPT | Summary: The strongest evidence for DYF-3's core role: dyf-3 mutants directly show defective sensory cilium formation, and dyf-3 acts cell-autonomously in ciliated neurons and is regulated by DAF-19/RFX as part of the ciliary gene battery. Reason: Core biological process, established by direct experimental evidence in the primary characterization of the gene. Supporting Evidence: PMID:15713455 dyf-3 acts cell-autonomously for fluorescent dye uptake PMID:15713455 dyf-3 expression is regulated by DAF-19 transcription factor, and DYF-3 may be involved in the intraflagellar transport system |
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Download this section (compressed HTML)Q: Which IFT-B subunits does DYF-3 directly contact in C. elegans, and is the CH-domain interaction with IFT80 and the coiled-coil heterodimer with IFT57 (as characterized for CLUAP1/IFT38 in other systems) conserved in the worm?
Suggested experts: Guangshuo Ou
Q: Does DYF-3 confer selectivity for particular ciliary cargoes (e.g. che-3/dynein-2), or is its role purely architectural within IFT-B?
Experiment: Compare the ciliary proteome (and live-imaged transport of candidate cargoes such as che-3/dynein-2) between wild-type and dyf-3 loss-of-function animals to identify cargoes whose ciliary entry specifically depends on DYF-3.
Hypothesis: DYF-3 is required for the ciliary import of specific cargoes rather than for bulk IFT.
Type: proteomics / live imaging
Experiment: Map DYF-3 protein-protein interactions in C. elegans (e.g. affinity purification-mass spectrometry, split fluorophore assays) and test predicted contacts with IFT80/che-2 and IFT57 orthologs.
Hypothesis: DYF-3 organizes the worm IFT-B2 subcomplex through conserved CH-domain and coiled-coil interactions.
Type: interaction mapping
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The direct molecular activity of DYF-3/CLUAP1 is undefined. It is unresolved whether it acts purely as a structural constituent of IFT-B, as a scaffold/adaptor that bridges specific subunits, and which of its partner interactions are load-bearing in C. elegans. No GO molecular function term adequately expresses "structural subunit of the IFT-B complex", so the gene reads MF-dark despite a well-defined cellular role.
OPEN BIOLOGYONTOLOGY MF_DARK
What is known: Firmly established: DYF-3 is an integral subunit of IFT complex B required for sensory cilium assembly and intraflagellar transport; the ortholog CLUAP1/IFT38 is an integral component of the IFT-B peripheral (IFT-B2) subcomplex and its ciliogenesis function depends on binding other IFT-B components. The protein has a coiled-coil region and an acidic disordered C-terminus and no catalytic domain.
Significance: IFT-B is the anterograde transport backbone of ciliogenesis; understanding DYF-3's precise molecular contribution would sharpen mechanistic models of IFT train assembly and explain how CLUAP1/IFT38 loss produces ciliopathy. The absence of an adequate MF term is a systematic ontology gap shared by many structural complex subunits.
What would resolve it: Structure/interaction mapping of the worm IFT-B2 module (which subunits DYF-3 directly contacts); in vitro reconstitution of IFT-B subcomplexes; and a new GO molecular function term for IFT structural-subunit activity.
Provenance (the field's own admissions):
Proposed term (ontology gap):
Gap: Which specific ciliary cargoes DYF-3 is required to import or transport in C. elegans, and whether it confers cargo selectivity, is not established. UniProt only tentatively links it to entry of the dynein-2 heavy chain che-3 ("May be required...").
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Firmly established: the IFT-B complex is required for ciliary entry of cytoplasmic dynein-2 (che-3), and dyf-3 loss disrupts overall cilium structure. The worm IFT-B2 architecture and DYF-3's specific cargo contacts are inferred from vertebrate/algal biochemistry rather than measured directly in the worm.
Significance: Cargo selectivity would distinguish a purely architectural role from an adaptor role and clarify why IFT-B subunit losses have distinguishable phenotypes.
What would resolve it: Cilium proteomics comparing wild-type and dyf-3 mutant cilia; live imaging of candidate cargo (e.g. che-3) transport in dyf-3 alleles.
Provenance (the field's own admissions):
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