dyf-6 encodes the Caenorhabditis elegans ortholog of intraflagellar transport protein 46 (IFT46), a structural subunit of intraflagellar transport (IFT) complex B. IFT-B, with IFT-A and the kinesin-2 and dynein-2 motors, drives the bidirectional movement of ciliary cargo that builds and maintains the cilia of ciliated sensory neurons. The 471-residue protein has a large N-terminal disordered/acidic region and no recognizable catalytic domain. DYF-6 is expressed in ciliated amphid and phasmid sensory neurons (and hypodermis), localizes to the cilium, the ciliary base/basal body region, dendrites and the neuronal cell body, and undergoes processive IFT movement within the ciliated dendritic endings. It is required to build full-length sensory cilia: in dyf-6 mutants the amphid and phasmid ciliary endings are foreshortened, the IFT-B marker OSM-6 is mislocalized in a pattern typical of complex B mutants, and the animals are defective in dye filling and chemotaxis. The ciliary role is conserved, with orthologs in Drosophila (CG15161, expressed in sensory cilia) and mammals (human IFT46). C. elegans has only non-motile sensory cilia, so the cilium DYF-6 builds is a non-motile sensory cilium.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005815 microtubule organizing center | IBA GO_REF:0000033 | MODIFY | Summary: IFT46 orthologs concentrate at and inject IFT trains from the ciliary base. In C. elegans this is the basal body / transition-zone region; UniProt curates DYF-6 basal-body localization from PMID:16648645. The basal body is a type of microtubule organizing center, so the term is not wrong, but the specific "ciliary basal body" (GO:0036064) is the accurate, informative CC. Reason: Term too general. DYF-6's documented location at the ciliary base is better captured by ciliary basal body (GO:0036064) than by the generic microtubule organizing center. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000332669 · IFT46 family node SUPPORTS TRANSFER The IFT46 family node correctly places DYF-6 at the microtubule organizing center (basal body), but the transferred term is coarser than the specific ciliary basal body location documented for the worm protein. Proposed replacements: ciliary basal body |
| GO:0030992 intraciliary transport particle B | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-6/IFT46 is a subunit of intraflagellar transport complex B (IFT-B). This phylogenetic transfer is corroborated by Bell et al.'s inference from the OSM-6 mislocalization pattern and by biochemical assignment to ComplexPortal CPX-1290. Reason: Core cellular-component identity of DYF-6 as an IFT-B structural subunit. Supporting Evidence: PMID:28479320 intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary localization file:worm/dyf-6/dyf-6-deep-research-falcon.md IFT46 is a pivotal subunit of the IFT-B1 core subcomplex |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: IFT is required to assemble and maintain cilia; dyf-6 mutants have foreshortened amphid and phasmid ciliary endings, so DYF-6 is required for cilium assembly. Reason: Core biological process, supported experimentally in worm (PMID:16648645). The more specific worm-appropriate term non-motile cilium assembly is also annotated (IMP). Supporting Evidence: PMID:16648645 the cilia of the amphid and phasmid dendritic endings are foreshortened |
| GO:0031514 motile cilium | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: This IBA transfer from mammalian IFT46 assigns a motile-cilium location. C. elegans, however, has no motile cilia — all its cilia, including the amphid and phasmid sensory cilia in which DYF-6 acts, are non-motile. The matching worm annotation is non-motile cilium assembly (GO:1905515, IMP). Reason: Taxonomically inappropriate over-propagation: C. elegans lacks motile cilia. DYF-6 acts in non-motile sensory cilia; the generic ciliary location (cilium, GO:0005929) is separately and correctly annotated. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000332669 · IFT46 family node SUPPORTS SOURCE BUT NOT TARGET The IFT46 family node includes vertebrate members that function in motile cilia, but the C. elegans ortholog acts only in non-motile sensory cilia, so the motile-cilium location does not transfer. |
| GO:0042073 intraciliary transport | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-6 functions in intraflagellar (intraciliary) transport as an IFT-B subunit; DYF-6::GFP undergoes IFT movement within ciliated endings. Reason: Core biological process, confirmed experimentally in worm (PMID:16648645). Supporting Evidence: PMID:16648645 Movement of DYF-6::GFP within the ciliated endings of the neurons indicates that DYF-6 is involved in IFT |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic mapping of the UniProt cilium subcellular-location keyword. DYF-6 is directly observed within cilia, where it undergoes IFT. Reason: Correct core ciliary location, corroborated by experimental IFT movement within ciliated endings (PMID:16648645). Supporting Evidence: PMID:16648645 Movement of DYF-6::GFP within the ciliated endings of the neurons indicates that DYF-6 is involved in IFT |
| GO:0030425 dendrite | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: DYF-6 is present in the sensory dendrites through which IFT cargo is trafficked to the ciliated ending; UniProt curates dendrite localization from PMID:16648645 and WormBase makes the same call by IDA. Reason: Real localization (the dendritic route to the cilium) but not the core site of DYF-6 function, which is the cilium/IFT machinery. |
| GO:0042073 intraciliary transport | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO transfer (IPR022088, IFT complex B) to intraciliary transport. Duplicates the IBA/NAS/IDA intraciliary-transport annotations and is correct. Reason: Core biological process; redundant with experimental IDA (PMID:16648645) but consistent. Supporting Evidence: PMID:16648645 Movement of DYF-6::GFP within the ciliated endings of the neurons indicates that DYF-6 is involved in IFT |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic mapping of the UniProt perikaryon subcellular-location keyword, the same call made experimentally (EXP) from PMID:16648645. DYF-6 is present in the neuronal cell body/perikaryon in addition to the cilium. Reason: Real localization but not the core functional site; the cell body reflects the neuron of expression rather than DYF-6's IFT role. |
| GO:0120025 plasma membrane bounded cell projection | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA machine-learning annotation to a high-level grouping term that is the parent of both cilium and dendrite, which are already specifically annotated for DYF-6. Reason: Over-general electronic grouping term; its informative descendants (cilium, dendrite) are already annotated, so it adds no information. |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal (CPX-1290) assertion that DYF-6 localizes to the cilium, consistent with the experimental observation that DYF-6 undergoes IFT within cilia. Reason: Correct core ciliary location. Supporting Evidence: PMID:16648645 Movement of DYF-6::GFP within the ciliated endings of the neurons indicates that DYF-6 is involved in IFT |
| GO:0030992 intraciliary transport particle B | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal (CPX-1290) assignment of DYF-6 to IFT complex B, based on the affinity-purification / mass-spectrometry of the worm IFT-B complex in Yi et al. 2017 and reflected in the UniProt SUBUNIT statement. Reason: Core cellular-component identity; biochemically supported IFT-B membership. 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: ComplexPortal assertion that DYF-6, as an IFT-B subunit, functions in intraciliary transport, consistent with the worm experimental data. Reason: Core biological process; consistent with IFT-B membership and experimental IFT movement (PMID:16648645). Supporting Evidence: PMID:16648645 Movement of DYF-6::GFP within the ciliated endings of the neurons indicates that DYF-6 is involved in IFT |
| GO:0060271 cilium assembly | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal assertion that DYF-6 functions in cilium assembly, consistent with the foreshortened-cilia phenotype of dyf-6 mutants. Reason: Core biological process; supported by the dyf-6 mutant cilium phenotype (PMID:16648645). Supporting Evidence: PMID:16648645 the cilia of the amphid and phasmid dendritic endings are foreshortened |
| GO:0043204 perikaryon | EXP PMID:16648645 The molecular identities of the Caenorhabditis elegans intra... | KEEP AS NON CORE | Summary: Experimental localization of DYF-6 to the neuronal perikaryon (cell body) in addition to the cilium and dendrite. DYF-6::GFP is expressed throughout the ciliated sensory neurons. Reason: Real experimental localization but not DYF-6's core functional site; the cell body reflects the site of expression rather than the IFT role. Supporting Evidence: PMID:16648645 DYF-6::GFP is expressed in amphid and phasmid neurons |
| GO:0030425 dendrite | IDA PMID:16648645 The molecular identities of the Caenorhabditis elegans intra... | KEEP AS NON CORE | Summary: WormBase IDA localization of DYF-6 to the sensory dendrites, the route along which IFT cargo travels between the cell body and the ciliated ending. Reason: Real localization along the trafficking route to the cilium, but not the core functional site (the cilium/IFT machinery). |
| GO:0042073 intraciliary transport | IDA PMID:16648645 The molecular identities of the Caenorhabditis elegans intra... | ACCEPT | Summary: Direct observation that DYF-6::GFP moves within the ciliated endings of amphid and phasmid neurons demonstrates that DYF-6 participates in intraflagellar (intraciliary) transport. This is the primary experimental basis for the core function. Reason: Core biological process; strongest, directly observed evidence (PMID:16648645). Supporting Evidence: PMID:16648645 Movement of DYF-6::GFP within the ciliated endings of the neurons indicates that DYF-6 is involved in IFT |
| GO:0043025 neuronal cell body | IDA PMID:16648645 The molecular identities of the Caenorhabditis elegans intra... | KEEP AS NON CORE | Summary: WormBase IDA localization of DYF-6 to the neuronal cell body, consistent with the EXP perikaryon annotation and with expression throughout ciliated sensory neurons. Reason: Real localization but not the core functional site; reflects the neuron of expression rather than the IFT role. Supporting Evidence: PMID:16648645 DYF-6::GFP is expressed in amphid and phasmid neurons |
| GO:1905515 non-motile cilium assembly | IMP PMID:16648645 The molecular identities of the Caenorhabditis elegans intra... | ACCEPT | Summary: C. elegans sensory cilia are non-motile, and DYF-6 is required to build them: dyf-6 mutants have foreshortened amphid and phasmid ciliary endings. This is the most specific and organism-appropriate biological-process term for DYF-6. Reason: Core biological process; the non-motile-cilium wording matches the worm sensory cilium and is directly supported by the mutant phenotype (PMID:16648645). Supporting Evidence: PMID:16648645 the cilia of the amphid and phasmid dendritic endings are foreshortened |
Loading supporting content…
Download this section (compressed HTML)Q: Does C. elegans DYF-6/IFT46 act as a cargo adaptor within IFT-B (as Chlamydomonas IFT46 does for outer dynein arms), or purely as a structural scaffold, and which IFT-B subunits does it directly contact?
Experiment: Affinity purification / cross-linking mass spectrometry and structural modeling of DYF-6 within the worm IFT-B complex to define its direct binding partners and position in the particle.
Type: interaction mapping
Experiment: Isoform-specific rescue and separation-of-function alleles (including N-terminal deletions) to test for a cargo-adaptor role and to determine whether the long dyf-6/F46F6.3 fusion isoform has any distinct function.
Type: genetics
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular function of DYF-6/IFT46 is undefined. It has a large disordered N-terminus and no recognizable catalytic domain, and no GO molecular-function term is assigned to it in C. elegans. Whether it acts as a cargo adaptor (Chlamydomonas IFT46 uses its N-terminal region to load outer dynein arms) or purely as an IFT-B scaffold, and which IFT-B subunit(s) it directly contacts in the worm, is not established.
OPEN ONTOLOGYBIOLOGY MF_DARK
What is known: DYF-6 is firmly established as an IFT complex B subunit that localizes to the cilium and ciliary base, undergoes IFT movement, and is required to build full-length non-motile sensory cilia. In other organisms the conserved C-terminal IFT46_B_C domain mediates direct binding to IFT52 (and, via a ternary module, IFT88) to build the IFT-B1 core, while the N-terminal region binds the ODA16 cargo adaptor to load outer dynein arms — a role restricted to motile cilia and therefore not expected in the worm. What is missing is a GO molecular-function representation of this structural/scaffolding activity (the MF aspect cannot express "structural constituent of IFT particle B"), and the specific IFT-B contacts and any cargo-adaptor role of DYF-6 have not been demonstrated for the C. elegans protein.
Significance: IFT46 is a conserved core IFT-B protein; defining its molecular activity (scaffolding vs a specific cargo-adaptor interaction) is central to understanding IFT-B architecture and cargo selection in cilia.
What would resolve it: Map DYF-6's direct IFT-B interaction partners by biochemistry/structure; test for cargo-adaptor activity; introduce a molecular-function term for an IFT-particle structural/adaptor subunit activity.
Provenance (the field's own admissions):
Proposed term (ontology gap):
Gap: dyf-6 is a complex locus that, besides the short conserved IFT46 isoforms, produces a longer nematode-specific transcript fusing the dyf-6 ORF to the upstream gene F46F6.3; the biological role of this long product is uncharacterized. All functional and rescue data derive from the short isoforms, so whether the long isoform contributes anything beyond the conserved IFT-B function is unknown.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: The short (conserved) dyf-6 isoforms confer full dye-filling rescue and undergo IFT; the F46F6.3-fused long transcript is nematode-specific and has no assigned function, and existing alleles/reporters primarily report on the short forms.
Significance: Establishing whether the nematode-specific long isoform has a distinct role would clarify whether the dyf-6 locus encodes more than the conserved IFT-B subunit function.
What would resolve it: Isoform-specific knockouts/rescue and expression analysis of the long dyf-6/F46F6.3 fusion product.
Provenance (the field's own admissions):
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)