DYF-2 is the Caenorhabditis elegans ortholog of human WDR19 (IFT144 in Chlamydomonas), a core subunit of the intraflagellar transport complex A (IFT-A). It is a large (1364 aa) WD40 Ξ²-propeller plus tetratricopeptide-repeat (TPR) solenoid scaffold protein with no catalytic domain, expressed selectively in ciliated sensory neurons and localizing along the axoneme of the non-motile sensory cilium. As part of IFT-A, DYF-2 is required for retrograde (tip-to-base) intraflagellar transport and for the assembly and structural integrity of the IFT particle as a whole. Its conserved WD40 domain is the key factor that reassembles the IFT-B subcomplex into the IFT-Aβdynein machinery for retrograde transport at the ciliary tip, and it couples the BBSome to moving IFT particles (WDR19 interacts directly with BBS1). Loss of DYF-2 produces severely truncated cilia with disrupted IFT and mislocalized IFT-A and IFT-B components; a hypomorphic WD40-domain allele selectively abolishes retrograde IFT and causes IFT-B accumulation at the ciliary tip. Because sensory cilia are the sites of chemo- and osmosensation in the worm, dyf-2 mutants are dye-filling defective and show impaired chemotaxis and osmotic avoidance. WDR19 mutations cause human ciliopathies (e.g. cranioectodermal dysplasia/Sensenbrenner and nephronophthisis), underscoring a conserved role in cilium biogenesis.
Definition: The action of a protein that contributes to the structural integrity of an intraflagellar transport (IFT) particle (IFT-A or IFT-B subcomplex), for example by acting as a WD40/TPR scaffold that holds core IFT subunits together and enables their bidirectional transport along the ciliary axoneme, without itself catalyzing a biochemical reaction.
Parent term: structural molecule activity
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005929 cilium | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-2/WDR19 is an IFT-A subunit that acts within the cilium; ciliary localization is directly demonstrated in the worm and conserved (the mouse ortholog WDR19 also localizes to cilia). Reason: Core localization. Phylogenetic inference agrees with direct experimental evidence in C. elegans (see the IDA non-motile cilium annotation) and with conservation of WDR19 ciliary localization. Supporting Evidence: PMID:16957054 the mouse orthologue of DYF-2, WDR19, also localizes to cilia |
| GO:0035721 intraciliary retrograde transport | IBA GO_REF:0000033 | ACCEPT | Summary: As a core IFT-A subunit, DYF-2 is required for retrograde (tip-to-base) intraflagellar transport, the defining function of the IFT-A complex. Reason: Represents the core biological process of the gene. Phylogenetic inference is corroborated by direct experimental evidence that a dyf-2 WD40 allele selectively abolishes retrograde IFT. Supporting Evidence: PMID:22922713 in dyf-2(jhu616), IFT-B component OSM-6 showed characteristic anterograde IFT movement, but lost almost all retrograde IFT movements |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Retrograde IFT by IFT-A is required to build and maintain the ciliary axoneme; loss of DYF-2 gives severely truncated cilia. Reason: Well-supported by phylogeny and by the null-allele phenotype (truncated cilia, disrupted IFT). A core process, though downstream of the direct IFT transport activity. Supporting Evidence: PMID:22922713 the latter show severely truncated cilia and completely disrupted IFT transport |
| GO:0030991 intraciliary transport particle A | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-2 is a core subunit of the IFT-A complex, established by orthology to WDR19/IFT144 and by direct mass-spec identification in the worm IFT-A complex. Reason: Core complex membership. Phylogenetic inference agrees with the experimental (NAS/mass-spec) IFT-A assignment. Supporting Evidence: PMID:22922713 In Chlamydomonas, IFT144 (the homolog of DYF-2) is an IFT-A component |
| GO:0005929 cilium | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (SubCell/ARBA) assertion of ciliary localization, redundant with the experimental IDA and IBA cilium annotations. Reason: Correct location; consistent with direct experimental evidence, albeit redundant with the higher-evidence cilium annotations. |
| GO:0008104 intracellular protein localization | IEA GO_REF:0000117 | MODIFY | Summary: Generic ARBA electronic term. DYF-2's actual role is transporting/localizing IFT and cargo proteins within the cilium; a cilium-specific term is more accurate and informative. Reason: "intracellular protein localization" is uninformatively broad. The experimental basis (loss of DYF-2 mislocalizes ciliary IFT-A/IFT-B proteins) and DYF-2's IFT-A function are better captured by "protein localization to cilium". Proposed replacements: protein localization to cilium |
| GO:0030990 intraciliary transport particle | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic assertion of membership in the (generic) intraflagellar transport particle. This is the parent of the specific, experimentally supported IFT-A membership. Reason: Not wrong, but subsumed by and less informative than the IFT particle A (GO:0030991) annotation, which is the correct specific complex. Retained as a correct but non-core generalization. |
| GO:0035721 intraciliary retrograde transport | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic annotation of the IFT-A retrograde-transport role, redundant with the IBA/NAS/IMP annotations to the same term. Reason: Correct core process; consistent with, though redundant with, the experimental and phylogenetic annotations to this term. |
| GO:0044782 cilium organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic annotation to the parent term of cilium assembly. Reason: Correct but general; the more specific "cilium assembly" / "non-motile cilium assembly" annotations capture the role more precisely. |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal (CPX-1289) NAS assertion of ciliary localization for the IFT-A complex, based on the mass-spec study of worm retrograde IFT. Reason: Correct core localization, consistent with experimental IDA evidence. |
| GO:0030991 intraciliary transport particle A | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal NAS annotation placing DYF-2 in the IFT-A complex, based on affinity purification / mass spectrometry of the worm IFT-A complex. Reason: Core complex membership, experimentally grounded (mass-spec identification of DYF-2 in IFT-A). |
| GO:0035721 intraciliary retrograde transport | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal NAS annotation of the IFT-A retrograde-transport role. Reason: Core process, consistent with the experimental and phylogenetic evidence. |
| GO:0060271 cilium assembly | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal NAS annotation of the cilium-assembly role of IFT-A. Reason: Correct; downstream outcome of the IFT-A transport function. Consistent with the null-allele phenotype. |
| GO:0060271 cilium assembly | IMP PMID:22922713 The BBSome controls IFT assembly and turnaround in cilia. | ACCEPT | Summary: Mutant analysis: dyf-2(m160) null shows severely truncated cilia, demonstrating a requirement for DYF-2 in ciliary assembly/maintenance. Reason: Directly supported by the mutant phenotype; a core process (downstream of the direct retrograde-IFT activity). Supporting Evidence: PMID:22922713 the latter show severely truncated cilia and completely disrupted IFT transport |
| GO:0035721 intraciliary retrograde transport | IMP PMID:22922713 The BBSome controls IFT assembly and turnaround in cilia. | ACCEPT | Summary: The hypomorphic dyf-2(jhu616) WD40-domain allele selectively abolishes retrograde IFT while leaving anterograde IFT intact, directly implicating DYF-2 in retrograde intraflagellar transport. Reason: Strong, direct experimental evidence for the core molecular process of the gene. Supporting Evidence: PMID:22922713 our observations reveal a role for the WD40 domain of DYF-2 as the key factor in reassembling IFT-B subcomplex into IFT-A-dynein retrograde machinery |
| GO:0006935 chemotaxis | IMP PMID:16957054 Caenorhabditis elegans DYF-2, an orthologue of human WDR19, ... | KEEP AS NON CORE | Summary: dyf-2 mutants have defective sensory cilia and are impaired in chemotaxis to volatile odorants. This is a whole-organism sensory phenotype downstream of the ciliary/IFT defect, not a direct molecular function of DYF-2. Reason: Valid IMP phenotype but a pleiotropic downstream consequence of ciliary dysfunction shared by essentially all cilium/IFT genes; not part of the core molecular/cellular function of DYF-2. Supporting Evidence: PMID:16957054 leads to defects in cilia structure and chemosensation in the nematode |
| GO:0007635 chemosensory behavior | IMP PMID:16957054 Caenorhabditis elegans DYF-2, an orthologue of human WDR19, ... | KEEP AS NON CORE | Summary: Chemosensory-behavior defect in dyf-2 mutants, a downstream consequence of defective sensory cilia. Reason: Legitimate mutant phenotype but downstream of the ciliary/IFT defect; not a core function. Supporting Evidence: PMID:16957054 leads to defects in cilia structure and chemosensation in the nematode |
| GO:0008104 intracellular protein localization | IMP PMID:16957054 Caenorhabditis elegans DYF-2, an orthologue of human WDR19, ... | MODIFY | Summary: Loss of DYF-2 alters the assembly and motility of IFT components and mislocalizes ciliary IFT-A/IFT-B proteins. The generic "intracellular protein localization" term understates that this is protein localization within the cilium. Reason: The experimental readout is mislocalization of ciliary IFT proteins; "protein localization to cilium" is the accurate, informative term. Same replacement proposed for the redundant ARBA IEA annotation. Proposed replacements: protein localization to cilium Supporting Evidence: PMID:16957054 Loss of DYF-2 function selectively affects the assembly and motility of different IFT components |
| GO:0030992 intraciliary transport particle B | IDA PMID:16957054 Caenorhabditis elegans DYF-2, an orthologue of human WDR19, ... | MARK AS OVER ANNOTATED | Summary: The 2006 founding paper concluded that DYF-2 "can associate with IFT particle complex B" (based on DYF-2 co-migration behavior in a BBS mutant with partially disrupted IFT particles), while also noting that dyf-2 mutations interfere with IFT-A components. Subsequent work firmly places WDR19/IFT144/DYF-2 as a core IFT-A subunit (direct mass-spec identification in the worm IFT-A complex; Chlamydomonas IFT144 = IFT-A). Reason: DYF-2's stable complex membership is IFT-A, not IFT-B. The IFT-B "association" reflects DYF-2 acting at the IFT-A/IFT-B interface (its WD40 domain reassembles IFT-B into the IFT-Aβdynein retrograde machinery at the tip), a functional interplay rather than IFT-B core membership. The experimental observation is genuine but its complex-membership interpretation has been superseded; flagged as over-annotation rather than removed, in deference to the original experimental call. Supporting Evidence: PMID:16957054 we conclude that DYF-2 can associate with IFT particle complex B PMID:22922713 In Chlamydomonas, IFT144 (the homolog of DYF-2) is an IFT-A component |
| GO:0042048 olfactory behavior | IMP PMID:16957054 Caenorhabditis elegans DYF-2, an orthologue of human WDR19, ... | KEEP AS NON CORE | Summary: dyf-2 mutants are impaired in responses to volatile (olfactory) odorants such as pyrazine and iso-amyl alcohol, a downstream consequence of the sensory-cilia defect. Reason: Valid mutant phenotype (odorant response requires functional AWA/AWC sensory cilia) but a pleiotropic downstream consequence of the ciliary/IFT defect, not a core function of DYF-2. |
| GO:0042073 intraciliary transport | IDA PMID:16957054 Caenorhabditis elegans DYF-2, an orthologue of human WDR19, ... | ACCEPT | Summary: DYF-2 is a component of the intraflagellar transport machinery that moves along the sensory-cilium axoneme; direct experimental evidence in the worm. Reason: Core process. This general IFT term is the parent of the more specific retrograde-IFT annotation; both are appropriate for a bidirectionally transported IFT-A subunit. Supporting Evidence: PMID:16957054 component of the intraflagellar transport machinery in sensory cilia |
| GO:0097730 non-motile cilium | IDA PMID:16957054 Caenorhabditis elegans DYF-2, an orthologue of human WDR19, ... | ACCEPT | Summary: DYF-2 localizes to the non-motile sensory cilia of C. elegans neurons (direct experimental evidence). Reason: Core localization, accurately specific to the worm's non-motile sensory cilia. Supporting Evidence: PMID:16957054 component of the intraflagellar transport machinery in sensory cilia |
| GO:1905515 non-motile cilium assembly | IMP PMID:16957054 Caenorhabditis elegans DYF-2, an orthologue of human WDR19, ... | ACCEPT | Summary: DYF-2 is required to build the non-motile sensory cilium; loss of function gives defects in cilium structure. Reason: Correct and accurately specific for the worm's non-motile sensory cilia; a core process (downstream of the direct retrograde-IFT activity). Supporting Evidence: PMID:16957054 leads to defects in cilia structure and chemosensation in the nematode |
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Download this section (compressed HTML)Q: What is the subunit-resolved architecture of the C. elegans IFT-A complex, and which IFT-A subunits does DYF-2/WDR19 directly contact?
Suggested experts: Ou G
Q: What is the structural basis of the DYF-2/WDR19 WD40-domain interface that docks the BBSome onto moving IFT particles?
Suggested experts: Hu J
Experiment: Generate structure-guided separation-of-function alleles across the DYF-2 WD40 surface and score, in vivo, retrograde IFT (kymography of IFT-B markers), BBSome co-migration/docking (BiFC or dual-color imaging), and cilium length, to map the BBSome-docking interface independently of IFT-A assembly.
Hypothesis: The DYF-2 WD40 domain provides a dedicated docking surface for the BBSome on IFT particles, separable from its role in IFT-A integrity.
Type: structure-function mutagenesis
Experiment: Reconstitute or affinity-purify the worm IFT-A complex and determine its architecture by cryo-EM, assigning DYF-2/WDR19 and its direct neighbors and testing whether ciliopathy-mimicking substitutions perturb specific interfaces.
Hypothesis: DYF-2 occupies a defined position within an IFT-A scaffold that can be resolved structurally.
Type: structural biology
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: DYF-2 has no assigned molecular function and no term to express one. Its role is to be a structural constituent of the IFT-A particle, but GO has no "structural constituent of the intraflagellar transport particle" molecular function term, so the gene reads as MF-dark despite a well-understood cellular and process-level role.
OPEN ONTOLOGYCURATION MF_DARK
What is known: It is firmly established that DYF-2 = WDR19/IFT144 is a WD40+TPR scaffolding subunit of IFT-A with no catalytic domain, required for retrograde IFT and cilium assembly. What is missing is a molecular-function representation: the worm GOA record carries only cellular-component and biological-process terms and no molecular_function annotation at all.
Significance: This is the canonical "structural subunit" ontology gap: a mechanistically well-understood protein that cannot be annotated with an informative MF term, contributing to apparent molecular-function darkness across the IFT/ciliopathy gene set.
What would resolve it: Develop/adopt a molecular-function term for a structural constituent of the IFT particle (analogous to "structural constituent of ribosome"), then annotate DYF-2 (and other IFT-A/IFT-B core subunits) to it.
Provenance (the field's own admissions):
Proposed term (ontology gap):
Gap: The molecular interface by which the DYF-2/WDR19 WD40 domain docks the BBSome onto moving IFT particles, and the direct IFT-A subunit contacts of DYF-2 in the worm, are inferred (from point mutants, BiFC and cross-species proteomics), not resolved structurally. How the WD40 domain physically "reassembles" IFT-B into the IFT-Aβdynein machinery at the ciliary tip is a model, not a solved mechanism.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Genetics and imaging establish that the conserved WD40 residue (worm G361 / mouse WDR19 G341) is required for BBSome association and retrograde IFT, and that WDR19 interacts with BBS1; the worm IFT-A composition (che-11, daf-10, dyf-2, ift-139, ift-43, ifta-1) is known from mass spectrometry. The subunit-resolved architecture and the DYF-2βBBSome binding interface are not determined.
Significance: The tip-reassembly/BBSome-docking step is the load-bearing, incompletely understood mechanism of IFT turnaround; resolving it would explain how retrograde transport is licensed and how ciliopathy-causing WDR19 mutations disrupt it.
What would resolve it: Cryo-EM of the worm IFT-A complex and of an IFT-AβBBSome assembly; structure- guided separation-of-function mutagenesis of the DYF-2 WD40 surface with retrograde-IFT and BBSome-docking readouts.
Provenance (the field's own admissions):
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