IFT-74 is the Caenorhabditis elegans ortholog of IFT74, a core coiled-coil subunit of the intraflagellar transport complex B (IFT-B1 core). It forms a heterodimer with IFT-81 through their coiled-coil domains, and the pair forms the tubulin-binding module of the IFT particle; the flexible, basic N-terminal region of IFT-74 (about residues 1-130) binds tubulin together with the calponin-homology domain of IFT-81. IFT-74 is expressed in ciliated sensory neurons, colocalizes with IFT-81 at the ciliary base and moves within sensory cilia. ift-74 and ift-81 loss-of-function mutants have similar phenotypes: mild defects in cilium formation, strongly disrupted IFT in mature cilia, dye-filling and chemosensory defects and small body size. At the ciliary tip the MAK-family kinase DYF-5 phosphorylates multiple sites in the IFT-74 N-terminal region, lowering the tubulin affinity of IFT-74/81 about sixfold and promoting tubulin unloading; phospho-dead and phospho-mimic ift-74 alleles produce elongated and shortened cilia respectively.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:17535250 IFT-81 and IFT-74 are required for intraflagellar transport ... | REMOVE | Summary: IPI from Kobayashi et al. 2007 showing that IFT-74 interacts and colocalizes with IFT-81 (WB:WBGene00017973). Reason: The IFT-74/IFT-81 interaction is real and well established (it forms the IFT-B1 coiled-coil heterodimer), but generic protein binding carries no functional information. The interaction is captured by part_of IFT-B, and the functional output of the heterodimer by tubulin binding annotations. Removal does not dispute the interaction. Supporting Evidence: PMID:17535250 We also demonstrated that IFT-81 interacts and co-localizes with IFT-74 |
| GO:0005929 cilium | IBA GO_REF:0000033 | ACCEPT | Summary: IBA to cilium; the worm gene is among the descendant evidence. Reason: IFT-74 localizes to sensory cilia (IDA, PMID:17535250; IFT-74::GFP knock-in labels the axoneme). Supporting Evidence: PMID:33997658 In controls, IFT-74::GFP was strongly recruited to cilia, labeling the complete axoneme |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: NAS from Yi et al. 2017, which used IFT-B in dynein-2 ciliary entry assays. Reason: Correct. 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 |
| GO:0006935 chemotaxis | IMP PMID:17535250 IFT-81 and IFT-74 are required for intraflagellar transport ... | KEEP AS NON CORE | Summary: IMP from Kobayashi et al. 2007: ift-74 mutants show behavioral (chemosensory) defects phenocopying ift-81. Reason: Chemotaxis defects are a consequence of defective sensory cilia; IFT-74 does no step of chemotaxis itself. Kept as non-core, consistent with other worm IFT genes. Supporting Evidence: PMID:17535250 The ift-74 loss-of-function mutants showed phenocopies with ift-81 mutants |
| GO:0008017 microtubule binding | IDA PMID:35969738 DYF-5/MAK-dependent phosphorylation promotes ciliary tubulin... | ACCEPT | Summary: IDA from Jiang et al. 2022: TIRF microtubule decoration assays with purified IFT-74/81/IFTA-2 complex showed colocalization with microtubules, reduced by DYF-5 phosphorylation of IFT-74. Reason: Directly assayed with recombinant worm proteins. The microtubule association is shown for the IFT-74/81(/IFTA-2) complex, so it is a property of the heterodimer rather than of IFT-74 alone, but the claim is supported. The better characterized activity is tubulin-dimer binding (beta-tubulin binding rows), which is the core MF. Supporting Evidence: PMID:35969738 We found that the colocalization between IFT-74/81/IFTA-2 and MTs was reduced by DYF-5 phosphorylation |
| GO:0030992 intraciliary transport particle B | IBA GO_REF:0000033 | ACCEPT | Summary: IBA to IFT-B; IFT74 is a conserved IFT-B1 core subunit. Reason: Core complex membership. Supporting Evidence: PMID:35969738 A recent study showed that IFT-74, an IFT-B complex subunit, functions with IFT-81 to bind and transport ciliary tubulins |
| GO:0030992 intraciliary transport particle B | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR029602, IFT74) mapping to IFT-B. Reason: Correct family-level mapping. Supporting Evidence: PMID:35969738 A recent study showed that IFT-74, an IFT-B complex subunit, functions with IFT-81 to bind and transport ciliary tubulins |
| GO:0030992 intraciliary transport particle B | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: NAS from Yi et al. 2017. Reason: Correct; redundant with IBA. 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 |
| GO:0035264 multicellular organism growth | IMP PMID:17535250 IFT-81 and IFT-74 are required for intraflagellar transport ... | MARK AS OVER ANNOTATED | Summary: IMP from Kobayashi et al. 2007; ift-74 and ift-81 mutants have small body size. Reason: Small body size in worm cilium mutants is an indirect consequence of loss of sensory input (cilia-dependent neuroendocrine control of growth); IFT-74 performs no step of organismal growth. The phenotype is real, but a process annotation to growth overstates the role of a ciliary transport subunit. Supporting Evidence: PMID:17535250 The similar phenotypes with ift-81 mutants were also observed in several IFT mutants, suggesting these defects are caused by inability of IFT. |
| GO:0035735 intraciliary transport involved in cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: IBA to intraciliary transport involved in cilium assembly. Reason: IFT-74/81 carries tubulin into the cilium for axoneme assembly; ift-74 mutants have cilium formation defects and phosphorylation-site mutants alter cilium length. Supporting Evidence: PMID:35969738 Ablation or constitutive activation of IFT-74 phosphorylation abnormally elongates or shortens sensory cilia in Caenorhabditis elegans neurons. |
| GO:0042073 intraciliary transport | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping to intraciliary transport. Reason: Correct. Supporting Evidence: PMID:17535250 IFT-81 and IFT-74 coordinately act in IFT in C. elegans sensory cilia |
| GO:0042073 intraciliary transport | IMP PMID:17535250 IFT-81 and IFT-74 are required for intraflagellar transport ... | ACCEPT | Summary: IMP from Kobayashi et al. 2007: ift-74 mutants show obvious disruption of IFT in mature cilia. Reason: Core process, directly supported in the worm. Supporting Evidence: PMID:17535250 ift-81 and ift-74 mutants similarly exhibited weak anomalies in cilia formation and obvious disruptions of transport in mature cilia |
| GO:0042073 intraciliary transport | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: NAS from Yi et al. 2017. Reason: Correct; redundant with IMP. Supporting Evidence: PMID:17535250 IFT-81 and IFT-74 coordinately act in IFT in C. elegans sensory cilia |
| GO:0048487 beta-tubulin binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA to beta-tubulin binding. The basic N-terminal domain of IFT74 binds tubulin (the beta-tubulin C-terminal tail in the human/Chlamydomonas structural work), and worm IFT-74N with IFT-81 binds tubulin in pull-down and microscale thermophoresis assays. Reason: Core MF; experimentally supported in the worm (PMID:35969738) and in human cells (PMID:23990561). Supporting Evidence: PMID:23990561 the two core IFT proteins IFT74 and IFT81 form a tubulin-binding module and mapped the interaction to a calponin homology domain of IFT81 and a highly basic domain in IFT74 PMID:23990561 IFT81N appears to bind the globular domain of tubulin to provide specificity, and IFT74N recognizes the Ξ²-tubulin tail to increase affinity PMID:35969738 Tubulin dimers are loaded to IFT machinery through an interaction between tubulin and the IFT-74/81 module |
| GO:0048487 beta-tubulin binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR029602) mapping to beta-tubulin binding. Reason: Consistent with IBA and worm biochemistry. Supporting Evidence: PMID:35969738 the ciliary kinase DYF-5/MAK phosphorylates multiple sites within the tubulin-binding module of IFT-74, reducing the tubulin-binding affinity of IFT-74/81 approximately sixfold |
| GO:0050906 detection of stimulus involved in sensory perception | IMP PMID:17535250 IFT-81 and IFT-74 are required for intraflagellar transport ... | KEEP AS NON CORE | Summary: IMP from Kobayashi et al. 2007 (behavioral/sensory defects of ift-74 mutants). Reason: Sensory detection fails because the sensory cilia are defective; IFT-74 is required for, but does not perform, stimulus detection. Supporting Evidence: PMID:17535250 The ift-74 loss-of-function mutants showed phenocopies with ift-81 mutants |
| GO:0060271 cilium assembly | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping to cilium assembly. Reason: Correct; ift-74 mutants have cilium formation defects and altered cilium length. Supporting Evidence: PMID:17535250 ift-81 and ift-74 mutants similarly exhibited weak anomalies in cilia formation and obvious disruptions of transport in mature cilia |
| GO:0060271 cilium assembly | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: NAS from Yi et al. 2017. Reason: Correct. Supporting Evidence: PMID:35969738 Ablation or constitutive activation of IFT-74 phosphorylation abnormally elongates or shortens sensory cilia in Caenorhabditis elegans neurons. |
| GO:0097730 non-motile cilium | IDA PMID:17535250 IFT-81 and IFT-74 are required for intraflagellar transport ... | ACCEPT | Summary: IDA from Kobayashi et al. 2007; IFT-74 colocalizes with IFT-81 at the base of sensory cilia. Reason: Direct localization; all worm cilia are non-motile sensory cilia. Supporting Evidence: PMID:17535250 We also demonstrated that IFT-81 interacts and co-localizes with IFT-74 |
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Download this section (compressed HTML)Q: Do the 11 DYF-5 phosphosites in IFT-74N act only in tubulin release, or do they also regulate IFT train remodeling and kinesin handover at the middle-segment and distal-segment tips?
Q: Does the worm IFT-74/81 module carry specific tubulin isotypes (e.g. TBB-4 vs TBA-5) with different affinities?
Experiment: Measure binding of recombinant IFT-74/81 to purified tubulin isotypes and image isotype-specific tubulin transport in ift-74 phospho-mutant knock-ins.
Experiment: Image IFT train turnaround and kinesin-II/OSM-3 handover at the ciliary tip in ift-74 phospho-dead and phospho-mimic alleles.
ift-74 encodes a protein that interacts with the intraflagellar transport (IFT) component IFT-81; ift-74 along with ift-81 is involved in growth, chemotaxis, intraflagellar transport and the morphogenesis of cilia; ift-74 colocalizes with ift-81 in the ciliary transition zone; ift-74 binds ift-81 in protien binding assays; the physical interaction of ift-74 and ift-81 and their co-localization indicate that they might form a complex in ciliated neurons.
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Download this section (compressed HTML)Loading supporting contentβ¦
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