IFT-81 is the Caenorhabditis elegans ortholog of IFT81, a core subunit of the intraflagellar transport complex B (IFT-B1 core). It has an N-terminal calponin-homology (CH) domain followed by long coiled-coil segments, through which it forms a heterodimer with IFT-74. The IFT-74/81 heterodimer is the tubulin-binding module of the IFT particle: the IFT81 CH domain recognizes the globular part of tubulin and the basic IFT74 N-terminus binds the beta-tubulin tail, so tubulin dimers are carried into the cilium for axoneme assembly. IFT-81 is expressed in ciliated sensory neurons, localizes at the ciliary base and in sensory cilia, and colocalizes with IFT-74. ift-81 loss-of-function mutants have mild defects in cilium formation, strongly disrupted IFT in mature cilia, chemosensory and dye-filling defects and small body size. Phosphorylation of IFT-74 by the ciliary kinase DYF-5 reduces the tubulin affinity of the IFT-74/81 module and promotes tubulin unloading at the ciliary tip.
| 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 IFT-81 interacts with IFT-74 (WB:WBGene00016005). Reason: The IFT-81/IFT-74 heterodimer is real and well established, but generic protein binding carries no functional information; the interaction is captured by part_of IFT-B and its functional output by tubulin binding. Removal does not dispute the interaction. Supporting Evidence: PMID:17535250 We also demonstrated that IFT-81 interacts and co-localizes with IFT-74 |
| GO:0005815 microtubule organizing center | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic annotation to microtubule organizing center. The ciliary basal body is a microtubule organizing center in GO, and IFT-81 localizes at the base of cilia. Reason: Correct as a general parent of the basal body location; the more specific ciliary basal body (IBA) row is retained as core. Supporting Evidence: PMID:17535250 IFT-81 is expressed in sensory neurons, and localized at the base of cilia |
| GO:0005929 cilium | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic annotation to cilium. Reason: Correct; IFT-81 is a ciliary IFT-B subunit. Supporting Evidence: PMID:17535250 IFT-81 and IFT-74 coordinately act in IFT in C. elegans sensory cilia |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: NAS from Yi et al. 2017. 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-81 mutants show an unusual behavioral (chemosensory) phenotype. Reason: Chemotaxis defects follow from defective sensory cilia; IFT-81 does no step of chemotaxis itself. Kept as non-core, consistent with other worm IFT genes. Supporting Evidence: PMID:17535250 its loss-of-function mutants show an unusual behavioral property and small body size |
| GO:0007018 microtubule-based movement | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic annotation to microtubule-based movement, a GO ancestor of intraciliary transport. Reason: IFT-81 is not a motor, but as an IFT-B subunit it participates in IFT, which GO places under microtubule-based movement. The general term is acceptable; the informative term is intraciliary transport. Supporting Evidence: PMID:17535250 IFT-81 and IFT-74 coordinately act in IFT in C. elegans sensory cilia |
| 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 worm IFT-74/81/IFTA-2 complex showed microtubule colocalization, reduced by DYF-5 phosphorylation. Reason: Directly assayed with recombinant worm proteins; the activity belongs to the IFT-74/81 heterodimer rather than IFT-81 alone. IFT74/81 microtubule binding is also shown by sedimentation assays for the orthologs (PMID:23990561). Supporting Evidence: PMID:35969738 We found that the colocalization between IFT-74/81/IFTA-2 and MTs was reduced by DYF-5 phosphorylation PMID:23990561 IFT74/81 displayed robust MT binding in sedimentation assays |
| GO:0015631 tubulin binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA to tubulin binding; the worm gene is among the descendant evidence. The IFT81 CH domain binds the globular domain of alphabeta-tubulin. Reason: Core MF, supported in the worm and orthologs. Supporting Evidence: 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:0015631 tubulin binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR029600, IFT81) mapping to tubulin binding. Reason: Consistent with IBA and biochemistry. 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 |
| GO:0030992 intraciliary transport particle B | IBA GO_REF:0000033 | ACCEPT | Summary: IBA to IFT-B; IFT81 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:0000120 | ACCEPT | Summary: ARBA/InterPro electronic annotation to IFT-B. Reason: Correct. 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-81 mutants have small body size. Reason: Small body size of worm cilium mutants is an indirect consequence of loss of sensory input; IFT-81 performs no step of organismal growth. The phenotype is real, but a growth process annotation 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:0036064 ciliary basal body | IBA GO_REF:0000033 | ACCEPT | Summary: IBA to ciliary basal body; IFT-81 localizes at the base of sensory cilia. Reason: Consistent with worm localization data and conserved IFT81 localization. Supporting Evidence: PMID:17535250 IFT-81 is expressed in sensory neurons, and localized at the base of cilia |
| GO:0042073 intraciliary transport | IBA GO_REF:0000033 | ACCEPT | Summary: IBA to intraciliary transport; the worm gene is among the descendant evidence. Reason: Core process. Supporting Evidence: PMID:17535250 IFT-81 and IFT-74 coordinately act in IFT in C. elegans sensory cilia |
| 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-81 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 and IBA. Supporting Evidence: PMID:17535250 IFT-81 and IFT-74 coordinately act in IFT in C. elegans sensory cilia |
| 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-81 mutants). Reason: Sensory detection fails because sensory cilia are defective; IFT-81 is required for, but does not perform, stimulus detection. Supporting Evidence: PMID:17535250 its loss-of-function mutants show an unusual behavioral property and small body size |
| GO:0060271 cilium assembly | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/InterPro electronic annotation to cilium assembly. Reason: Correct; ift-81 mutants have cilium formation defects, and tubulin binding by IFT81 is required for ciliogenesis in human cells. Supporting Evidence: PMID:23990561 tubulin binding by IFT81 was required for ciliogenesis in human cells |
| 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:17535250 ift-81 and ift-74 mutants similarly exhibited weak anomalies in cilia formation and obvious disruptions of transport in mature cilia |
| 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-81 localizes at the base of sensory cilia. Reason: Direct localization; all worm cilia are non-motile sensory cilia. Supporting Evidence: PMID:17535250 IFT-81 is expressed in sensory neurons, and localized at the base of cilia |
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Download this section (compressed HTML)Q: Is the tubulin-binding CH domain of worm IFT-81 required in vivo for axoneme elongation, as it is in human cells, and does its loss mimic the ift-74 phospho-dead or phospho-mimic phenotypes?
Experiment: Introduce CH-domain point mutations that abolish tubulin binding into endogenous ift-81 and measure cilium length and tubulin (TBB-4) transport by live imaging.
ift-81 encodes an ortholog of the intraflagellar transport component IFT-81 in Chlamydomonas; ift-81 along with ift-74 is involved in growth, chemotaxis, intraflagellar transport and the morphogenesis of cilia; ift-81 binds ift-74 in protein binding assays and co-localizes with ift-74 to the transition zone of cilia in neurons, indicating that ift-81 may form a complex with ift-74.
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