dyf-11 encodes the Caenorhabditis elegans ortholog of MIP-T3/TRAF3IP1 (IFT54), a 535-residue structural subunit of intraflagellar transport (IFT) complex B. IFT-B, together with IFT-A and the kinesin-2 and dynein-2 motors, drives the bidirectional transport of ciliary cargo that builds and maintains the sensory cilia of ciliated neurons. The protein has no catalytic domain; it comprises conserved N- and C-terminal TRAF3IP1 domains flanking a long charged/disordered central region and a C-terminal coiled coil. DYF-11 is expressed under X-box/RFX (daf-19) control specifically in ciliated sensory neurons and localizes to the ciliary base (transition zone/basal body) and along the ciliary axoneme, where it undergoes processive IFT movement. It is required to assemble and maintain an intact motor-IFT particle: in its absence kinesin-II, IFT-A, IFT-dynein and BBSome components fail to enter cilia and the axoneme is severely truncated, so full-length medial and distal ciliary segments do not form. Loss of dyf-11 therefore disrupts cilium-dependent sensory behaviors (chemosensation, osmotic avoidance, dauer formation, dye filling) and perturbs lipid homeostasis. The ciliary role is conserved: human MIP-T3 localizes to basal bodies and cilia, and zebrafish mipt3 is required for gastrulation movements and interacts genetically with the Bardet-Biedl protein Bbs4.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030992 intraciliary transport particle B | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-11/IFT54 is a subunit of intraflagellar transport complex B (IFT-B). This IBA transfer is strongly corroborated by C. elegans experimental data and by biochemical assignment to ComplexPortal CPX-1290. Reason: Core cellular-component identity. Phylogenetically inferred and independently confirmed experimentally (PMID:18369462). Supporting Evidence: PMID:18369462 DYF-11 functions as a novel component of IFT subcomplex B |
| GO:0005930 axoneme | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-11 acts within the ciliary axoneme, where IFT trains move. The is_active_in qualifier is appropriate for an IFT-B component that translocates along the axoneme. Reason: Consistent with the experimental IDA axoneme localization (PMID:18369462). Supporting Evidence: PMID:18369462 the DYF-11::GFP protein was found to be highly enriched at transition zones and within ciliary axonemes |
| GO:0036064 ciliary basal body | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-11 localizes to and functions at the ciliary base (transition zone/basal body), where IFT trains assemble and load. Reason: Corroborated by the experimental IDA basal-body/transition-zone localization (PMID:18369462). Supporting Evidence: PMID:18369462 the DYF-11::GFP protein was found to be highly enriched at transition zones and within ciliary axonemes |
| GO:0070507 regulation of microtubule cytoskeleton organization | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: DYF-11's effect on microtubules is to build the axonemal microtubule structure via IFT, which is more precisely captured by cilium assembly (GO:0060271). The general "regulation of microtubule cytoskeleton organization" term over-generalizes this structural role and is not directly supported by evidence of a regulatory activity. Reason: Over-general phylogenetic transfer; DYF-11 does not regulate microtubule dynamics per se — it is a structural IFT-B subunit whose microtubule-related role is axoneme assembly, already annotated as cilium assembly and intraciliary transport. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000773545 · TRAF3IP1 family node SUPPORTS SOURCE BUT NOT TARGET The IFT54/TRAF3IP1 family node's microtubule-related activity is axonemal assembly via IFT, not regulation of microtubule dynamics; the transferred term is scoped too broadly for the structural role. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-11 is required to build full-length sensory cilia; dyf-11 nulls have severely truncated cilia lacking medial and distal segments. Reason: Core biological process, strongly supported experimentally (PMID:18369462; PMID:18245347). Supporting Evidence: PMID:18369462 the cilia of dyf-11 mutants were truncated substantially |
| GO:0042073 intraciliary transport | IBA GO_REF:0000033 | ACCEPT | Summary: DYF-11 functions in intraflagellar (intraciliary) transport as an IFT-B subunit that undergoes bidirectional IFT movement along the axoneme. Reason: Core biological process, confirmed experimentally in worm (PMID:18369462). Supporting Evidence: PMID:18369462 the GFP-tagged protein moves bi-directionally along the length of amphid and phasmid ciliary axonemes |
| GO:0005930 axoneme | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic mapping of the UniProt cilium-axoneme subcellular-location keyword. Redundant with the experimental IDA axoneme annotation and correct. Reason: Correct location, corroborated by experimental IDA (PMID:18369462). Supporting Evidence: PMID:18369462 the DYF-11::GFP protein was found to be highly enriched at transition zones and within ciliary axonemes |
| GO:0008017 microtubule binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO transfer for the TRAF3IP1/MIP-T3 family, which is named for its microtubule-interacting property; human MIP-T3 was shown to bind microtubules, and Li et al. suggest a proportion of C. elegans DYF-11 may associate directly with microtubules. This is the most informative molecular-function term available for DYF-11, though direct microtubule binding by the worm protein has not been experimentally demonstrated. Reason: Best-supported molecular function; consistent with family identity and IFT-B axonemal role. Supporting Evidence: PMID:18369462 MIP-T3 proteins range in size from 484 to 625 amino acids and have no recognizable domains except for a predicted coiled-coil region near the C-terminus |
| GO:0048513 animal organ development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Over-general ARBA machine-learning inference. C. elegans lacks the vertebrate organs implied, and DYF-11's characterized role is restricted to sensory ciliogenesis. Not informative. Reason: Vague electronic annotation with no experimental support in this organism; DYF-11's role is specific to sensory cilium assembly/function. |
| GO:0048731 system development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Over-general ARBA machine-learning inference; uninformative for a sensory-cilium IFT protein. Reason: Vague electronic annotation; DYF-11's characterized function is ciliogenesis, better captured by cilium assembly. |
| GO:0070507 regulation of microtubule cytoskeleton organization | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Duplicate of the IBA transfer of the same term via an ARBA model. Over-generalizes DYF-11's structural axoneme-assembly role. Reason: DYF-11 is a structural IFT-B subunit, not a regulator of microtubule dynamics; the microtubule-related role is axoneme assembly (cilium assembly / intraciliary transport). |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal (CPX-1290) assertion that DYF-11 localizes to the cilium. Correct but general; the more specific axoneme and basal-body IDA locations are also annotated. Reason: Correct ciliary location; consistent with experimental IDA localization. |
| GO:0030992 intraciliary transport particle B | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal (CPX-1290) assertion of IFT-B membership, consistent with the experimental IDA and phylogenetic annotations. Reason: Core cellular-component identity; independently confirmed (PMID:18369462). 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-11 functions in intraciliary transport, consistent with experimental data. Reason: Core biological process; confirmed experimentally (PMID:18369462). |
| GO:0060271 cilium assembly | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal assertion that DYF-11 functions in cilium assembly, consistent with the truncated-cilia phenotype of dyf-11 mutants. Reason: Core biological process; strongly supported (PMID:18369462; PMID:18245347). |
| GO:0008306 associative learning | IMP PMID:20837997 Reversal of salt preference is directed by the insulin/PI3K ... | KEEP AS NON CORE | Summary: A dyf-11 defect in salt-chemotaxis plasticity would be an indirect consequence of loss of functional sensory (ASE) cilia rather than a direct role in learning/memory. The cited paper is cached abstract-only and its abstract does not mention dyf-11, so the specific evidence cannot be verified here. Retained as a pleiotropic, non-core sensory phenotype rather than removed (experimental IMP; defer to curator). Reason: Downstream/pleiotropic behavioral consequence of ciliary dysfunction, not a core molecular function of an IFT-B structural subunit; supporting full text unavailable in the cache. |
| GO:0036064 ciliary basal body | IDA PMID:18369462 An essential role for DYF-11/MIP-T3 in assembling functional... | ACCEPT | Summary: DYF-11::GFP is highly enriched at the transition zone/basal body in ciliated sensory neurons; human MIP-T3 likewise localizes to the basal body. Reason: Core, directly observed cellular-component location. Supporting Evidence: PMID:18369462 V5 epitope-tagged human MIP-T3 also localizes to the basal body |
| GO:0005930 axoneme | IDA PMID:18369462 An essential role for DYF-11/MIP-T3 in assembling functional... | ACCEPT | Summary: DYF-11::GFP is directly observed enriched within ciliary axonemes and moves along their length. Reason: Core, directly observed cellular-component location. Supporting Evidence: PMID:18369462 the DYF-11::GFP protein was found to be highly enriched at transition zones and within ciliary axonemes |
| GO:0030992 intraciliary transport particle B | IDA PMID:18369462 An essential role for DYF-11/MIP-T3 in assembling functional... | ACCEPT | Summary: DYF-11 was directly characterized as a novel component of IFT subcomplex B based on its IFT movement and genetic behavior relative to kinesin/BBS/IFT mutants. Reason: Core cellular-component identity, directly established. Supporting Evidence: PMID:18369462 DYF-11 functions as a novel component of IFT subcomplex B |
| GO:0042073 intraciliary transport | IMP PMID:18369462 An essential role for DYF-11/MIP-T3 in assembling functional... | ACCEPT | Summary: Loss of dyf-11 disrupts IFT, mislocalizing kinesin-II, IFT-A, dynein and BBSome components and truncating cilia, demonstrating a functional requirement in IFT. Reason: Core biological process; strong loss-of-function evidence. Supporting Evidence: PMID:18369462 DYF-11 is an intraflagellar transport protein critical for the formation of full-length, functional sensory cilia |
| GO:0045184 establishment of protein localization | IMP PMID:18369462 An essential role for DYF-11/MIP-T3 in assembling functional... | MODIFY | Summary: In dyf-11 mutants, IFT-associated proteins (CHE-11/IFT-A, OSM-5/IFT-B, XBX-1/dynein, BBS-7, KAP-1/kinesin-II) fail to enter cilia. This is specifically the failure to localize proteins to the cilium, better captured by GO:0061512 "protein localization to cilium" than by the very general "establishment of protein localization". Reason: Term too general; the experiment shows DYF-11 is required for delivering IFT proteins into the cilium. Proposed replacements: protein localization to cilium Supporting Evidence: PMID:18369462 none of the proteins were observed to enter the (truncated) amphid and phasmid cilia |
| GO:0055088 lipid homeostasis | IMP PMID:18369462 An essential role for DYF-11/MIP-T3 in assembling functional... | KEEP AS NON CORE | Summary: dyf-11 mutants show increased intestinal Nile Red (lipid) staining, rescued by DYF-11::GFP, reflecting the conserved cilia-lipid connection. This is a downstream systemic consequence of ciliary dysfunction, not a core molecular function. Reason: Real, rescued loss-of-function phenotype but pleiotropic/indirect (secondary to defective sensory-cilia signaling), not a core function of an IFT-B subunit. Supporting Evidence: PMID:18369462 indicative of an increased lipid accumulation phenotype |
| GO:0065003 protein-containing complex assembly | IMP PMID:18369462 An essential role for DYF-11/MIP-T3 in assembling functional... | ACCEPT | Summary: DYF-11 is required to assemble a functional motor-IFT particle, including loading of the kinesin-II motor; in its absence multiple IFT components fail to assemble/enter cilia. The term is general but captures this assembly role. Reason: Supported by loss-of-function mislocalization of IFT-machinery components; DYF-11 is needed for assembly/integrity of the IFT particle. Supporting Evidence: PMID:18369462 may help with the assembly of Kinesin-II onto the IFT complex |
| GO:0006935 chemotaxis | IMP PMID:18245347 The conserved proteins CHE-12 and DYF-11 are required for se... | KEEP AS NON CORE | Summary: dyf-11 mutants are chemotaxis-defective because their sensory cilia are truncated and nonfunctional. This is a sensory readout downstream of the ciliary defect rather than a direct chemotaxis function. Reason: Pleiotropic sensory-behavior phenotype secondary to loss of functional cilia; not a core molecular function. Supporting Evidence: PMID:18245347 chemotaxis defective |
| GO:0006972 hyperosmotic response | IMP PMID:18245347 The conserved proteins CHE-12 and DYF-11 are required for se... | KEEP AS NON CORE | Summary: Annotation reflects the osmotic-avoidance (Osm) phenotype of dyf-11 mutants, a cilium-dependent sensory behavior. It is a downstream consequence of nonfunctional sensory cilia rather than a direct role in the cellular hyperosmotic stress response. Reason: Pleiotropic sensory-behavior phenotype secondary to ciliary dysfunction; retained as non-core (experimental IMP; defer to curator on full text). |
| GO:0043053 dauer entry | IMP PMID:18245347 The conserved proteins CHE-12 and DYF-11 are required for se... | KEEP AS NON CORE | Summary: dyf-11 mutants are dauer-formation defective, consistent with loss of the ciliary sensory input that governs the dauer decision. Downstream consequence of ciliary dysfunction. Reason: Pleiotropic developmental phenotype secondary to defective sensory-cilia signaling; not a core molecular function. Supporting Evidence: PMID:18369462 found that dyf-11 mutants are Daf-d at both temperatures |
| GO:1905515 non-motile cilium assembly | IMP PMID:18245347 The conserved proteins CHE-12 and DYF-11 are required for se... | ACCEPT | Summary: C. elegans sensory cilia are non-motile, and DYF-11 is required to build them: in dyf-11 mutants the medial and distal ciliary segments are absent. This is the most specific and accurate biological-process term for DYF-11. Reason: Core biological process; the specific non-motile-cilium wording matches the worm sensory cilium and is directly supported. Supporting Evidence: PMID:18245347 medial and distal segments are absent |
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Download this section (compressed HTML)Q: Does C. elegans DYF-11 bind microtubules directly, or is its microtubule association mediated through other IFT-B subunits?
Q: Which IFT-B subunit(s) does DYF-11 contact directly, and does it partner with an IFT20 ortholog as vertebrate IFT54 does?
Experiment: In vitro microtubule co-sedimentation and IFT-B reconstitution assays with purified DYF-11 to define direct microtubule binding and subunit interactions.
Experiment: Live-imaging epistasis of GFP-tagged IFT components in dyf-11 and other IFT-B mutant backgrounds to order DYF-11 within the IFT-B assembly hierarchy.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The specific molecular function of DYF-11/IFT54 within IFT complex B is undefined. It has no catalytic domain and only a C-terminal coiled coil; whether it binds microtubules directly in C. elegans, and which specific IFT-B subunit(s) it bridges (vertebrate IFT54 partners with IFT20), is not established. It reads as MF-dark despite a well-defined cellular role.
OPEN BIOLOGYONTOLOGY MF_DARK
What is known: DYF-11 is firmly established as an IFT-B subunit that localizes to the transition zone/basal body and axoneme, undergoes bidirectional IFT, and is required for assembling a functional motor-IFT particle and building full-length sensory cilia. Its only informative GO molecular-function term is the family-level microtubule binding (GO:0008017), which has not been experimentally demonstrated for the worm protein.
Significance: IFT54/TRAF3IP1 is a conserved core IFT-B protein whose human ortholog is linked to ciliopathy phenotypes; defining its molecular activity (microtubule binding vs a specific IFT-B scaffolding interaction) is central to understanding IFT-B architecture.
What would resolve it: Test direct microtubule binding of purified DYF-11; map its IFT-B interaction partners (e.g. an IFT20 ortholog) by biochemistry/structure; isolate separation-of-function alleles; consider a molecular-function term for an IFT-B structural/scaffolding subunit activity.
Provenance (the field's own admissions):
Gap: How DYF-11 promotes assembly/loading of the kinesin-II motor and other IFT components onto trains at the ciliary base is not understood at the mechanistic level, nor is it resolved whether it acts specifically at an early step of IFT-B particle assembly.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Loss of dyf-11 mislocalizes kinesin-II (KAP-1), IFT-A (CHE-11), dynein (XBX-1) and BBSome (BBS-7) components so they fail to enter cilia, and DYF-11 undergoes IFT-like movement and may act early in IFT-B assembly; the molecular steps linking DYF-11 to motor/particle assembly are undefined.
Significance: DYF-11 has a more severe assembly phenotype than typical IFT-B mutants and uniquely affects kinesin-II loading, so its mechanism bears on how the anterograde motor is coupled to IFT trains.
What would resolve it: Order the IFT-B assembly hierarchy with epistasis/live-imaging and in vitro reconstitution; determine whether DYF-11 directly contacts kinesin-II or acts through other IFT-B subunits.
Provenance (the field's own admissions):
Gap: Whether C. elegans DYF-11 has an IFT-independent role — for example in dendrite/neurite protein trafficking, analogous to the vertebrate MIP-T3/DISC1 axis — is untested.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: DYF-11::GFP is occasionally seen in dendritic extensions beyond the cilium, and vertebrate MIP-T3 interacts with DISC1 and microtubules in neurite/centrosome contexts; no non-ciliary function has been assayed in the worm.
Significance: Distinguishing a dedicated ciliary IFT role from a broader neuronal trafficking role would clarify whether MIP-T3/TRAF3IP1 acquired dual functions during evolution.
What would resolve it: Assay dyf-11 dendritic transport and non-ciliary phenotypes with cell-type-specific rescue and cargo-trafficking reporters.
Provenance (the field's own admissions):
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