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 β 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
|
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 β 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 β 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):
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The dyf-6 (abnormal dye filling protein 6) gene in Caenorhabditis elegans (ORF: F46F6.4; UniProt: Q0G838) encodes the worm ortholog of Intraflagellar Transport Protein 46 (IFT46). The protein belongs to the IFT46 family and contains a conserved Intraflagellar Transport Complex B C-terminal domain (IFT46_B_C; PF12317/IPR022088). DYF-6/IFT46 is a structural subunit of the intraflagellar transport (IFT) machinery, functioning as a core component of the IFT-B complex that is essential for the assembly, maintenance, and cargo transport functions of cilia in sensory neurons.
DYF-6/IFT46 does not function as an enzyme, transporter, or signaling molecule in the conventional sense. Rather, it serves as a structural and adapter subunit of the IFT-B complex, an essential multi-protein machine that mediates bidirectional transport of cargo along ciliary axonemal microtubules. Cilia lack protein synthesis machinery, and thus all ciliary proteins must be synthesized in the cell body and transported into the cilium by IFT (lv2017intraflagellartransportprotein pages 4-7). DYF-6/IFT46 fulfills dual roles within this system:
IFT46 is a pivotal subunit of the IFT-B1 core subcomplex, which consists of approximately 10 subunits: IFT22, IFT25, IFT27, IFT46, IFT52, IFT56, IFT70, IFT74, IFT81, and IFT88 (liu2025structuremakesa pages 1-2, nakayama2018ciliaryproteintrafficking pages 3-3). Within this core, IFT46 belongs to the B1-2 subgroup alongside IFT52, IFT56, IFT70, and IFT88 (nakayama2018ciliaryproteintrafficking pages 3-3). IFT46 directly interacts with IFT52 through large hydrophobic surfaces at their carboxy-terminal domains, and these two proteins together interact with IFT88 to form a stable ternary complex (IFT46βIFT52βIFT88) that constitutes a critical core module of IFT-B (lucker2010directinteractionsof pages 9-9, taschner2016theintraflagellartransport pages 5-6). IFT46 plays a stabilization role for both IFT52 and IFT88 within this complex (lucker2010directinteractionsof pages 9-9).
In organisms with motile cilia, IFT46 has a specialized function in transporting outer dynein arms (ODAs) via its interaction with the cargo adapter ODA16 (DAW1 in mammals). The N-terminal domain of IFT46 (approximately amino acids 1β147 in Chlamydomonas), which is predicted to be intrinsically disordered, binds directly to ODA16. ODA16 is a WD-repeat protein whose eight-bladed Ξ²-propeller contains a structural cleft that accommodates IFT46's unstructured N-terminal domain (lechtreck2022cargoadaptersexpand pages 3-4, lechtreck2022cargoadaptersexpand pages 2-3). This ODA16βIFT46 interaction is essential for efficient ODA transport to the ciliary tip. In Chlamydomonas, mutants expressing N-terminally truncated IFT46 can assemble flagella but these flagella specifically lack most outer dynein arms (nakayama2018ciliaryproteintrafficking pages 4-5, fassad2017c11orf70mutationscausing pages 40-46). Notably, the direct ODA16βIFT46 interaction has not been demonstrated in human cells, where additional factors may be required (huang2023arl3regulatesoda16mediated pages 8-12).
Since C. elegans possesses only non-motile sensory cilia that lack dynein arms, the ODA transport function of IFT46's N-terminus may be less relevant in nematodes, though the protein's core IFT-B assembly function is fully conserved.
DYF-6/IFT46 localizes to two principal subcellular compartments: the basal body (the ciliary base) and the cilium itself. Detailed studies in Chlamydomonas demonstrated that YFP-tagged IFT46 concentrates at the basal body and shows punctate distribution along the length of the flagellum, consistent with its association with moving IFT trains (lv2017intraflagellartransportprotein pages 4-7, lucker2010directinteractionsof pages 6-6). IFT-B proteins, including IFT46, form a semi-circular tri-lobed arc at the basal body (lv2017intraflagellartransportprotein pages 4-7). Anterograde IFT trains containing IFT-B proteins measure approximately 233 nm and move along B-microtubules of the axoneme (lv2017intraflagellartransportprotein pages 4-7).
The basal body localization of IFT46 depends critically on IFT52 but not vice versa, establishing a hierarchical recruitment mechanism. IFT52 and IFT46 preassemble as subcomplexes in the cytoplasm or at the trans-Golgi network (TGN) before being delivered to the basal body through vesicular or non-vesicle-mediated transport pathways (lv2017intraflagellartransportprotein pages 40-45, lv2017intraflagellartransportprotein pages 11-14). The C-terminal sequence of IFT46 (amino acids 246β321, designated BBTS3) serves as the basal body targeting sequence, which is also necessary for ciliary targeting (lv2017intraflagellartransportprotein pages 1-4). The specific leucine residues L285 and L286 within IFT46 are critical for the binding interface with IFT52 and, consequently, for proper basal body localization (lv2017intraflagellartransportprotein pages 9-11, lv2017intraflagellartransportprotein pages 11-14).
In C. elegans, DYF-6 functions in the sensory cilia of amphid and phasmid neurons, where it participates in IFT-mediated protein trafficking along the axoneme (cevik2013activetransportand pages 6-8, cevik2013activetransportand pages 8-10).
The known protein-protein interactions of DYF-6/IFT46 are summarized below:
| Interaction Partner | Binding Domain on IFT46 | Organism Studied | Functional Role of Interaction | Key Reference |
|---|---|---|---|---|
| IFT52 | C-terminal domain of IFT46; hydrophobic interface, including residues around L285/L286 important for recruitment | Chlamydomonas reinhardtii; human/cross-species IFT studies | Direct IFT46-IFT52 binding supports IFT-B1 core complex assembly and recruits IFT46 to the basal body/ciliary base before train assembly (lv2017intraflagellartransportprotein pages 35-40, lv2017intraflagellartransportprotein pages 40-45, lv2017intraflagellartransportprotein pages 9-11, lv2017intraflagellartransportprotein pages 11-14, lv2017intraflagellartransportprotein pages 1-4) | Lv et al., 2017; Taschner & Lorentzen, 2016 (lv2017intraflagellartransportprotein pages 35-40, lv2017intraflagellartransportprotein pages 1-4, taschner2016theintraflagellartransport pages 5-6) |
| IFT88 | No independent IFT46-only binding domain resolved here; interacts as part of an IFT46-IFT52-IFT88 ternary core complex | Chlamydomonas reinhardtii | Stabilizes the IFT-B core architecture; IFT46, IFT52, and IFT88 form a direct ternary complex essential for core IFT-B complex integrity (lucker2010directinteractionsof pages 9-9, lucker2010directinteractionsof pages 1-1) | Lucker et al., 2010 (lucker2010directinteractionsof pages 9-9) |
| ODA16/DAW1 | N-terminal domain of IFT46, especially aa 1-147 in Chlamydomonas; not clearly conserved in human DAW1-IFT46 binding | Chlamydomonas reinhardtii; comparative human studies | Cargo-adapter interaction for outer dynein arm (ODA) transport into cilia/flagella; truncation of the IFT46 N-terminus impairs ODA transport and causes axonemes lacking most ODAs (lechtreck2022cargoadaptersexpand pages 3-4, lechtreck2022cargoadaptersexpand pages 2-3, huang2023arl3regulatesoda16mediated pages 8-12, nakayama2018ciliaryproteintrafficking pages 4-5, fassad2017c11orf70mutationscausing pages 40-46) | Lechtreck, 2022; Wang et al., 2020; Nakayama & Katoh, 2018 (lechtreck2022cargoadaptersexpand pages 3-4, huang2023arl3regulatesoda16mediated pages 8-12, nakayama2018ciliaryproteintrafficking pages 4-5) |
| ARL13B | Indirectly via the IFT46-IFT56 dimer/subcomplex rather than a mapped standalone IFT46 motif | human; Caenorhabditis elegans | Supports ciliary membrane protein localization/retention and ciliary trafficking regulation; ARL13B/ARL-13 associates with IFT-B through IFT46-IFT56, and dyf-6/IFT46 affects ARL-13 compartmentalization in worm cilia (nozaki2017regulationofciliary pages 4-7, nozaki2017regulationofciliary pages 31-35, cevik2013activetransportand pages 10-11, cevik2013activetransportand pages 8-10, cevik2013activetransportand pages 6-8) | Cevik et al., 2013; Nozaki et al., 2017 (nozaki2017regulationofciliary pages 4-7, cevik2013activetransportand pages 10-11, nozaki2017regulationofciliary pages 7-10) |
| IFT81/IFT74 | Via higher-order IFT-B core interactions; IFT46 pairs with IFT52, which associates with the IFT81/IFT74 module during core assembly | Multiple organisms | Promotes IFT-B core complex formation; IFT46-IFT52 associates with IFT81/IFT74 to build the core scaffold that underlies anterograde IFT train assembly (lv2017intraflagellartransportprotein pages 9-11, liu2025structuremakesa pages 1-2, nakayama2018ciliaryproteintrafficking pages 3-3, taschner2016theintraflagellartransport pages 5-6, lucker2010directinteractionsof pages 9-9) | Taschner & Lorentzen, 2016; Nakayama & Katoh, 2018; Lucker et al., 2010 (nakayama2018ciliaryproteintrafficking pages 3-3, taschner2016theintraflagellartransport pages 5-6, lucker2010directinteractionsof pages 9-9) |
Table: This table summarizes the main known DYF-6/IFT46 interaction partners, the mapped or inferred IFT46 binding regions, and the functional significance of each interaction in IFT-B assembly, cargo transport, and ciliary localization.
A particularly important interaction in the context of C. elegans sensory cilia is the association of IFT46 with IFT56 to form a heterodimer that serves as the binding site for ARL13B (ARL-13 in C. elegans), a Joubert syndrome-associated small GTPase critical for ciliary membrane composition (nozaki2017regulationofciliary pages 4-7, nozaki2017regulationofciliary pages 31-35, nozaki2017regulationofciliary pages 7-10). In C. elegans, dyf-6 mutants show reduced ARL-13 at ciliary membranes and mislocalization of ARL-13 to the periciliary membrane, indicating that DYF-6/IFT46 is essential for maintaining ARL-13 within its proper ciliary membrane subdomain through active transport mechanisms (cevik2013activetransportand pages 6-8). FRAP analyses revealed that in dyf-6 mutants, ARL-13 shows slow diffusion rates between ciliary and periciliary membrane compartments, suggesting intact transition zone barriers but defective active transport (cevik2013activetransportand pages 6-8, cevik2013activetransportand pages 8-10).
The distinct functional regions of DYF-6/IFT46 highlight how the protein's N-terminal and C-terminal halves serve separable functions in cargo transport and complex assembly, respectively:
| Domain/Region | Amino Acid Range (approximate) | Function | Evidence |
|---|---|---|---|
| N-terminal domain | aa 1-147 (Chlamydomonas IFT46) | Predicted intrinsically disordered region that binds the cargo adapter ODA16 and is required for efficient outer dynein arm (ODA) transport; this N-terminal ODA16-binding function is conserved mainly in organisms with motile cilia | Reviews and primary studies describe direct ODA16 interaction with the IFT46 N-terminus, and truncation causes strong ODA loss from flagella (lechtreck2022cargoadaptersexpand pages 3-4, lechtreck2022cargoadaptersexpand pages 2-3, nakayama2018ciliaryproteintrafficking pages 4-5, fassad2017c11orf70mutationscausing pages 40-46) |
| Assembly-critical internal segment | aa 26-50 | Required for functional rescue of flagellar assembly in Chlamydomonas ift46 mutants; indicates this short N-proximal segment contributes to core ciliogenic activity beyond the extreme N-terminus | Recombinant rescue experiments showed aa 26-50 are necessary for flagellar assembly rescue, whereas the first 25 aa are dispensable (lucker2010directinteractionsof pages 9-9) |
| C-terminal domain / BBTS3 | aa 246-321 | Basal body targeting sequence (BBTS3); mediates recruitment to basal bodies/ciliary base, supports interaction with IFT52, and corresponds to the conserved IFT46_B_C region important for IFT-B incorporation and trafficking | Localization and mutational studies mapped the basal body targeting sequence to the C-terminus and showed direct functional coupling to IFT52 (lv2017intraflagellartransportprotein pages 9-11, lv2017intraflagellartransportprotein pages 11-14, lv2017intraflagellartransportprotein pages 4-7, lv2017intraflagellartransportprotein pages 1-4) |
| IFT52-binding interface residues | L285/L286 | Critical residues within the C-terminal region for IFT52 binding; disruption impairs IFT46 recruitment/localization and the IFT52-IFT46 interaction | Point-mutation analysis identified L285/L286 as essential for the IFT52 interaction interface (lv2017intraflagellartransportprotein pages 40-45, lv2017intraflagellartransportprotein pages 9-11, lv2017intraflagellartransportprotein pages 11-14, lv2017intraflagellartransportprotein pages 1-4) |
| Full C-terminus | Broadly the C-terminal half, including the terminal interaction surface | Required for IFT-B complex stability and assembly through hydrophobic interactions with IFT52; supports formation of the IFT46-IFT52-IFT88 core module and incorporation into the IFT-B1 complex | Structural/biochemical studies show the C-terminus stabilizes IFT-B core assembly via IFT52 interaction and contributes to ternary complex formation with IFT88 (lucker2010directinteractionsof pages 9-9, taschner2016theintraflagellartransport pages 5-6) |
Table: This table summarizes the main functional regions of IFT46/DYF-6, linking specific sequence segments to basal body targeting, IFT-B complex assembly, and cargo-adapter interactions. It is useful for distinguishing the conserved ciliogenic core functions of the protein from the motile-cilia-specific ODA transport role of its N-terminus.
The ift46-1 null mutant in Chlamydomonas reinhardtii produces stunted, paralyzed flagella significantly shorter than wild-type cells, with daughter cells remaining restricted within the mother cell wall (lv2017intraflagellartransportprotein pages 4-7). The ift46-2 strain carries a deletion of most of the IFT46 gene and displays a predominantly bald (non-flagellated) phenotype, with only approximately 6% of cells assembling short flagella averaging 3 Β΅m in length (lucker2010directinteractionsof pages 1-1, lucker2010directinteractionsof pages 6-6, lucker2010directinteractionsof pages 5-6). This phenotype is slightly less severe than ift52 or ift88 mutants (lucker2010directinteractionsof pages 1-1). Electroporation of recombinant IFT46 protein successfully rescued the flagellar assembly defect, restoring motile flagella within 4 hours post-electroporation, including normal photophobic and phototactic responses (lucker2010directinteractionsof pages 6-6, lucker2010directinteractionsof pages 5-6). Rescue experiments further demonstrated that amino acids 26β50 are required for flagellar assembly function, whereas the first 25 amino acids are dispensable (lucker2010directinteractionsof pages 9-9).
In C. elegans, dyf-6 mutants exhibit the characteristic dye-filling defective (Dyf) phenotype, which is the hallmark of ciliary dysfunction in worm sensory neurons. The Dyf phenotype indicates that the amphid and phasmid cilia are structurally compromised, preventing uptake of lipophilic fluorescent dyes such as DiI that normally enter neurons through intact sensory cilia (cevik2013activetransportand pages 8-10, cevik2013activetransportand pages 6-8). The study by Cevik et al. (2013) demonstrated that in dyf-6 IFT-B mutants, the Joubert syndrome protein ARL-13 is mislocalized, with reduced amounts in the ciliary middle segment and aberrant accumulation at periciliary membranes (cevik2013activetransportand pages 6-8). Additionally, dyf-6 mutants display defects in IFT-dependent anthelmintic drug uptake through amphid sensory cilia, as IFT genes including dyf-6 are among the ciliary genes required for proper avermectin sensitivity in C. elegans (brinzer2021theuptakeof pages 10-12, brinzer2021theuptakeof pages 14-17).
Expression of ciliary genes in C. elegans, including those encoding IFT-B complex components, is regulated by the RFX transcription factor DAF-19, which binds to conserved X-box motifs in promoter regions. DAF-19 is essential for ciliary gene expressionβwhen DAF-19 is non-functional, ciliated neurons lose their cilia and exhibit sensory defects (chu2012finetuningof pages 1-2). C. elegans possesses approximately 60 ciliated sensory neurons organized in three main clusters: labial and amphid neurons in the head, and phasmid neurons in the tail (warrington2018computationalandmolecular pages 21-25). The dyf-6 gene, like other ciliary genes, is expected to be under DAF-19/RFX transcriptional control given that its homolog CG15161 in Drosophila has been identified as an RFX target gene (chu2012finetuningof pages 1-2). Multiple X-box motifs can cooperate to fine-tune the expression levels of ciliary genes in specific ciliated neuron subtypes (chu2012finetuningof pages 5-8).
IFT46 is broadly conserved across eukaryotes that possess cilia, from the green alga Chlamydomonas reinhardtii to nematodes, zebrafish, and mammals. The C-terminal IFT46_B_C domain (PF12317) that mediates IFT-B complex interactions is conserved across all species, while the N-terminal region involved in ODA16 binding is specifically conserved in organisms with motile cilia (lechtreck2022cargoadaptersexpand pages 3-4, lechtreck2022cargoadaptersexpand pages 2-3). In zebrafish, IFT46 plays an essential role in cilia development, and mutations lead to typical ciliopathy-related phenotypes. In human cells, IFT46 is part of the IFT-B1 core subcomplex where it participates in the same core interactions with IFT52 and IFT88, though the ODA16-IFT46 interaction for dynein transport may involve additional factors compared to Chlamydomonas (huang2023arl3regulatesoda16mediated pages 8-12).
DYF-6/IFT46 in C. elegans is a core structural subunit of the IFT-B1 complex that is indispensable for intraflagellar transport and sensory cilium assembly. It localizes to the basal body and the ciliary axoneme of sensory neurons, where it functions as part of the IFT machinery that transports ciliary proteins between the cell body and the cilium. Its C-terminal domain mediates incorporation into the IFT-B core complex through direct interaction with IFT52, while its N-terminal domain serves as a binding site for the cargo adapter ODA16 in organisms with motile cilia. Through its interaction with IFT56, IFT46 also contributes to the localization and retention of ciliary membrane proteins such as ARL13B. Loss of DYF-6 in C. elegans results in dye-filling defects indicative of structurally compromised sensory cilia, mislocalization of ciliary membrane proteins, and consequent sensory deficits. The gene's expression is regulated by the ciliary transcription factor DAF-19/RFX, placing it within the core ciliogenesis transcriptional program.
References
(lv2017intraflagellartransportprotein pages 4-7): Bo Lv, Lei Wan, Michael Taschner, Xi Cheng, Esben Lorentzen, and Kaiyao Huang. Intraflagellar transport protein ift52 recruits ift46 to the basal body and flagella. Journal of Cell Science, 130:1662-1674, May 2017. URL: https://doi.org/10.1242/jcs.200758, doi:10.1242/jcs.200758. This article has 47 citations and is from a domain leading peer-reviewed journal.
(liu2025structuremakesa pages 1-2): Ying Liu, Yong Zhang, Hua Ni, and Peiwei Liu. Structure makes a difference:
(nakayama2018ciliaryproteintrafficking pages 3-3): Kazuhisa Nakayama and Yohei Katoh. Ciliary protein trafficking mediated by ift and bbsome complexes with the aid of kinesin-2 and dynein-2 motors. Journal of biochemistry, 163 3:155-164, Mar 2018. URL: https://doi.org/10.1093/jb/mvx087, doi:10.1093/jb/mvx087. This article has 160 citations and is from a peer-reviewed journal.
(lucker2010directinteractionsof pages 9-9): Ben F. Lucker, Mark S. Miller, Slawomir A. Dziedzic, Philip T. Blackmarr, and Douglas G. Cole. Direct interactions of intraflagellar transport complex b proteins ift88, ift52, and ift46. Jul 2010. URL: https://doi.org/10.1074/jbc.m110.106997, doi:10.1074/jbc.m110.106997. This article has 104 citations and is from a domain leading peer-reviewed journal.
(taschner2016theintraflagellartransport pages 5-6): Michael Taschner and Esben Lorentzen. The intraflagellar transport machinery. Cold Spring Harbor perspectives in biology, 8 10:a028092, Oct 2016. URL: https://doi.org/10.1101/cshperspect.a028092, doi:10.1101/cshperspect.a028092. This article has 419 citations and is from a peer-reviewed journal.
(lechtreck2022cargoadaptersexpand pages 3-4): Karl Lechtreck. Cargo adapters expand the transport range of intraflagellar transport. Journal of cell science, Dec 2022. URL: https://doi.org/10.1242/jcs.260408, doi:10.1242/jcs.260408. This article has 47 citations and is from a domain leading peer-reviewed journal.
(lechtreck2022cargoadaptersexpand pages 2-3): Karl Lechtreck. Cargo adapters expand the transport range of intraflagellar transport. Journal of cell science, Dec 2022. URL: https://doi.org/10.1242/jcs.260408, doi:10.1242/jcs.260408. This article has 47 citations and is from a domain leading peer-reviewed journal.
(nakayama2018ciliaryproteintrafficking pages 4-5): Kazuhisa Nakayama and Yohei Katoh. Ciliary protein trafficking mediated by ift and bbsome complexes with the aid of kinesin-2 and dynein-2 motors. Journal of biochemistry, 163 3:155-164, Mar 2018. URL: https://doi.org/10.1093/jb/mvx087, doi:10.1093/jb/mvx087. This article has 160 citations and is from a peer-reviewed journal.
(fassad2017c11orf70mutationscausing pages 40-46): Mahmoud R. Fassad, Amelia Shoemark, Pierrick le Borgne, France Koll, Mitali Patel, Mellisa Dixon, Jane Hayward, Charlotte Richardson, Emily Frost, Lucy Jenkins, Thomas Cullup, Eddie MK Chung, Michel Lemullois, Anne Aubusson-Fleury, Claire Hogg, David R. Mitchell, Anne-Marie Tassin, and Hannah M. Mitchison. C11orf70 mutations causing primary ciliary dyskinesia disrupt a conserved step in the intraflagellar transport-dependent assembly of multiple axonemal dyneins. bioRxiv, Oct 2017. URL: https://doi.org/10.1101/211953, doi:10.1101/211953. This article has 2 citations.
(huang2023arl3regulatesoda16mediated pages 8-12): Yameng Huang, Xiaoduo Dong, Stella Y. Sun, Teck-Kwang Lim, Qingsong Lin, and Cynthia Y. He. Arl3 regulates oda16-mediated intraflagellar transport in motile cilia biogenesis. bioRxiv, Apr 2023. URL: https://doi.org/10.1101/2023.04.12.536397, doi:10.1101/2023.04.12.536397. This article has 3 citations.
(lucker2010directinteractionsof pages 6-6): Ben F. Lucker, Mark S. Miller, Slawomir A. Dziedzic, Philip T. Blackmarr, and Douglas G. Cole. Direct interactions of intraflagellar transport complex b proteins ift88, ift52, and ift46. Jul 2010. URL: https://doi.org/10.1074/jbc.m110.106997, doi:10.1074/jbc.m110.106997. This article has 104 citations and is from a domain leading peer-reviewed journal.
(lv2017intraflagellartransportprotein pages 40-45): Bo Lv, Lei Wan, Michael Taschner, Xi Cheng, Esben Lorentzen, and Kaiyao Huang. Intraflagellar transport protein ift52 recruits ift46 to the basal body and flagella. Journal of Cell Science, 130:1662-1674, May 2017. URL: https://doi.org/10.1242/jcs.200758, doi:10.1242/jcs.200758. This article has 47 citations and is from a domain leading peer-reviewed journal.
(lv2017intraflagellartransportprotein pages 11-14): Bo Lv, Lei Wan, Michael Taschner, Xi Cheng, Esben Lorentzen, and Kaiyao Huang. Intraflagellar transport protein ift52 recruits ift46 to the basal body and flagella. Journal of Cell Science, 130:1662-1674, May 2017. URL: https://doi.org/10.1242/jcs.200758, doi:10.1242/jcs.200758. This article has 47 citations and is from a domain leading peer-reviewed journal.
(lv2017intraflagellartransportprotein pages 1-4): Bo Lv, Lei Wan, Michael Taschner, Xi Cheng, Esben Lorentzen, and Kaiyao Huang. Intraflagellar transport protein ift52 recruits ift46 to the basal body and flagella. Journal of Cell Science, 130:1662-1674, May 2017. URL: https://doi.org/10.1242/jcs.200758, doi:10.1242/jcs.200758. This article has 47 citations and is from a domain leading peer-reviewed journal.
(lv2017intraflagellartransportprotein pages 9-11): Bo Lv, Lei Wan, Michael Taschner, Xi Cheng, Esben Lorentzen, and Kaiyao Huang. Intraflagellar transport protein ift52 recruits ift46 to the basal body and flagella. Journal of Cell Science, 130:1662-1674, May 2017. URL: https://doi.org/10.1242/jcs.200758, doi:10.1242/jcs.200758. This article has 47 citations and is from a domain leading peer-reviewed journal.
(cevik2013activetransportand pages 6-8): Sebiha Cevik, Anna A. W. M. Sanders, Erwin Van Wijk, Karsten Boldt, Lara Clarke, Jeroen van Reeuwijk, Yuji Hori, Nicola Horn, Lisette Hetterschijt, Anita Wdowicz, Andrea Mullins, Katarzyna Kida, Oktay I. Kaplan, Sylvia E. C. van Beersum, Ka Man Wu, Stef J. F. Letteboer, Dorus A. Mans, Toshiaki Katada, Kenji Kontani, Marius Ueffing, Ronald Roepman, Hannie Kremer, and Oliver E. Blacque. Active transport and diffusion barriers restrict joubert syndrome-associated arl13b/arl-13 to an inv-like ciliary membrane subdomain. PLoS Genetics, 9:e1003977, Dec 2013. URL: https://doi.org/10.1371/journal.pgen.1003977, doi:10.1371/journal.pgen.1003977. This article has 115 citations and is from a domain leading peer-reviewed journal.
(cevik2013activetransportand pages 8-10): Sebiha Cevik, Anna A. W. M. Sanders, Erwin Van Wijk, Karsten Boldt, Lara Clarke, Jeroen van Reeuwijk, Yuji Hori, Nicola Horn, Lisette Hetterschijt, Anita Wdowicz, Andrea Mullins, Katarzyna Kida, Oktay I. Kaplan, Sylvia E. C. van Beersum, Ka Man Wu, Stef J. F. Letteboer, Dorus A. Mans, Toshiaki Katada, Kenji Kontani, Marius Ueffing, Ronald Roepman, Hannie Kremer, and Oliver E. Blacque. Active transport and diffusion barriers restrict joubert syndrome-associated arl13b/arl-13 to an inv-like ciliary membrane subdomain. PLoS Genetics, 9:e1003977, Dec 2013. URL: https://doi.org/10.1371/journal.pgen.1003977, doi:10.1371/journal.pgen.1003977. This article has 115 citations and is from a domain leading peer-reviewed journal.
(lv2017intraflagellartransportprotein pages 35-40): Bo Lv, Lei Wan, Michael Taschner, Xi Cheng, Esben Lorentzen, and Kaiyao Huang. Intraflagellar transport protein ift52 recruits ift46 to the basal body and flagella. Journal of Cell Science, 130:1662-1674, May 2017. URL: https://doi.org/10.1242/jcs.200758, doi:10.1242/jcs.200758. This article has 47 citations and is from a domain leading peer-reviewed journal.
(lucker2010directinteractionsof pages 1-1): Ben F. Lucker, Mark S. Miller, Slawomir A. Dziedzic, Philip T. Blackmarr, and Douglas G. Cole. Direct interactions of intraflagellar transport complex b proteins ift88, ift52, and ift46. Jul 2010. URL: https://doi.org/10.1074/jbc.m110.106997, doi:10.1074/jbc.m110.106997. This article has 104 citations and is from a domain leading peer-reviewed journal.
(nozaki2017regulationofciliary pages 4-7): Shohei Nozaki, Yohei Katoh, Masaya Terada, Saki Michisaka, Teruki Funabashi, Senye Takahashi, Kenji Kontani, and Kazuhisa Nakayama. Regulation of ciliary retrograde protein trafficking by the joubert syndrome proteins arl13b and inpp5e. Journal of Cell Science, 130:563-576, Feb 2017. URL: https://doi.org/10.1242/jcs.197004, doi:10.1242/jcs.197004. This article has 113 citations and is from a domain leading peer-reviewed journal.
(nozaki2017regulationofciliary pages 31-35): Shohei Nozaki, Yohei Katoh, Masaya Terada, Saki Michisaka, Teruki Funabashi, Senye Takahashi, Kenji Kontani, and Kazuhisa Nakayama. Regulation of ciliary retrograde protein trafficking by the joubert syndrome proteins arl13b and inpp5e. Journal of Cell Science, 130:563-576, Feb 2017. URL: https://doi.org/10.1242/jcs.197004, doi:10.1242/jcs.197004. This article has 113 citations and is from a domain leading peer-reviewed journal.
(cevik2013activetransportand pages 10-11): Sebiha Cevik, Anna A. W. M. Sanders, Erwin Van Wijk, Karsten Boldt, Lara Clarke, Jeroen van Reeuwijk, Yuji Hori, Nicola Horn, Lisette Hetterschijt, Anita Wdowicz, Andrea Mullins, Katarzyna Kida, Oktay I. Kaplan, Sylvia E. C. van Beersum, Ka Man Wu, Stef J. F. Letteboer, Dorus A. Mans, Toshiaki Katada, Kenji Kontani, Marius Ueffing, Ronald Roepman, Hannie Kremer, and Oliver E. Blacque. Active transport and diffusion barriers restrict joubert syndrome-associated arl13b/arl-13 to an inv-like ciliary membrane subdomain. PLoS Genetics, 9:e1003977, Dec 2013. URL: https://doi.org/10.1371/journal.pgen.1003977, doi:10.1371/journal.pgen.1003977. This article has 115 citations and is from a domain leading peer-reviewed journal.
(nozaki2017regulationofciliary pages 7-10): Shohei Nozaki, Yohei Katoh, Masaya Terada, Saki Michisaka, Teruki Funabashi, Senye Takahashi, Kenji Kontani, and Kazuhisa Nakayama. Regulation of ciliary retrograde protein trafficking by the joubert syndrome proteins arl13b and inpp5e. Journal of Cell Science, 130:563-576, Feb 2017. URL: https://doi.org/10.1242/jcs.197004, doi:10.1242/jcs.197004. This article has 113 citations and is from a domain leading peer-reviewed journal.
(lucker2010directinteractionsof pages 5-6): Ben F. Lucker, Mark S. Miller, Slawomir A. Dziedzic, Philip T. Blackmarr, and Douglas G. Cole. Direct interactions of intraflagellar transport complex b proteins ift88, ift52, and ift46. Jul 2010. URL: https://doi.org/10.1074/jbc.m110.106997, doi:10.1074/jbc.m110.106997. This article has 104 citations and is from a domain leading peer-reviewed journal.
(brinzer2021theuptakeof pages 10-12): Robert A. Brinzer, David J. France, Claire McMaster, Stuart Ruddell, Alan D. Winter, and Antony P. Page. The uptake of avermectins in caenorhabditis elegans is dependent on intra-flagellar transport and other protein trafficking pathways. bioRxiv, Oct 2021. URL: https://doi.org/10.1101/2021.10.22.465401, doi:10.1101/2021.10.22.465401. This article has 1 citations.
(brinzer2021theuptakeof pages 14-17): Robert A. Brinzer, David J. France, Claire McMaster, Stuart Ruddell, Alan D. Winter, and Antony P. Page. The uptake of avermectins in caenorhabditis elegans is dependent on intra-flagellar transport and other protein trafficking pathways. bioRxiv, Oct 2021. URL: https://doi.org/10.1101/2021.10.22.465401, doi:10.1101/2021.10.22.465401. This article has 1 citations.
(chu2012finetuningof pages 1-2): J. S. C. Chu, M. Tarailo-Graovac, D. Zhang, J. Wang, B. Uyar, D. Tu, J. Trinh, D. L. Baillie, and N. Chen. Fine tuning of rfx/daf-19-regulated target gene expression through binding to multiple sites in caenorhabditis elegans. Nucleic Acids Research, 40:53-64, Sep 2012. URL: https://doi.org/10.1093/nar/gkr690, doi:10.1093/nar/gkr690. This article has 13 citations and is from a highest quality peer-reviewed journal.
(warrington2018computationalandmolecular pages 21-25): Timothy Burton Warrington. Computational and molecular dissection of an x-box cis-regulatory module. Preprint, Jan 2018. URL: https://doi.org/10.48550/arxiv.1810.00478, doi:10.48550/arxiv.1810.00478. This article has 2 citations.
(chu2012finetuningof pages 5-8): J. S. C. Chu, M. Tarailo-Graovac, D. Zhang, J. Wang, B. Uyar, D. Tu, J. Trinh, D. L. Baillie, and N. Chen. Fine tuning of rfx/daf-19-regulated target gene expression through binding to multiple sites in caenorhabditis elegans. Nucleic Acids Research, 40:53-64, Sep 2012. URL: https://doi.org/10.1093/nar/gkr690, doi:10.1093/nar/gkr690. This article has 13 citations and is from a highest quality peer-reviewed journal.
DYF-6 is (very likely) an IFT complex B component. Bell 2006 inferred this from the OSM-6::GFP mislocalization pattern; Yi 2017/ComplexPortal biochemically place it in IFT-B.
UniProt SUBUNIT + ComplexPortal CPX-1290 (from PMID:28479320) list dyf-6 in IFT-B.
DYF-6 is required to build/maintain sensory cilia; loss foreshortens amphid & phasmid cilia.
C. elegans sensory cilia are non-motile, so the specific process term is non-motile cilium assembly (GO:1905515, WormBase IMP).
DYF-6 acts cell-autonomously in the amphid sensory neurons; loss causes dye-filling/chemotaxis defects.
Expression: DYF-6::GFP in amphid & phasmid (and IL-region) ciliated neurons, plus hypodermis; expressed hatchingβadult incl. dauer.
Conservation: orthologs in fly (CG15161, ciliary) and mammals; human ortholog conserved throughout.
DYF-6/IFT-B is needed for dynein-2 ciliary entry (retrograde IFT context).
Cache: PMID:16648645 full text available (Bell et al. 2006, Genetics, PMC1526656). PMID:28479320 abstract-only (Yi et al. 2017, Curr Biol) β IFT-B membership rests on full-text mass-spec not in cache; annotations from it are ComplexPortal NAS, accepted deferring to curator/ComplexPortal.
Genuine, gene-correct report (40 citations, 2 artifacts). Key points that refine but do not
contradict the review:
Not independently re-verified (LLM synthesis with internal citation keys); used as supporting
context. The two ontology/biology knowledge gaps in the review reflect this: partners known in
other species but (a) no GO MF term and (b) worm-specific contacts/adaptor role unproven.
id: Q0G838
gene_symbol: dyf-6
product_type: PROTEIN
status: COMPLETE
aliases:
- IFT46
- F46F6.4
taxon:
id: NCBITaxon:6239
label: Caenorhabditis elegans
description: >-
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.
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO
terms
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: >-
InterPro2GO mapping of the IFT complex B family (IPR022088) to intraciliary
transport (GO:0042073). The family/domain identity (Pfam IFT46_B_C,
PANTHER PTHR13376) is correct for DYF-6, and the transferred biological
process is independently confirmed by C. elegans experimental data, so the
transfer is sound.
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: >-
Standard GO_Central IBA pipeline. The IFT-B membership, intraciliary
transport and cilium-assembly transfers are all corroborated by worm
experimental data (PMID:16648645). The "motile cilium" (GO:0031514)
transfer is a mammalian-biased over-propagation: C. elegans has no motile
cilia, only non-motile sensory cilia.
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt
findings: []
reference_review:
relevance: LOW
correctness: VERIFIED
review_notes: >-
Electronic mapping of UniProt subcellular-location keywords (cilium,
dendrite, perikaryon) to GO CC terms. Redundant with the experimental
WormBase/UniProt annotations from PMID:16648645 but not incorrect.
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
reference_review:
relevance: LOW
correctness: LOW_QUALITY
review_notes: >-
ARBA machine-learning annotation to the over-general grouping term
"plasma membrane bounded cell projection" (GO:0120025), whose informative
descendants (cilium, dendrite) are already annotated. Uninformative for
this protein.
- id: PMID:16648645
title: The molecular identities of the Caenorhabditis elegans intraflagellar transport
genes dyf-6, daf-10 and osm-1.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: >-
Bell et al. 2006 (Genetics, PMC1526656), the primary cloning and functional
characterization of dyf-6. Establishes DYF-6 as an IFT protein that moves
within amphid/phasmid ciliated endings, that dyf-6 mutants have foreshortened
cilia, that dyf-6 functions cell-autonomously in amphid sensilla, and that
the protein has no recognized motifs but is conserved to flies and mammals.
Source of the WormBase IDA/IMP/EXP annotations. (Cache exposes the abstract;
the full text additionally infers IFT complex B membership from the OSM-6
mislocalization pattern.)
- id: PMID:28479320
title: Dynein-Driven Retrograde Intraflagellar Transport Is Triphasic in C. elegans
Sensory Cilia.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: >-
Yi et al. 2017 (Curr Biol). Source of the ComplexPortal (CPX-1290) NAS
annotations placing DYF-6 in IFT complex B and of the UniProt SUBUNIT list.
Cached record is abstract-only; the abstract confirms that an intact IFT-B
complex is required for dynein-2 ciliary entry, and the full text is the
basis (affinity purification / mass spectrometry) for DYF-6's IFT-B
membership. NAS annotations accepted, deferring to ComplexPortal/curator.
- id: PMID:7705621
title: Mutations affecting the chemosensory neurons of Caenorhabditis elegans.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: >-
Starich et al. 1995 (Genetics), the genetic screen that isolated dyf-6 among
the dye-filling-defective (Dyf) mutants and characterized its chemotaxis /
dye-filling disruption phenotype; cited by UniProt as a FUNCTION and
DISRUPTION PHENOTYPE reference for dyf-6. Cached record is abstract-only (the
abstract summarizes the screen without naming dyf-6), so it is included as
background establishing the loss-of-function phenotype rather than as a
verbatim source for a specific annotation.
- id: file:worm/dyf-6/dyf-6-deep-research-falcon.md
title: "Deep research report (Falcon/Edison): DYF-6/IFT46 in Caenorhabditis elegans"
findings: []
reference_review:
relevance: MEDIUM
correctness: UNVERIFIED
review_notes: >-
AI-generated (Falcon/Edison) deep-research synthesis. Corroborates the
primary-literature-grounded review: DYF-6/IFT46 is a structural IFT-B1 core
subunit whose conserved C-terminal IFT46_B_C domain mediates direct IFT52
(and, via a ternary module, IFT88) binding, while the N-terminal ODA16
cargo-adaptor role is confined to organisms with motile cilia and is not
expected in C. elegans non-motile sensory cilia. Also surfaces worm-specific
literature (Cevik et al. 2013 on ARL-13 ciliary membrane trafficking in
dyf-6 mutants) not in the GOA set. Underlying claims are drawn from
Chlamydomonas/human work cited by internal keys, not independently
re-verified here; treated as supporting context, not primary evidence.
existing_annotations:
- term:
id: GO:0005815
label: microtubule organizing center
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
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.
action: MODIFY
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.
proposed_replacement_terms:
- id: GO:0036064
label: ciliary basal body
propagation_review:
root_cause: TERM_SCOPING_PROBLEM
failure_modes:
- GRANULARITY_MISMATCH
source_entities:
- source_id: PANTHER:PTN000332669
source_label: IFT46 family node
source_status: SUPPORTS_TRANSFER
comment: >-
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.
- term:
id: GO:0030992
label: intraciliary transport particle B
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: part_of
review:
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.
action: ACCEPT
reason: >-
Core cellular-component identity of DYF-6 as an IFT-B structural subunit.
supported_by:
- reference_id: PMID:28479320
supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's
ciliary localization
reference_section_type: ABSTRACT
- reference_id: file:worm/dyf-6/dyf-6-deep-research-falcon.md
supporting_text: IFT46 is a pivotal subunit of the IFT-B1 core subcomplex
reference_section_type: OTHER
- term:
id: GO:0060271
label: cilium assembly
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
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.
action: ACCEPT
reason: >-
Core biological process, supported experimentally in worm (PMID:16648645).
The more specific worm-appropriate term non-motile cilium assembly is also
annotated (IMP).
supported_by:
- reference_id: PMID:16648645
supporting_text: the cilia of the amphid and phasmid dendritic endings are
foreshortened
reference_section_type: ABSTRACT
- term:
id: GO:0031514
label: motile cilium
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: >-
This IBA transfer from mammalian IFT46 assigns a motile-cilium location.
C. elegans, however, has no motile cilia β 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).
action: MARK_AS_OVER_ANNOTATED
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
source_entities:
- source_id: PANTHER:PTN000332669
source_label: IFT46 family node
source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
comment: >-
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.
- term:
id: GO:0042073
label: intraciliary transport
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: >-
DYF-6 functions in intraflagellar (intraciliary) transport as an IFT-B
subunit; DYF-6::GFP undergoes IFT movement within ciliated endings.
action: ACCEPT
reason: >-
Core biological process, confirmed experimentally in worm (PMID:16648645).
supported_by:
- reference_id: PMID:16648645
supporting_text: Movement of DYF-6::GFP within the ciliated endings of the
neurons indicates that DYF-6 is involved in IFT
reference_section_type: ABSTRACT
- term:
id: GO:0005929
label: cilium
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: >-
Electronic mapping of the UniProt cilium subcellular-location keyword.
DYF-6 is directly observed within cilia, where it undergoes IFT.
action: ACCEPT
reason: >-
Correct core ciliary location, corroborated by experimental IFT movement
within ciliated endings (PMID:16648645).
supported_by:
- reference_id: PMID:16648645
supporting_text: Movement of DYF-6::GFP within the ciliated endings of the
neurons indicates that DYF-6 is involved in IFT
reference_section_type: ABSTRACT
- term:
id: GO:0030425
label: dendrite
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
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.
action: KEEP_AS_NON_CORE
reason: >-
Real localization (the dendritic route to the cilium) but not the core
site of DYF-6 function, which is the cilium/IFT machinery.
- term:
id: GO:0042073
label: intraciliary transport
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: involved_in
review:
summary: >-
InterPro2GO transfer (IPR022088, IFT complex B) to intraciliary transport.
Duplicates the IBA/NAS/IDA intraciliary-transport annotations and is
correct.
action: ACCEPT
reason: >-
Core biological process; redundant with experimental IDA (PMID:16648645)
but consistent.
supported_by:
- reference_id: PMID:16648645
supporting_text: Movement of DYF-6::GFP within the ciliated endings of the
neurons indicates that DYF-6 is involved in IFT
reference_section_type: ABSTRACT
- term:
id: GO:0043204
label: perikaryon
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
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.
action: KEEP_AS_NON_CORE
reason: >-
Real localization but not the core functional site; the cell body reflects
the neuron of expression rather than DYF-6's IFT role.
- term:
id: GO:0120025
label: plasma membrane bounded cell projection
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: located_in
review:
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.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Over-general electronic grouping term; its informative descendants (cilium,
dendrite) are already annotated, so it adds no information.
- term:
id: GO:0005929
label: cilium
evidence_type: NAS
original_reference_id: PMID:28479320
qualifier: located_in
review:
summary: >-
ComplexPortal (CPX-1290) assertion that DYF-6 localizes to the cilium,
consistent with the experimental observation that DYF-6 undergoes IFT
within cilia.
action: ACCEPT
reason: >-
Correct core ciliary location.
supported_by:
- reference_id: PMID:16648645
supporting_text: Movement of DYF-6::GFP within the ciliated endings of the
neurons indicates that DYF-6 is involved in IFT
reference_section_type: ABSTRACT
- term:
id: GO:0030992
label: intraciliary transport particle B
evidence_type: NAS
original_reference_id: PMID:28479320
qualifier: part_of
review:
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.
action: ACCEPT
reason: >-
Core cellular-component identity; biochemically supported IFT-B membership.
supported_by:
- reference_id: PMID:28479320
supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's
ciliary localization
reference_section_type: ABSTRACT
- term:
id: GO:0042073
label: intraciliary transport
evidence_type: NAS
original_reference_id: PMID:28479320
qualifier: involved_in
review:
summary: >-
ComplexPortal assertion that DYF-6, as an IFT-B subunit, functions in
intraciliary transport, consistent with the worm experimental data.
action: ACCEPT
reason: >-
Core biological process; consistent with IFT-B membership and experimental
IFT movement (PMID:16648645).
supported_by:
- reference_id: PMID:16648645
supporting_text: Movement of DYF-6::GFP within the ciliated endings of the
neurons indicates that DYF-6 is involved in IFT
reference_section_type: ABSTRACT
- term:
id: GO:0060271
label: cilium assembly
evidence_type: NAS
original_reference_id: PMID:28479320
qualifier: involved_in
review:
summary: >-
ComplexPortal assertion that DYF-6 functions in cilium assembly, consistent
with the foreshortened-cilia phenotype of dyf-6 mutants.
action: ACCEPT
reason: >-
Core biological process; supported by the dyf-6 mutant cilium phenotype
(PMID:16648645).
supported_by:
- reference_id: PMID:16648645
supporting_text: the cilia of the amphid and phasmid dendritic endings are
foreshortened
reference_section_type: ABSTRACT
- term:
id: GO:0043204
label: perikaryon
evidence_type: EXP
original_reference_id: PMID:16648645
qualifier: located_in
review:
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.
action: KEEP_AS_NON_CORE
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.
supported_by:
- reference_id: PMID:16648645
supporting_text: DYF-6::GFP is expressed in amphid and phasmid neurons
reference_section_type: ABSTRACT
- term:
id: GO:0030425
label: dendrite
evidence_type: IDA
original_reference_id: PMID:16648645
qualifier: located_in
review:
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.
action: KEEP_AS_NON_CORE
reason: >-
Real localization along the trafficking route to the cilium, but not the
core functional site (the cilium/IFT machinery).
- term:
id: GO:0042073
label: intraciliary transport
evidence_type: IDA
original_reference_id: PMID:16648645
qualifier: involved_in
review:
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.
action: ACCEPT
reason: >-
Core biological process; strongest, directly observed evidence
(PMID:16648645).
supported_by:
- reference_id: PMID:16648645
supporting_text: Movement of DYF-6::GFP within the ciliated endings of the
neurons indicates that DYF-6 is involved in IFT
reference_section_type: ABSTRACT
- term:
id: GO:0043025
label: neuronal cell body
evidence_type: IDA
original_reference_id: PMID:16648645
qualifier: located_in
review:
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.
action: KEEP_AS_NON_CORE
reason: >-
Real localization but not the core functional site; reflects the neuron of
expression rather than the IFT role.
supported_by:
- reference_id: PMID:16648645
supporting_text: DYF-6::GFP is expressed in amphid and phasmid neurons
reference_section_type: ABSTRACT
- term:
id: GO:1905515
label: non-motile cilium assembly
evidence_type: IMP
original_reference_id: PMID:16648645
qualifier: involved_in
review:
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.
action: ACCEPT
reason: >-
Core biological process; the non-motile-cilium wording matches the worm
sensory cilium and is directly supported by the mutant phenotype
(PMID:16648645).
supported_by:
- reference_id: PMID:16648645
supporting_text: the cilia of the amphid and phasmid dendritic endings are
foreshortened
reference_section_type: ABSTRACT
core_functions:
- description: >-
DYF-6/IFT46 is a structural subunit of intraflagellar transport (IFT) complex
B in ciliated sensory neurons. It localizes to the cilium and the ciliary base
(basal body / transition-zone region), undergoes bidirectional IFT movement
within the ciliated dendritic endings, and is required to build full-length
non-motile sensory cilia β dyf-6 loss foreshortens the amphid and phasmid
ciliary endings and produces the OSM-6 mislocalization pattern typical of IFT
complex B mutants. It has no catalytic domain and acts as a structural/adaptor
component of IFT-B; no informative molecular-function term is currently
assignable (MF-dark; see knowledge_gaps).
in_complex:
id: GO:0030992
label: intraciliary transport particle B
directly_involved_in:
- id: GO:0042073
label: intraciliary transport
- id: GO:1905515
label: non-motile cilium assembly
locations:
- id: GO:0005929
label: cilium
- id: GO:0036064
label: ciliary basal body
supported_by:
- reference_id: PMID:16648645
supporting_text: Movement of DYF-6::GFP within the ciliated endings of the
neurons indicates that DYF-6 is involved in IFT
reference_section_type: ABSTRACT
- reference_id: PMID:16648645
supporting_text: the cilia of the amphid and phasmid dendritic endings are
foreshortened
reference_section_type: ABSTRACT
- reference_id: PMID:28479320
supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's
ciliary localization
reference_section_type: ABSTRACT
knowledge_gaps:
- gap_statement: >-
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.
boundary: >-
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 β 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.
gap_kind:
- ONTOLOGY
- BIOLOGY
dark_aspect: MF_DARK
status: OPEN
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.
resolution: >-
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:
- reference_id: PMID:16648645
supporting_text: DYF-6, the product of a complex locus, lacks known motifs,
but orthologs are present in flies and mammals
reference_section_type: ABSTRACT
proposed_terms:
- proposed_name: structural constituent of intraflagellar transport particle B
proposed_definition: >-
The action of a macromolecule that contributes to the structural integrity
or scaffolding of an intraflagellar transport particle B (IFT-B) complex,
as distinct from any catalytic or motor activity.
justification: >-
IFT-B subunits such as DYF-6/IFT46 have a well-defined cellular role (be
part of, and maintain, the IFT-B particle) but no GO molecular-function term
can currently express this structural/scaffolding activity, leaving them
MF-dark despite complete BP/CC annotation.
proposed_parent:
id: GO:0005198
label: structural molecule activity
- gap_statement: >-
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.
boundary: >-
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.
gap_kind:
- BIOLOGY
dark_aspect: RESIDUAL_SUBGAP
status: OPEN
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.
resolution: >-
Isoform-specific knockouts/rescue and expression analysis of the long
dyf-6/F46F6.3 fusion product.
provenance:
- reference_id: PMID:16648645
supporting_text: DYF-6, the product of a complex locus, lacks known motifs,
but orthologs are present in flies and mammals
reference_section_type: ABSTRACT
suggested_questions:
- question: >-
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?
suggested_experiments:
- description: >-
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.
experiment_type: interaction mapping
- description: >-
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.
experiment_type: genetics