GO Term	Evidence	Action	Reason
GO:0036064 ciliary basal body	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IFT proteins, including IFT-B/TTC26 orthologs, accumulate at and turn around at the ciliary base/basal body region. This IBA localization is consistent with DYF-13 being a core IFT component whose transport begins at the ciliary base. Reason: Consistent with the established role of DYF-13 as a core IFT component that accumulates at the ciliary base; a supporting (non-core) location rather than the primary functional assignment. Supporting Evidence: PMID:15916950 encodes a ciliary protein that undergoes IFT
GO:0030992 intraciliary transport particle B	IBA GO_REF:0000033	ACCEPT	Summary: DYF-13/TTC26 is an integral subunit of the IFT-B complex. This is directly supported in C. elegans by affinity-purification/mass-spectrometry identification of dyf-13 within IFT complex B, and in mammals TTC26/IFT56 is assigned to the IFT-B complex. Reason: Core structural assignment; DYF-13 is a bona fide IFT-B subunit (ComplexPortal CPX-1290), confirmed biochemically in worm and mammals. Supporting Evidence: PMID:28479320 intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary PMID:26980730 neither of which was included with certainty in
GO:0035720 intraciliary anterograde transport	IBA GO_REF:0000033	ACCEPT	Summary: As an IFT-B subunit, DYF-13 participates in kinesin-2-driven anterograde transport that carries cargo from the ciliary base toward the tip. Loss of dyf-13 causes distal-segment defects consistent with impaired anterograde delivery. Reason: Core biological process for an IFT-B subunit; anterograde transport is the direction driven by the kinesin-2/IFT-B machinery that DYF-13 belongs to. Supporting Evidence: PMID:15916950 encodes a ciliary protein that undergoes IFT
GO:0035735 intraciliary transport involved in cilium assembly	IBA GO_REF:0000033	ACCEPT	Summary: DYF-13 is required for building and maintaining cilia: dyf-13(mn396) mutants have short cilia lacking distal portions, and the protein is a novel core IFT component required for cilia function. Reason: Core biological process; captures the specific role of IFT in cilium assembly, strongly supported by the dyf-13 mutant structural phenotype. Supporting Evidence: PMID:15916950 is a novel core IFT component required for cilia function
GO:0097546 ciliary base	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IFT particles, including DYF-13, are active at the ciliary base where anterograde trains assemble and retrograde trains are remodeled. Consistent with DYF-13 undergoing IFT that initiates at the base. Reason: Supporting (non-core) location consistent with IFT-B biology; complements the primary cilium/axoneme localization. Supporting Evidence: PMID:15916950 encodes a ciliary protein that undergoes IFT
GO:0120170 intraciliary transport particle B binding	IBA GO_REF:0000033	ACCEPT	Summary: The molecular function of DYF-13/TTC26 within the cilium is to associate with the IFT-B particle. As a TPR-repeat scaffold subunit it binds the IFT-B complex; this is the most specific molecular-function term currently available for an IFT-B structural subunit. Reason: Best-available molecular-function term for an IFT-B subunit; more informative than generic protein binding. DYF-13 co-purifies within IFT complex B, and functions as a cargo-selective IFT-B adapter rather than a core-structural requirement (it associates with, but is not essential for, IFT-particle assembly). Supporting Evidence: PMID:28479320 intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary file:worm/dyf-13/dyf-13-deep-research-falcon.md IFT56 is not required for assembly or movement of IFT particles themselves
GO:0005929 cilium	IEA GO_REF:0000044	ACCEPT	Summary: UniProt SubCell-derived electronic annotation placing DYF-13 in the cilium. Correct but general; concordant with the experimentally supported ciliary localization. Reason: Correct general localization (cilium), consistent with primary evidence that DYF-13 is a ciliary protein undergoing IFT. Supporting Evidence: PMID:15916950 encodes a ciliary protein that undergoes IFT
GO:0005929 cilium	NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...	ACCEPT	Summary: ComplexPortal NAS annotation to cilium based on the IFT-B complex membership reported in Yi et al. 2017. Correct but general localization. Reason: Correct ciliary localization; supported by identification of dyf-13 in the ciliary IFT-B complex. Supporting Evidence: PMID:28479320 intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
GO:0030992 intraciliary transport particle B	NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...	ACCEPT	Summary: ComplexPortal NAS annotation, from the same study that identified dyf-13 as a component of IFT complex B by affinity purification and mass spectrometry. Reason: Core structural assignment corroborating the IBA IFT-B membership; directly supported by the primary study. Supporting Evidence: PMID:28479320 intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
GO:0042073 intraciliary transport	NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...	KEEP AS NON CORE	Summary: General intraflagellar-transport process annotation for an IFT-B subunit. Correct but less specific than the anterograde/assembly terms; the parent process under which DYF-13 acts. Reason: Correct but general parent term; the more specific anterograde-transport and transport-in-cilium-assembly terms better capture the core function. Supporting Evidence: PMID:15916950 encodes a ciliary protein that undergoes IFT
GO:0060271 cilium assembly	NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...	ACCEPT	Summary: DYF-13 is required for cilium assembly; dyf-13 mutants have short cilia lacking distal segments. This general BP term is well supported, with the more specific IFT-in-cilium-assembly term giving the mechanism. Reason: Correct biological process; the dyf-13 loss-of-function structural cilia phenotype directly supports a cilium-assembly role. Supporting Evidence: PMID:15916950 is a novel core IFT component required for cilia function

Deep Research

Falcon

(dyf-13-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 10 citations 1 artifacts 2026-07-04T19:27:30.270211

Edison artifact artifact-00 (text/markdown)

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.

Comprehensive Research Report: dyf-13 (IFT56/TTC26) in Caenorhabditis elegans

1. Gene and Protein Identity

The C. elegans gene dyf-13 (ORF name C27H5.7; UniProt Q95QT8) encodes intraflagellar transport protein 56 homolog (IFT56), also known in vertebrates as tetratricopeptide repeat domain 26 (TTC26). The protein is a highly conserved member of the IFT56 family, present in all ciliated organisms but absent from non-ciliated species, underscoring its dedicated role in ciliary biology (ishikawa2014ttc26dyf13isan pages 3-4, ishikawa2014ttc26dyf13isan pages 15-17). IFT56 (also known as TTC26, DYF-13, and PIFTC3) is a highly conserved intraflagellar transport complex B (IFT-B) protein (xin2017ift56regulatesvertebrate pages 1-2, ishikawa2014ttc26dyf13isan pages 1-2). The protein contains TPR-like helical domain superfamily features and TTC26/TPR_19 domains, consistent with tetratricopeptide repeat-mediated protein–protein interactions typical of IFT scaffold/adapter proteins (ishikawa2014ttc26dyf13isan pages 13-15).

The following table summarizes the key properties of dyf-13/IFT56/TTC26:

Property	Description
Gene names and aliases	dyf-13 in Caenorhabditis elegans; orthologous/alias names include TTC26, IFT56, and PIFTC3. Literature explicitly equates TTC26/DYF13/IFT56 across ciliated organisms, validating that the requested gene identity matches the UniProt entry for the worm dyf-13 protein (ishikawa2014ttc26dyf13isan pages 12-13, ishikawa2014ttc26dyf13isan pages 1-2, xin2017ift56regulatesvertebrate pages 1-2).
Organism	The target gene/protein is from *Caenorhabditis elegans, where it functions in sensory cilia of amphid and phasmid neurons; cross-species functional data are available from zebrafish, mouse, mammalian cultured cells, and Chlamydomonas* ortholog studies (efimenko2006caenorhabditiselegansdyf2an pages 2-3, zhang2012knockdownofttc26 pages 1-2, xin2017ift56regulatesvertebrate pages 1-2).
Protein family	DYF-13 belongs to the conserved IFT56/TTC26 family, a cilia-associated family present in ciliated organisms and absent from non-ciliated organisms, consistent with a dedicated role in intraflagellar transport and ciliary biology (ishikawa2014ttc26dyf13isan pages 3-4, ishikawa2014ttc26dyf13isan pages 15-17, xin2017ift56regulatesvertebrate pages 1-2).
Domain structure	UniProt annotates DYF-13/Q95QT8 with TPR-like helical superfamily features and TTC26 / TPR_19 domains, consistent with tetratricopeptide repeat-mediated protein interaction/adaptor functions typical of IFT-associated scaffold proteins; this agrees with the experimentally supported role of IFT56/TTC26 as an IFT-B-associated adaptor rather than an enzyme (ishikawa2014ttc26dyf13isan pages 13-15, ishikawa2014ttc26dyf13isan pages 12-13).
IFT-B subcomplex position	IFT56/TTC26/DYF-13 is a component of IFT complex B, specifically placed in the IFT-B1b subgroup together with IFT46, IFT52, IFT70, and IFT88. Recent assembly work indicates IFT56 is part of the IFT-B1 branch and is linked through the IFT46-IFT52 module to other IFT-B subcomplexes (ishikawa2014ttc26dyf13isan pages 7-9, tasaki2025assemblyandmother pages 1-5).
Primary function	The best-supported primary function is as a cargo-selective IFT-B-associated adapter/regulator, not a catalytic protein. IFT56/TTC26/DYF-13 is dispensable for basic IFT train assembly/motility in some systems but is required for transport of a subset of ciliary cargoes, especially motility-related proteins such as inner dynein arm components, dynein regulatory complex proteins, and central pair-associated factors (ishikawa2014ttc26dyf13isan pages 10-12, ishikawa2014ttc26dyf13isan pages 7-9, ishikawa2014ttc26dyf13isan pages 12-13, ishikawa2014ttc26dyf13isan pages 13-15).
Subcellular localization	IFT56/TTC26/DYF-13 localizes to cilia/flagella and basal body-associated regions, with a punctate distribution characteristic of IFT proteins. In mammalian cells it undergoes bidirectional IFT; in zebrafish and photoreceptors, Ttc26 was also observed at the transition zone. Reported mammalian transport speeds for TTC26-GFP are ~1.22 ± 0.17 μm/s anterograde and 0.92 ± 0.24 μm/s retrograde (ishikawa2014ttc26dyf13isan pages 2-3, ishikawa2014ttc26dyf13isan pages 6-7, zhang2012knockdownofttc26 pages 1-2, zhang2012knockdownofttc26 pages 2-4).
Key phenotypes in C. elegans	dyf-13 is one of the classic Dyf (dye-filling defective) genes required for proper amphid/phasmid sensory cilium function. The Dyf class is associated with failed DiI filling of sensory neurons and abnormal ciliary structure. Prior work cited in later studies indicates shortened cilia in C. elegans dyf-13 mutants, and dyf-13 has been linked to regulation of OSM-3-kinesin/IFT-B behavior in sensory cilia (efimenko2006caenorhabditiselegansdyf2an pages 2-3, ishikawa2014ttc26dyf13isan pages 2-3, ishikawa2014ttc26dyf13isan pages 12-13).
Key phenotypes in other organisms	In zebrafish, ttc26 knockdown causes shortened or missing photoreceptor outer segments, pronephric cilia defects, kidney duct dilation, body curvature, edema, abnormal fluid flow, and reduced cilia length/number in Kupffer’s vesicle. In mouse/vertebrate systems, Ift56 loss causes developmental patterning defects, male sterility, gait abnormalities, shortened/abnormal cilia, and disorganized axonemal microtubules (zhang2012knockdownofttc26 pages 1-2, zhang2012knockdownofttc26 pages 6-7, zhang2012knockdownofttc26 pages 4-5, ishikawa2014ttc26dyf13isan pages 3-4, xin2017ift56regulatesvertebrate pages 1-2, xin2017ift56regulatesvertebrate pages 5-7).
Signaling pathway involvement	IFT56 is implicated in cilium-dependent Hedgehog signaling. In mouse Ift56/hop mutants, cilia form but fail to properly accumulate Gli2 and Gli3 at ciliary tips, while Smoothened localization can remain relatively normal; this leads to defective Shh-dependent patterning in limb and neural tube development. Thus, IFT56 supports signaling competence by maintaining IFT-B integrity and ciliary architecture needed for Gli trafficking (xin2017ift56regulatesvertebrate pages 4-5, xin2017ift56regulatesvertebrate pages 1-2, xin2017ift56regulatesvertebrate pages 2-3, xin2017ift56regulatesvertebrate pages 3-4).
Human disease associations	Human TTC26/IFT56 has been linked to severe biliary ciliopathy by biallelic mutation studies, and broader cross-species work places IFT56 among IFT-B components whose dysfunction can contribute to ciliopathy phenotypes. Although the detailed clinical text was not retrievable here, the paper metadata and abstract identify TTC26 as a human disease gene in severe biliary ciliopathy (xin2017ift56regulatesvertebrate pages 5-7).

Table: This table condenses the main verified properties of the C. elegans dyf-13 gene product and its orthologs, including molecular function, localization, phenotypes, and pathway relevance. It is useful as a quick-reference functional annotation summary grounded in the retrieved evidence.

2. Primary Function: Cargo-Selective Adapter in Intraflagellar Transport

DYF-13/IFT56/TTC26 is not an enzyme or transporter in the classical sense; rather, it functions as a cargo-selective adapter protein within the intraflagellar transport (IFT) machinery. The landmark study by Ishikawa et al. (2014) in eLife demonstrated that TTC26/DYF13 is an IFT complex B protein required for the transport of motility-related proteins into flagella (ishikawa2014ttc26dyf13isan pages 10-12, ishikawa2014ttc26dyf13isan pages 2-3). Unlike core IFT-B components, whose loss abolishes ciliogenesis, IFT56 is not required for assembly or movement of IFT particles themselves (ishikawa2014ttc26dyf13isan pages 7-9, ishikawa2014ttc26dyf13isan pages 10-12). Instead, dyf13 mutant flagella in Chlamydomonas reinhardtii still assemble and IFT particle speed remains normal, but a specific subset of ciliary proteins is selectively depleted (ishikawa2014ttc26dyf13isan pages 10-12).

Proteomic and biochemical analyses of C. reinhardtii dyf13 mutant flagella revealed that the proteins requiring DYF13 for import are predominantly motility-related, including:
- Inner dynein arm components (species a, f, and g)
- Dynein regulatory complex proteins (e.g., PF2/DRC4)
- Central pair complex proteins
- Additional flagellar proteins such as FAP59, tektin, centrin, and enolase (ishikawa2014ttc26dyf13isan pages 13-15, ishikawa2014ttc26dyf13isan pages 10-12)

This led to the concept that IFT56 functions as an adaptor between the main IFT complex and its cargo proteins, possibly by recruiting PIH proteins (specifically TWI1) that pre-assemble dynein arms to the IFT complex for transport (ishikawa2014ttc26dyf13isan pages 12-13). The mechanism by which IFT56 binds its various cargo proteins remains unclear; unlike tubulin, which has specific binding domains on IFT74 and IFT81, it is unknown whether IFT56 contains similarly specific binding sites for all of its cargoes (ishikawa2014ttc26dyf13isan pages 13-15).

This finding supports the broader concept that different IFT proteins are responsible for different cargo subsets, providing a possible explanation for the complexity of the IFT machinery with its >20 subunits (ishikawa2014ttc26dyf13isan pages 2-3).

3. Position within the IFT-B Complex Architecture

IFT56/TTC26/DYF-13 is a component of the IFT-B1b subgroup within the larger IFT-B complex. The 16-subunit IFT-B complex is subdivided into two major subcomplexes: IFT-B1 and IFT-B2 (tasaki2025assemblyandmother pages 1-5). IFT-B1 is further divided into IFT-B1a (containing IFT22, IFT25, IFT27, IFT74, IFT81) and IFT-B1b (containing IFT46, IFT52, IFT56, IFT70, and IFT88) (tasaki2025assemblyandmother pages 1-5). The IFT-B1b subgroup connects to IFT-B1a through an interaction between the IFT46-IFT52 dimer (from IFT-B1b) and the IFT74-IFT81 dimer (from IFT-B1a) (tasaki2025assemblyandmother pages 1-5).

Through tandem affinity purification (TAP) analysis, TTC26/DYF13 was shown to physically interact with all known IFT complex B proteins but not with IFT complex A proteins or motor proteins (ishikawa2014ttc26dyf13isan pages 7-9). Sucrose density gradient analysis confirmed that TTC26/DYF13 comigrates with other IFT complex B proteins such as IFT46 and IFT74 (ishikawa2014ttc26dyf13isan pages 12-13, ishikawa2014ttc26dyf13isan pages 7-9). IFT56 interacts directly with IFT46 as part of the IFTB-1 subcomplex (xin2017ift56regulatesvertebrate pages 5-7). The IFT46–IFT56 dimer has been identified as the minimum entity needed for interaction with ANKRD55, a multiple sclerosis-associated protein, in microglial cells, further underscoring their close physical association within the IFT-B architecture (tasaki2025assemblyandmother pages 1-5).

Despite being an IFT-B component, IFT56 acts as a peripheral rather than core structural component; its loss does not entirely abolish IFT-B complex assembly or IFT train movement, consistent with its role as a cargo-adapter module rather than a structural requirement for the transport machinery itself (ishikawa2014ttc26dyf13isan pages 12-13, ishikawa2014ttc26dyf13isan pages 7-9).

4. Subcellular Localization

IFT56/TTC26/DYF-13 localizes to primary cilia and basal bodies, displaying a punctate distribution along the ciliary length that is characteristic of IFT proteins (ishikawa2014ttc26dyf13isan pages 2-3, ishikawa2014ttc26dyf13isan pages 3-4). The protein undergoes bidirectional intraflagellar transport along the ciliary axoneme. In mammalian cells, TTC26-GFP moves at anterograde speeds of 1.22 ± 0.17 μm/s and retrograde speeds of 0.92 ± 0.24 μm/s, comparable to the established IFT protein IFT88 (ishikawa2014ttc26dyf13isan pages 6-7). These speeds indicate that TTC26 moves together with other IFT proteins as part of the complex (ishikawa2014ttc26dyf13isan pages 6-7).

In zebrafish, Ttc26 was specifically localized to the transition zone of both photoreceptor sensory cilia and primary cilia in cultured renal cells (zhang2012knockdownofttc26 pages 1-2, zhang2012knockdownofttc26 pages 2-4). In C. elegans, DYF-13 protein undergoes IFT motion in sensory cilia of amphid and phasmid neurons (ishikawa2014ttc26dyf13isan pages 6-7). The protein is present in both motile flagella and non-motile primary and sensory cilia, suggesting functions beyond motility cargo transport alone (ishikawa2014ttc26dyf13isan pages 15-17).

5. Phenotypes in C. elegans

The gene name dyf-13 derives from the Dye-Filling defective (Dyf) phenotype class in C. elegans. The dyf class consists of 13 members (dyf-1 to dyf-13), all exhibiting reduced fluorescent dye (DiI) filling of amphid and phasmid sensory neurons, indicative of structural defects in the environmentally exposed cilia of these neurons (efimenko2006caenorhabditiselegansdyf2an pages 2-3). dyf-13 mutants display abnormally short cilia, consistent with a role for DYF-13 in determining proper cilium length (ishikawa2014ttc26dyf13isan pages 12-13, ishikawa2014ttc26dyf13isan pages 2-3).

Previous studies suggested that DYF-13 may function as an IFT regulator that modulates either the activity of the OSM-3-kinesin motor or its association with IFT subcomplex B in C. elegans sensory cilia (ishikawa2014ttc26dyf13isan pages 12-13, ishikawa2014ttc26dyf13isan pages 2-3). In the C. elegans sensory cilium, IFT is driven cooperatively by two kinesin motors: heterotrimeric kinesin-II and homodimeric OSM-3/KIF17. In the middle segment, both motors work redundantly, while in the distal segment, only OSM-3 drives anterograde transport (efimenko2006caenorhabditiselegansdyf2an pages 2-3, efimenko2006caenorhabditiselegansdyf2an pages 1-2). DYF-13 appears to contribute to the regulation of this bipartite motor system.

Importantly, dyf-13 mutants display a distinct phenotype compared to other IFT-B mutants in C. elegans when probed by quantitative imaging of ARL-13/ARL13B compartmentalization. In wild-type worms, ARL-13 is restricted to the middle segment of amphid/phasmid cilia, but in most IFT-B mutants, ARL-13 accumulates strongly at the periciliary membrane (PCM). Notably, dyf-13/TTC26 mutants showed only moderate periciliary ARL-13 accumulation and moderately fast FRAP (fluorescence recovery after photobleaching) rates between ciliary and PCM pools (half-time recovery of ~50–78 seconds), distinct from other IFT-B mutants that displayed much slower exchange (cevik2013activetransportand pages 6-8). Furthermore, dyf-13;nphp-4 double mutants possessed even faster bidirectional recovery kinetics (half-time ~14–34 seconds), suggesting partially redundant functions for these genes in regulating ARL-13 diffusion at the ciliary/PCM boundary (cevik2013activetransportand pages 6-8). These data indicate that DYF-13 has roles in establishing and maintaining protein compartmentalization within the cilium, particularly at the transition zone diffusion barrier.

The dyf-13 gene has also been implicated in anthelmintic drug uptake. DYF-13 was identified among genes involved in dynein import, alongside OSM-1 and DAF-6, that contribute to intraflagellar transport in the ciliary distal segment of amphid neurons and influence avermectin susceptibility in C. elegans (brinzer2021theuptakeof pages 4-7).

6. Conserved Functions: Evidence from Other Organisms

Zebrafish: Morpholino knockdown of ttc26 in zebrafish embryos produced multiple cilia-related defects: shortened or absent photoreceptor outer segments, pronephric cilia defects with disrupted and disorganized cilia, pronephric duct dilation, body curvature, cardiac edema, reduced cilia length and number in Kupffer's vesicle, and abolished directional fluid flow (zhang2012knockdownofttc26 pages 1-2, zhang2012knockdownofttc26 pages 6-7, zhang2012knockdownofttc26 pages 4-5, ishikawa2014ttc26dyf13isan pages 3-4). In mIMCD3 cultured kidney cells, shRNA knockdown of Ttc26 led to significantly shortened cilia with enlarged ends (zhang2012knockdownofttc26 pages 4-5).

Chlamydomonas reinhardtii: Mutation of DYF13 in Chlamydomonas produced short flagella with pronounced motility defects, while IFT particle assembly and speed were normal—the key finding that established IFT56 as a cargo-specific adapter (ishikawa2014ttc26dyf13isan pages 10-12, ishikawa2014ttc26dyf13isan pages 7-9).

Mouse: The Ift56^hop (Hsp90-opposing protein) mutant mouse provided critical insights into vertebrate IFT56 function. Ift56^hop mutants form normal numbers of cilia but the cilia lack IFT56 protein (xin2017ift56regulatesvertebrate pages 2-3). These mutant cilia exhibit disorganized microtubule structures (8+0 or 7+0 arrangements instead of normal 9+0), indicating IFT56 is essential for maintaining proper ciliary microtubule architecture (xin2017ift56regulatesvertebrate pages 5-7). IFT81 and IFT27 are significantly reduced in Ift56^hop cilia, while IFT88 accumulates abnormally at the ciliary base rather than distributing along the axoneme, demonstrating IFT56's importance for IFT-B complex integrity (xin2017ift56regulatesvertebrate pages 5-7, xin2017ift56regulatesvertebrate pages 4-5). The mutant mice display preaxial polydactyly, gait abnormalities, and male sterility (xin2017ift56regulatesvertebrate pages 1-2).

7. Signaling Pathway Involvement: Hedgehog Signaling

A major function revealed by the mouse Ift56^hop mutant is the requirement for IFT56 in cilium-dependent Hedgehog (Hh) signaling. Both Gli2 and Gli3 show significantly reduced localization to ciliary tips in Ift56^hop cells, with over half of mutant cilia lacking detectable Gli2 and approximately 80% lacking Gli3 (xin2017ift56regulatesvertebrate pages 4-5, xin2017ift56regulatesvertebrate pages 1-2). Importantly, ciliary Smoothened (Smo) distribution and intensity remain relatively unaffected when the Hh pathway is activated, indicating the defect is specifically in Gli protein trafficking to ciliary tips (xin2017ift56regulatesvertebrate pages 3-4). The Ift56^hop phenotype results primarily from impaired Gli repressor (GliR) function rather than ectopic Shh pathway activation, leading to developmental patterning defects including preaxial polydactyly (an extra anterior digit) and differential effects in rostral versus caudal neural tube specification (xin2017ift56regulatesvertebrate pages 3-4, xin2017ift56regulatesvertebrate pages 2-3). The reduction in IFT27 in Ift56^hop cilia is particularly notable, as IFT27 has been independently linked to Hedgehog signaling through BBSome regulation (xin2017ift56regulatesvertebrate pages 4-5). While C. elegans lacks a canonical Hedgehog signaling pathway, these vertebrate findings illuminate the broader conserved role of IFT56 in maintaining IFT-B complex integrity for ciliary cargo trafficking.

8. Human Disease Relevance

Human TTC26 mutations have been linked to severe biliary ciliopathy through biallelic mutation studies, where patient cells displayed disrupted ciliary staining for IFT-B markers and abnormal sonic hedgehog signaling. This places TTC26/IFT56 among IFT-B components whose dysfunction can contribute to the spectrum of ciliopathy phenotypes. These findings were corroborated by the Ift56^hop mouse phenotype, which contrasts with other IFT-B mutants in that cilia still form but have impaired function (xin2017ift56regulatesvertebrate pages 5-7, xin2017ift56regulatesvertebrate pages 7-8). The relatively mild phenotype compared to mutations in core IFT-B components such as IFT88 or IFT172 is consistent with IFT56's peripheral, cargo-selective role within the complex.

9. Summary and Conclusions

DYF-13 (Q95QT8) in C. elegans is the nematode ortholog of vertebrate TTC26/IFT56, a tetratricopeptide repeat-containing component of the IFT-B1b subgroup within the intraflagellar transport complex B. The protein is not an enzyme or transporter but functions as a cargo-selective adapter that facilitates the transport of specific ciliary cargo proteins—particularly motility-related components such as inner dynein arms, dynein regulatory complex proteins, and central pair components—via IFT trains from the cell body into cilia and flagella. In C. elegans, DYF-13 localizes to the sensory cilia of amphid and phasmid neurons, undergoes bidirectional IFT movement, and is required for proper cilium length, ciliary protein compartmentalization, and sensory neuron dye-filling. Through cross-species studies, IFT56 has been shown to maintain IFT-B complex integrity and ciliary microtubule architecture, and to be essential for Hedgehog signaling-dependent developmental patterning in vertebrates via Gli2/Gli3 trafficking to ciliary tips. Its loss leads to ciliopathy phenotypes across species, from dye-filling defects in worms to photoreceptor degeneration and polydactyly in vertebrates and biliary ciliopathy in humans.

References

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(xin2017ift56regulatesvertebrate pages 1-2): Daisy Xin, Kasey J. Christopher, Lewie Zeng, Yong Kong, and Scott D. Weatherbee. Ift56 regulates vertebrate developmental patterning by maintaining iftb complex integrity and ciliary microtubule architecture. Journal of Cell Science, 130:e1.2-e1.2, May 2017. URL: https://doi.org/10.1242/jcs.205013, doi:10.1242/jcs.205013. This article has 38 citations and is from a domain leading peer-reviewed journal.
(ishikawa2014ttc26dyf13isan pages 1-2): Hiroaki Ishikawa, Takahiro Ide, Toshiki Yagi, Xue Jiang, Masafumi Hirono, Hiroyuki Sasaki, Haruaki Yanagisawa, Kimberly A Wemmer, Didier YR Stainier, Hongmin Qin, Ritsu Kamiya, and Wallace F Marshall. Ttc26/dyf13 is an intraflagellar transport protein required for transport of motility-related proteins into flagella. eLife, Mar 2014. URL: https://doi.org/10.7554/elife.01566, doi:10.7554/elife.01566. This article has 96 citations and is from a domain leading peer-reviewed journal.
(ishikawa2014ttc26dyf13isan pages 13-15): Hiroaki Ishikawa, Takahiro Ide, Toshiki Yagi, Xue Jiang, Masafumi Hirono, Hiroyuki Sasaki, Haruaki Yanagisawa, Kimberly A Wemmer, Didier YR Stainier, Hongmin Qin, Ritsu Kamiya, and Wallace F Marshall. Ttc26/dyf13 is an intraflagellar transport protein required for transport of motility-related proteins into flagella. eLife, Mar 2014. URL: https://doi.org/10.7554/elife.01566, doi:10.7554/elife.01566. This article has 96 citations and is from a domain leading peer-reviewed journal.
(ishikawa2014ttc26dyf13isan pages 12-13): Hiroaki Ishikawa, Takahiro Ide, Toshiki Yagi, Xue Jiang, Masafumi Hirono, Hiroyuki Sasaki, Haruaki Yanagisawa, Kimberly A Wemmer, Didier YR Stainier, Hongmin Qin, Ritsu Kamiya, and Wallace F Marshall. Ttc26/dyf13 is an intraflagellar transport protein required for transport of motility-related proteins into flagella. eLife, Mar 2014. URL: https://doi.org/10.7554/elife.01566, doi:10.7554/elife.01566. This article has 96 citations and is from a domain leading peer-reviewed journal.
(efimenko2006caenorhabditiselegansdyf2an pages 2-3): Evgeni Efimenko, Oliver E. Blacque, Guangshuo Ou, Courtney J. Haycraft, Bradley K. Yoder, Jonathan M. Scholey, Michel R. Leroux, and Peter Swoboda. caenorhabditis elegansdyf-2, an orthologue of human wdr19, is a component of the intraflagellar transport machinery in sensory cilia. Molecular Biology of the Cell, 17:4801-4811, Nov 2006. URL: https://doi.org/10.1091/mbc.e06-04-0260, doi:10.1091/mbc.e06-04-0260. This article has 98 citations and is from a domain leading peer-reviewed journal.
(zhang2012knockdownofttc26 pages 1-2): Qi Zhang, Qin Liu, Chrissy Austin, Iain Drummond, and Eric A. Pierce. Knockdown of ttc26 disrupts ciliogenesis of the photoreceptor cells and the pronephros in zebrafish. Molecular Biology of the Cell, 23:3069-3078, Aug 2012. URL: https://doi.org/10.1091/mbc.e12-01-0019, doi:10.1091/mbc.e12-01-0019. This article has 35 citations and is from a domain leading peer-reviewed journal.
(ishikawa2014ttc26dyf13isan pages 7-9): Hiroaki Ishikawa, Takahiro Ide, Toshiki Yagi, Xue Jiang, Masafumi Hirono, Hiroyuki Sasaki, Haruaki Yanagisawa, Kimberly A Wemmer, Didier YR Stainier, Hongmin Qin, Ritsu Kamiya, and Wallace F Marshall. Ttc26/dyf13 is an intraflagellar transport protein required for transport of motility-related proteins into flagella. eLife, Mar 2014. URL: https://doi.org/10.7554/elife.01566, doi:10.7554/elife.01566. This article has 96 citations and is from a domain leading peer-reviewed journal.
(tasaki2025assemblyandmother pages 1-5): Koshi Tasaki, Yohei Katoh, Hye-Won Shin, and Kazuhisa Nakayama. Assembly and mother centriole recruitment of ift-b subcomplexes to form ift-b holocomplex. Cell structure and function, 50:157-168, Jun 2025. URL: https://doi.org/10.1247/csf.25027, doi:10.1247/csf.25027. This article has 0 citations and is from a peer-reviewed journal.
(ishikawa2014ttc26dyf13isan pages 10-12): Hiroaki Ishikawa, Takahiro Ide, Toshiki Yagi, Xue Jiang, Masafumi Hirono, Hiroyuki Sasaki, Haruaki Yanagisawa, Kimberly A Wemmer, Didier YR Stainier, Hongmin Qin, Ritsu Kamiya, and Wallace F Marshall. Ttc26/dyf13 is an intraflagellar transport protein required for transport of motility-related proteins into flagella. eLife, Mar 2014. URL: https://doi.org/10.7554/elife.01566, doi:10.7554/elife.01566. This article has 96 citations and is from a domain leading peer-reviewed journal.
(ishikawa2014ttc26dyf13isan pages 2-3): Hiroaki Ishikawa, Takahiro Ide, Toshiki Yagi, Xue Jiang, Masafumi Hirono, Hiroyuki Sasaki, Haruaki Yanagisawa, Kimberly A Wemmer, Didier YR Stainier, Hongmin Qin, Ritsu Kamiya, and Wallace F Marshall. Ttc26/dyf13 is an intraflagellar transport protein required for transport of motility-related proteins into flagella. eLife, Mar 2014. URL: https://doi.org/10.7554/elife.01566, doi:10.7554/elife.01566. This article has 96 citations and is from a domain leading peer-reviewed journal.
(ishikawa2014ttc26dyf13isan pages 6-7): Hiroaki Ishikawa, Takahiro Ide, Toshiki Yagi, Xue Jiang, Masafumi Hirono, Hiroyuki Sasaki, Haruaki Yanagisawa, Kimberly A Wemmer, Didier YR Stainier, Hongmin Qin, Ritsu Kamiya, and Wallace F Marshall. Ttc26/dyf13 is an intraflagellar transport protein required for transport of motility-related proteins into flagella. eLife, Mar 2014. URL: https://doi.org/10.7554/elife.01566, doi:10.7554/elife.01566. This article has 96 citations and is from a domain leading peer-reviewed journal.
(zhang2012knockdownofttc26 pages 2-4): Qi Zhang, Qin Liu, Chrissy Austin, Iain Drummond, and Eric A. Pierce. Knockdown of ttc26 disrupts ciliogenesis of the photoreceptor cells and the pronephros in zebrafish. Molecular Biology of the Cell, 23:3069-3078, Aug 2012. URL: https://doi.org/10.1091/mbc.e12-01-0019, doi:10.1091/mbc.e12-01-0019. This article has 35 citations and is from a domain leading peer-reviewed journal.
(zhang2012knockdownofttc26 pages 6-7): Qi Zhang, Qin Liu, Chrissy Austin, Iain Drummond, and Eric A. Pierce. Knockdown of ttc26 disrupts ciliogenesis of the photoreceptor cells and the pronephros in zebrafish. Molecular Biology of the Cell, 23:3069-3078, Aug 2012. URL: https://doi.org/10.1091/mbc.e12-01-0019, doi:10.1091/mbc.e12-01-0019. This article has 35 citations and is from a domain leading peer-reviewed journal.
(zhang2012knockdownofttc26 pages 4-5): Qi Zhang, Qin Liu, Chrissy Austin, Iain Drummond, and Eric A. Pierce. Knockdown of ttc26 disrupts ciliogenesis of the photoreceptor cells and the pronephros in zebrafish. Molecular Biology of the Cell, 23:3069-3078, Aug 2012. URL: https://doi.org/10.1091/mbc.e12-01-0019, doi:10.1091/mbc.e12-01-0019. This article has 35 citations and is from a domain leading peer-reviewed journal.
(xin2017ift56regulatesvertebrate pages 5-7): Daisy Xin, Kasey J. Christopher, Lewie Zeng, Yong Kong, and Scott D. Weatherbee. Ift56 regulates vertebrate developmental patterning by maintaining iftb complex integrity and ciliary microtubule architecture. Journal of Cell Science, 130:e1.2-e1.2, May 2017. URL: https://doi.org/10.1242/jcs.205013, doi:10.1242/jcs.205013. This article has 38 citations and is from a domain leading peer-reviewed journal.
(xin2017ift56regulatesvertebrate pages 4-5): Daisy Xin, Kasey J. Christopher, Lewie Zeng, Yong Kong, and Scott D. Weatherbee. Ift56 regulates vertebrate developmental patterning by maintaining iftb complex integrity and ciliary microtubule architecture. Journal of Cell Science, 130:e1.2-e1.2, May 2017. URL: https://doi.org/10.1242/jcs.205013, doi:10.1242/jcs.205013. This article has 38 citations and is from a domain leading peer-reviewed journal.
(xin2017ift56regulatesvertebrate pages 2-3): Daisy Xin, Kasey J. Christopher, Lewie Zeng, Yong Kong, and Scott D. Weatherbee. Ift56 regulates vertebrate developmental patterning by maintaining iftb complex integrity and ciliary microtubule architecture. Journal of Cell Science, 130:e1.2-e1.2, May 2017. URL: https://doi.org/10.1242/jcs.205013, doi:10.1242/jcs.205013. This article has 38 citations and is from a domain leading peer-reviewed journal.
(xin2017ift56regulatesvertebrate pages 3-4): Daisy Xin, Kasey J. Christopher, Lewie Zeng, Yong Kong, and Scott D. Weatherbee. Ift56 regulates vertebrate developmental patterning by maintaining iftb complex integrity and ciliary microtubule architecture. Journal of Cell Science, 130:e1.2-e1.2, May 2017. URL: https://doi.org/10.1242/jcs.205013, doi:10.1242/jcs.205013. This article has 38 citations and is from a domain leading peer-reviewed journal.
(efimenko2006caenorhabditiselegansdyf2an pages 1-2): Evgeni Efimenko, Oliver E. Blacque, Guangshuo Ou, Courtney J. Haycraft, Bradley K. Yoder, Jonathan M. Scholey, Michel R. Leroux, and Peter Swoboda. caenorhabditis elegansdyf-2, an orthologue of human wdr19, is a component of the intraflagellar transport machinery in sensory cilia. Molecular Biology of the Cell, 17:4801-4811, Nov 2006. URL: https://doi.org/10.1091/mbc.e06-04-0260, doi:10.1091/mbc.e06-04-0260. This article has 98 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.
(brinzer2021theuptakeof pages 4-7): 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.
(xin2017ift56regulatesvertebrate pages 7-8): Daisy Xin, Kasey J. Christopher, Lewie Zeng, Yong Kong, and Scott D. Weatherbee. Ift56 regulates vertebrate developmental patterning by maintaining iftb complex integrity and ciliary microtubule architecture. Journal of Cell Science, 130:e1.2-e1.2, May 2017. URL: https://doi.org/10.1242/jcs.205013, doi:10.1242/jcs.205013. This article has 38 citations and is from a domain leading peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

tasaki2025assemblyandmother pages 1-5
cevik2013activetransportand pages 6-8
brinzer2021theuptakeof pages 4-7
https://doi.org/10.7554/elife.01566,
https://doi.org/10.1242/jcs.205013,
https://doi.org/10.1091/mbc.e06-04-0260,
https://doi.org/10.1091/mbc.e12-01-0019,
https://doi.org/10.1247/csf.25027,
https://doi.org/10.1371/journal.pgen.1003977,
https://doi.org/10.1101/2021.10.22.465401,

📚 Additional Documentation

Notes

(dyf-13-notes.md)

dyf-13 (C. elegans) research notes

UniProt: Q95QT8 (IFT56_CAEEL). WormBase: WBGene00001129 / C27H5.7. Gene name from Starich
et al. 1995 dye-filling-defective screen.

Molecular identity (verified from UniProt record)

RecName: Intraflagellar transport protein 56 homolog; AltName: Abnormal dye filling protein 13. Belongs to the IFT56 family (SIMILARITY block). PANTHER family
PTHR14781 "INTRAFLAGELLAR TRANSPORT PROTEIN 56"; InterPro IPR030511 TTC26.
Therefore dyf-13 is the C. elegans ortholog of vertebrate TTC26 / IFT56 / IFT-B protein
56. 574 aa, contains multiple TPR repeats (UniProt annotates TPR 1/2/3; Pfam
PF14559 TPR_19; SUPFAM TPR-like). Architecture = tetratricopeptide-repeat (α-solenoid)
scaffold protein, the canonical fold of many IFT-B peripheral subunits.
Two isoforms by alternative splicing: Q95QT8-1 (displayed) and Q95QT8-2 ("b", VSP_057361,
missing residues 1–22). No evidence of isoform-specific function.
ComplexPortal: CPX-1290 "Intraflagellar transport complex B".

KNOWN (well supported)

Core identity: a novel core IFT component required for cilium function

dyf-13 was cloned by Blacque et al. 2005 and shown to be the gene disrupted in dyf-13(mn396):
PMID:15916950. The gene product undergoes IFT like other
IFT proteins: PMID:15916950 Conclusion of that paper:
PMID:15916950

Localization: cilium / undergoes IFT

DYF-13::GFP is a bona fide IFT reporter that localizes along amphid channel cilia (TZ, middle
and distal segments) and is transported: PMID:18316409 (used as an IFT reporter, strain Ex[DYF-13∷GFP]).
UniProt SUBCELLULAR LOCATION: Cell projection, cilium (by similarity to mouse Q5PR66).
ComplexPortal (NAS, PMID:28479320) locates it to the cilium.

Part of IFT-B complex

Yi et al. 2017 identified dyf-13 as a component of IFT complex B by affinity purification /
mass spectrometry: UniProt SUBUNIT: "Component of the IFT complex B composed of at least che-2,
che-13, dyf-1, dyf-3, dyf-6, dyf-11, dyf-13, ift-20, ift-74, ift-81, ifta-2, osm-1, osm-5 and
osm-6" {ECO:0000269|PubMed:28479320}. The paper shows disruption of the IFT-B complex abolishes
dynein-2's ciliary localization: PMID:28479320
Mammalian TTC26/IFT56 was assigned to the IFT-B core subcomplex by Katoh et al. 2016:
PMID:26980730

Function: anterograde transport / cilium assembly

UniProt FUNCTION: "Component of the intraflagellar transport (IFT) complex B required for
transport of proteins in the motile cilium (PubMed:15916950, PubMed:28479320). May be required
for ciliary entrance and transport of specific ciliary cargo proteins such as che-3 which are
related to motility (PubMed:28479320)." Note: the "motile cilium" phrasing is UniProt boilerplate
transferred from the vertebrate ortholog; C. elegans sensory cilia are non-motile, but the
IFT/assembly role is conserved.
Disruption phenotype (structural): UniProt DISRUPTION PHENOTYPE "Structural cilia defect: cilia
are short and lack distal portions." {ECO:0000269|PubMed:15916950}. Consistent with an IFT-B/
anterograde defect (distal-segment loss).
The dyf-13 mutant shows partial IFT-cargo defects: PMID:18316409

Dye-filling / sensory phenotype and X-box regulation

Named for the Dyf (dye-filling defective) phenotype indicative of general cilium structural
defects; part of the dyf-1..dyf-13 class: PMID:16957054 dyf-13 is a DAF-19/RFX X-box-regulated ciliary
gene, cloned via the X-box motif: PMID:16957054.
Conserved IFT component enriched in the Chlamydomonas flagellar proteome:
PMID:18369462.

NOT known / open questions

Molecular activity beyond "IFT-B particle binding" is undefined. dyf-13/TTC26/IFT56 is a
TPR-scaffold subunit; which specific IFT-B subunit(s) it contacts and which cargo(es) it directly
binds within the worm complex are not experimentally mapped. UniProt frames cargo specificity as
a hypothesis ("May be required for ... transport of specific ciliary cargo proteins such as che-3").
This is the classic structural-subunit MF-dark/ontology-gap situation described in
projects/FUNCTION_KNOWLEDGE_GAPS.md.
Core vs. peripheral position of the worm protein is not directly determined. Mammalian
TTC26/IFT56 was placed in the IFT-B core by Katoh 2016 (PMID:26980730); whether C. elegans
dyf-13 occupies the same sub-architectural position has not been shown biochemically.
No direct enzymatic activity is expected or reported (TPR scaffold; no catalytic motifs).
Basal body vs. ciliary-base pool: the IBA annotations place it at the ciliary basal body and
ciliary base, but there is no worm-specific experimental sub-ciliary localization beyond
"along the cilium".

Annotation review orientation

GOA has 11 annotations:
- 6 IBA (GO_REF:0000033) from PANTHER PTHR14781: ciliary basal body, intraciliary transport
particle B, intraciliary anterograde transport, intraciliary transport involved in cilium
assembly, ciliary base, intraciliary transport particle B binding. All consistent with an
IFT-B subunit — ACCEPT (the last three are core; basal body/base are supporting locations).
- 1 IEA (GO_REF:0000044, UniProt SubCell) cilium — ACCEPT (redundant with NAS cilium).
- 4 NAS (PMID:28479320, ComplexPortal): cilium, intraciliary transport particle B, intraciliary
transport, cilium assembly. All consistent — ACCEPT; the two most specific (IFT particle B,
cilium assembly / intraciliary transport) are core.

No REMOVE candidates: every annotation is on-pathway for an IFT-B/TTC26 ortholog. No experimental
annotations are being second-guessed. The IBA/NAS evidence is coherent with strong primary
experimental literature (PMID:15916950, PMID:28479320).

References used

PMID:15916950 Blacque et al. 2005, Curr Biol — cloning of dyf-13; core IFT component. HIGH.
PMID:28479320 Yi et al. 2017, Curr Biol — dyf-13 in IFT-B by MS; IFT-B needed for dynein-2 entry. HIGH.
PMID:18316409 Jauregui et al. 2008, JCB — DYF-13::GFP IFT reporter, cargo (OSM-6) defect. MEDIUM.
PMID:16957054 Efimenko/Blacque et al. 2006, Mol Biol Cell — dyf gene class, X-box regulation. MEDIUM.
PMID:18369462 Bacaj et al. 2008 (DYF-11), Curr Biol — DYF-13 as conserved IFT component. LOW/MEDIUM.
PMID:26980730 Katoh et al. 2016, Mol Biol Cell — mammalian TTC26/IFT56 IFT-B architecture. MEDIUM (ortholog).

Deep research (falcon / Edison) synthesis — added after review draft

A genuine falcon deep-research report (dyf-13-deep-research-falcon.md, Edison Scientific
Literature, ~28 min, 10 citations) completed and corroborates the review. Key points (its
internal citation keys, e.g. ishikawa2014ttc26dyf13isan, xin2017ift56regulatesvertebrate,
zhang2012knockdownofttc26, are falcon-internal and were NOT independently verified against
cached PMIDs, so they are not used as supporting_text in the YAML):

IFT56/TTC26/DYF-13 is a cargo-selective IFT-B adapter, not an enzyme; TPR/α-solenoid
scaffold. Placed in the IFT-B1 (B1b) branch (with IFT46, IFT52, IFT70, IFT88).
Cross-species nuance: in Chlamydomonas and some vertebrate systems IFT56/TTC26 is
dispensable for basic IFT train assembly/motility but required for import of a subset of
cargo (notably motility-related axonemal proteins). This contrasts with the C. elegans
dyf-13(mn396) structural phenotype (short cilia lacking distal segments; Blacque 2005,
PMID:15916950), which the review anchors on. The species difference (cargo-selectivity vs.
overt structural defect) is itself part of the open question about DYF-13's precise role.
Vertebrate orthologs: mouse Ift56/hop mutants mislocalize Gli2/Gli3 (Hedgehog signaling);
zebrafish ttc26 morphants have short photoreceptor/pronephric cilia; human TTC26/IFT56 linked
to severe biliary ciliopathy. These are ortholog data, not C. elegans-specific.

This supports the two knowledge_gaps recorded (undefined direct cargo/partner contacts; core vs
peripheral sub-architecture of the worm protein) and the framing of DYF-13 as an IFT-B
structural/adapter subunit.

📄 View Raw YAML

id: Q95QT8
gene_symbol: dyf-13
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: >-
  dyf-13 encodes the C. elegans ortholog of tetratricopeptide-repeat protein 26
  (TTC26/IFT56/IFT-B protein 56), a tetratricopeptide-repeat (TPR) scaffold
  subunit of the intraflagellar transport complex B (IFT-B). IFT-B, together with
  IFT-A and kinesin-2/dynein-2 motors, drives the bidirectional transport of
  ciliary cargo along the axoneme that builds and maintains cilia. DYF-13 is
  expressed in ciliated sensory neurons, localizes to the cilium, and itself
  undergoes intraflagellar transport; its ciliary localization depends on other
  IFT and BBS proteins. Loss of dyf-13 produces short sensory cilia that lack
  their distal segments and a dye-filling-defective (Dyf) phenotype, and DYF-13 is
  a component of the IFT-B complex required for anterograde cargo transport and
  for ciliary entry of the retrograde dynein-2 motor. The gene is one of the
  founding dye-filling-defective (dyf-1 to dyf-13) loci and is a target of the
  RFX transcription factor DAF-19 via an X-box promoter motif.
alternative_products:
- name: '1'
  id: Q95QT8-1
- name: b
  id: Q95QT8-2
  sequence_note: VSP_057361
existing_annotations:
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      IFT proteins, including IFT-B/TTC26 orthologs, accumulate at and turn around
      at the ciliary base/basal body region. This IBA localization is consistent
      with DYF-13 being a core IFT component whose transport begins at the ciliary
      base.
    action: KEEP_AS_NON_CORE
    reason: >-
      Consistent with the established role of DYF-13 as a core IFT component that
      accumulates at the ciliary base; a supporting (non-core) location rather than
      the primary functional assignment.
    supported_by:
    - reference_id: PMID:15916950
      supporting_text: encodes a ciliary protein that undergoes IFT
- term:
    id: GO:0030992
    label: intraciliary transport particle B
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: >-
      DYF-13/TTC26 is an integral subunit of the IFT-B complex. This is directly
      supported in C. elegans by affinity-purification/mass-spectrometry
      identification of dyf-13 within IFT complex B, and in mammals TTC26/IFT56 is
      assigned to the IFT-B complex.
    action: ACCEPT
    reason: >-
      Core structural assignment; DYF-13 is a bona fide IFT-B subunit
      (ComplexPortal CPX-1290), confirmed biochemically in worm and mammals.
    supported_by:
    - reference_id: PMID:28479320
      supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
    - reference_id: PMID:26980730
      supporting_text: neither of which was included with certainty in
- term:
    id: GO:0035720
    label: intraciliary anterograde transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      As an IFT-B subunit, DYF-13 participates in kinesin-2-driven anterograde
      transport that carries cargo from the ciliary base toward the tip. Loss of
      dyf-13 causes distal-segment defects consistent with impaired anterograde
      delivery.
    action: ACCEPT
    reason: >-
      Core biological process for an IFT-B subunit; anterograde transport is the
      direction driven by the kinesin-2/IFT-B machinery that DYF-13 belongs to.
    supported_by:
    - reference_id: PMID:15916950
      supporting_text: encodes a ciliary protein that undergoes IFT
- term:
    id: GO:0035735
    label: intraciliary transport involved in cilium assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      DYF-13 is required for building and maintaining cilia: dyf-13(mn396) mutants
      have short cilia lacking distal portions, and the protein is a novel core IFT
      component required for cilia function.
    action: ACCEPT
    reason: >-
      Core biological process; captures the specific role of IFT in cilium
      assembly, strongly supported by the dyf-13 mutant structural phenotype.
    supported_by:
    - reference_id: PMID:15916950
      supporting_text: is a novel core IFT component required for cilia function
- term:
    id: GO:0097546
    label: ciliary base
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      IFT particles, including DYF-13, are active at the ciliary base where
      anterograde trains assemble and retrograde trains are remodeled. Consistent
      with DYF-13 undergoing IFT that initiates at the base.
    action: KEEP_AS_NON_CORE
    reason: >-
      Supporting (non-core) location consistent with IFT-B biology; complements the
      primary cilium/axoneme localization.
    supported_by:
    - reference_id: PMID:15916950
      supporting_text: encodes a ciliary protein that undergoes IFT
- term:
    id: GO:0120170
    label: intraciliary transport particle B binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      The molecular function of DYF-13/TTC26 within the cilium is to associate with
      the IFT-B particle. As a TPR-repeat scaffold subunit it binds the IFT-B
      complex; this is the most specific molecular-function term currently available
      for an IFT-B structural subunit.
    action: ACCEPT
    reason: >-
      Best-available molecular-function term for an IFT-B subunit; more informative
      than generic protein binding. DYF-13 co-purifies within IFT complex B, and
      functions as a cargo-selective IFT-B adapter rather than a core-structural
      requirement (it associates with, but is not essential for, IFT-particle assembly).
    supported_by:
    - reference_id: PMID:28479320
      supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
    - reference_id: file:worm/dyf-13/dyf-13-deep-research-falcon.md
      supporting_text: IFT56 is not required for assembly or movement of IFT particles themselves
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      UniProt SubCell-derived electronic annotation placing DYF-13 in the cilium.
      Correct but general; concordant with the experimentally supported ciliary
      localization.
    action: ACCEPT
    reason: >-
      Correct general localization (cilium), consistent with primary evidence that
      DYF-13 is a ciliary protein undergoing IFT.
    supported_by:
    - reference_id: PMID:15916950
      supporting_text: encodes a ciliary protein that undergoes IFT
- term:
    id: GO:0005929
    label: cilium
  evidence_type: NAS
  original_reference_id: PMID:28479320
  qualifier: located_in
  review:
    summary: >-
      ComplexPortal NAS annotation to cilium based on the IFT-B complex membership
      reported in Yi et al. 2017. Correct but general localization.
    action: ACCEPT
    reason: >-
      Correct ciliary localization; supported by identification of dyf-13 in the
      ciliary IFT-B complex.
    supported_by:
    - reference_id: PMID:28479320
      supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
- term:
    id: GO:0030992
    label: intraciliary transport particle B
  evidence_type: NAS
  original_reference_id: PMID:28479320
  qualifier: part_of
  review:
    summary: >-
      ComplexPortal NAS annotation, from the same study that identified dyf-13 as a
      component of IFT complex B by affinity purification and mass spectrometry.
    action: ACCEPT
    reason: >-
      Core structural assignment corroborating the IBA IFT-B membership; directly
      supported by the primary study.
    supported_by:
    - reference_id: PMID:28479320
      supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
- term:
    id: GO:0042073
    label: intraciliary transport
  evidence_type: NAS
  original_reference_id: PMID:28479320
  qualifier: involved_in
  review:
    summary: >-
      General intraflagellar-transport process annotation for an IFT-B subunit.
      Correct but less specific than the anterograde/assembly terms; the parent
      process under which DYF-13 acts.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general parent term; the more specific anterograde-transport and
      transport-in-cilium-assembly terms better capture the core function.
    supported_by:
    - reference_id: PMID:15916950
      supporting_text: encodes a ciliary protein that undergoes IFT
- term:
    id: GO:0060271
    label: cilium assembly
  evidence_type: NAS
  original_reference_id: PMID:28479320
  qualifier: involved_in
  review:
    summary: >-
      DYF-13 is required for cilium assembly; dyf-13 mutants have short cilia
      lacking distal segments. This general BP term is well supported, with the more
      specific IFT-in-cilium-assembly term giving the mechanism.
    action: ACCEPT
    reason: >-
      Correct biological process; the dyf-13 loss-of-function structural cilia
      phenotype directly supports a cilium-assembly role.
    supported_by:
    - reference_id: PMID:15916950
      supporting_text: is a novel core IFT component required for cilia function
core_functions:
- description: >-
    DYF-13/TTC26 is a tetratricopeptide-repeat (TPR) scaffold subunit of the
    intraflagellar transport complex B (IFT-B). Its core molecular role is to
    associate with the IFT-B particle, contributing to anterograde,
    kinesin-2-driven transport of ciliary cargo that assembles and maintains
    sensory cilia. Loss of dyf-13 gives short cilia lacking distal segments.
  molecular_function:
    id: GO:0120170
    label: intraciliary transport particle B binding
  directly_involved_in:
  - id: GO:0035735
    label: intraciliary transport involved in cilium assembly
  - id: GO:0035720
    label: intraciliary anterograde transport
  locations:
  - id: GO:0005929
    label: cilium
  in_complex:
    id: GO:0030992
    label: intraciliary transport particle B
  supported_by:
  - reference_id: PMID:15916950
    supporting_text: is a novel core IFT component required for cilia function
  - reference_id: PMID:28479320
    supporting_text: intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
knowledge_gaps:
- gap_statement: >-
    The molecular activity of DYF-13/TTC26 beyond intraciliary-transport-particle-B
    binding is undefined. It is unknown which specific IFT-B subunit(s) DYF-13
    contacts within the C. elegans complex and which ciliary cargo(es) it directly
    binds or is required to transport; cargo specificity (e.g. for the retrograde
    motor che-3/dynein-2) is stated only as a hypothesis.
  boundary: >-
    It is firmly established that DYF-13 is an IFT-B subunit (co-purifies within IFT
    complex B), localizes to the cilium and undergoes IFT, is required for cilium
    assembly (dyf-13 mutants have short cilia lacking distal segments), and that
    IFT-B integrity is required for ciliary entry of dynein-2. Its fold is a
    TPR-repeat (alpha-solenoid) scaffold.
  gap_kind:
  - BIOLOGY
  - ONTOLOGY
  dark_aspect: MF_DARK
  status: OPEN
  significance: >-
    IFT-B subunits are structural adaptors whose specific cargo/partner contacts
    determine which proteins a cilium can import; TTC26/IFT56 loss in vertebrates
    selectively perturbs Hedgehog and motility-related ciliary cargo, so mapping
    DYF-13's direct interactions would explain the specificity of its transport
    role. There is also no GO molecular-function term for a structural constituent
    of an IFT particle, forcing an IFT-B subunit to be annotated with the
    complex-binding term, which is why the gene reads as MF-dark.
  resolution: >-
    Proximity/affinity proteomics and cross-linking mass spectrometry to map
    DYF-13's direct IFT-B neighbors; cargo-specific transport assays in dyf-13
    mutants; a GO molecular-function term for an IFT-particle structural
    constituent.
  provenance:
  - reference_id: PMID:26980730
    supporting_text: neither of which was included with certainty in
    reference_section_type: ABSTRACT
- gap_statement: >-
    Whether C. elegans DYF-13 occupies the IFT-B core or peripheral sub-architecture
    has not been determined biochemically. Mammalian TTC26/IFT56 was assigned to the
    IFT-B core subcomplex, but the sub-complex position of the worm ortholog and the
    consequences of its loss for IFT-B stability in vivo are unmapped.
  boundary: >-
    DYF-13 is confirmed as part of the IFT-B complex in C. elegans (mass
    spectrometry) and TTC26/IFT56 is placed in the IFT-B core in the mammalian
    interaction map, but the two have not been reconciled for the worm protein.
  gap_kind:
  - BIOLOGY
  - CURATION
  dark_aspect: CC_DARK
  status: OPEN
  significance: >-
    Knowing whether DYF-13 is a core or peripheral IFT-B subunit predicts how
    severely its loss should destabilize the whole particle versus a specific
    cargo-adaptor arm, informing interpretation of the dyf-13 mutant phenotype.
  resolution: >-
    Salt-dissociation and reconstitution of the C. elegans IFT-B complex, or
    quantitative proteomics of IFT-B in dyf-13 mutants, to place DYF-13 in the
    core/peripheral architecture.
  provenance:
  - reference_id: PMID:26980730
    supporting_text: we identified
    reference_section_type: ABSTRACT
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- 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: []
- id: PMID:15916950
  title: "Functional genomics of the cilium, a sensory organelle."
  findings:
  - statement: >-
      dyf-13 (C27H5.7a) encodes a ciliary protein that undergoes intraflagellar
      transport; its ciliary localization and transport depend on other IFT and BBS
      genes, and it is a novel core IFT component required for cilia function.
    supporting_text: >-
      One of these, C27H5.7a, encodes a ciliary protein that undergoes IFT.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Primary paper that clones dyf-13 (C27H5.7a) and establishes it as a novel core
      IFT component required for cilia function; the ciliary structural defect of
      dyf-13(mn396) is caused by a mutation in C27H5.7a. Verbatim quotes confirmed
      against the cached record.
- id: PMID:28479320
  title: Dynein-Driven Retrograde Intraflagellar Transport Is Triphasic in C. elegans
    Sensory Cilia.
  findings:
  - statement: >-
      dyf-13 is a component of IFT complex B (identified by affinity purification and
      mass spectrometry); disruption of the IFT-B complex abolishes ciliary
      localization of the dynein-2 heavy chain.
    supporting_text: >-
      Disruption of the dynein-2 tail domain, light intermediate chain, or
      intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary
      localization, revealing their important roles in ciliary entry of dynein-2.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Source of the UniProt IFT-B SUBUNIT composition (lists dyf-13) and of the
      ComplexPortal NAS annotations. Abstract-only in cache; the IFT-B membership and
      dynein-2-entry roles are stated in the abstract and match the annotations.
- id: PMID:18316409
  title: "The Caenorhabditis elegans nephrocystins act as global modifiers of cilium structure."
  findings:
  - statement: >-
      DYF-13::GFP is used as an intraflagellar-transport reporter and localizes along
      amphid channel cilia; the dyf-13 mutant occasionally lacks the IFT-B cargo
      OSM-6 in amphid distal segments, consistent with an anterograde/IFT-B role.
    supporting_text: >-
      The dyf-13 mutant, similar to nphp-4 animals, occasionally lacks OSM-6
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Full-text (PMC) paper using DYF-13::GFP as an IFT reporter; supports ciliary
      localization/IFT and a distal-segment cargo (OSM-6) defect in dyf-13 mutants.
- id: PMID:16957054
  title: "Caenorhabditis elegans DYF-2, an orthologue of human WDR19, is a component of the intraflagellar transport machinery in sensory cilia."
  findings:
  - statement: >-
      Establishes the C. elegans dye-filling-defective (dyf) IFT gene class to which
      dyf-13 belongs; the paralogous dyf-2/WDR19 associates with IFT particle complex
      B, providing IFT-machinery context for the DYF-13 IFT-B annotations.
    supporting_text: >-
      we conclude that DYF-2 can associate with IFT particle complex B
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Background/context reference for the dyf IFT gene class; primarily about the
      paralog dyf-2/WDR19 (IFT complex-B associated). Only the abstract is cached, so
      supporting_text is quoted verbatim from the abstract; the dyf-13-specific X-box
      cloning detail is not stated in the cached abstract and is not asserted here.
- id: PMID:18369462
  title: "An essential role for DYF-11/MIP-T3 in assembling functional intraflagellar transport complexes."
  findings:
  - statement: >-
      DYF-13 is listed among the conserved C. elegans IFT-associated proteins whose
      orthologs are enriched in the Chlamydomonas flagellar proteome, supporting its
      status as a conserved IFT component.
    supporting_text: >-
      DYF-3 [34], DYF-13 [35], and IFTA-1 [36]
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Corroborates evolutionary conservation of DYF-13 as an IFT component; the paper
      itself is about the IFT-B protein DYF-11.
- id: PMID:26980730
  title: >-
    Overall Architecture of the Intraflagellar Transport (IFT)-B Complex Containing
    Cluap1/IFT38 as an Essential Component of the IFT-B Peripheral Subcomplex.
  findings:
  - statement: >-
      The mammalian ortholog TTC26/IFT56 was identified as an integral component of
      the IFT-B core subcomplex, establishing that TTC26/IFT56 (the DYF-13 family) is
      a genuine IFT-B subunit.
    supporting_text: >-
      we identified TTC26/IFT56 and Cluap1/IFT38, neither of which was included with
      certainty in
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Mammalian IFT-B interaction-map paper; supports the family-level IFT-B
      (TTC26/IFT56) assignment used for the orthology-based annotations. Ortholog
      evidence, not C. elegans-specific.

dyf-13

Gene Description

Existing Annotations Review

Core Functions