Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0060294 cilium movement involved in cell motility	IBA GO_REF:0000033	REMOVE	Summary: CHE-3 is expressed in sensory cilia which are non-motile (9+0 structure) in C. elegans. The IBA annotation appears to derive from phylogenetic inference from motile cilium orthologs in other species (e.g., Drosophila, mouse). However, C. elegans sensory cilia lack the outer dynein arms required for ciliary beating and cell motility. Reason: C. elegans sensory cilia are non-motile primary cilia-like structures (PMID:10790327). CHE-3 functions in retrograde IFT, not in ciliary motility. This annotation represents incorrect phylogenetic transfer from organisms with motile cilia. Supporting Evidence: PMID:10790327 This isoform of dynein shows temporally and spatially restricted expression in ciliated sensory neurons, and mutants show progressive developmental defects of the chemosensory cilia. file:worm/che-3/che-3-deep-research-falcon.md model: Edison Scientific Literature
GO:0097729 9+2 motile cilium	IBA GO_REF:0000033	REMOVE	Summary: C. elegans sensory cilia have a modified non-motile structure, not a 9+2 motile cilium. CHE-3 localizes to non-motile sensory cilia in chemosensory neurons. The IBA annotation is based on orthologs that localize to motile cilia in other organisms. Reason: CHE-3 is localized to non-motile sensory cilia in C. elegans (PMID:10790327). The annotation to 9+2 motile cilium is incorrect for this species. The IDA annotation to GO:0097730 (non-motile cilium) from the same paper accurately captures the localization. Supporting Evidence: PMID:10790327 These disruptions were mapped and cloned using a newly developed PCR-based transposon display. The mutations were demonstrated to be allelic to the che-3 genetic locus.
GO:0045505 dynein intermediate chain binding	IBA GO_REF:0000033	ACCEPT	Summary: Dynein heavy chains are known to interact with intermediate chains to form functional dynein complexes. CHE-3 as a cytoplasmic dynein 2 heavy chain would be expected to bind intermediate chains as part of its role in the cytoplasmic dynein 2 complex. UniProt indicates CHE-3 forms a homodimer and associates with light intermediate chains. Reason: The IBA annotation is phylogenetically sound. Dynein heavy chains characteristically bind intermediate chains to form the complete dynein complex. UniProt notes that "The cytoplasmic dynein complex 2 is probably composed by a heavy chain che-3 homodimer and a number of light intermediate chains." Supporting Evidence: PMID:10545497 The Chlamydomonas DHC1b polypeptide shares high homology with the C. elegans CHE-3 protein
GO:0051959 dynein light intermediate chain binding	IBA GO_REF:0000033	ACCEPT	Summary: CHE-3 as a cytoplasmic dynein 2 heavy chain interacts with light intermediate chains to form the functional IFT-dynein complex. This is a conserved feature of cytoplasmic dynein 2 complexes. Reason: Well-supported by phylogeny and consistent with the known architecture of cytoplasmic dynein 2 complexes. UniProt states the complex includes light intermediate chains. Supporting Evidence: PMID:10545497 The DHC1b class of dyneins is placed phylogenetically between the axonemal and cytoplasmic classes of DHC.
GO:0005868 cytoplasmic dynein complex	IBA GO_REF:0000033	ACCEPT	Summary: CHE-3 is the heavy chain subunit of the cytoplasmic dynein 2 complex. The IBA annotation is phylogenetically sound and well-supported by the molecular characterization. Reason: CHE-3 is the C. elegans ortholog of DHC1b/DYNC2H1, forming the catalytic core of the cytoplasmic dynein 2 complex that drives retrograde IFT (PMID:10545497). Supporting Evidence: PMID:10545497 Thus, we propose that the class DHC1b cytoplasmic dynein, CHE-3, is specifically responsible for the retrograde transport of the anterograde motor, kinesin-II, and its cargo within sensory cilia, but not within dendrites.
GO:0060271 cilium assembly	IBA GO_REF:0000033	ACCEPT	Summary: CHE-3 is required for proper cilium assembly and maintenance. Loss of CHE-3 function results in shortened cilia with structural abnormalities. This reflects its essential role in retrograde IFT, which is necessary for cilium formation. Reason: Well-supported by experimental evidence. che-3 mutants have defective cilia formation (PMID:10790327, PMID:28479320). The IBA annotation is consistent with direct experimental data in C. elegans. Supporting Evidence: PMID:10790327 mutants show progressive developmental defects of the chemosensory cilia. These results are consistent with a role for this motor protein in the process of intraflagellar transport PMID:28479320 Cytoplasmic dynein-2 powers retrograde intraflagellar transport that is essential for cilium formation and maintenance.
GO:0008569 minus-end-directed microtubule motor activity	IBA GO_REF:0000033	ACCEPT	Summary: CHE-3 is a dynein heavy chain with AAA+ ATPase domains that provide minus-end-directed microtubule motor activity. This is the fundamental molecular function enabling retrograde IFT transport from the cilium tip toward the base. Reason: Core molecular function of CHE-3. Dyneins are minus-end-directed motors, and CHE-3's role in retrograde transport demonstrates this activity (PMID:10545497). The protein has conserved AAA+ ATPase domains and P-loop motifs characteristic of dynein motors. Supporting Evidence: PMID:10545497 To test the hypothesis that the minus end-directed microtubule motor protein, cytoplasmic dynein, drives this retrograde transport pathway, we visualized movement of kinesin-II and its cargo along dendrites and cilia in a che-3 cytoplasmic dynein mutant background
GO:0005930 axoneme	IBA GO_REF:0000033	ACCEPT	Summary: CHE-3 is localized to and functions within the axoneme of sensory cilia, where it drives retrograde transport along axonemal microtubules. Reason: CHE-3 moves along axonemal microtubules during retrograde IFT. The protein is observed within the ciliary axoneme and its activity is specifically required there (PMID:10545497). Supporting Evidence: PMID:10545497 observed an inhibition of retrograde transport in cilia but not in dendrites. In contrast, anterograde IFT proceeds normally in che-3 mutants.
GO:0035721 intraciliary retrograde transport	IBA GO_REF:0000033	ACCEPT	Summary: This is the primary biological process function of CHE-3. The protein powers retrograde intraflagellar transport, moving IFT particles from the cilium tip back to the base. This is directly demonstrated by live imaging in C. elegans. Reason: This is the core function of CHE-3, directly demonstrated by time-lapse microscopy showing that che-3 mutants completely lack retrograde IFT in cilia (PMID:10545497). This is among the best-characterized annotations for this gene. Supporting Evidence: PMID:10545497 Strikingly, over many hours of observation, we never saw retrograde IFT in cilia of che-3 mutants, in contrast to the robust transport that we consistently observed in wild-type worms. PMID:28479320 Cytoplasmic dynein-2 powers retrograde intraflagellar transport that is essential for cilium formation and maintenance.
GO:0000166 nucleotide binding	IEA GO_REF:0000043	ACCEPT	Summary: CHE-3 contains multiple AAA+ ATPase domains with P-loop nucleotide-binding motifs. Nucleotide binding is essential for motor function. Reason: Correct but overly general. CHE-3 has six AAA domains with P-loop motifs that bind ATP. The IEA annotation from UniProt keywords is accurate but the more specific ATP binding annotation is preferred.
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: CHE-3 is an AAA+ ATPase with multiple ATP-binding P-loop motifs. ATP binding and hydrolysis power the motor activity. Reason: Essential for motor function. UniProt annotates multiple ATP-binding sites at positions 115-122, 1637-1644, 1921-1928, 2226-2233, and 2565-2572. The protein belongs to the dynein heavy chain family of AAA+ ATPases. Supporting Evidence: PMID:28479320 By knocking the conserved ciliopathy-related mutations into the C. elegans dynein-2 heavy chain, we find that these mutations reduce its transport speed and frequency.
GO:0005856 cytoskeleton	IEA GO_REF:0000044	ACCEPT	Summary: CHE-3 associates with microtubules as a motor protein. The cytoskeleton annotation is broad but accurate. Reason: General but not incorrect. CHE-3 functions on microtubule tracks. More specific annotations to microtubule and axoneme are also present.
GO:0005874 microtubule	IEA GO_REF:0000043	ACCEPT	Summary: CHE-3 is a microtubule motor protein that walks along microtubule tracks. The annotation captures its association with microtubules. Reason: CHE-3 moves along axonemal microtubules during retrograde IFT. The K2935 mutation in the microtubule-binding domain abolishes microtubule binding (UniProt). Supporting Evidence: PMID:28479320 Disruption of the dynein-2 tail domain, light intermediate chain, or intraflagellar transport (IFT)-B complex abolishes dynein-2's ciliary localization
GO:0005929 cilium	IEA GO_REF:0000117	ACCEPT	Summary: CHE-3 is localized to and functions within sensory cilia. This is supported by direct experimental evidence. Reason: CHE-3 is expressed in and functions within sensory cilia (PMID:10790327, PMID:10545497). The IEA annotation is consistent with experimental data. The more specific annotation to non-motile cilium (IDA) provides additional precision. Supporting Evidence: PMID:10790327 This isoform of dynein shows temporally and spatially restricted expression in ciliated sensory neurons
GO:0007018 microtubule-based movement	IEA GO_REF:0000002	ACCEPT	Summary: CHE-3 is a microtubule motor that drives retrograde transport along axonemal microtubules. The annotation accurately captures this motor function. Reason: Accurate annotation. CHE-3 powers microtubule-based movement during retrograde IFT. The more specific term GO:0035721 (intraciliary retrograde transport) provides greater precision for the biological context. Supporting Evidence: PMID:10545497 Thus, we propose that the class DHC1b cytoplasmic dynein, CHE-3, is specifically responsible for the retrograde transport of the anterograde motor, kinesin-II, and its cargo within sensory cilia, but not within dendrites.
GO:0008569 minus-end-directed microtubule motor activity	IEA GO_REF:0000002	ACCEPT	Summary: Duplicate of IBA annotation for same term. CHE-3 has minus-end-directed motor activity as a dynein heavy chain. Reason: Same term as IBA annotation above. The IEA from InterPro correctly identifies CHE-3 as a minus-end-directed motor based on its dynein heavy chain domain structure.
GO:0030030 cell projection organization	IEA GO_REF:0000043	ACCEPT	Summary: CHE-3 is involved in organization of cilia, which are cell projections. The annotation is broad but appropriate. Reason: CHE-3 is required for proper cilium structure and organization. che-3 mutants have disorganized cilia with structural abnormalities. The more specific annotation to cilium assembly provides greater detail. Supporting Evidence: PMID:10790327 mutants show progressive developmental defects of the chemosensory cilia
GO:0030286 dynein complex	IEA GO_REF:0000120	ACCEPT	Summary: CHE-3 is a subunit of the cytoplasmic dynein 2 complex. The annotation is accurate but GO:0005868 (cytoplasmic dynein complex) is more specific. Reason: Accurate annotation. CHE-3 is the heavy chain of a dynein complex. The more specific cytoplasmic dynein complex annotation (IBA) is also present.
GO:0045505 dynein intermediate chain binding	IEA GO_REF:0000002	ACCEPT	Summary: Duplicate of IBA annotation. CHE-3 as a dynein heavy chain binds intermediate chains. Reason: Same term as IBA annotation. The IEA from InterPro correctly identifies this binding function based on dynein heavy chain domain structure.
GO:0050793 regulation of developmental process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: CHE-3 mutants have developmental phenotypes including dauer formation defects. However, this is an indirect consequence of ciliary defects affecting sensory signaling, not a direct role in developmental regulation. Reason: The annotation is not incorrect but represents downstream phenotypic effects rather than core function. CHE-3's role in development is indirect, mediated through its essential function in cilium-dependent sensory signaling that controls dauer formation. Supporting Evidence: PMID:1732156 Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia, thereby blocking chemosensation.
GO:0051959 dynein light intermediate chain binding	IEA GO_REF:0000002	ACCEPT	Summary: Duplicate of IBA annotation. Dynein heavy chains bind light intermediate chains. Reason: Same term as IBA annotation. Consistent with dynein complex architecture.
GO:0060170 ciliary membrane	IEA GO_REF:0000044	ACCEPT	Summary: CHE-3 is associated with the ciliary membrane as a peripheral membrane protein on the cytoplasmic side. UniProt annotates this subcellular location. Reason: UniProt annotation indicates CHE-3 is a peripheral membrane protein on the cytoplasmic side of the cilium membrane. This is consistent with its role in transporting cargo along axonemal microtubules beneath the ciliary membrane.
GO:0060271 cilium assembly	IEA GO_REF:0000117	ACCEPT	Summary: Duplicate of IBA annotation. CHE-3 is required for cilium assembly. Reason: Same term as IBA annotation. Well-supported by experimental evidence showing che-3 mutants have defective cilia formation.
GO:0043053 dauer entry	IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ...	KEEP AS NON CORE	Summary: che-3 mutants affect dauer entry through their effects on chemosensory signaling. The IGI annotation reflects genetic interactions with other dauer pathway genes. However, this is a downstream phenotype of ciliary defects. Reason: The annotation reflects real genetic data but represents an indirect effect of ciliary defects on chemosensory-dependent dauer signaling (PMID:1732156). CHE-3's role is in cilium function, not directly in dauer pathway signaling. Supporting Evidence: PMID:1732156 Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia, thereby blocking chemosensation.
GO:0060271 cilium assembly	IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ...	ACCEPT	Summary: Genetic evidence from epistasis analysis showing che-3 is in the same functional class as other cilium structure genes. This supports its role in cilium assembly. Reason: Consistent with other experimental evidence. The genetic analysis places che-3 with other genes required for cilium structure and function. Supporting Evidence: PMID:1732156 Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia
GO:0061066 positive regulation of dauer larval development	IMP PMID:6583682 A pheromone-induced developmental switch in Caenorhabditis e...	KEEP AS NON CORE	Summary: che-3 mutants are dauer-defective, meaning they fail to form dauer larvae under conditions that normally induce dauer formation. This is due to ciliary defects blocking chemosensory signaling. Reason: The phenotype is real but represents an indirect consequence of ciliary defects disrupting chemosensory signaling required for normal dauer induction. This is a pleiotropic effect, not a core function of CHE-3. Supporting Evidence: PMID:6583682 Dauer-defective mutants fail to respond to added pheromone
GO:0051959 dynein light intermediate chain binding	ISS PMID:10545497 Role of a class DHC1b dynein in retrograde transport of IFT ...	ACCEPT	Summary: ISS annotation based on similarity to mouse DHC1b. The binding to light intermediate chains is a conserved feature of cytoplasmic dynein 2 complexes. Reason: Consistent with IBA and IEA annotations for the same term. CHE-3 is orthologous to mouse Dync2h1 which binds light intermediate chains. UniProt confirms the complex includes light intermediate chains. Supporting Evidence: PMID:10545497 The Chlamydomonas DHC1b polypeptide shares high homology with the C. elegans CHE-3 protein
GO:1905515 non-motile cilium assembly	IMP PMID:10790327 CHE-3, a cytosolic dynein heavy chain, is required for senso...	ACCEPT	Summary: Direct experimental evidence that CHE-3 is required for assembly of non-motile sensory cilia. che-3 mutants have defective sensory cilia. Reason: This is the correct specific term for CHE-3's role in cilium assembly. C. elegans sensory cilia are non-motile, and CHE-3 is required for their formation and maintenance. Supporting Evidence: PMID:10790327 mutants show progressive developmental defects of the chemosensory cilia. These results are consistent with a role for this motor protein in the process of intraflagellar transport
GO:0097730 non-motile cilium	IDA PMID:10790327 CHE-3, a cytosolic dynein heavy chain, is required for senso...	ACCEPT	Summary: Direct experimental evidence of CHE-3 localization to non-motile sensory cilia. This is the appropriate cellular component term for C. elegans sensory cilia. Reason: Correct localization supported by direct experimental evidence. CHE-3 is expressed in and localizes to non-motile sensory cilia in C. elegans chemosensory neurons. Supporting Evidence: PMID:10790327 This isoform of dynein shows temporally and spatially restricted expression in ciliated sensory neurons
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway	IGI PMID:11677050 DAF-7/TGF-beta expression required for the normal larval dev...	MARK AS OVER ANNOTATED	Summary: The annotation reflects genetic placement of che-3 between daf-11 and daf-7 (TGF-beta) in the dauer signaling pathway. However, this is an indirect effect of ciliary defects on sensory signaling, not a direct role in TGF-beta regulation. Reason: The genetic interaction is real but the annotation implies a more direct role in TGF-beta signaling than warranted. CHE-3's effect on TGF-beta signaling is indirect, mediated through its essential role in cilium structure and chemosensory function. The paper states che-3 is "placed between daf-11 and daf-7" but this reflects sensory pathway architecture, not direct regulation of TGF-beta signaling. Supporting Evidence: PMID:11677050 cilium-related genes che-2 and che-3 are placed between daf-11 and daf-7, in the genetic pathway controlling dauer formation
GO:0008104 intracellular protein localization	IMP PMID:11290289 The C. elegans homolog of the murine cystic kidney disease g...	MODIFY	Summary: CHE-3 is required for proper localization of IFT proteins within cilia. In che-3 mutants, IFT particles accumulate at cilium tips. This reflects its role in retrograde transport of proteins. Reason: While not incorrect, the term is too general. CHE-3's role is specifically in retrograde IFT, which is a specialized form of intracellular transport. The term GO:0035721 (intraciliary retrograde transport) is more precise and already annotated. Proposed replacements: intraciliary retrograde transport Supporting Evidence: PMID:11290289 Overall, the data support a crucial role for osm-5 in a conserved ciliogenic pathway, most likely as a component of the IFT process.
GO:0003777 microtubule motor activity	ISS PMID:10790327 CHE-3, a cytosolic dynein heavy chain, is required for senso...	ACCEPT	Summary: CHE-3 has microtubule motor activity as a dynein heavy chain. This is the parent term of the more specific minus-end-directed microtubule motor activity. Reason: Accurate annotation based on sequence similarity to other dynein heavy chains. The more specific term GO:0008569 (minus-end-directed microtubule motor activity) is also annotated and provides greater precision. Supporting Evidence: PMID:10790327 Forward genetic screens using novel assays of nematode chemotaxis to soluble compounds identified three independent transposon-insertion mutations in the gene encoding the Caenorhabditis elegans dynein heavy chain (DHC) 1b isoform.
GO:0007635 chemosensory behavior	IMP PMID:10790327 CHE-3, a cytosolic dynein heavy chain, is required for senso...	KEEP AS NON CORE	Summary: che-3 mutants show defects in chemosensory behavior due to defective sensory cilia. This is a downstream phenotype of ciliary dysfunction. Reason: The phenotype is well-documented but represents an indirect consequence of ciliary defects. CHE-3 does not directly participate in chemosensory signal transduction; rather, its role in maintaining cilium structure is required for proper chemosensory function. Supporting Evidence: PMID:10790327 Forward genetic screens using novel assays of nematode chemotaxis to soluble compounds identified three independent transposon-insertion mutations in the gene encoding the Caenorhabditis elegans dynein heavy chain (DHC) 1b isoform.

Core Functions

CHE-3 is the motor protein that powers retrograde intraflagellar transport in sensory cilia. It moves IFT particles and their cargo from the cilium tip back toward the base. This is the primary and essential function of CHE-3.

Molecular Function:

minus-end-directed microtubule motor activity

Directly Involved In:

intraciliary retrograde transport

Cellular Locations:

non-motile cilium

In Complex:

cytoplasmic dynein complex

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10545497

Role of a class DHC1b dynein in retrograde transport of IFT motors and IFT raft particles along cilia, but not dendrites, in chemosensory neurons of living Caenorhabditis elegans.

CHE-3 is the C. elegans ortholog of Chlamydomonas DHC1b

"The Chlamydomonas DHC1b polypeptide shares high homology with the C. elegans CHE-3 protein"
CHE-3 drives retrograde transport specifically in cilia, not dendrites

"Thus, we propose that the class DHC1b cytoplasmic dynein, CHE-3, is specifically responsible for the retrograde transport of the anterograde motor, kinesin-II, and its cargo within sensory cilia, but not within dendrites."
che-3 mutants show complete loss of retrograde IFT with accumulation of cargo at cilium tips

"Strikingly, over many hours of observation, we never saw retrograde IFT in cilia of che-3 mutants, in contrast to the robust transport that we consistently observed in wild-type worms."
Anterograde IFT is unaffected in che-3 mutants

"In contrast, anterograde IFT proceeds normally in che-3 mutants."

PMID:10790327

CHE-3, a cytosolic dynein heavy chain, is required for sensory cilia structure and function in Caenorhabditis elegans.

CHE-3 is the DHC1b isoform expressed specifically in ciliated sensory neurons

"This isoform of dynein shows temporally and spatially restricted expression in ciliated sensory neurons"
che-3 mutants have progressive developmental defects of chemosensory cilia

"mutants show progressive developmental defects of the chemosensory cilia"
CHE-3 is required for intraflagellar transport and cilium structural integrity

"These results are consistent with a role for this motor protein in the process of intraflagellar transport"

PMID:11290289

The C. elegans homolog of the murine cystic kidney disease gene Tg737 functions in a ciliogenic pathway and is disrupted in osm-5 mutant worms.

OSM-5 is part of the conserved IFT process

"Overall, the data support a crucial role for osm-5 in a conserved ciliogenic pathway, most likely as a component of the IFT process."

PMID:11677050

DAF-7/TGF-beta expression required for the normal larval development in C. elegans is controlled by a presumed guanylyl cyclase DAF-11.

Cilium-related genes che-2 and che-3 are genetically placed in the dauer signaling pathway

"cilium-related genes che-2 and che-3 are placed between daf-11 and daf-7, in the genetic pathway controlling dauer formation"

PMID:1732156

Genetic analysis of chemosensory control of dauer formation in Caenorhabditis elegans.

che-3 is among nine genes causing structurally defective chemosensory cilia

"Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia, thereby blocking chemosensation."

PMID:6583682

A pheromone-induced developmental switch in Caenorhabditis elegans - Temperature-sensitive mutants reveal a wild-type temperature-dependent process.

Dauer-defective mutants fail to respond to dauer pheromone

"Dauer-defective mutants fail to respond to added pheromone"

PMID:28479320

Dynein-Driven Retrograde Intraflagellar Transport Is Triphasic in C. elegans Sensory Cilia.

Cytoplasmic dynein-2 powers retrograde IFT essential for cilium formation and maintenance

"Cytoplasmic dynein-2 powers retrograde intraflagellar transport that is essential for cilium formation and maintenance."
Ciliopathy-related mutations in dynein-2 heavy chain reduce transport speed and frequency

"By knocking the conserved ciliopathy-related mutations into the C. elegans dynein-2 heavy chain, we find that these mutations reduce its transport speed and frequency."

file:worm/che-3/che-3-deep-research-falcon.md

Deep research report on che-3

Suggested Experiments

Experiment: Live imaging of fluorescently tagged CHE-3 to directly visualize its movement pattern

Experiment: Mass spectrometry analysis of CHE-3 interacting proteins in C. elegans

Experiment: Structure-function analysis of individual AAA domains to determine their specific roles

📚 Additional Documentation

Deep Research Falcon

(che-3-deep-research-falcon.md)

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organism_full: Caenorhabditis elegans.
protein_family: Belongs to the dynein heavy chain family. .
protein_domains: AAA_6. (IPR035699); AAA_9. (IPR035706); AAA_lid_11. (IPR041658);
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q19542
Protein Description: RecName: Full=Cytoplasmic dynein 2 heavy chain 1; AltName: Full=Abnormal chemotaxis protein 3;
Gene Information: Name=che-3 {ECO:0000312|WormBase:F18C12.1}; ORFNames=F18C12.1 {ECO:0000312|WormBase:F18C12.1};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the dynein heavy chain family. .
Key Domains: AAA_6. (IPR035699); AAA_9. (IPR035706); AAA_lid_11. (IPR041658); AAA_lid_11_sf. (IPR042219); DHC. (IPR026983)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "che-3" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'che-3' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene che-3 (gene ID: che-3, UniProt: Q19542) in worm.

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.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q19542
Protein Description: RecName: Full=Cytoplasmic dynein 2 heavy chain 1; AltName: Full=Abnormal chemotaxis protein 3;
Gene Information: Name=che-3 {ECO:0000312|WormBase:F18C12.1}; ORFNames=F18C12.1 {ECO:0000312|WormBase:F18C12.1};
Organism (full): Caenorhabditis elegans.
Protein Family: Belongs to the dynein heavy chain family. .
Key Domains: AAA_6. (IPR035699); AAA_9. (IPR035706); AAA_lid_11. (IPR041658); AAA_lid_11_sf. (IPR042219); DHC. (IPR026983)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "che-3" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene che-3 (gene ID: che-3, UniProt: Q19542) in worm.

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.

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.

Plan and verification
- Identity check: che-3 in Caenorhabditis elegans encodes the dynein-2 (IFT-dynein) heavy chain, the ortholog of human DYNC2H1, matching UniProt Q19542. It is a dynein heavy chain family member with AAA+ ATPase modules, consistent with the listed domains. Organism: C. elegans. Stop criteria for symbol ambiguity not triggered; literature consistently assigns che-3 to dynein-2 heavy chain in C. elegans (non-motile sensory cilia) (jensen2018roleforintraflagellar pages 1-2, vuolo2020cytoplasmicdynein2at pages 1-2).

Executive summary
CHE-3 is the core heavy chain motor of the dynein-2 complex that powers retrograde intraflagellar transport (IFT) in C. elegans sensory cilia. It localizes to cilia and is essential for cilium maintenance, transition zone (TZ) gating, and clearance of periciliary and membrane proteins from the axoneme. Temperature-sensitive che-3 enables reversible, adult-onset perturbations revealing roles for dynein-2 in TZ assembly and ciliary homeostasis. Recent work “hot-wiring” dynein-2 by disabling autoinhibition shows IFT-A promotes dynein-2 coupling and initiation of retrograde motility. Quantitatively, che-3 loss reduces retrograde IFT frequency and velocity and shortens cilia; translationally, the human ortholog DYNC2H1 is a major skeletal ciliopathy gene (e.g., Jeune asphyxiating thoracic dystrophy), underscoring conserved function (jensen2018roleforintraflagellar pages 5-7, jensen2018roleforintraflagellar pages 1-2, goncalvessantos2023hotwiringdynein2uncovers pages 1-3, vuolo2020cytoplasmicdynein2at pages 1-2).

1) Key concepts and definitions
- Intraflagellar transport (IFT): Bidirectional movement of large “train” assemblies composed of IFT-B (anterograde) and IFT-A (retrograde-associated) complexes with cargoes along axonemal microtubules; kinesin-2 drives anterograde, dynein-2 drives retrograde transport. The BBSome stabilizes trains and contributes to membrane protein trafficking in the retrograde direction (JCS “At a glance” review) (vuolo2020cytoplasmicdynein2at pages 1-2).
- Dynein-2 (IFT dynein): A cytoplasmic dynein specialized for cilia; its heavy chain (CHE-3 in C. elegans) contains AAA+ ATPase modules and generates force for retrograde IFT. Autoinhibition keeps dynein-2 inactive during anterograde carriage until activation at/near the ciliary tip initiates retrograde motility (vuolo2020cytoplasmicdynein2at pages 1-2, goncalvessantos2023hotwiringdynein2uncovers pages 1-3).
- Transition zone (TZ): The ciliary gate at the ciliary base that controls entry/exit and maintains compartmentalization. IFT integrity influences TZ assembly and gating; dynein-2-mediated retrograde transport contributes to clearing mislocalized proteins from cilia (jensen2018roleforintraflagellar pages 5-7, jensen2018roleforintraflagellar pages 1-2).

2) Recent developments and latest research (2023–2024 priority)
- Hot-wiring dynein-2 (2023): CRISPR-engineered mutations that disable the conserved autoinhibitory “closed” conformation of CHE-3 in vivo reinstated retrograde movement even in IFT-A–deficient cilia, revealing that IFT-A promotes dynein-2 coupling to retrograde trains and initiation at the tip, and that multiple mechanisms restrain dynein-2 during anterograde IFT. Cilia length remained near wild type, indicating hot-wiring did not impair ciliogenesis (bioRxiv, May 2023) (goncalvessantos2023hotwiringdynein2uncovers pages 1-3).
- Transition zone–retrograde IFT interplay (preprint 2025, complements 2018 EMBO reports): Disrupting TZ components (e.g., mks-5 or nphp-4) can reduce accumulation of IFT/dynein-2 in retrograde-defective cilia and partially restore axoneme length by enabling passive diffusion and EV shedding as alternative clearance routes, indicating that a restrictive TZ exacerbates retrograde IFT failure. These findings refine the earlier 2018 discovery that IFT-dynein is required for proper TZ assembly and gating (bioRxiv, Oct 2025; EMBO reports, 2018) (decastro2025removalofthe pages 1-4, jensen2018roleforintraflagellar pages 5-7).
- Mechanistic perspective (2024): Synthesis of dynein-2 regulation highlights that the TZ barrier limits IFT train transit; weakening TZ (loss of NPHP-4 or MKS-5) increases IFT velocities across the TZ and can aid trains with reduced dynein-2 power, but complete TZ removal does not rescue nonmotile dynein-2 heavy chain mutants, indicating a minimal force requirement for retrograde IFT across the gate (2024 analysis) (rodrigues2024uncoveringthemechanisms pages 69-72, rodrigues2024uncoveringthemechanisms pages 112-115).

3) Primary function, localization, and pathways
- Primary function: CHE-3 (dynein-2 heavy chain) is the retrograde IFT motor. It carries IFT-A/IFT-B complexes and associated cargoes from the ciliary tip back to the base, clearing turnover products and maintaining ciliary composition and length. Dynein-2 works within polymeric IFT trains; the BBSome contributes to retrograde trafficking of membrane proteins (vuolo2020cytoplasmicdynein2at pages 1-2). Disruption of che-3 impairs retrograde transport while variably sparing anterograde IFT, producing stalled accumulations within cilia (jensen2018roleforintraflagellar pages 5-7, jensen2018roleforintraflagellar pages 1-2).
- Cellular localization: CHE-3 localizes to non-motile sensory cilia in C. elegans and functions on axonemal microtubules within the ciliary compartment, with critical roles at the tip (retrograde initiation) and at the transition zone (gate maintenance and clearance) (jensen2018roleforintraflagellar pages 5-7, vuolo2020cytoplasmicdynein2at pages 1-2).
- Pathway coupling and activation: During anterograde IFT, dynein-2 is carried in an autoinhibited conformation; at the ciliary tip, it is activated and coupled to retrograde trains. IFT-A promotes dynein-2 coupling and retrograde initiation. Disabling autoinhibition (“hot-wiring”) reenables retrograde movement in IFT-A–deficient cilia, indicating multiple restraints prevent premature activation during anterograde transport (goncalvessantos2023hotwiringdynein2uncovers pages 1-3).
- Transition zone and gating: Using a temperature-sensitive che-3 allele, dynein-2 was found essential for assembly of a functional TZ and for gating that prevents periciliary proteins from entering cilia. Restoring dynein-2 function in adults reverses ciliary structure, TZ protein localization, and gating defects, although reversibility declines with age (jensen2018roleforintraflagellar pages 5-7, jensen2018roleforintraflagellar pages 1-2).

4) Mutant phenotypes, quantitative data, and statistics
- Ciliary structure and IFT dynamics in ts-che-3: At restrictive temperature, ts-che-3 animals develop short, bulbous cilia with electron-dense, vesicle-like accumulations and abnormal membrane–microtubule connections. Quantitatively, cilia shorten over time: using BBS-7 as a reporter, cilium length decreased to ~3.8 µm after 18 hours and ~3.4 µm after 24 hours at restrictive temperature. Retrograde IFT is selectively reduced: the detectable retrograde-to-anterograde particle ratio fell to 0.273 in che-3(nx159ts) vs 0.926 in wild type (P < 0.001); retrograde velocities were slower while anterograde IFT could remain near wild type under some conditions (EMBO reports, 2018) (jensen2018roleforintraflagellar pages 5-7).
- Dye-filling and sensory phenotypes: The ts allele che-3(nx159ts) (Gly→Glu near the essential AAA2 Asp) shows a Dyf (dye-filling defective) phenotype upon upshift, consistent with disrupted ciliary function (jensen2018roleforintraflagellar pages 1-2).
- Autoinhibition/activation metrics: In hot-wired CHE-3, cilia lengths remained close to wild type (e.g., ~7.4 ± 0.61 µm vs 7.3 ± 0.64 µm), and retrograde motility occurred in IFT-A–deficient cilia without tug-of-war, indicating specific roles for IFT-A in coupling and initiation rather than basic motor function (bioRxiv, 2023) (goncalvessantos2023hotwiringdynein2uncovers pages 1-3).
- Transition zone modulation of retrograde defects: Removing TZ components reduces IFT/dynein-2 accumulation in retrograde-defective cilia and permits partial axoneme length rescue by passive diffusion and EV release; this emphasizes how gating strength shapes the outcome of dynein-2 dysfunction (bioRxiv, 2025; complements EMBO reports 2018) (decastro2025removalofthe pages 1-4, jensen2018roleforintraflagellar pages 5-7).

5) Current applications and real-world implementations
- Temporal control of dynein-2: The che-3(nx159ts) allele enables reversible adult-onset inhibition and restoration of dynein-2 function to dissect maintenance vs developmental roles in cilia, TZ assembly, and cargo gating (EMBO reports, 2018) (jensen2018roleforintraflagellar pages 5-7, jensen2018roleforintraflagellar pages 1-2).
- Mechanistic hot-wiring: Disabling dynein-2 autoinhibition in vivo provides a tool to probe stepwise coupling to IFT-A and turnaround at the tip, revealing checkpoints that prevent premature activation and suggesting strategies to modulate retrograde transport in disease models (bioRxiv, 2023) (goncalvessantos2023hotwiringdynein2uncovers pages 1-3).
- TZ manipulation: Genetic weakening of the TZ barrier illustrates potential avenues to mitigate retrograde IFT defects by enhancing diffusion/EV-based clearance, with caveats that full rescue requires sufficient dynein-2 force production (bioRxiv, 2025; EMBO reports, 2018) (decastro2025removalofthe pages 1-4, jensen2018roleforintraflagellar pages 5-7).

6) Expert opinions and authoritative synthesis
- The Journal of Cell Science “At a glance” review emphasizes dynein-2’s essential role in ciliary assembly/function, the coordination of IFT-A/B with kinesin-2 and dynein-2, and outstanding mechanistic issues around dynein-2 activation and regulation—all directly addressed by the 2018 and 2023–2024 C. elegans studies (vuolo2020cytoplasmicdynein2at pages 1-2).
- EMBO reports (2018) provided a paradigm shift by showing that retrograde IFT (dynein-2) supports not only retrograde transport but also TZ assembly and ciliary gating, revealing cross-talk between IFT and the ciliary gate (jensen2018roleforintraflagellar pages 5-7, jensen2018roleforintraflagellar pages 1-2).
- 2024 analysis underscores the concept of a “force threshold” for retrograde IFT across the TZ and the modulatory role of TZ composition (NPHP/MKS modules), reconciling phenotypes across IFT-A, dynein-2, and TZ mutants (rodrigues2024uncoveringthemechanisms pages 69-72, rodrigues2024uncoveringthemechanisms pages 112-115).

7) Translational relevance to human disease
- DYNC2H1 mutations cause skeletal ciliopathies such as Jeune asphyxiating thoracic dystrophy and related short-rib polydactyly syndromes; the C. elegans che-3 studies illuminate conserved mechanisms—retrograde transport, autoinhibition/activation, IFT-A coupling, and TZ gating—that likely underlie pathogenesis when disrupted in humans (vuolo2020cytoplasmicdynein2at pages 1-2, jensen2018roleforintraflagellar pages 1-2).

8) Limitations and open questions
- Outstanding issues include the precise molecular steps of dynein-2 tip activation, full composition of the worm dynein-2 complex and accessory chains in vivo, and how BBSome interfaces with dynein-2 under different signaling states. Preprints provide hypotheses (e.g., TZ removal enabling diffusion/EV-based clearance), but peer-reviewed confirmation and quantitative in vivo kinetics across neuron types remain needed (decastro2025removalofthe pages 1-4, goncalvessantos2023hotwiringdynein2uncovers pages 1-3, vuolo2020cytoplasmicdynein2at pages 1-2).

References with URLs and dates
- Jensen VL et al. Role for intraflagellar transport in building a functional transition zone. EMBO reports. Published Nov 2018. https://doi.org/10.15252/embr.201845862 (che-3 ts allele, TZ gating, reversible adult rescue, quantitative IFT metrics) (jensen2018roleforintraflagellar pages 5-7, jensen2018roleforintraflagellar pages 1-2).
- Gonçalves-Santos F et al. Hot-wiring dynein-2 uncovers roles for IFT-A in retrograde train assembly and motility. bioRxiv preprint. Posted May 2023. https://doi.org/10.1101/2023.05.10.539247 (autoinhibition, IFT-A coupling, retrograde initiation) (goncalvessantos2023hotwiringdynein2uncovers pages 1-3).
- De-Castro ARG et al. Removal of the Ciliary Gate Allows Axoneme Extension in the Absence of Retrograde IFT. bioRxiv preprint. Posted Oct 2025. https://doi.org/10.1101/2025.10.21.683645 (TZ removal enables diffusion/EV clearance in retrograde-defective cilia) (decastro2025removalofthe pages 1-4).
- Vuolo L et al. Cytoplasmic dynein-2 at a glance. Journal of Cell Science. Published Mar 2020. https://doi.org/10.1242/jcs.240614 (authoritative synthesis on dynein-2, IFT-A/B, BBSome, and disease) (vuolo2020cytoplasmicdynein2at pages 1-2).
- Rodrigues DRM. Uncovering the mechanisms regulating the essential roles of dynein-2 in cilia function. 2024 analysis/synthesis (TZ gate as a rate-limiting barrier; minimal force requirements; worm dynein-2 composition in vivo) (rodrigues2024uncoveringthemechanisms pages 69-72, rodrigues2024uncoveringthemechanisms pages 112-115).

Conclusion
CHE-3 encodes the dynein-2 heavy chain motor that powers retrograde IFT in C. elegans sensory cilia. It localizes to cilia and is essential for maintaining ciliary length and composition, for proper transition zone assembly and gating, and for clearing ciliary cargoes. Recent advances using temperature-sensitive che-3 and autoinhibition-disabling “hot-wiring” reveal mechanistic roles for IFT-A in dynein-2 coupling and initiation and for the transition zone in modulating outcomes of retrograde defects. Quantitative analyses document reductions in retrograde IFT frequency/velocity and time-dependent cilium shortening upon che-3 impairment. These conserved mechanisms link directly to human DYNC2H1 ciliopathies and provide a foundation for in vivo mechanistic and therapeutic exploration (jensen2018roleforintraflagellar pages 5-7, jensen2018roleforintraflagellar pages 1-2, goncalvessantos2023hotwiringdynein2uncovers pages 1-3, decastro2025removalofthe pages 1-4, vuolo2020cytoplasmicdynein2at pages 1-2).

References

(jensen2018roleforintraflagellar pages 1-2): Victor L Jensen, Nils J Lambacher, Chunmei Li, Swetha Mohan, Corey L Williams, Peter N Inglis, Bradley K Yoder, Oliver E Blacque, and Michel R Leroux. Role for intraflagellar transport in building a functional transition zone. EMBO reports, Nov 2018. URL: https://doi.org/10.15252/embr.201845862, doi:10.15252/embr.201845862. This article has 49 citations and is from a highest quality peer-reviewed journal.
(vuolo2020cytoplasmicdynein2at pages 1-2): Laura Vuolo, Nicola L. Stevenson, Aakash G. Mukhopadhyay, Anthony J. Roberts, and David J. Stephens. Cytoplasmic dynein-2 at a glance. Journal of Cell Science, Mar 2020. URL: https://doi.org/10.1242/jcs.240614, doi:10.1242/jcs.240614. This article has 39 citations and is from a domain leading peer-reviewed journal.
(jensen2018roleforintraflagellar pages 5-7): Victor L Jensen, Nils J Lambacher, Chunmei Li, Swetha Mohan, Corey L Williams, Peter N Inglis, Bradley K Yoder, Oliver E Blacque, and Michel R Leroux. Role for intraflagellar transport in building a functional transition zone. EMBO reports, Nov 2018. URL: https://doi.org/10.15252/embr.201845862, doi:10.15252/embr.201845862. This article has 49 citations and is from a highest quality peer-reviewed journal.
(goncalvessantos2023hotwiringdynein2uncovers pages 1-3): Francisco Gonçalves-Santos, Ana R. G. De-Castro, Diogo R. M. Rodrigues, Maria J. G. De-Castro, Reto Gassmann, Carla M. C. Abreu, and Tiago J. Dantas. Hot-wiring dynein-2 uncovers roles for ift-a in retrograde train assembly and motility. bioRxiv, May 2023. URL: https://doi.org/10.1101/2023.05.10.539247, doi:10.1101/2023.05.10.539247. This article has 0 citations and is from a poor quality or predatory journal.
(decastro2025removalofthe pages 1-4): Ana R. G. De-Castro, Maria J. G. De-Castro, Guus H. Haasnoot, Reto Gassmann, Erwin J. G. Peterman, Tiago J. Dantas, and Carla M. C. Abreu. Removal of the ciliary gate allows axoneme extension in the absence of retrograde ift. BioRxiv, Oct 2025. URL: https://doi.org/10.1101/2025.10.21.683645, doi:10.1101/2025.10.21.683645. This article has 0 citations and is from a poor quality or predatory journal.
(rodrigues2024uncoveringthemechanisms pages 69-72): DRM Rodrigues. Uncovering the mechanisms regulating the essential roles of dynein-2 in cilia function. Unknown journal, 2024.
(rodrigues2024uncoveringthemechanisms pages 112-115): DRM Rodrigues. Uncovering the mechanisms regulating the essential roles of dynein-2 in cilia function. Unknown journal, 2024.

Citations

jensen2018roleforintraflagellar pages 5-7
jensen2018roleforintraflagellar pages 1-2
decastro2025removalofthe pages 1-4
rodrigues2024uncoveringthemechanisms pages 69-72
rodrigues2024uncoveringthemechanisms pages 112-115
https://doi.org/10.15252/embr.201845862
https://doi.org/10.1101/2023.05.10.539247
https://doi.org/10.1101/2025.10.21.683645
https://doi.org/10.1242/jcs.240614
https://doi.org/10.15252/embr.201845862,
https://doi.org/10.1242/jcs.240614,
https://doi.org/10.1101/2023.05.10.539247,
https://doi.org/10.1101/2025.10.21.683645,

📄 View Raw YAML

id: Q19542
gene_symbol: che-3
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: CHE-3 is the C. elegans cytoplasmic dynein 2 heavy chain 1, 
  orthologous to human DYNC2H1 and Chlamydomonas DHC1b. It is an AAA+ ATPase 
  motor protein that powers retrograde intraflagellar transport (IFT) within 
  sensory cilia, moving IFT particles and cargo from the cilium tip back to the 
  base. CHE-3 is essential for the formation and maintenance of sensory cilia 
  structure in chemosensory neurons. Loss-of-function mutations cause 
  progressive developmental defects of chemosensory cilia, leading to defects in
  chemotaxis, osmotic avoidance, dye-filling capacity, and dauer formation. The 
  protein contains multiple AAA domains with P-loop nucleotide-binding motifs 
  and a stalk region for microtubule binding. CHE-3 specifically drives 
  retrograde transport in cilia but not in dendrites, where a different dynein 
  may function.
existing_annotations:
  - term:
      id: GO:0060294
      label: cilium movement involved in cell motility
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHE-3 is expressed in sensory cilia which are non-motile (9+0 
        structure) in C. elegans. The IBA annotation appears to derive from 
        phylogenetic inference from motile cilium orthologs in other species 
        (e.g., Drosophila, mouse). However, C. elegans sensory cilia lack the 
        outer dynein arms required for ciliary beating and cell motility.
      action: REMOVE
      reason: C. elegans sensory cilia are non-motile primary cilia-like 
        structures (PMID:10790327). CHE-3 functions in retrograde IFT, not in 
        ciliary motility. This annotation represents incorrect phylogenetic 
        transfer from organisms with motile cilia.
      supported_by:
        - reference_id: PMID:10790327
          supporting_text: This isoform of dynein shows temporally and spatially
            restricted expression in ciliated sensory neurons, and mutants show 
            progressive developmental defects of the chemosensory cilia.
        - reference_id: file:worm/che-3/che-3-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0097729
      label: 9+2 motile cilium
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: C. elegans sensory cilia have a modified non-motile structure, 
        not a 9+2 motile cilium. CHE-3 localizes to non-motile sensory cilia in 
        chemosensory neurons. The IBA annotation is based on orthologs that 
        localize to motile cilia in other organisms.
      action: REMOVE
      reason: CHE-3 is localized to non-motile sensory cilia in C. elegans 
        (PMID:10790327). The annotation to 9+2 motile cilium is incorrect for 
        this species. The IDA annotation to GO:0097730 (non-motile cilium) from 
        the same paper accurately captures the localization.
      supported_by:
        - reference_id: PMID:10790327
          supporting_text: These disruptions were mapped and cloned using a 
            newly developed PCR-based transposon display. The mutations were 
            demonstrated to be allelic to the che-3 genetic locus.
  - term:
      id: GO:0045505
      label: dynein intermediate chain binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Dynein heavy chains are known to interact with intermediate 
        chains to form functional dynein complexes. CHE-3 as a cytoplasmic 
        dynein 2 heavy chain would be expected to bind intermediate chains as 
        part of its role in the cytoplasmic dynein 2 complex. UniProt indicates 
        CHE-3 forms a homodimer and associates with light intermediate chains.
      action: ACCEPT
      reason: The IBA annotation is phylogenetically sound. Dynein heavy chains 
        characteristically bind intermediate chains to form the complete dynein 
        complex. UniProt notes that "The cytoplasmic dynein complex 2 is 
        probably composed by a heavy chain che-3 homodimer and a number of light
        intermediate chains."
      supported_by:
        - reference_id: PMID:10545497
          supporting_text: The Chlamydomonas DHC1b polypeptide shares high 
            homology with the C. elegans CHE-3 protein
  - term:
      id: GO:0051959
      label: dynein light intermediate chain binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHE-3 as a cytoplasmic dynein 2 heavy chain interacts with light 
        intermediate chains to form the functional IFT-dynein complex. This is a
        conserved feature of cytoplasmic dynein 2 complexes.
      action: ACCEPT
      reason: Well-supported by phylogeny and consistent with the known 
        architecture of cytoplasmic dynein 2 complexes. UniProt states the 
        complex includes light intermediate chains.
      supported_by:
        - reference_id: PMID:10545497
          supporting_text: The DHC1b class of dyneins is placed phylogenetically
            between the axonemal and cytoplasmic classes of DHC.
  - term:
      id: GO:0005868
      label: cytoplasmic dynein complex
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHE-3 is the heavy chain subunit of the cytoplasmic dynein 2 
        complex. The IBA annotation is phylogenetically sound and well-supported
        by the molecular characterization.
      action: ACCEPT
      reason: CHE-3 is the C. elegans ortholog of DHC1b/DYNC2H1, forming the 
        catalytic core of the cytoplasmic dynein 2 complex that drives 
        retrograde IFT (PMID:10545497).
      supported_by:
        - reference_id: PMID:10545497
          supporting_text: Thus, we propose that the class DHC1b cytoplasmic 
            dynein, CHE-3, is specifically responsible for the retrograde 
            transport of the anterograde motor, kinesin-II, and its cargo within
            sensory cilia, but not within dendrites.
  - term:
      id: GO:0060271
      label: cilium assembly
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHE-3 is required for proper cilium assembly and maintenance. 
        Loss of CHE-3 function results in shortened cilia with structural 
        abnormalities. This reflects its essential role in retrograde IFT, which
        is necessary for cilium formation.
      action: ACCEPT
      reason: Well-supported by experimental evidence. che-3 mutants have 
        defective cilia formation (PMID:10790327, PMID:28479320). The IBA 
        annotation is consistent with direct experimental data in C. elegans.
      supported_by:
        - reference_id: PMID:10790327
          supporting_text: mutants show progressive developmental defects of the
            chemosensory cilia. These results are consistent with a role for 
            this motor protein in the process of intraflagellar transport
        - reference_id: PMID:28479320
          supporting_text: Cytoplasmic dynein-2 powers retrograde intraflagellar
            transport that is essential for cilium formation and maintenance.
  - term:
      id: GO:0008569
      label: minus-end-directed microtubule motor activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHE-3 is a dynein heavy chain with AAA+ ATPase domains that 
        provide minus-end-directed microtubule motor activity. This is the 
        fundamental molecular function enabling retrograde IFT transport from 
        the cilium tip toward the base.
      action: ACCEPT
      reason: Core molecular function of CHE-3. Dyneins are minus-end-directed 
        motors, and CHE-3's role in retrograde transport demonstrates this 
        activity (PMID:10545497). The protein has conserved AAA+ ATPase domains 
        and P-loop motifs characteristic of dynein motors.
      supported_by:
        - reference_id: PMID:10545497
          supporting_text: To test the hypothesis that the minus end-directed 
            microtubule motor protein, cytoplasmic dynein, drives this 
            retrograde transport pathway, we visualized movement of kinesin-II 
            and its cargo along dendrites and cilia in a che-3 cytoplasmic 
            dynein mutant background
  - term:
      id: GO:0005930
      label: axoneme
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: CHE-3 is localized to and functions within the axoneme of sensory
        cilia, where it drives retrograde transport along axonemal microtubules.
      action: ACCEPT
      reason: CHE-3 moves along axonemal microtubules during retrograde IFT. The
        protein is observed within the ciliary axoneme and its activity is 
        specifically required there (PMID:10545497).
      supported_by:
        - reference_id: PMID:10545497
          supporting_text: observed an inhibition of retrograde transport in 
            cilia but not in dendrites. In contrast, anterograde IFT proceeds 
            normally in che-3 mutants.
  - term:
      id: GO:0035721
      label: intraciliary retrograde transport
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: This is the primary biological process function of CHE-3. The 
        protein powers retrograde intraflagellar transport, moving IFT particles
        from the cilium tip back to the base. This is directly demonstrated by 
        live imaging in C. elegans.
      action: ACCEPT
      reason: This is the core function of CHE-3, directly demonstrated by 
        time-lapse microscopy showing that che-3 mutants completely lack 
        retrograde IFT in cilia (PMID:10545497). This is among the 
        best-characterized annotations for this gene.
      supported_by:
        - reference_id: PMID:10545497
          supporting_text: Strikingly, over many hours of observation, we never 
            saw retrograde IFT in cilia of che-3 mutants, in contrast to the 
            robust transport that we consistently observed in wild-type worms.
        - reference_id: PMID:28479320
          supporting_text: Cytoplasmic dynein-2 powers retrograde intraflagellar
            transport that is essential for cilium formation and maintenance.
  - term:
      id: GO:0000166
      label: nucleotide binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: CHE-3 contains multiple AAA+ ATPase domains with P-loop 
        nucleotide-binding motifs. Nucleotide binding is essential for motor 
        function.
      action: ACCEPT
      reason: Correct but overly general. CHE-3 has six AAA domains with P-loop 
        motifs that bind ATP. The IEA annotation from UniProt keywords is 
        accurate but the more specific ATP binding annotation is preferred.
  - term:
      id: GO:0005524
      label: ATP binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: CHE-3 is an AAA+ ATPase with multiple ATP-binding P-loop motifs. 
        ATP binding and hydrolysis power the motor activity.
      action: ACCEPT
      reason: Essential for motor function. UniProt annotates multiple 
        ATP-binding sites at positions 115-122, 1637-1644, 1921-1928, 2226-2233,
        and 2565-2572. The protein belongs to the dynein heavy chain family of 
        AAA+ ATPases.
      supported_by:
        - reference_id: PMID:28479320
          supporting_text: By knocking the conserved ciliopathy-related 
            mutations into the C. elegans dynein-2 heavy chain, we find that 
            these mutations reduce its transport speed and frequency.
  - term:
      id: GO:0005856
      label: cytoskeleton
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: CHE-3 associates with microtubules as a motor protein. The 
        cytoskeleton annotation is broad but accurate.
      action: ACCEPT
      reason: General but not incorrect. CHE-3 functions on microtubule tracks. 
        More specific annotations to microtubule and axoneme are also present.
  - term:
      id: GO:0005874
      label: microtubule
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: CHE-3 is a microtubule motor protein that walks along microtubule
        tracks. The annotation captures its association with microtubules.
      action: ACCEPT
      reason: CHE-3 moves along axonemal microtubules during retrograde IFT. The
        K2935 mutation in the microtubule-binding domain abolishes microtubule 
        binding (UniProt).
      supported_by:
        - reference_id: PMID:28479320
          supporting_text: Disruption of the dynein-2 tail domain, light 
            intermediate chain, or intraflagellar transport (IFT)-B complex 
            abolishes dynein-2's ciliary localization
  - term:
      id: GO:0005929
      label: cilium
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHE-3 is localized to and functions within sensory cilia. This is
        supported by direct experimental evidence.
      action: ACCEPT
      reason: CHE-3 is expressed in and functions within sensory cilia 
        (PMID:10790327, PMID:10545497). The IEA annotation is consistent with 
        experimental data. The more specific annotation to non-motile cilium 
        (IDA) provides additional precision.
      supported_by:
        - reference_id: PMID:10790327
          supporting_text: This isoform of dynein shows temporally and spatially
            restricted expression in ciliated sensory neurons
  - term:
      id: GO:0007018
      label: microtubule-based movement
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: CHE-3 is a microtubule motor that drives retrograde transport 
        along axonemal microtubules. The annotation accurately captures this 
        motor function.
      action: ACCEPT
      reason: Accurate annotation. CHE-3 powers microtubule-based movement 
        during retrograde IFT. The more specific term GO:0035721 (intraciliary 
        retrograde transport) provides greater precision for the biological 
        context.
      supported_by:
        - reference_id: PMID:10545497
          supporting_text: Thus, we propose that the class DHC1b cytoplasmic 
            dynein, CHE-3, is specifically responsible for the retrograde 
            transport of the anterograde motor, kinesin-II, and its cargo within
            sensory cilia, but not within dendrites.
  - term:
      id: GO:0008569
      label: minus-end-directed microtubule motor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: Duplicate of IBA annotation for same term. CHE-3 has 
        minus-end-directed motor activity as a dynein heavy chain.
      action: ACCEPT
      reason: Same term as IBA annotation above. The IEA from InterPro correctly
        identifies CHE-3 as a minus-end-directed motor based on its dynein heavy
        chain domain structure.
  - term:
      id: GO:0030030
      label: cell projection organization
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: CHE-3 is involved in organization of cilia, which are cell 
        projections. The annotation is broad but appropriate.
      action: ACCEPT
      reason: CHE-3 is required for proper cilium structure and organization. 
        che-3 mutants have disorganized cilia with structural abnormalities. The
        more specific annotation to cilium assembly provides greater detail.
      supported_by:
        - reference_id: PMID:10790327
          supporting_text: mutants show progressive developmental defects of the
            chemosensory cilia
  - term:
      id: GO:0030286
      label: dynein complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: CHE-3 is a subunit of the cytoplasmic dynein 2 complex. The 
        annotation is accurate but GO:0005868 (cytoplasmic dynein complex) is 
        more specific.
      action: ACCEPT
      reason: Accurate annotation. CHE-3 is the heavy chain of a dynein complex.
        The more specific cytoplasmic dynein complex annotation (IBA) is also 
        present.
  - term:
      id: GO:0045505
      label: dynein intermediate chain binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: Duplicate of IBA annotation. CHE-3 as a dynein heavy chain binds 
        intermediate chains.
      action: ACCEPT
      reason: Same term as IBA annotation. The IEA from InterPro correctly 
        identifies this binding function based on dynein heavy chain domain 
        structure.
  - term:
      id: GO:0050793
      label: regulation of developmental process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: CHE-3 mutants have developmental phenotypes including dauer 
        formation defects. However, this is an indirect consequence of ciliary 
        defects affecting sensory signaling, not a direct role in developmental 
        regulation.
      action: KEEP_AS_NON_CORE
      reason: The annotation is not incorrect but represents downstream 
        phenotypic effects rather than core function. CHE-3's role in 
        development is indirect, mediated through its essential function in 
        cilium-dependent sensory signaling that controls dauer formation.
      supported_by:
        - reference_id: PMID:1732156
          supporting_text: Dauer-defective mutations in nine genes cause 
            structurally defective chemosensory cilia, thereby blocking 
            chemosensation.
  - term:
      id: GO:0051959
      label: dynein light intermediate chain binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: Duplicate of IBA annotation. Dynein heavy chains bind light 
        intermediate chains.
      action: ACCEPT
      reason: Same term as IBA annotation. Consistent with dynein complex 
        architecture.
  - term:
      id: GO:0060170
      label: ciliary membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: CHE-3 is associated with the ciliary membrane as a peripheral 
        membrane protein on the cytoplasmic side. UniProt annotates this 
        subcellular location.
      action: ACCEPT
      reason: UniProt annotation indicates CHE-3 is a peripheral membrane 
        protein on the cytoplasmic side of the cilium membrane. This is 
        consistent with its role in transporting cargo along axonemal 
        microtubules beneath the ciliary membrane.
  - term:
      id: GO:0060271
      label: cilium assembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Duplicate of IBA annotation. CHE-3 is required for cilium 
        assembly.
      action: ACCEPT
      reason: Same term as IBA annotation. Well-supported by experimental 
        evidence showing che-3 mutants have defective cilia formation.
  - term:
      id: GO:0043053
      label: dauer entry
    evidence_type: IGI
    original_reference_id: PMID:1732156
    review:
      summary: che-3 mutants affect dauer entry through their effects on 
        chemosensory signaling. The IGI annotation reflects genetic interactions
        with other dauer pathway genes. However, this is a downstream phenotype 
        of ciliary defects.
      action: KEEP_AS_NON_CORE
      reason: The annotation reflects real genetic data but represents an 
        indirect effect of ciliary defects on chemosensory-dependent dauer 
        signaling (PMID:1732156). CHE-3's role is in cilium function, not 
        directly in dauer pathway signaling.
      supported_by:
        - reference_id: PMID:1732156
          supporting_text: Dauer-defective mutations in nine genes cause 
            structurally defective chemosensory cilia, thereby blocking 
            chemosensation.
  - term:
      id: GO:0060271
      label: cilium assembly
    evidence_type: IGI
    original_reference_id: PMID:1732156
    review:
      summary: Genetic evidence from epistasis analysis showing che-3 is in the 
        same functional class as other cilium structure genes. This supports its
        role in cilium assembly.
      action: ACCEPT
      reason: Consistent with other experimental evidence. The genetic analysis 
        places che-3 with other genes required for cilium structure and 
        function.
      supported_by:
        - reference_id: PMID:1732156
          supporting_text: Dauer-defective mutations in nine genes cause 
            structurally defective chemosensory cilia
  - term:
      id: GO:0061066
      label: positive regulation of dauer larval development
    evidence_type: IMP
    original_reference_id: PMID:6583682
    review:
      summary: che-3 mutants are dauer-defective, meaning they fail to form 
        dauer larvae under conditions that normally induce dauer formation. This
        is due to ciliary defects blocking chemosensory signaling.
      action: KEEP_AS_NON_CORE
      reason: The phenotype is real but represents an indirect consequence of 
        ciliary defects disrupting chemosensory signaling required for normal 
        dauer induction. This is a pleiotropic effect, not a core function of 
        CHE-3.
      supported_by:
        - reference_id: PMID:6583682
          supporting_text: Dauer-defective mutants fail to respond to added 
            pheromone
  - term:
      id: GO:0051959
      label: dynein light intermediate chain binding
    evidence_type: ISS
    original_reference_id: PMID:10545497
    review:
      summary: ISS annotation based on similarity to mouse DHC1b. The binding to
        light intermediate chains is a conserved feature of cytoplasmic dynein 2
        complexes.
      action: ACCEPT
      reason: Consistent with IBA and IEA annotations for the same term. CHE-3 
        is orthologous to mouse Dync2h1 which binds light intermediate chains. 
        UniProt confirms the complex includes light intermediate chains.
      supported_by:
        - reference_id: PMID:10545497
          supporting_text: The Chlamydomonas DHC1b polypeptide shares high 
            homology with the C. elegans CHE-3 protein
  - term:
      id: GO:1905515
      label: non-motile cilium assembly
    evidence_type: IMP
    original_reference_id: PMID:10790327
    review:
      summary: Direct experimental evidence that CHE-3 is required for assembly 
        of non-motile sensory cilia. che-3 mutants have defective sensory cilia.
      action: ACCEPT
      reason: This is the correct specific term for CHE-3's role in cilium 
        assembly. C. elegans sensory cilia are non-motile, and CHE-3 is required
        for their formation and maintenance.
      supported_by:
        - reference_id: PMID:10790327
          supporting_text: mutants show progressive developmental defects of the
            chemosensory cilia. These results are consistent with a role for 
            this motor protein in the process of intraflagellar transport
  - term:
      id: GO:0097730
      label: non-motile cilium
    evidence_type: IDA
    original_reference_id: PMID:10790327
    review:
      summary: Direct experimental evidence of CHE-3 localization to non-motile 
        sensory cilia. This is the appropriate cellular component term for C. 
        elegans sensory cilia.
      action: ACCEPT
      reason: Correct localization supported by direct experimental evidence. 
        CHE-3 is expressed in and localizes to non-motile sensory cilia in C. 
        elegans chemosensory neurons.
      supported_by:
        - reference_id: PMID:10790327
          supporting_text: This isoform of dynein shows temporally and spatially
            restricted expression in ciliated sensory neurons
  - term:
      id: GO:0030512
      label: negative regulation of transforming growth factor beta receptor 
        signaling pathway
    evidence_type: IGI
    original_reference_id: PMID:11677050
    review:
      summary: The annotation reflects genetic placement of che-3 between daf-11
        and daf-7 (TGF-beta) in the dauer signaling pathway. However, this is an
        indirect effect of ciliary defects on sensory signaling, not a direct 
        role in TGF-beta regulation.
      action: MARK_AS_OVER_ANNOTATED
      reason: The genetic interaction is real but the annotation implies a more 
        direct role in TGF-beta signaling than warranted. CHE-3's effect on 
        TGF-beta signaling is indirect, mediated through its essential role in 
        cilium structure and chemosensory function. The paper states che-3 is 
        "placed between daf-11 and daf-7" but this reflects sensory pathway 
        architecture, not direct regulation of TGF-beta signaling.
      supported_by:
        - reference_id: PMID:11677050
          supporting_text: cilium-related genes che-2 and che-3 are placed 
            between daf-11 and daf-7, in the genetic pathway controlling dauer 
            formation
  - term:
      id: GO:0008104
      label: intracellular protein localization
    evidence_type: IMP
    original_reference_id: PMID:11290289
    review:
      summary: CHE-3 is required for proper localization of IFT proteins within 
        cilia. In che-3 mutants, IFT particles accumulate at cilium tips. This 
        reflects its role in retrograde transport of proteins.
      action: MODIFY
      reason: While not incorrect, the term is too general. CHE-3's role is 
        specifically in retrograde IFT, which is a specialized form of 
        intracellular transport. The term GO:0035721 (intraciliary retrograde 
        transport) is more precise and already annotated.
      proposed_replacement_terms:
        - id: GO:0035721
          label: intraciliary retrograde transport
      supported_by:
        - reference_id: PMID:11290289
          supporting_text: Overall, the data support a crucial role for osm-5 in
            a conserved ciliogenic pathway, most likely as a component of the 
            IFT process.
  - term:
      id: GO:0003777
      label: microtubule motor activity
    evidence_type: ISS
    original_reference_id: PMID:10790327
    review:
      summary: CHE-3 has microtubule motor activity as a dynein heavy chain. 
        This is the parent term of the more specific minus-end-directed 
        microtubule motor activity.
      action: ACCEPT
      reason: Accurate annotation based on sequence similarity to other dynein 
        heavy chains. The more specific term GO:0008569 (minus-end-directed 
        microtubule motor activity) is also annotated and provides greater 
        precision.
      supported_by:
        - reference_id: PMID:10790327
          supporting_text: Forward genetic screens using novel assays of 
            nematode chemotaxis to soluble compounds identified three 
            independent transposon-insertion mutations in the gene encoding the 
            Caenorhabditis elegans dynein heavy chain (DHC) 1b isoform.
  - term:
      id: GO:0007635
      label: chemosensory behavior
    evidence_type: IMP
    original_reference_id: PMID:10790327
    review:
      summary: che-3 mutants show defects in chemosensory behavior due to 
        defective sensory cilia. This is a downstream phenotype of ciliary 
        dysfunction.
      action: KEEP_AS_NON_CORE
      reason: The phenotype is well-documented but represents an indirect 
        consequence of ciliary defects. CHE-3 does not directly participate in 
        chemosensory signal transduction; rather, its role in maintaining cilium
        structure is required for proper chemosensory function.
      supported_by:
        - reference_id: PMID:10790327
          supporting_text: Forward genetic screens using novel assays of 
            nematode chemotaxis to soluble compounds identified three 
            independent transposon-insertion mutations in the gene encoding the 
            Caenorhabditis elegans dynein heavy chain (DHC) 1b isoform.
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning
      models
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:10545497
    title: Role of a class DHC1b dynein in retrograde transport of IFT motors 
      and IFT raft particles along cilia, but not dendrites, in chemosensory 
      neurons of living Caenorhabditis elegans.
    findings:
      - statement: CHE-3 is the C. elegans ortholog of Chlamydomonas DHC1b
        supporting_text: The Chlamydomonas DHC1b polypeptide shares high 
          homology with the C. elegans CHE-3 protein
      - statement: CHE-3 drives retrograde transport specifically in cilia, not 
          dendrites
        supporting_text: Thus, we propose that the class DHC1b cytoplasmic 
          dynein, CHE-3, is specifically responsible for the retrograde 
          transport of the anterograde motor, kinesin-II, and its cargo within 
          sensory cilia, but not within dendrites.
      - statement: che-3 mutants show complete loss of retrograde IFT with 
          accumulation of cargo at cilium tips
        supporting_text: Strikingly, over many hours of observation, we never 
          saw retrograde IFT in cilia of che-3 mutants, in contrast to the 
          robust transport that we consistently observed in wild-type worms.
      - statement: Anterograde IFT is unaffected in che-3 mutants
        supporting_text: In contrast, anterograde IFT proceeds normally in che-3
          mutants.
  - id: PMID:10790327
    title: CHE-3, a cytosolic dynein heavy chain, is required for sensory cilia 
      structure and function in Caenorhabditis elegans.
    findings:
      - statement: CHE-3 is the DHC1b isoform expressed specifically in ciliated
          sensory neurons
        supporting_text: This isoform of dynein shows temporally and spatially 
          restricted expression in ciliated sensory neurons
      - statement: che-3 mutants have progressive developmental defects of 
          chemosensory cilia
        supporting_text: mutants show progressive developmental defects of the 
          chemosensory cilia
      - statement: CHE-3 is required for intraflagellar transport and cilium 
          structural integrity
        supporting_text: These results are consistent with a role for this motor
          protein in the process of intraflagellar transport
  - id: PMID:11290289
    title: The C. elegans homolog of the murine cystic kidney disease gene Tg737
      functions in a ciliogenic pathway and is disrupted in osm-5 mutant worms.
    findings:
      - statement: OSM-5 is part of the conserved IFT process
        supporting_text: Overall, the data support a crucial role for osm-5 in a
          conserved ciliogenic pathway, most likely as a component of the IFT 
          process.
  - id: PMID:11677050
    title: DAF-7/TGF-beta expression required for the normal larval development 
      in C. elegans is controlled by a presumed guanylyl cyclase DAF-11.
    findings:
      - statement: Cilium-related genes che-2 and che-3 are genetically placed 
          in the dauer signaling pathway
        supporting_text: cilium-related genes che-2 and che-3 are placed between
          daf-11 and daf-7, in the genetic pathway controlling dauer formation
  - id: PMID:1732156
    title: Genetic analysis of chemosensory control of dauer formation in 
      Caenorhabditis elegans.
    findings:
      - statement: che-3 is among nine genes causing structurally defective 
          chemosensory cilia
        supporting_text: Dauer-defective mutations in nine genes cause 
          structurally defective chemosensory cilia, thereby blocking 
          chemosensation.
  - id: PMID:6583682
    title: A pheromone-induced developmental switch in Caenorhabditis elegans - 
      Temperature-sensitive mutants reveal a wild-type temperature-dependent 
      process.
    findings:
      - statement: Dauer-defective mutants fail to respond to dauer pheromone
        supporting_text: Dauer-defective mutants fail to respond to added 
          pheromone
  - id: PMID:28479320
    title: Dynein-Driven Retrograde Intraflagellar Transport Is Triphasic in C. 
      elegans Sensory Cilia.
    findings:
      - statement: Cytoplasmic dynein-2 powers retrograde IFT essential for 
          cilium formation and maintenance
        supporting_text: Cytoplasmic dynein-2 powers retrograde intraflagellar 
          transport that is essential for cilium formation and maintenance.
      - statement: Ciliopathy-related mutations in dynein-2 heavy chain reduce 
          transport speed and frequency
        supporting_text: By knocking the conserved ciliopathy-related mutations 
          into the C. elegans dynein-2 heavy chain, we find that these mutations
          reduce its transport speed and frequency.
  - id: file:worm/che-3/che-3-deep-research-falcon.md
    title: Deep research report on che-3
    findings: []
core_functions:
  - molecular_function:
      id: GO:0008569
      label: minus-end-directed microtubule motor activity
    description: CHE-3 is the motor protein that powers retrograde 
      intraflagellar transport in sensory cilia. It moves IFT particles and 
      their cargo from the cilium tip back toward the base. This is the primary 
      and essential function of CHE-3.
    directly_involved_in:
      - id: GO:0035721
        label: intraciliary retrograde transport
    locations:
      - id: GO:0097730
        label: non-motile cilium
    in_complex:
      id: GO:0005868
      label: cytoplasmic dynein complex
proposed_new_terms: []
suggested_questions:
  - question: Does CHE-3 have any function outside of sensory cilia, such as in 
      neuronal cell bodies?
  - question: Are there tissue-specific isoforms or regulatory mechanisms for 
      CHE-3 expression?
  - question: What is the precise mechanism of cargo release at the cilium base 
      during retrograde transport?
suggested_experiments:
  - description: Live imaging of fluorescently tagged CHE-3 to directly 
      visualize its movement pattern
  - description: Mass spectrometry analysis of CHE-3 interacting proteins in C. 
      elegans
  - description: Structure-function analysis of individual AAA domains to 
      determine their specific roles
tags:
  - caeel-ciliopathy

che-3

Gene Description

Existing Annotations Review

Core Functions

CHE-3 is the motor protein that powers retrograde intraflagellar transport in sensory cilia. It moves IFT particles and their cargo from the cilium tip back toward the base. This is the primary and essential function of CHE-3.

References

Suggested Questions for Experts

Suggested Experiments

Tags

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Citations

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