che-3

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.

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.

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."

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.

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).

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.

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.

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).

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.

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.

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.

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. [2026-08 SL project re-review] Uninformative parent from the UniProt subcellular-location pipeline. The sole source for this annotation is GO_REF:0000044 (UniProtKB-SubCell), and the gene already carries strictly more specific term(s) from independent evidence, namely GO:0005868 cytoplasmic dynein complex (IBA), GO:0005930 axoneme (IBA), and GO:0005874 microtubule. The term is not false; it is an under-specified location that adds no information over what is already annotated, which is the dominant failure mode of the SL pipeline (see projects/SL.md). Marked over-annotated rather than MODIFY because the more precise term is already present, so there is nothing to replace it with.

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).

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.

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.

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.

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.

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.

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.

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.

Summary: Duplicate of IBA annotation. Dynein heavy chains bind light intermediate chains.

Reason: Same term as IBA annotation. Consistent with dynein complex architecture.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.