CHE-13 is the Caenorhabditis elegans ortholog of human IFT57 (also called HIPPI; Chlamydomonas IFT57) and is a structural subunit of the intraflagellar transport complex B (IFT-B). Intraflagellar transport is the bidirectional, microtubule-motor-driven movement of large multiprotein particles that build and maintain cilia: kinesin-2 motors carry IFT-B particles and their ciliary-precursor cargo anterogradely from the ciliary base to the tip, and cytoplasmic dynein-2 returns them retrogradely. CHE-13/IFT57 is itself a component (and moving cargo) of the IFT-B particle rather than an enzyme; it has no known catalytic activity and contributes to assembly and integrity of the IFT-B complex, in part through a C-terminal coiled-coil. In C. elegans, che-13 is expressed in ciliated sensory neurons under control of the RFX transcription factor DAF-19, and the protein concentrates at the ciliary base (basal body, transition zone) and moves along the sensory (non-motile) ciliary axoneme, as expected for an IFT protein. CHE-13 is required to build the ciliary axoneme: loss-of-function mutants retain normal transition zones but have severely truncated axonemes with ectopically assembled doublet microtubules, and they mislocalize other IFT-B proteins such as OSM-5 and OSM-6. Because the 60 ciliated sensory neurons mediate chemosensation, osmotic avoidance and dauer-pathway signaling, che-13 mutants are broadly defective in these sensory behaviors as a downstream consequence of lacking functional cilia, and are dye-filling defective. IFT57 is conserved from algae to humans, and the IFT pathway it serves is central to the biology of ciliopathies.
Definition: A structural molecule activity in which a protein acts as a structural subunit of an intraflagellar transport (IFT) particle (IFT-A or IFT-B), contributing to the assembly and integrity of the particle that is trafficked along the ciliary axoneme by kinesin-2 and dynein-2 motors.
Justification: CHE-13/IFT57 and its IFT-B/IFT-A paralogs act as structural subunits of the IFT particle, a role currently expressible only as the generic GO:0005198 structural molecule activity. A dedicated MF term would capture the shared function of IFT structural subunits.
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030992 intraciliary transport particle B | IBA GO_REF:0000033 | ACCEPT | Summary: CHE-13/IFT57 is a structural subunit of the IFT-B particle; this is the single most important annotation for the gene, supported by orthology to IFT57 and by ComplexPortal (CPX-1290). Reason: Core molecular role. CHE-13 is the C. elegans IFT57 ortholog and a member of Intraflagellar transport complex B; phylogenetic inference agrees with the direct C. elegans data. Supporting Evidence: PMID:12651157 loss of che-13 differentially affects the localization of two known IFT complex B proteins, OSM-5 and OSM-6, implying that CHE-13 functions as part of this complex. |
| GO:0042073 intraciliary transport | IBA GO_REF:0000033 | ACCEPT | Summary: As an IFT-B subunit and moving IFT cargo, CHE-13 is directly involved in intraciliary transport. Reason: Core biological process. Fluorescent CHE-13 moves along the axoneme as an IFT protein and is part of the transported IFT-B particle. Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:0005929 cilium | IBA GO_REF:0000033 | ACCEPT | Summary: CHE-13 localizes to and functions within the cilium; phylogenetic inference agrees with direct C. elegans localization data. Reason: Cilium localization is directly supported (CHE-13 concentrates at the ciliary base and moves along the axoneme) and is a core aspect of che-13 function. Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:0005815 microtubule organizing center | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically propagated MTOC localization. In C. elegans the directly demonstrated site is the ciliary basal body, which is a specialized (docked, modified centriole) microtubule organizing center. Reason: Not wrong but generic; the experimentally supported location is the more specific ciliary basal body (GO:0036064). Retained as a non-core, orthology-based location rather than removed. |
| GO:1905515 non-motile cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: CHE-13 is required to build the sensory (non-motile) ciliary axoneme; phylogenetic inference is corroborated by the loss-of-function ultrastructural phenotype. Reason: Core process, appropriately specific (C. elegans sensory cilia are non-motile). che-13 mutants have severely truncated axonemes. Supporting Evidence: PMID:2428682 The cilia in che-13 (e1805), osm-1 (p808), osm-5 (p813), and osm-6 (p811) mutants have normal transition zones and severely shortened axonemes. |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Phylogenetically propagated Golgi localization from the IFT57/HIPPI family. There is no experimental support for a Golgi pool of CHE-13 in C. elegans; the protein's demonstrated sites are the ciliary base, basal body, transition zone and axoneme. Reason: Over-propagated IBA. IFT57/HIPPI family members have varied non-ciliary associations, but CHE-13's directly observed localization is entirely ciliary. No C. elegans evidence places CHE-13 in the Golgi. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000410691 · IFT57/HIPPI family node SUPPORTS SOURCE BUT NOT TARGET Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:0005930 axoneme | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping to axoneme, consistent with the direct C. elegans IDA localization data. Reason: Core ciliary localization; CHE-13 moves along the axoneme and is directly observed there (corroborated by IDA in PMID:12651157/18337471). Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:0005929 cilium | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal (CPX-1290) statement that CHE-13 localizes to the cilium, consistent with direct experimental data. Reason: Core ciliary localization; corroborated by IDA/IBA evidence. 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:0030992 intraciliary transport particle B | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal assertion of CHE-13 membership in IFT particle B, the core structural annotation, based on the C. elegans IFT-B complex identified by mass spectrometry. Reason: Core molecular role, redundant with and reinforcing the IBA/IDA IFT-B membership annotations. 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:0042073 intraciliary transport | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal statement of IFT-B involvement in intraciliary transport. Reason: Core process consistent with CHE-13 being a transported IFT-B subunit. 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:0060271 cilium assembly | NAS PMID:28479320 Dynein-Driven Retrograde Intraflagellar Transport Is Triphas... | ACCEPT | Summary: ComplexPortal statement of IFT-B involvement in cilium assembly. Reason: Core process; redundant with the IMP/IGI cilium-assembly annotations. The non-motile cilium assembly child term (GO:1905515) is the most specific form for C. elegans. Supporting Evidence: PMID:2428682 The cilia in che-13 (e1805), osm-1 (p808), osm-5 (p813), and osm-6 (p811) mutants have normal transition zones and severely shortened axonemes. |
| GO:0060271 cilium assembly | IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | ACCEPT | Summary: Genetic-interaction evidence placing che-13 among cilium-structure genes required for chemosensory cilium function in the dauer pathway. Reason: Core process; che-13 is one of the cilium-structure genes whose mutation gives structurally defective chemosensory cilia. Supporting Evidence: PMID:1732156 Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia, thereby blocking chemosensation. |
| GO:0003674 molecular_function | ND GO_REF:0000015 | KEEP AS NON CORE | Summary: Root-level placeholder recording that no specific molecular function had been assigned at the time of annotation. Reason: Retained as the standard ND placeholder. A subunit-specific molecular function (structural molecule activity within IFT-B) is now proposed as a NEW annotation and in core_functions; no catalytic activity is known or expected for this scaffolding subunit. |
| GO:0005198 structural molecule activity | IBA GO_REF:0000033 | NEW | Summary: CHE-13/IFT57 has no catalytic activity; as an IFT-B subunit its molecular function is best captured as a subunit-specific structural molecule activity. Reason: Proposed new molecular-function annotation reflecting CHE-13's role as a structural subunit of the IFT-B particle (the current GOA carries only the ND root MF for this gene). This IBA/GO_REF:0000033 evidence pairing does NOT currently exist in the GOA export; it is the expected phylogenetic evidence basis if the annotation were made (IFT57 orthologues across species are IFT-B structural subunits). Ideally a more specific 'structural constituent of intraflagellar transport particle' term (see proposed_new_terms) would be used. Supporting Evidence: PMID:12651157 loss of che-13 differentially affects the localization of two known IFT complex B proteins, OSM-5 and OSM-6, implying that CHE-13 functions as part of this complex. |
| GO:0005930 axoneme | IDA PMID:12651157 Identification of CHE-13, a novel intraflagellar transport p... | ACCEPT | Summary: CHE-13 is directly observed moving along the ciliary axoneme. Reason: Core ciliary localization directly demonstrated by fluorescent-tagged CHE-13. Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:0030992 intraciliary transport particle B | IDA PMID:17314406 Sensory ciliogenesis in Caenorhabditis elegans: assignment o... | ACCEPT | Summary: che-13 is assigned to the IFT subcomplex B module based on in vivo transport and phenotypic profiling. Reason: Core molecular role; direct assignment of che-13 to the IFT-B module. Supporting Evidence: PMID:17314406 the C. elegans IFT machinery has a modular design, consisting of modules IFT-subcomplex A, IFT-subcomplex B, and a BBS protein complex |
| GO:0035720 intraciliary anterograde transport | IEP PMID:12651157 Identification of CHE-13, a novel intraflagellar transport p... | ACCEPT | Summary: CHE-13 moves anterogradely along the axoneme as an IFT-B particle component. Reason: Core process. Directly reflects the observed IFT movement of tagged CHE-13 from the ciliary base toward the tip. Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:0035721 intraciliary retrograde transport | IEP PMID:12651157 Identification of CHE-13, a novel intraflagellar transport p... | ACCEPT | Summary: As an IFT-B particle component, CHE-13 is also recycled retrogradely along the axoneme. Reason: Core process. IFT-B particles (including CHE-13) are carried bidirectionally; retrograde recycling is part of the IFT cycle. Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:1905515 non-motile cilium assembly | IMP PMID:2428682 Mutant sensory cilia in the nematode Caenorhabditis elegans. | ACCEPT | Summary: che-13 mutants fail to build full sensory (non-motile) cilia; this is the most precise cilium-assembly term for the worm's sensory cilia. Reason: Core process, and appropriately specific. Directly supported by the ultrastructural phenotype (severely shortened axonemes). Supporting Evidence: PMID:2428682 The cilia in che-13 (e1805), osm-1 (p808), osm-5 (p813), and osm-6 (p811) mutants have normal transition zones and severely shortened axonemes. |
| GO:0035869 ciliary transition zone | IDA PMID:12651157 Identification of CHE-13, a novel intraflagellar transport p... | ACCEPT | Summary: CHE-13 is directly localized at/through the ciliary transition zone as it moves between the ciliary base and the axoneme. Reason: Core localization consistent with IFT trafficking through the transition zone. Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:0036064 ciliary basal body | IDA PMID:22922713 The BBSome controls IFT assembly and turnaround in cilia. | ACCEPT | Summary: CHE-13 localizes to the ciliary basal body, where IFT particles assemble before entering the cilium. Reason: Core localization at the site of IFT assembly; consistent with CHE-13 concentrating at the ciliary base. The MGI reference (PMID:22922713) is a DYF-2/BBSome paper that does not name che-13, but basal-body localization is independently established for CHE-13 and the experimental annotation is not overruled. Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:0005930 axoneme | IDA PMID:18337471 Functional redundancy of the B9 proteins and nephrocystins i... | ACCEPT | Summary: A second WormBase IDA supporting CHE-13 axoneme localization. Reason: Core ciliary localization; redundant with the PMID:12651157 axoneme IDA. The cited B9/nephrocystin paper does not foreground che-13, but axoneme localization is well established and the annotation is not overruled. Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:0008104 intracellular protein localization | IMP PMID:16957054 Caenorhabditis elegans DYF-2, an orthologue of human WDR19, ... | MODIFY | Summary: che-13 loss-of-function mislocalizes the IFT-B proteins OSM-5 and OSM-6, i.e. CHE-13 is required for delivering/localizing ciliary proteins. The generic "intracellular protein localization" term understates this; the specific process is protein localization to the cilium. Reason: The evidence (che-13 mutant mislocalizes IFT-B proteins into cilia) supports a more specific and informative term. Replace the generic GO:0008104 with GO:0061512 protein localization to cilium. Proposed replacements: protein localization to cilium Supporting Evidence: PMID:12651157 loss of che-13 differentially affects the localization of two known IFT complex B proteins, OSM-5 and OSM-6, implying that CHE-13 functions as part of this complex. |
| GO:0036064 ciliary basal body | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of basal-body localization from the mouse IFT57 ortholog (UniProtKB:Q8BXG3), consistent with the direct C. elegans data. Reason: Core localization; redundant with the IDA basal-body annotation and consistent with CHE-13 concentrating at the ciliary base. Supporting Evidence: PMID:12651157 concentrates at the base of cilia and moves along the axoneme as expected for an IFT protein |
| GO:0007635 chemosensory behavior | IMP PMID:2428682 Mutant sensory cilia in the nematode Caenorhabditis elegans. | KEEP AS NON CORE | Summary: che-13 mutants are chemosensory-defective (dye-filling defective) because their chemosensory cilia are truncated; this is a downstream consequence of defective cilia, not a direct signalling role of CHE-13. Reason: Indirect, downstream sensory phenotype of ciliary loss rather than a core molecular/biological function of CHE-13. Retained (curator IMP) but marked non-core. Supporting Evidence: PMID:2428682 Mutations in 14 genes prevent dye uptake and disrupt chemosensory behaviors. |
Loading supporting content…
Download this section (compressed HTML)Q: Which IFT-B subunits does CHE-13/IFT57 directly contact in C. elegans, and is the C-terminal coiled-coil required for those contacts?
Suggested experts: Oliver E. Blacque
Q: Do the two che-13 splice isoforms (a/b) have distinct expression or function in ciliated sensory neurons?
Experiment: Perform in vivo proximity labeling (TurboID) with full-length and coiled-coil-deleted CHE-13 expressed in ciliated neurons, followed by mass spectrometry, to map region-specific IFT-B interaction partners.
Hypothesis: CHE-13/IFT57 bridges specific IFT-B subunits via its C-terminal coiled-coil, and disrupting this region selectively destabilizes part of IFT-B.
Type: proximity labeling / interaction mapping
Experiment: Use live imaging of tagged tubulin and IFT-B markers (e.g. OSM-6) in che-13 partial loss-of-function backgrounds to quantify anterograde cargo delivery versus transition-zone integrity.
Hypothesis: The truncated axoneme of che-13 mutants reflects failure to deliver axonemal cargo by IFT-B rather than a transition-zone defect.
Type: live-cell imaging
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The specific intra-complex protein contacts of CHE-13/IFT57 within the C. elegans IFT-B particle have not been experimentally mapped. In vertebrates IFT57 sits in the peripheral IFT-B1 region and helps couple IFT-B to the IFT-A/dynein-2 machinery, but which IFT-B subunits CHE-13 directly contacts in the worm, and whether its C-terminal coiled-coil versus its disordered N-terminal/central segments mediate these contacts, is undetermined.
OPEN BIOLOGYONTOLOGY MF_DARK
What is known: It is firmly established that CHE-13 is an IFT-B/IFT57 structural subunit that concentrates at the ciliary base, moves bidirectionally by IFT along the axoneme, is required for axoneme assembly, and is needed for proper localization of other IFT-B proteins (OSM-5, OSM-6).
Significance: Defining CHE-13's specific IFT-B contacts would explain how the IFT-B particle is built in vivo and how the IFT57 orthologue contributes to IFT-B integrity and ciliopathy-relevant IFT defects.
What would resolve it: In vivo proximity labeling (BioID/TurboID) or cross-linking mass spectrometry of tagged CHE-13 in ciliated neurons, plus structure determination of the C. elegans IFT-B subcomplex, paired with an ontology term for structural constituent of the IFT particle.
Provenance (the field's own admissions):
Proposed term (ontology gap):
Gap: It is not resolved whether the severely truncated axoneme of che-13 mutants reflects failure to deliver specific axonemal cargo (e.g. tubulin or motility- related proteins) versus a general loss of IFT-B particle integrity that mislocalizes the whole complex. The che-13 mutant phenotype (short axonemes; OSM-5/OSM-6 mislocalization) is consistent with either mechanism.
OPEN BIOLOGY MF_DARK
What is known: che-13 is required for axoneme assembly and for proper localization of other IFT-B proteins; UniProt notes a possible role in ciliary entrance/transport of specific cargo, but no direct CHE-13 cargo-selection activity has been demonstrated.
Significance: Distinguishing a cargo-delivery role from a particle-integrity role would clarify whether IFT57/CHE-13 has any cargo-specific function beyond scaffolding IFT-B.
What would resolve it: Separation-of-function alleles or domain deletions of che-13 with live imaging of tagged axonemal cargo (tubulin) and IFT-B markers to test whether specific cargo delivery can be uncoupled from IFT-B assembly.
Provenance (the field's own admissions):
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)