che-11

UniProt ID: P90757
Organism: Caenorhabditis elegans
Review Status: DRAFT
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Gene Description

CHE-11 is the Caenorhabditis elegans ortholog of human IFT140, a core subunit of intraflagellar transport complex A (IFT-A). It is a large (1437 aa) scaffolding protein built from two N-terminal WD40 Ξ²-propellers followed by an extended tetratricopeptide-repeat (TPR)/Ξ±-solenoid, with no catalytic domain. CHE-11 is expressed in ciliated sensory neurons and localizes to the non-motile sensory cilium, where it moves along the axoneme as part of the IFT machinery and concentrates at the ciliary base/basal body. As an IFT-A subunit, CHE-11 is required for retrograde (tip-to-base) intraflagellar transport and, because retrograde return of IFT components sustains the whole transport cycle, for building and maintaining a normal-length ciliary axoneme. Loss of CHE-11 produces truncated sensory cilia with disrupted IFT and a dye-filling-defective (Dyf) phenotype; because these cilia mediate chemo- and osmosensation, che-11 mutants show impaired chemosensory behaviours, altered dauer formation, and a range of downstream sensory-dependent phenotypes (extended lifespan, resistance to paraquat/oxidative stress and heat). Human IFT140 mutations cause skeletal ciliopathies and retinal dystrophy, underscoring a conserved role in cilium biogenesis.

Proposed New Ontology Terms

structural constituent of intraflagellar transport particle

Definition: The action of a protein that contributes to the structural integrity of an intraflagellar transport (IFT) particle (IFT-A or IFT-B subcomplex), for example by acting as a WD40/TPR scaffold that holds core IFT subunits together and enables their bidirectional transport along the ciliary axoneme, without itself catalyzing a biochemical reaction.

Parent term: structural molecule activity

Existing Annotations Review

GO Term Evidence Action Reason
GO:0035721 intraciliary retrograde transport
IBA
GO_REF:0000033
ACCEPT
Summary: As a core IFT-A subunit (IFT140 ortholog), CHE-11 is required for retrograde (tip-to-base) intraflagellar transport, the defining function of the IFT-A complex.
Reason: Represents the core biological process of the gene. Phylogenetic inference agrees with direct evidence that CHE-11 is an IFT-A ("Complex A") subunit essential for IFT.
Supporting Evidence:
PMID:27930654
which is a component of IFT-A essential for IFT
GO:0036064 ciliary basal body
IBA
GO_REF:0000033
ACCEPT
Summary: IFT-A subunits, including the IFT140 ortholog CHE-11, concentrate at and act from the ciliary base/basal body where IFT trains are assembled and turned around.
Reason: Consistent core localization for an IFT-A subunit; phylogenetically inferred and in line with the ciliary/base localization of IFT proteins.
GO:0005930 axoneme
IBA
GO_REF:0000033
ACCEPT
Summary: CHE-11 moves along the ciliary axoneme as part of the IFT machinery.
Reason: Core localization; IFT-A subunits traffic along the axoneme. Corroborated by direct observation that CHE-11 moves along C. elegans sensory cilia.
Supporting Evidence:
PMID:11301258
move at the same rate
GO:0030991 intraciliary transport particle A
IBA
GO_REF:0000033
ACCEPT
Summary: CHE-11 is a core subunit of the IFT-A complex, established by orthology to IFT140 and by direct identification as a Complex A polypeptide in the worm.
Reason: The defining cellular-component assignment for this gene; strongly supported by phylogeny and experiment.
Supporting Evidence:
PMID:11301258
two Complex A polypeptides
IEA
GO_REF:0000120
ACCEPT
Summary: Electronic annotation placing CHE-11 in the cilium; correct but less specific than the experimentally supported non-motile cilium term.
Reason: Correct ciliary localization. A more specific term (non-motile cilium) is also annotated by IDA; the general term is retained as consistent.
NAS
PMID:28479320
Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...
ACCEPT
Summary: ComplexPortal (CPX-1289) complex-based assertion that CHE-11, as an IFT-A subunit, localizes to the cilium.
Reason: Correct ciliary localization consistent with all other evidence; a more specific non-motile cilium term is also present.
GO:0030991 intraciliary transport particle A
NAS
PMID:28479320
Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...
ACCEPT
Summary: ComplexPortal complex-membership assertion that CHE-11 is part of IFT-A; redundant with, and corroborated by, the IBA and ISS IFT-A annotations.
Reason: Core complex membership; consistent across ComplexPortal, phylogeny and experimental identification as a Complex A polypeptide.
GO:0035721 intraciliary retrograde transport
NAS
PMID:28479320
Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...
ACCEPT
Summary: ComplexPortal assertion that the IFT-A complex containing CHE-11 mediates retrograde intraflagellar transport.
Reason: Core biological process for an IFT-A subunit; redundant with the IBA retrograde-transport annotation.
GO:0060271 cilium assembly
NAS
PMID:28479320
Dynein-Driven Retrograde Intraflagellar Transport Is Triphas...
ACCEPT
Summary: IFT-A function (via CHE-11) is required to build and maintain the ciliary axoneme; ComplexPortal complex-based assertion.
Reason: Core process, downstream of the direct IFT transport activity; corroborated by the truncated-cilia phenotype of che-11 mutants.
Supporting Evidence:
PMID:27930654
Although GFP::RAB-28 is observed within the truncated cilia of che-11 mutants, we could not detect processive movement of the GFP signals
GO:1905798 positive regulation of intraciliary anterograde transport
IMP
PMID:27930654
Whole-Organism Developmental Expression Profiling Identifies...
KEEP AS NON CORE
Summary: In che-11 mutants, processive (anterograde and retrograde) movement of the ciliary cargo RAB-28 is abolished, so CHE-11 is required for anterograde IFT of cargo.
Reason: CHE-11/IFT-A is mechanistically the retrograde module; the requirement for anterograde cargo transport is largely indirect (failure to recycle IFT components and truncated cilia). Real but peripheral to the core retrograde role, so retained as non-core.
Supporting Evidence:
PMID:27930654
Although GFP::RAB-28 is observed within the truncated cilia of che-11 mutants, we could not detect processive movement of the GFP signals
GO:1905801 positive regulation of intraciliary retrograde transport
IMP
PMID:27930654
Whole-Organism Developmental Expression Profiling Identifies...
ACCEPT
Summary: CHE-11 is required for retrograde intraflagellar transport of ciliary cargo; loss abolishes processive movement in cilia.
Reason: On-target with the core retrograde IFT function of IFT-A; CHE-11 is essential for IFT and its loss abolishes ciliary cargo transport.
Supporting Evidence:
PMID:27930654
which is a component of IFT-A essential for IFT
GO:0097730 non-motile cilium
IDA
PMID:17420466
Mutation of the MAP kinase DYF-5 affects docking and undocki...
ACCEPT
Summary: Direct imaging localizes CHE-11 to the non-motile sensory cilium.
Reason: Core cellular-component localization, directly observed. C. elegans sensory cilia are non-motile.
GO:0043053 dauer entry
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
KEEP AS NON CORE
Summary: che-11 is one of the cilium-structure genes whose mutations perturb the chemosensory control of dauer formation; genetic interactions with daf genes.
Reason: Dauer formation is a downstream, sensory-dependent behavioural output of cilium integrity, not a molecular/cellular function of CHE-11. Retained as a non-core pleiotropic phenotype.
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: Loss of che-11 gives structurally defective chemosensory cilia, indicating a requirement in building the sensory cilium.
Reason: Core process for an IFT-A subunit; the structurally defective cilia of che-11 mutants support a role in cilium assembly/integrity.
Supporting Evidence:
PMID:1732156
Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia, thereby blocking chemosensation
GO:0097730 non-motile cilium
IDA
PMID:11301258
An autosomal recessive polycystic kidney disease gene homolo...
ACCEPT
Summary: CHE-11 localizes to and moves within C. elegans sensory (non-motile) cilia.
Reason: Core cellular-component localization, directly observed as a Complex A polypeptide moving along sensory cilia.
Supporting Evidence:
PMID:11301258
two Complex A polypeptides
GO:0008340 determination of adult lifespan
IMP
PMID:14982934
Mutations in chemosensory cilia cause resistance to paraquat...
KEEP AS NON CORE
Summary: A che-11 nonsense mutant (mev-4) is long-lived; lifespan extension is a downstream consequence of impaired chemosensory (ciliary) signaling.
Reason: Adult-lifespan modulation is an indirect, sensory-dependent phenotype of losing ciliary function (the paper notes it is daf-16-dependent), not a molecular function of CHE-11. Retained as non-core.
Supporting Evidence:
PMID:14982934
One mutant named mev-4 was long-lived and showed cross-resistance to heat and Dyf phenotype
GO:0008340 determination of adult lifespan
IMP
PMID:19208769
Functional interactions between the ciliopathy-associated Me...
KEEP AS NON CORE
Summary: Second IMP for determination of adult lifespan from a transition-zone (MKS) study, using a che-11 variant.
Reason: Same downstream, sensory-dependent lifespan phenotype as the PMID:14982934 annotation; a pleiotropic consequence of ciliary dysfunction, not a core function.
GO:0030991 intraciliary transport particle A
ISS
PMID:14982934
Mutations in chemosensory cilia cause resistance to paraquat...
ACCEPT
Summary: Sequence-similarity annotation (from an IFT140 ortholog) placing CHE-11 in the IFT-A particle.
Reason: Core complex membership; consistent with the IBA and ComplexPortal IFT-A annotations and with experimental identification as a Complex A polypeptide.
GO:0042073 intraciliary transport
ISS
PMID:14982934
Mutations in chemosensory cilia cause resistance to paraquat...
ACCEPT
Summary: CHE-11 participates in intraflagellar transport, the general process subsuming its retrograde IFT-A role.
Reason: Core biological process; the more specific retrograde-transport term is also annotated. Corroborated by direct observation of CHE-11 IFT motility.
Supporting Evidence:
PMID:11301258
move at the same rate
GO:0006972 hyperosmotic response
IMP
PMID:14982934
Mutations in chemosensory cilia cause resistance to paraquat...
KEEP AS NON CORE
Summary: WB IMP annotation for hyperosmotic response, based on a che-11 mutant.
Reason: Osmotic-response phenotypes of che-11 mutants reflect loss of sensory (ciliary) function rather than a molecular role of CHE-11 in osmotic signaling. Retained as a non-core downstream phenotype.
GO:0006979 response to oxidative stress
IMP
PMID:14982934
Mutations in chemosensory cilia cause resistance to paraquat...
KEEP AS NON CORE
Summary: che-11 (mev-4) mutants are resistant to paraquat, an oxidative-stress generator.
Reason: Paraquat/oxidative-stress resistance is a downstream, sensory-dependent consequence of ciliary dysfunction (the authors conclude chemosensory neurons are a target of oxidative stress influencing longevity), not a molecular function of CHE-11.
Supporting Evidence:
PMID:14982934
We isolated mutants resistant to paraquat from nematode
GO:0009408 response to heat
IMP
PMID:14982934
Mutations in chemosensory cilia cause resistance to paraquat...
KEEP AS NON CORE
Summary: che-11 (mev-4) mutants show cross-resistance to heat.
Reason: Heat cross-resistance is a downstream, sensory-dependent phenotype of cilium loss, not a molecular function of CHE-11. Retained as non-core.
Supporting Evidence:
PMID:14982934
One mutant named mev-4 was long-lived and showed cross-resistance to heat and Dyf phenotype

Core Functions

Structural constituent of intraflagellar transport complex A (IFT-A) that drives retrograde (tip-to-base) intraflagellar transport along the sensory cilium. As the IFT140 ortholog, CHE-11 has no catalytic activity; it is a WD40 Ξ²-propeller + TPR/Ξ±-solenoid scaffold that helps hold the IFT-A particle together and is essential for IFT.

Supporting Evidence:

Required for assembly and structural integrity of the non-motile sensory cilium: IFT-A function via CHE-11 is needed to build and maintain the ciliary axoneme, and its loss produces truncated cilia with abolished processive ciliary transport.

Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • PMID:27930654
    Although GFP::RAB-28 is observed within the truncated cilia of che-11 mutants, we could not detect processive movement of the GFP signals
  • PMID:1732156
    Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia, thereby blocking chemosensation

References

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Suggested Questions for Experts

Q: Does CHE-11/IFT140 make direct, separable contributions to anterograde IFT, or is the anterograde defect in che-11 mutants entirely secondary to failed retrograde recycling and cilium truncation?

Q: What is the subunit-resolved architecture of the C. elegans IFT-A complex and the CHE-11 interface with dynein-2 during retrograde turnaround?

Suggested Experiments

Experiment: Cryo-EM of the intact worm IFT-A complex and of an IFT-A–dynein-2 assembly to map CHE-11 subunit contacts and the retrograde-turnaround interface.

Hypothesis: CHE-11/IFT140 occupies a defined structural position in IFT-A that mediates dynein-2 engagement for retrograde transport.

Experiment: Allele-specific, time-resolved IFT imaging using separation-of-function CHE-11 alleles to measure anterograde train formation before secondary cilium truncation, separating direct from indirect anterograde requirements.

Hypothesis: The anterograde-transport defect in che-11 mutants is an indirect consequence of failed retrograde recycling rather than a direct CHE-11 anterograde role.

Knowledge Gaps

What is not known β€” curated, literature-grounded statements of the open unknowns (the inverse of core functions).

Gap: CHE-11 has no molecular_function annotation and there is no adequate GO term to express one. Its role is to be a structural constituent of the IFT-A particle, but GO has no "structural constituent of the intraflagellar transport particle" molecular function term, so the gene reads as MF-dark despite a well-understood cellular and process-level role.

OPEN ONTOLOGYCURATION MF_DARK

What is known: It is firmly established that CHE-11 = IFT140 is a WD40+TPR scaffolding subunit of IFT-A with no catalytic domain, required for retrograde IFT and cilium assembly. What is missing is a molecular-function representation: the worm GOA record carries only cellular-component and biological-process terms and no molecular_function annotation at all.

Significance: This is the canonical "structural subunit" ontology gap shared across the IFT/ciliopathy gene set (e.g. its paralog dyf-2/WDR19): a mechanistically well-understood protein that cannot be annotated with an informative MF term, contributing to apparent molecular-function darkness.

What would resolve it: Develop/adopt a molecular-function term for a structural constituent of the IFT particle (analogous to "structural constituent of ribosome"), then annotate CHE-11 (and other IFT-A/IFT-B core subunits) to it.

Provenance (the field's own admissions):

Proposed term (ontology gap):

Gap: The subunit-resolved architecture of the worm IFT-A complex and the precise role of CHE-11 in the retrograde turnaround are not solved: how CHE-11 (IFT140) contacts the other IFT-A subunits (DAF-10/IFT122, DYF-2/WDR19, IFT-139, IFT-43, IFTA-1) and how IFT-A licenses dynein-2 for retrograde transport in C. elegans are inferred from orthology and proteomics, not from a worm structure.

OPEN BIOLOGY RESIDUAL_SUBGAP

What is known: IFT-A composition and the essentiality of CHE-11 for IFT are established genetically and biochemically, and the general IFT-A architecture (including the IFT140–IFT144/DYF-2 TPR heterodimer that forms the A1 core) has been solved by cryo-EM in other species. What remains incompletely understood is how the dynein-2 motor moves and is regulated within the cilium, how CHE-11/ IFT-A licenses retrograde turnaround in C. elegans, and the subunit-resolved arrangement of the worm complex specifically.

Significance: The retrograde turnaround and dynein-2 engagement is the load-bearing, incompletely understood step of the IFT cycle; resolving it would explain how IFT-A subunits such as CHE-11/IFT140 organize retrograde transport and how ciliopathy-causing IFT140 mutations disrupt it.

What would resolve it: Cryo-EM of the worm IFT-A complex (and of an IFT-A–dynein-2 assembly) plus structure-guided separation-of-function mutagenesis of CHE-11 with retrograde-IFT readouts.

Provenance (the field's own admissions):

Gap: Whether CHE-11 has any direct role in anterograde intraflagellar transport, as opposed to an indirect requirement, is unresolved. che-11 mutants lose both anterograde and retrograde processive movement of ciliary cargo, but IFT-A is mechanistically the retrograde module, so the anterograde effect may be a secondary consequence of failed IFT-component recycling and truncated cilia.

OPEN BIOLOGYCURATION BP_DARK

What is known: It is established that loss of CHE-11 abolishes processive ciliary transport of cargo (e.g. RAB-28) in both directions and that IFT-A powers retrograde IFT; what is not separated is a direct CHE-11 contribution to anterograde train formation versus an indirect downstream effect.

Significance: Distinguishing direct from indirect anterograde requirement determines whether the "positive regulation of intraciliary anterograde transport" annotation reflects a genuine CHE-11 activity or a system-level consequence, affecting how IFT-A subunits are modelled in ciliary transport.

What would resolve it: Time-resolved, allele-specific IFT imaging (separation-of-function CHE-11 alleles) that measures anterograde train formation before secondary cilium truncation, distinguishing a direct contribution from an indirect effect.

Provenance (the field's own admissions):

Deep Research

Falcon

(che-11-deep-research-falcon.md)

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Notes

(che-11-notes.md)

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