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
GO:0005929 cilium	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.
GO:0005929 cilium	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 β-propeller + TPR/α-solenoid scaffold that helps hold the IFT-A particle together and is essential for IFT.

Molecular Function:

structural molecule activity

Directly Involved In:

intraciliary retrograde transport intraciliary transport

Cellular Locations:

non-motile cilium

In Complex:

intraciliary transport particle A

Supporting Evidence:

PMID:11301258
two Complex A polypeptides
PMID:27930654
which is a component of IFT-A essential for IFT

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:

cilium assembly

Cellular Locations:

non-motile cilium

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

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:11301258

An autosomal recessive polycystic kidney disease gene homolog is involved in intraflagellar transport in C. elegans ciliated sensory neurons.

PMID:14982934

Mutations in chemosensory cilia cause resistance to paraquat in nematode Caenorhabditis elegans.

PMID:1732156

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

PMID:17420466

Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans.

PMID:19208769

Functional interactions between the ciliopathy-associated Meckel syndrome 1 (MKS1) protein and two novel MKS1-related (MKSR) proteins.

PMID:27930654

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport.

PMID:28479320

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

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 — 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):

"which is a component of IFT-A essential for IFT" — PMID:27930654

Proposed term (ontology gap):

structural constituent of intraflagellar transport particle

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):

"it remains unclear how the dynein-2 heavy chain moves in cilia" — PMID:28479320

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):

"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:27930654

Deep Research

Falcon

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

Comprehensive Functional Annotation of *C. elegans* CHE-11 (IFT140) Falcon Edison Scientific Literature 30 citations 2 artifacts 2026-07-04T17:16:47.644627

Edison artifact artifact-00 (text/markdown)

Edison artifact artifact-01 (text/markdown)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive Functional Annotation of C. elegans CHE-11 (IFT140)

1. Gene and Protein Identity

The che-11 gene (ORF name C27A7.4; UniProt P90757) of Caenorhabditis elegans encodes a WD-repeat- and TPR-domain-containing protein that is the ortholog of human intraflagellar transport protein 140 (IFT140). Multiple independent studies have confirmed this orthology based on sequence conservation, domain architecture, and functional complementation experiments (scheidel2018intraflagellartransportcomplex pages 1-3, blacque2006thewdrepeatcontaining pages 6-8, jensen2016wholeorganismdevelopmentalexpression pages 8-9). The gene was originally identified through forward genetic screens for chemotaxis-defective mutants in C. elegans, hence the "che" designation (scheidel2018intraflagellartransportcomplex pages 1-3).

The following table summarizes the key properties of CHE-11/IFT140:

Property	Description
Gene name	che-11; the provided UniProt annotation and C. elegans literature align che-11 with the IFT140 ortholog in sensory cilia (scheidel2018intraflagellartransportcomplex pages 1-3, brocalruiz2023forkheadtranscriptionfactor pages 3-5)
Protein name	CHE-11 / IFT-140; a WD-repeat/TPR-containing intraflagellar transport protein and core IFT-A subunit (blacque2006thewdrepeatcontaining pages 6-8, picariello2019aglobalanalysis pages 4-6)
UniProt ID	P90757 (provided target identity)
Organism	Caenorhabditis elegans (worm) (scheidel2018intraflagellartransportcomplex pages 1-3, brocalruiz2023forkheadtranscriptionfactor pages 3-5)
ORF name	C27A7.4 (provided target identity)
Human ortholog	IFT140; che-11 is identified as the C. elegans ortholog of mammalian/human IFT140 (scheidel2018intraflagellartransportcomplex pages 1-3, OpenTargets Search: -IFT140)
Protein complex	IFT-A core complex; IFT140/CHE-11 belongs to the IFT-A core together with IFT122 and IFT144 (meleppattu2022mechanismofifta pages 3-5, nakayama2018ciliaryproteintrafficking pages 3-3)
Key domains	N-terminal WD repeats / β-propeller domains plus C-terminal TPR domains; WD repeats contribute to membrane-associated cargo transport and retrograde transport performance, whereas TPR domains stabilize IFT-A assembly and mediate core subunit interactions (picariello2019aglobalanalysis pages 6-8, picariello2019aglobalanalysis pages 13-15, meleppattu2022mechanismofifta pages 3-5)
Molecular function	Structural/adaptor subunit of the IFT-A complex required for retrograde intraflagellar transport and for proper assembly/stability of IFT-A; broader comparative work indicates IFT140-containing IFT-A also specializes in trafficking membrane-associated ciliary cargoes (blacque2006thewdrepeatcontaining pages 6-8, blacque2006thewdrepeatcontaining pages 8-9, picariello2019aglobalanalysis pages 6-8, picariello2019aglobalanalysis pages 1-4)
Subcellular localization	Localizes to sensory cilia, including the axoneme and ciliary region visualized in phasmid/amphid neurons; genetic evidence also places IFT-A/CHE-11 function at the transition zone/periciliary gating interface, and in some mutant contexts CHE-11 can become restricted near the transition zone (scheidel2018intraflagellartransportcomplex pages 3-4, efimenko2006caenorhabditiselegansdyf2an pages 6-8, scheidel2018intraflagellartransportcomplex pages 4-6)
Expression pattern	Expressed broadly in the ciliated sensory neuron system, with reporter activity in ~30 or more ciliated neurons (brocalruiz2023forkheadtranscriptionfactor pages 3-5)
Mutant phenotypes	Truncated/short cilia, defective retrograde IFT with accumulation of IFT material in cilia, dye-filling defects, and chemotaxis/sensory defects; cell-type-specific defects include collapsed AWC cilia and CEP abnormalities (blacque2006thewdrepeatcontaining pages 6-8, jensen2016wholeorganismdevelopmentalexpression pages 8-9, scheidel2018intraflagellartransportcomplex pages 1-3)
Transcriptional regulation	Regulated by DAF-19/RFX, with additional cooperative input from FKH-8; che-11 contains validated X-box regulatory elements and retains partial expression in daf-19 mutants, indicating combinatorial control (brocalruiz2023forkheadtranscriptionfactor pages 3-5, brocalruiz2023forkheadtranscriptionfactor pages 2-3)
Human disease associations	Human IFT140 is associated with ciliopathies including Mainzer-Saldino syndrome, Jeune syndrome, short-rib thoracic dysplasia, retinitis pigmentosa, and cystic kidney disease / polycystic kidney disease (OpenTargets Search: -IFT140)

Table: This table summarizes the core identifiers, molecular role, localization, regulation, mutant phenotypes, and human disease relevance of C. elegans che-11/CHE-11. It is useful as a quick reference for the full research report.

2. Primary Molecular Function: Core Subunit of the IFT-A Complex

CHE-11 functions as a core structural and adaptor subunit of the intraflagellar transport complex A (IFT-A). It is not an enzyme; rather, it serves as a scaffold protein within the IFT-A macromolecular assembly that is essential for retrograde intraflagellar transport (IFT)—the directed movement of protein cargo from the ciliary tip back to the ciliary base (blacque2006thewdrepeatcontaining pages 6-8, blacque2006thewdrepeatcontaining pages 8-9).

2.1 IFT-A Complex Architecture

The IFT-A complex is a six-subunit assembly organized into two modules. CHE-11/IFT140 resides in the core (A1) subcomplex together with IFT144 (DYF-2 in C. elegans) and IFT122 (DAF-10). The peripheral (A2) module contains IFT139, IFT121, and IFT43 (meleppattu2022mechanismofifta pages 3-5, nakayama2018ciliaryproteintrafficking pages 3-3). Cryo-electron microscopy and integrative modeling studies have revealed that IFT140 and IFT144 form a heterodimer through antiparallel TPR-TPR interactions involving the first five helices of their respective TPR domains, creating a characteristic V-shaped architecture with their tandem β-propeller domains splayed approximately 50 Å apart (meleppattu2022mechanismofifta pages 3-5). IFT122 serves as a linker, bridging the A1 and A2 modules by extending its TPR domain to engage both IFT140 and IFT144 at the apex of the V-shape (meleppattu2022mechanismofifta pages 5-6).

Subunit Name	C. elegans Ortholog	Subcomplex	Domain Architecture	Key Function
IFT140	CHE-11	Core / A1	N-terminal WD repeats / β-propellers plus C-terminal TPR domains	Stabilizes the IFT-A complex, contributes to retrograde IFT, and supports transport of membrane-associated ciliary cargoes (meleppattu2022mechanismofifta pages 3-5, picariello2019aglobalanalysis pages 6-8, picariello2019aglobalanalysis pages 13-15)
IFT144	DYF-2	Core / A1	WD repeats / β-propellers plus TPR domains	Forms a heterodimeric core unit with IFT140 through TPR-mediated interactions and helps build the A1 V-shaped architecture (meleppattu2022mechanismofifta pages 3-5, meleppattu2022mechanismofifta pages 5-6)
IFT122	DAF-10 / IFT-122	Core linker between A1 and A2	WD repeats / β-propellers plus TPR domains	Bridges the core and peripheral modules; its TPR region extends to contact IFT140 and IFT144, linking A1 and A2 (meleppattu2022mechanismofifta pages 3-5, meleppattu2022mechanismofifta pages 5-6, nakayama2018ciliaryproteintrafficking pages 3-3)
IFT139	IFT-139	Peripheral / A2	TPR domains throughout	Peripheral IFT-A component important for peripheral module stability and retrograde IFT-related organization (picariello2019aglobalanalysis pages 4-6, scheidel2018intraflagellartransportcomplex pages 4-6)
IFT121	IFT-121	Peripheral / A2	WD repeats / β-propellers plus TPR domains	Peripheral component of A2; interacts with IFT43 and contacts the core via IFT122 (meleppattu2022mechanismofifta pages 5-6, nakayama2018ciliaryproteintrafficking pages 3-3)
IFT43	IFT-43	Peripheral / A2	Coiled-coil domain	Peripheral component that directly interacts with IFT121 and supports A2 integrity and localization (nakayama2018ciliaryproteintrafficking pages 3-3, zhu2017functionalexplorationof pages 9-12)

Table: This table summarizes the six-subunit IFT-A complex with emphasis on the CHE-11/IFT140-containing core module, domain architecture, and inferred functional roles. It is useful for linking the worm che-11 gene to conserved IFT-A assembly and cargo-transport mechanisms.

2.2 Domain-Specific Functions

The CHE-11/IFT140 protein contains two principal functional regions:

N-terminal WD-repeat (β-propeller) domains: Studies in Chlamydomonas reinhardtii using a truncated IFT140 lacking the N-terminal WD repeats demonstrated that these domains are required for proper retrograde IFT velocity, likely by affecting dynein-1b motor activation or IFT train–motor interaction (picariello2019aglobalanalysis pages 13-15). Critically, the WD repeats are also essential for proper trafficking of membrane-associated proteins—including small GTPases, lipid-anchored proteins (myristoylated and geranylgeranylated), and cell signaling components—into cilia (picariello2019aglobalanalysis pages 6-8, picariello2019aglobalanalysis pages 13-15). When the WD repeats are absent, the truncated protein still supports half-length flagella with normal axonemal ultrastructure, but these flagella show dramatic decreases in membrane-associated signaling proteins (picariello2019aglobalanalysis pages 1-4, picariello2019aglobalanalysis pages 17-19).

C-terminal TPR domains: These tetratricopeptide repeat domains are sufficient to stabilize IFT-A complex assembly. Expression of only the TPR region of IFT140 partially rescues IFT-A formation and supports partial flagellar assembly, indicating that the TPR domains mediate the essential protein–protein interactions within the IFT-A core (picariello2019aglobalanalysis pages 13-15, picariello2019aglobalanalysis pages 4-6).

2.3 Functional Specialization: Membrane Protein Cargo Transport

A landmark study by Picariello et al. (2019) using Chlamydomonas IFT140 null mutants revealed a key functional specialization of IFT-A: it is specifically dedicated to importing membrane-associated proteins into cilia, while IFT-B handles the import of axonemal structural proteins (picariello2019aglobalanalysis pages 1-4, picariello2019aglobalanalysis pages 17-19). The IFT-A complex, via IFT140, transports G protein-coupled receptors (GPCRs), Smoothened, rhodopsin/opsin, Arl13b, and various lipid-modified signaling proteins into the ciliary compartment (picariello2019aglobalanalysis pages 17-19). This is accomplished in part through the adaptor protein TULP3, which bridges IFT-A core subunits (including IFT140) and membrane phosphoinositides (nakayama2018ciliaryproteintrafficking pages 3-3).

3. Subcellular Localization

CHE-11 protein localizes to the sensory cilia of C. elegans ciliated neurons. Using GFP-tagged CHE-11 constructs, the protein has been visualized in both amphid and phasmid sensory cilia, where it undergoes bidirectional IFT—moving anterogradely from the ciliary base to tip and retrogradely from tip to base (scheidel2018intraflagellartransportcomplex pages 3-4). In C. elegans, IFT-A (including CHE-11) travels at the slow speed characteristic of heterotrimeric kinesin-II (~0.5 μm/s) during anterograde transport, while IFT-B moves at faster speeds characteristic of the homodimeric kinesin OSM-3 (blacque2006thewdrepeatcontaining pages 6-8, taschner2016theintraflagellartransport pages 12-13). The BBSome is responsible for holding IFT-A and IFT-B subcomplexes together during transport; in BBS mutant backgrounds, CHE-11/IFT-A and IFT-B separate and move independently at their respective motor speeds (taschner2016theintraflagellartransport pages 12-13, bhogaraju2013intraflagellartransportcomplex pages 6-7).

In dyf-2 (IFT144) mutant backgrounds, CHE-11 protein becomes restricted to the transition zone and is unable to enter the ciliary axoneme, demonstrating the dependence of CHE-11 ciliary entry on other core IFT-A components (efimenko2006caenorhabditiselegansdyf2an pages 6-8).

4. Biological Processes and Pathway Involvement

4.1 Retrograde Intraflagellar Transport

The primary biological process in which CHE-11 participates is retrograde IFT. Loss of CHE-11 function phenocopies classic retrograde IFT defects: IFT machinery components accumulate within the ciliary axoneme, retrograde motility is severely abrogated, and cilia become truncated (blacque2006thewdrepeatcontaining pages 6-8, blacque2006thewdrepeatcontaining pages 8-9). CHE-11 is also required for proper incorporation of other IFT components—such as IFTA-1—into the IFT machinery. In che-11 mutants, IFTA-1 fails to localize to ciliary structures (blacque2006thewdrepeatcontaining pages 6-8, blacque2006thewdrepeatcontaining pages 8-9).

4.2 Transition Zone Gating

CHE-11/IFT-140 plays a cell-type-specific role in transition zone (TZ) function. The TZ is a specialized ciliary gate at the base of the cilium that regulates protein entry and exit. Scheidel and Blacque (2018) demonstrated that IFT-A genes differentially regulate TZ gating in C. elegans: while non-core IFT-A genes (IFT-43, IFT-121, IFT-139) control ciliary removal of MKS module proteins, IFT-140 controls the ciliary entry/accumulation of MKS module proteins into cilia in these non-core mutant backgrounds (scheidel2018intraflagellartransportcomplex pages 4-6). IFT-140 also targets the peripheral component IFT-121 to cilia and mediates IFT-139's association with IFT trains (scheidel2018intraflagellartransportcomplex pages 4-6). These findings reveal that IFT-A maintains, rather than initially establishes, TZ restriction of gating proteins.

4.3 Cilium Formation and Morphogenesis

CHE-11 is essential for cilium formation across all examined cilium types in C. elegans. Mutants display cell-type-specific structural defects: for example, ift-140 mutants show collapsed wing-shaped AWC cilia and abnormal rod-shaped CEP cilia (scheidel2018intraflagellartransportcomplex pages 1-3). The interaction between IFT-A and MKS module components works synergistically to determine cilium structure (scheidel2018intraflagellartransportcomplex pages 1-3).

4.4 Sensory Signaling

Because CHE-11 is essential for proper ciliary structure and composition, its loss leads to defective sensory behaviors including chemotaxis defects (hence the gene name "che") and dye-filling defects—a hallmark phenotype of ciliary structural compromise in C. elegans sensory neurons (scheidel2018intraflagellartransportcomplex pages 1-3, blacque2006thewdrepeatcontaining pages 6-8). Additionally, IFT-A's role in transporting membrane-associated signaling receptors implies that CHE-11 is indirectly required for sensory signal transduction through its role in localizing receptors and signaling components to the ciliary membrane (picariello2019aglobalanalysis pages 17-19).

4.5 Cytoplasmic Precursor Transport

Studies in Chlamydomonas have identified a novel role for IFT-A, including IFT140, in mobilizing ciliary precursors from the cytoplasmic pool to the peri-basal body region prior to their entry into the cilium. In ift140 null mutants, the peri-basal body localization of IFT-A proteins is disrupted, and flagellar regeneration requiring recruitment of preexisting precursors is blocked (zhu2017functionalexplorationof pages 9-12).

5. Transcriptional Regulation

The che-11 gene is expressed in essentially all ciliated sensory neurons in C. elegans (~30+ neurons), as shown by reporter gene analysis (brocalruiz2023forkheadtranscriptionfactor pages 3-5). Its expression is regulated in part by the DAF-19/RFX transcription factor, an evolutionarily conserved master regulator of ciliome genes, acting through X-box regulatory elements in the che-11 promoter. Loss of DAF-19 dramatically reduces but does not eliminate che-11 expression, indicating that additional transcription factors cooperate in its regulation (brocalruiz2023forkheadtranscriptionfactor pages 3-5). The Forkhead transcription factor FKH-8 has been identified as an additional direct co-regulator that works synergistically with DAF-19/RFX to control ciliome gene expression, including che-11 (brocalruiz2023forkheadtranscriptionfactor pages 2-3, brocalruiz2023forkheadtranscriptionfactor pages 3-5).

6. Evolutionary Conservation and Human Disease Relevance

IFT140 is highly conserved across eukaryotes. The human ortholog IFT140 is strongly associated with multiple ciliopathies, as documented by OpenTargets disease-target associations (OpenTargets Search: -IFT140). Mutations in human IFT140 cause Mainzer-Saldino syndrome (characterized by retinitis pigmentosa, cerebellar ataxia, and renal disease), Jeune asphyxiating thoracic dystrophy (short-rib thoracic dysplasia with or without polydactyly), retinitis pigmentosa, and autosomal dominant polycystic kidney disease (OpenTargets Search: -IFT140). The pleiotropic nature of these ciliopathies can be explained by IFT-A's specialized role in transporting membrane-associated signaling proteins into cilia: abnormal levels of these proteins would disrupt multiple ciliary signaling pathways across diverse tissues (picariello2019aglobalanalysis pages 1-4, picariello2019aglobalanalysis pages 17-19).

7. Summary

CHE-11 (UniProt P90757) is the C. elegans ortholog of IFT140, a core structural subunit of the IFT-A complex essential for retrograde intraflagellar transport and ciliary membrane protein import. It is not an enzyme but rather serves as a multi-domain scaffold within the IFT-A core, using its C-terminal TPR domains for complex assembly and its N-terminal WD-repeat/β-propeller domains for cargo recognition and retrograde motor regulation. CHE-11 localizes to the axoneme and transition zone region of all sensory cilia in C. elegans, where it undergoes bidirectional IFT movement. Its loss results in truncated cilia, disrupted retrograde IFT, defective transition zone gating, dye-filling defects, and chemotaxis behavioral impairment. Transcriptional regulation of che-11 involves the cooperative action of DAF-19/RFX and FKH-8 transcription factors. The deep conservation of IFT140 from worms to humans, and its association with multiple human ciliopathies, underscores the fundamental importance of this protein in ciliary biology.

References

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(picariello2019aglobalanalysis pages 1-4): Tyler Picariello, Jason M. Brown, Yuqing Hou, Gregory Swank, Deborah A. Cochran, Oliver D. King, Karl Lechtreck, Gregory J. Pazour, and George B. Witman. A global analysis of ift-a function reveals specialization for transport of membrane-associated proteins into cilia. Journal of Cell Science, Feb 2019. URL: https://doi.org/10.1242/jcs.220749, doi:10.1242/jcs.220749. This article has 84 citations and is from a domain leading peer-reviewed journal.
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(efimenko2006caenorhabditiselegansdyf2an pages 6-8): Evgeni Efimenko, Oliver E. Blacque, Guangshuo Ou, Courtney J. Haycraft, Bradley K. Yoder, Jonathan M. Scholey, Michel R. Leroux, and Peter Swoboda. caenorhabditis elegansdyf-2, an orthologue of human wdr19, is a component of the intraflagellar transport machinery in sensory cilia. Nov 2006. URL: https://doi.org/10.1091/mbc.e06-04-0260, doi:10.1091/mbc.e06-04-0260. This article has 98 citations and is from a domain leading peer-reviewed journal.
(scheidel2018intraflagellartransportcomplex pages 4-6): Noémie Scheidel and Oliver E. Blacque. Intraflagellar transport complex a genes differentially regulate cilium formation and transition zone gating. Current Biology, 28:3279-3287.e2, Oct 2018. URL: https://doi.org/10.1016/j.cub.2018.08.017, doi:10.1016/j.cub.2018.08.017. This article has 59 citations and is from a highest quality peer-reviewed journal.
(brocalruiz2023forkheadtranscriptionfactor pages 2-3): Rebeca Brocal-Ruiz, Ainara Esteve-Serrano, Carlos Mora-Martínez, Maria Luisa Franco-Rivadeneira, Peter Swoboda, Juan J Tena, Marçal Vilar, and Nuria Flames. Forkhead transcription factor fkh-8 cooperates with rfx in the direct regulation of sensory cilia in caenorhabditis elegans. eLife, Jul 2023. URL: https://doi.org/10.7554/elife.89702, doi:10.7554/elife.89702. This article has 15 citations and is from a domain leading peer-reviewed journal.
(meleppattu2022mechanismofifta pages 5-6): Shimi Meleppattu, Haixia Zhou, Jin Dai, Miao Gui, and Alan Brown. Mechanism of ift-a polymerization into trains for ciliary transport. Cell, 185:4986-4998.e12, Dec 2022. URL: https://doi.org/10.1016/j.cell.2022.11.033, doi:10.1016/j.cell.2022.11.033. This article has 50 citations and is from a highest quality peer-reviewed journal.
(zhu2017functionalexplorationof pages 9-12): Bing Zhu, Xin Zhu, Limei Wang, Yinwen Liang, Qianqian Feng, and Junmin Pan. Functional exploration of the ift-a complex in intraflagellar transport and ciliogenesis. PLOS Genetics, 13:e1006627, Feb 2017. URL: https://doi.org/10.1371/journal.pgen.1006627, doi:10.1371/journal.pgen.1006627. This article has 78 citations and is from a domain leading peer-reviewed journal.
(picariello2019aglobalanalysis pages 17-19): Tyler Picariello, Jason M. Brown, Yuqing Hou, Gregory Swank, Deborah A. Cochran, Oliver D. King, Karl Lechtreck, Gregory J. Pazour, and George B. Witman. A global analysis of ift-a function reveals specialization for transport of membrane-associated proteins into cilia. Journal of Cell Science, Feb 2019. URL: https://doi.org/10.1242/jcs.220749, doi:10.1242/jcs.220749. This article has 84 citations and is from a domain leading peer-reviewed journal.
(taschner2016theintraflagellartransport pages 12-13): Michael Taschner and Esben Lorentzen. The intraflagellar transport machinery. Cold Spring Harbor perspectives in biology, 8 10:a028092, Oct 2016. URL: https://doi.org/10.1101/cshperspect.a028092, doi:10.1101/cshperspect.a028092. This article has 419 citations and is from a peer-reviewed journal.
(bhogaraju2013intraflagellartransportcomplex pages 6-7): Sagar Bhogaraju, Benjamin D Engel, and Esben Lorentzen. Intraflagellar transport complex structure and cargo interactions. Cilia, 2:10-10, Aug 2013. URL: https://doi.org/10.1186/2046-2530-2-10, doi:10.1186/2046-2530-2-10. This article has 125 citations.

Artifacts

Citations

scheidel2018intraflagellartransportcomplex pages 1-3
brocalruiz2023forkheadtranscriptionfactor pages 3-5
meleppattu2022mechanismofifta pages 3-5
meleppattu2022mechanismofifta pages 5-6
picariello2019aglobalanalysis pages 13-15
picariello2019aglobalanalysis pages 17-19
nakayama2018ciliaryproteintrafficking pages 3-3
scheidel2018intraflagellartransportcomplex pages 3-4
scheidel2018intraflagellartransportcomplex pages 4-6
zhu2017functionalexplorationof pages 9-12
blacque2006thewdrepeatcontaining pages 6-8
jensen2016wholeorganismdevelopmentalexpression pages 8-9
picariello2019aglobalanalysis pages 4-6
picariello2019aglobalanalysis pages 6-8
blacque2006thewdrepeatcontaining pages 8-9
picariello2019aglobalanalysis pages 1-4
brocalruiz2023forkheadtranscriptionfactor pages 2-3
taschner2016theintraflagellartransport pages 12-13
bhogaraju2013intraflagellartransportcomplex pages 6-7
https://doi.org/10.1016/j.cub.2018.08.017,
https://doi.org/10.1091/mbc.e06-06-0571,
https://doi.org/10.1371/journal.pgen.1006469,
https://doi.org/10.7554/elife.89702,
https://doi.org/10.1242/jcs.220749,
https://doi.org/10.1016/j.cell.2022.11.033,
https://doi.org/10.1093/jb/mvx087,
https://doi.org/10.1091/mbc.e06-04-0260,
https://doi.org/10.1371/journal.pgen.1006627,
https://doi.org/10.1101/cshperspect.a028092,
https://doi.org/10.1186/2046-2530-2-10,

📚 Additional Documentation

Notes

(che-11-notes.md)

che-11 (C. elegans) — research notes

Gene: che-11 / ORF C27A7.4 / WormBase WBGene00000490 / UniProt P90757 (1437 aa).
Ortholog: IFT140 (human IFT140; UniProt Q96RY7). PANTHER PTHR15722:SF7 "INTRAFLAGELLAR
TRANSPORT PROTEIN 140 HOMOLOG". Domain architecture (UniProt P90757): two N-terminal
WD40 β-propellers ("IFT140 first/second beta-propeller", Pfam PF23383/PF23385) followed by a
long TPR/α-solenoid ("IF140/IFT172/WDR19 TPR", PF24762; "IF140 C-terminal TPR", PF24760).
No catalytic domain. ComplexPortal CPX-1289 = Intraflagellar transport complex A. Reactome
R-CEL-5620924 (Intraflagellar transport), R-CEL-5610787 (Hedgehog 'off' state).

Note on nomenclature: che-11 = IFT140 (retrograde IFT-A core subunit). This is distinct
from the paralogous IFT-A subunit dyf-2 = WDR19/IFT144 (already reviewed in this repo).
Both are IFT-A core subunits; do not conflate them.

KNOWN (well supported)

1. CHE-11 is a core subunit of the IFT-A ("Complex A") particle

PMID:11301258 — Qin, Rosenbaum & Barr
(2001) directly identified CHE-11 as one of the two Complex A (IFT-A) polypeptides assayed
(with DAF-10), alongside OSM-5 (Complex B) and CHE-2.
ComplexPortal CPX-1289 (IFT complex A) records CHE-11 as a subunit (NAS, GOA reference
PMID:28479320).
PMID:27930654
— Jensen et al. (2016) describe CHE-11 as the IFT140 component of IFT-A that is essential
for IFT.

2. CHE-11 undergoes/drives intraflagellar transport in sensory cilia

PMID:11301258 — OSM-5, DAF-10, CHE-11 and CHE-2 all move at the
same rate along C. elegans sensory cilia (i.e. as part of the moving IFT machinery).
The IFT-A complex is the retrograde (tip-to-base) module of IFT (driven by cytoplasmic
dynein-2); the anterograde module is IFT-B + kinesin-2. As an IFT-A subunit CHE-11 is
required for retrograde transport and, because retrograde return of IFT components is needed
to sustain the whole cycle, for IFT/cilium assembly overall.

3. CHE-11 is required for ciliary IFT and cilium assembly (loss-of-function phenotype)

PMID:27930654 — che-11(e1810)
mutants have truncated cilia and abolished processive ciliary transport of the IFT cargo
RAB-28; this establishes CHE-11 as required for (a positive regulator of) IFT of ciliary
cargo and for building a normal-length cilium.
Localizes to the (non-motile) sensory cilium: CHE-11 moves within cilia (PMID:11301258) and
CHE-11::GFP is imaged in cilia in IFT studies. GOA carries IDA "non-motile cilium"
(PMID:11301258, PMID:17420466).

4. che-11 mutants are Dyf (dye-filling defective) with structurally defective chemosensory cilia

PMID:1732156 — Vowels & Thomas (1992): che-11 is
one of the cilium-structure genes whose mutations block chemosensation and perturb
chemosensory (dauer) decision-making.
PMID:14982934 — the paraquat-resistance
mutant mev-4 is a che-11 nonsense allele with a Dyf phenotype (dye-filling defective).

5. Downstream / pleiotropic sensory consequences of losing ciliary function

These are phenotypes of the cilium-defective animal, not molecular activities of CHE-11.
- Extended adult lifespan: PMID:14982934. (Also GOA IMP determination of adult lifespan
from PMID:19208769.)
- Resistance to oxidative stress (paraquat): PMID:14982934; paraquat is an oxidative-stress generator.
- Cross-resistance to heat (response to heat): PMID:14982934 (same quote as lifespan).
- Hyperosmotic response: GOA IMP (PMID:14982934) — WB curator annotation; not stated in the
abstract but consistent with Dyf/osmotic-avoidance phenotypes of ciliary mutants.
- Dauer entry: GOA IGI (PMID:1732156) — genetic interactions with daf genes; cilium-structure
gene acting in chemosensory control of the dauer decision.
These are best captured as KEEP_AS_NON_CORE (pleiotropic, downstream of the ciliary sensory
defect) rather than core molecular/cellular functions.

6. Conserved disease relevance

Human IFT140 mutations cause skeletal ciliopathies and retinal dystrophy (short-rib thoracic
dysplasia / Mainzer–Saldino syndrome / non-syndromic retinitis pigmentosa). Not separately
cached here; used only as conserved-function context, not for any worm annotation.

NOT known / gaps

No molecular_function annotation and no adequate MF term. CHE-11 is a structural IFT-A
scaffold with no catalytic activity; GO has no "structural constituent of intraflagellar
transport particle" term, so its MF is effectively dark (same ontology gap as its paralog
dyf-2). The worm GOA record for che-11 carries only CC and BP terms.
Subunit-resolved IFT-A architecture in the worm is not solved. The precise CHE-11
contacts within IFT-A (with DAF-10/IFT122, DYF-2/WDR19, IFT-139, IFT-43, IFTA-1) and how
IFT-A engages dynein-2 for retrograde turnaround are inferred from orthology/proteomics, not
from a worm structure.
Anterograde vs retrograde requirement. GOA carries both "positive regulation of
intraciliary anterograde transport" and "...retrograde transport" (IMP, PMID:27930654) for
che-11; mechanistically CHE-11/IFT-A is primarily the retrograde module, and the anterograde
effect is largely an indirect consequence of failed IFT-component recycling. The direct vs
indirect boundary for anterograde regulation is not resolved.

Annotation review plan (summary)

IFT-A membership (GO:0030991), retrograde IFT (GO:0035721), IFT (GO:0042073), cilium
assembly (GO:0060271), ciliary localization (non-motile cilium GO:0097730, cilium
GO:0005929, axoneme GO:0005930, ciliary basal body GO:0036064): ACCEPT (core / core CC).
positive regulation of intraciliary retrograde/anterograde transport (PMID:27930654): KEEP —
retrograde is on-target (near-core); anterograde is an indirect requirement, non-core.
Stress/lifespan/dauer/hyperosmotic (PMID:14982934, PMID:1732156, PMID:19208769):
KEEP_AS_NON_CORE — pleiotropic downstream sensory phenotypes.
Core function: structural constituent of IFT-A (MF: structural molecule activity), in_complex
IFT particle A, driving intraciliary retrograde transport and cilium assembly.

Update after falcon deep research (Edison Scientific, 2026-07-04)

Genuine falcon report landed at 17:16 after the wrapper's 600s timeout (kept and
committed as che-11-deep-research-falcon.md; 30 citations to real papers). It
corroborates the PMID-grounded review above and adds context (citations here are to
the falcon report's sources, not cached in publications/, so used as context only):

IFT-A architecture is cryo-EM-solved (general/cross-species). CHE-11/IFT140 sits in
the IFT-A core (A1) with DYF-2/IFT144 and DAF-10/IFT122; IFT140 and IFT144 form an
antiparallel TPR–TPR heterodimer (V-shaped, β-propellers splayed ~50 Å), IFT122 bridges
A1 to the peripheral A2 module (IFT139/IFT121/IFT43) [Meleppattu et al. 2022 Cell,
10.1016/j.cell.2022.11.033]. This is why the review's gap #2 boundary now notes the
general architecture is solved while the worm-specific/dynein-2 turnaround remains open.
Domain division of labour: N-terminal WD40 β-propellers → retrograde velocity +
import of membrane-associated cargo (GPCRs, lipid-anchored signaling proteins); C-terminal
TPR → IFT-A assembly [Picariello et al. 2019 J Cell Sci, 10.1242/jcs.220749].
CHE-11 is required to recruit other IFT-A subunits: in che-11 mutants IFTA-1 fails to
localize to cilia [Blacque et al. 2006 Mol Biol Cell, 10.1091/mbc.e06-06-0571].
Transition-zone gating (worm-specific): IFT-140 controls ciliary entry/accumulation of
MKS-module proteins and targets IFT-121/IFT-139 to trains [Scheidel & Blacque 2018 Curr
Biol, 10.1016/j.cub.2018.08.017] — a worm IFT-140 function not captured in current GOA.
Transcriptional regulation: che-11 is a DAF-19/RFX X-box target, co-regulated by FKH-8
[Brocal-Ruiz et al. 2023 eLife, 10.7554/eLife.89702]. Consistent with expression in ~30+
ciliated sensory neurons.
Nomenclature confirmed: CHE-11 = IFT140 (distinct from DYF-2 = WDR19/IFT144). No
contradiction with any ACCEPT/KEEP decision in the review.

📄 View Raw YAML

id: P90757
gene_symbol: che-11
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
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 β-propellers followed by an
  extended tetratricopeptide-repeat (TPR)/α-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.
references:
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:11301258
    title: An autosomal recessive polycystic kidney disease gene homolog is involved
      in intraflagellar transport in C. elegans ciliated sensory neurons.
    findings: []
    reference_review:
      relevance: HIGH
      correctness: VERIFIED
      review_notes: >-
        Primary paper directly identifying CHE-11 as one of two Complex A (IFT-A)
        polypeptides that move along C. elegans sensory cilia at the IFT rate.
        Note the title's "ARPKD gene homolog" refers to osm-5/IFT88, not che-11;
        the che-11 evidence is in the body (Complex A subunit, IFT motility).
  - id: PMID:14982934
    title: Mutations in chemosensory cilia cause resistance to paraquat in nematode
      Caenorhabditis elegans.
    findings: []
    reference_review:
      relevance: MEDIUM
      correctness: VERIFIED
      review_notes: >-
        Identifies the paraquat-resistant, long-lived mutant mev-4 as a che-11
        nonsense allele with a Dyf phenotype. Supports stress/lifespan phenotypes
        that are downstream consequences of ciliary/sensory dysfunction rather than
        molecular functions of CHE-11.
  - id: PMID:1732156
    title: Genetic analysis of chemosensory control of dauer formation in Caenorhabditis
      elegans.
    findings: []
    reference_review:
      relevance: MEDIUM
      correctness: VERIFIED
      review_notes: >-
        Classic genetic study placing che-11 among the cilium-structure genes whose
        mutations give structurally defective chemosensory cilia and block
        chemosensation; basis for the dauer-entry (IGI) and cilium-assembly (IGI)
        annotations.
  - id: PMID:17420466
    title: Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2
      motors and reduces their speed in the cilia of Caenorhabditis elegans.
    findings: []
    reference_review:
      relevance: LOW
      correctness: VERIFIED
      review_notes: >-
        Study of the DYF-5 MAP kinase that also imaged IFT proteins in cilia;
        source of the IDA non-motile cilium localization for CHE-11. Abstract-only
        cache does not name che-11, but the curator read the full text.
  - id: PMID:19208769
    title: Functional interactions between the ciliopathy-associated Meckel syndrome
      1 (MKS1) protein and two novel MKS1-related (MKSR) proteins.
    findings: []
    reference_review:
      relevance: LOW
      correctness: VERIFIED
      review_notes: >-
        MKS1/MKSR transition-zone study; source of a WB IMP determination-of-adult-
        lifespan annotation for a che-11 variant. Lifespan is a downstream sensory
        consequence, not a core CHE-11 function.
  - id: PMID:27930654
    title: Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a
      Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport.
    findings: []
    reference_review:
      relevance: HIGH
      correctness: VERIFIED
      review_notes: >-
        Uses che-11(e1810) as an IFT-A loss-of-function background and describes
        CHE-11 as the IFT140 component of IFT-A essential for IFT; RAB-28 IFT
        movement is abolished in che-11 mutant truncated cilia. Basis for the
        positive-regulation-of-IFT annotations.
  - id: PMID:28479320
    title: Dynein-Driven Retrograde Intraflagellar Transport Is Triphasic in C. elegans
      Sensory Cilia.
    findings: []
    reference_review:
      relevance: MEDIUM
      correctness: VERIFIED
      review_notes: >-
        Retrograde (dynein-2/IFT-A) transport study; cited by ComplexPortal (CPX-1289)
        for the NAS IFT-A complex-membership and retrograde-transport annotations.
        The abstract discusses IFT-A subunits IFT-139/IFT-43 and dynein-2, not che-11
        by name.
existing_annotations:
  - term:
      id: GO:0035721
      label: intraciliary retrograde transport
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: involved_in
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:27930654
          supporting_text: which is a component of IFT-A essential for IFT
  - term:
      id: GO:0036064
      label: ciliary basal body
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: is_active_in
    review:
      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.
      action: ACCEPT
      reason: >-
        Consistent core localization for an IFT-A subunit; phylogenetically
        inferred and in line with the ciliary/base localization of IFT proteins.
  - term:
      id: GO:0005930
      label: axoneme
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: is_active_in
    review:
      summary: >-
        CHE-11 moves along the ciliary axoneme as part of the IFT machinery.
      action: ACCEPT
      reason: >-
        Core localization; IFT-A subunits traffic along the axoneme. Corroborated
        by direct observation that CHE-11 moves along C. elegans sensory cilia.
      supported_by:
        - reference_id: PMID:11301258
          supporting_text: move at the same rate
  - term:
      id: GO:0030991
      label: intraciliary transport particle A
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    qualifier: part_of
    review:
      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.
      action: ACCEPT
      reason: >-
        The defining cellular-component assignment for this gene; strongly
        supported by phylogeny and experiment.
      supported_by:
        - reference_id: PMID:11301258
          supporting_text: two Complex A polypeptides
  - term:
      id: GO:0005929
      label: cilium
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    qualifier: located_in
    review:
      summary: >-
        Electronic annotation placing CHE-11 in the cilium; correct but less
        specific than the experimentally supported non-motile cilium term.
      action: ACCEPT
      reason: >-
        Correct ciliary localization. A more specific term (non-motile cilium) is
        also annotated by IDA; the general term is retained as consistent.
  - term:
      id: GO:0005929
      label: cilium
    evidence_type: NAS
    original_reference_id: PMID:28479320
    qualifier: located_in
    review:
      summary: >-
        ComplexPortal (CPX-1289) complex-based assertion that CHE-11, as an IFT-A
        subunit, localizes to the cilium.
      action: ACCEPT
      reason: >-
        Correct ciliary localization consistent with all other evidence; a more
        specific non-motile cilium term is also present.
  - term:
      id: GO:0030991
      label: intraciliary transport particle A
    evidence_type: NAS
    original_reference_id: PMID:28479320
    qualifier: part_of
    review:
      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.
      action: ACCEPT
      reason: >-
        Core complex membership; consistent across ComplexPortal, phylogeny and
        experimental identification as a Complex A polypeptide.
  - term:
      id: GO:0035721
      label: intraciliary retrograde transport
    evidence_type: NAS
    original_reference_id: PMID:28479320
    qualifier: involved_in
    review:
      summary: >-
        ComplexPortal assertion that the IFT-A complex containing CHE-11 mediates
        retrograde intraflagellar transport.
      action: ACCEPT
      reason: >-
        Core biological process for an IFT-A subunit; redundant with the IBA
        retrograde-transport annotation.
  - term:
      id: GO:0060271
      label: cilium assembly
    evidence_type: NAS
    original_reference_id: PMID:28479320
    qualifier: involved_in
    review:
      summary: >-
        IFT-A function (via CHE-11) is required to build and maintain the ciliary
        axoneme; ComplexPortal complex-based assertion.
      action: ACCEPT
      reason: >-
        Core process, downstream of the direct IFT transport activity; corroborated
        by the truncated-cilia phenotype of che-11 mutants.
      supported_by:
        - reference_id: PMID:27930654
          supporting_text: Although GFP::RAB-28 is observed within the truncated cilia
            of che-11 mutants, we could not detect processive movement of the GFP signals
  - term:
      id: GO:1905798
      label: positive regulation of intraciliary anterograde transport
    evidence_type: IMP
    original_reference_id: PMID:27930654
    qualifier: involved_in
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:27930654
          supporting_text: Although GFP::RAB-28 is observed within the truncated cilia
            of che-11 mutants, we could not detect processive movement of the GFP signals
  - term:
      id: GO:1905801
      label: positive regulation of intraciliary retrograde transport
    evidence_type: IMP
    original_reference_id: PMID:27930654
    qualifier: involved_in
    review:
      summary: >-
        CHE-11 is required for retrograde intraflagellar transport of ciliary cargo;
        loss abolishes processive movement in cilia.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:27930654
          supporting_text: which is a component of IFT-A essential for IFT
  - term:
      id: GO:0097730
      label: non-motile cilium
    evidence_type: IDA
    original_reference_id: PMID:17420466
    qualifier: located_in
    review:
      summary: >-
        Direct imaging localizes CHE-11 to the non-motile sensory cilium.
      action: ACCEPT
      reason: >-
        Core cellular-component localization, directly observed. C. elegans sensory
        cilia are non-motile.
  - term:
      id: GO:0043053
      label: dauer entry
    evidence_type: IGI
    original_reference_id: PMID:1732156
    qualifier: involved_in
    review:
      summary: >-
        che-11 is one of the cilium-structure genes whose mutations perturb the
        chemosensory control of dauer formation; genetic interactions with daf
        genes.
      action: KEEP_AS_NON_CORE
      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.
      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
    qualifier: involved_in
    review:
      summary: >-
        Loss of che-11 gives structurally defective chemosensory cilia, indicating
        a requirement in building the sensory cilium.
      action: ACCEPT
      reason: >-
        Core process for an IFT-A subunit; the structurally defective cilia of
        che-11 mutants support a role in cilium assembly/integrity.
      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:0097730
      label: non-motile cilium
    evidence_type: IDA
    original_reference_id: PMID:11301258
    qualifier: located_in
    review:
      summary: >-
        CHE-11 localizes to and moves within C. elegans sensory (non-motile) cilia.
      action: ACCEPT
      reason: >-
        Core cellular-component localization, directly observed as a Complex A
        polypeptide moving along sensory cilia.
      supported_by:
        - reference_id: PMID:11301258
          supporting_text: two Complex A polypeptides
  - term:
      id: GO:0008340
      label: determination of adult lifespan
    evidence_type: IMP
    original_reference_id: PMID:14982934
    qualifier: involved_in
    review:
      summary: >-
        A che-11 nonsense mutant (mev-4) is long-lived; lifespan extension is a
        downstream consequence of impaired chemosensory (ciliary) signaling.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:14982934
          supporting_text: One mutant named mev-4 was long-lived and showed cross-resistance
            to heat and Dyf phenotype
  - term:
      id: GO:0008340
      label: determination of adult lifespan
    evidence_type: IMP
    original_reference_id: PMID:19208769
    qualifier: involved_in
    review:
      summary: >-
        Second IMP for determination of adult lifespan from a transition-zone
        (MKS) study, using a che-11 variant.
      action: KEEP_AS_NON_CORE
      reason: >-
        Same downstream, sensory-dependent lifespan phenotype as the PMID:14982934
        annotation; a pleiotropic consequence of ciliary dysfunction, not a core
        function.
  - term:
      id: GO:0030991
      label: intraciliary transport particle A
    evidence_type: ISS
    original_reference_id: PMID:14982934
    qualifier: part_of
    review:
      summary: >-
        Sequence-similarity annotation (from an IFT140 ortholog) placing CHE-11 in
        the IFT-A particle.
      action: ACCEPT
      reason: >-
        Core complex membership; consistent with the IBA and ComplexPortal IFT-A
        annotations and with experimental identification as a Complex A polypeptide.
  - term:
      id: GO:0042073
      label: intraciliary transport
    evidence_type: ISS
    original_reference_id: PMID:14982934
    qualifier: involved_in
    review:
      summary: >-
        CHE-11 participates in intraflagellar transport, the general process
        subsuming its retrograde IFT-A role.
      action: ACCEPT
      reason: >-
        Core biological process; the more specific retrograde-transport term is
        also annotated. Corroborated by direct observation of CHE-11 IFT motility.
      supported_by:
        - reference_id: PMID:11301258
          supporting_text: move at the same rate
  - term:
      id: GO:0006972
      label: hyperosmotic response
    evidence_type: IMP
    original_reference_id: PMID:14982934
    qualifier: involved_in
    review:
      summary: >-
        WB IMP annotation for hyperosmotic response, based on a che-11 mutant.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0006979
      label: response to oxidative stress
    evidence_type: IMP
    original_reference_id: PMID:14982934
    qualifier: involved_in
    review:
      summary: >-
        che-11 (mev-4) mutants are resistant to paraquat, an oxidative-stress
        generator.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:14982934
          supporting_text: We isolated mutants resistant to paraquat from nematode
  - term:
      id: GO:0009408
      label: response to heat
    evidence_type: IMP
    original_reference_id: PMID:14982934
    qualifier: involved_in
    review:
      summary: >-
        che-11 (mev-4) mutants show cross-resistance to heat.
      action: KEEP_AS_NON_CORE
      reason: >-
        Heat cross-resistance is a downstream, sensory-dependent phenotype of
        cilium loss, not a molecular function of CHE-11. Retained as non-core.
      supported_by:
        - reference_id: PMID:14982934
          supporting_text: One mutant named mev-4 was long-lived and showed cross-resistance
            to heat and Dyf phenotype
core_functions:
  - description: >-
      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 β-propeller + TPR/α-solenoid scaffold that helps hold the IFT-A particle
      together and is essential for IFT.
    molecular_function:
      id: GO:0005198
      label: structural molecule activity
    directly_involved_in:
      - id: GO:0035721
        label: intraciliary retrograde transport
      - id: GO:0042073
        label: intraciliary transport
    locations:
      - id: GO:0097730
        label: non-motile cilium
    in_complex:
      id: GO:0030991
      label: intraciliary transport particle A
    supported_by:
      - reference_id: PMID:11301258
        supporting_text: two Complex A polypeptides
      - reference_id: PMID:27930654
        supporting_text: which is a component of IFT-A essential for IFT
  - description: >-
      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:
      - id: GO:0060271
        label: cilium assembly
    locations:
      - id: GO:0097730
        label: non-motile cilium
    supported_by:
      - reference_id: PMID:27930654
        supporting_text: Although GFP::RAB-28 is observed within the truncated cilia
          of che-11 mutants, we could not detect processive movement of the GFP signals
      - reference_id: PMID:1732156
        supporting_text: Dauer-defective mutations in nine genes cause structurally
          defective chemosensory cilia, thereby blocking chemosensation
knowledge_gaps:
  - gap_statement: >-
      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.
    boundary: >-
      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.
    gap_kind:
      - ONTOLOGY
      - CURATION
    dark_aspect: MF_DARK
    status: OPEN
    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.
    resolution: >-
      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:
      - reference_id: PMID:27930654
        supporting_text: which is a component of IFT-A essential for IFT
        reference_section_type: RESULTS
    proposed_terms:
      - proposed_name: structural constituent of intraflagellar transport particle
        proposed_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.
        proposed_parent:
          id: GO:0005198
          label: structural molecule activity
  - gap_statement: >-
      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.
    boundary: >-
      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.
    gap_kind:
      - BIOLOGY
    dark_aspect: RESIDUAL_SUBGAP
    status: OPEN
    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.
    resolution: >-
      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:
      - reference_id: PMID:28479320
        supporting_text: it remains unclear how the dynein-2 heavy chain moves in cilia
        reference_section_type: ABSTRACT
  - gap_statement: >-
      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.
    boundary: >-
      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.
    gap_kind:
      - BIOLOGY
      - CURATION
    dark_aspect: BP_DARK
    status: OPEN
    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.
    resolution: >-
      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:
      - reference_id: PMID:27930654
        supporting_text: Although GFP::RAB-28 is observed within the truncated cilia
          of che-11 mutants, we could not detect processive movement of the GFP signals
        reference_section_type: RESULTS
proposed_new_terms:
  - proposed_name: structural constituent of intraflagellar transport particle
    proposed_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.
    proposed_parent:
      id: GO:0005198
      label: structural molecule activity
suggested_questions:
  - question: >-
      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?
  - question: >-
      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:
  - description: >-
      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.
  - description: >-
      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.

che-11

Gene Description

Proposed New Ontology Terms

structural constituent of intraflagellar transport particle

Existing Annotations Review

Core Functions

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.

References

Suggested Questions for Experts

Suggested Experiments

Knowledge Gaps

Deep Research

Falcon

Comprehensive Functional Annotation of C. elegans CHE-11 (IFT140)

1. Gene and Protein Identity

2. Primary Molecular Function: Core Subunit of the IFT-A Complex

2.1 IFT-A Complex Architecture

2.2 Domain-Specific Functions

2.3 Functional Specialization: Membrane Protein Cargo Transport

3. Subcellular Localization

4. Biological Processes and Pathway Involvement

4.1 Retrograde Intraflagellar Transport

4.2 Transition Zone Gating

4.3 Cilium Formation and Morphogenesis

4.4 Sensory Signaling

4.5 Cytoplasmic Precursor Transport

5. Transcriptional Regulation

6. Evolutionary Conservation and Human Disease Relevance

7. Summary

Artifacts

Citations

📚 Additional Documentation

Notes

che-11 (C. elegans) — research notes

KNOWN (well supported)

1. CHE-11 is a core subunit of the IFT-A ("Complex A") particle

2. CHE-11 undergoes/drives intraflagellar transport in sensory cilia

3. CHE-11 is required for ciliary IFT and cilium assembly (loss-of-function phenotype)

4. che-11 mutants are Dyf (dye-filling defective) with structurally defective chemosensory cilia

5. Downstream / pleiotropic sensory consequences of losing ciliary function

6. Conserved disease relevance

NOT known / gaps

Annotation review plan (summary)

Update after falcon deep research (Edison Scientific, 2026-07-04)

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