daf-11

UniProt ID: Q8I4N4
Organism: Caenorhabditis elegans
Review Status: COMPLETE
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Gene Description

daf-11 encodes a receptor-type (transmembrane) guanylate cyclase of C. elegans chemosensory neurons. The protein has an extracellular ligand-binding-like domain of unknown ligand, a single transmembrane helix, an intracellular kinase-homology (pseudokinase) domain and a C-terminal class-4 guanylate cyclase domain that converts GTP to cGMP. DAF-11 is expressed in five pairs of amphid chemosensory neurons (ASI, ASJ, ASK, AWB, AWC) and is concentrated in their non-motile sensory cilia; its ciliary targeting requires the MYND-domain protein DAF-25, and its activity depends on the Hsp90 chaperone DAF-21. DAF-11-generated cGMP gates the TAX-2/TAX-4 cyclic nucleotide-gated channel and activates the PKG EGL-4. Through this second-messenger output DAF-11 is required for chemotaxis to AWC-sensed volatile odorants and ASE-sensed water-soluble attractants, for phototransduction downstream of the LITE-1 photoreceptor in ASJ/ASK/ASI, for NO-evoked calcium responses in ASJ, and for repression of dauer entry, partly by maintaining daf-7 TGF-beta expression in ASI. Loss of daf-11 also affects adult lifespan, oxidative-stress responses, sensory axon maintenance and AWC str-2 olfactory receptor expression.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001653 peptide receptor activity
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: PANTHER IBA transfer of peptide receptor activity from vertebrate natriuretic-peptide receptor guanylyl cyclases (NPR-A/NPR-B) at a deep node of the receptor guanylyl cyclase family.
Reason: DAF-11 is an orphan receptor-type guanylyl cyclase. No peptide (or any other) ligand has been identified for its extracellular domain, and the experimental literature places it as the cGMP source downstream of diverse sensory inputs (pheromone, odorants, light via LITE-1, NO), not as a peptide receptor. The receptor-for-peptide function is a lineage-specific property of the natriuretic peptide receptors and is not demonstrated for the nematode chemosensory rGC radiation; marking as over-annotated rather than removing because a ligand could still be found.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: FUNCTIONAL DIVERGENCE
Sources checked:
PANTHER:PTN000229249 SUPPORTS SOURCE BUT NOT TARGET
Peptide-receptor activity is grounded in vertebrate natriuretic peptide receptor guanylyl cyclases (NPR-A/NPR-B); the C. elegans sensory receptor guanylyl cyclase radiation has no demonstrated peptide ligand.
Supporting Evidence:
PMID:10790386
We report that daf-11 encodes one of a large family of C. elegans transmembrane guanylyl cyclases (TM-GCs).
GO:0004383 guanylate cyclase activity
EXP
PMID:24015261
The Receptor-Bound Guanylyl Cyclase DAF-11 Is the Mediator o...
ACCEPT
Summary: Direct biochemical evidence: DAF-11 is required for the H2O2-induced rise in cGMP measured by HPLC-MS/MS (UniProt cites this paper for EC 4.6.1.2 catalytic activity). Core molecular function.
Supporting Evidence:
file:worm/daf-11/daf-11-uniprot.txt
Guanylate cyclase involved in the production of the second messenger cGMP
PMID:24015261
mutants lacking the function of a specific receptor-bound guanylyl cyclase, DAF-11, have an increased life expectancy.
GO:0004383 guanylate cyclase activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA for guanylate cyclase activity; DAF-11 has a C-terminal guanylate cyclase domain and is a member of the receptor guanylyl cyclase family that inherited this catalytic activity. Core.
Supporting Evidence:
PMID:10790386
We report that daf-11 encodes one of a large family of C. elegans transmembrane guanylyl cyclases (TM-GCs).
GO:0004383 guanylate cyclase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Combined automated (EC/RHEA) assignment of guanylate cyclase activity, consistent with domain architecture and the experimental/IBA annotations. Core.
Supporting Evidence:
file:worm/daf-11/daf-11-uniprot.txt
Guanylate cyclase involved in the production of the second messenger cGMP
GO:0004383 guanylate cyclase activity
ISS
PMID:10790386
A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21)...
ACCEPT
Summary: ISS from the DAF-11 cloning paper, which identified daf-11 as a transmembrane guanylyl cyclase and showed that 8-bromo-cGMP rescues a daf-11 sensory defect. Core.
Supporting Evidence:
PMID:10790386
We report that daf-11 encodes one of a large family of C. elegans transmembrane guanylyl cyclases (TM-GCs).
PMID:10790386
The cyclic GMP analogue 8-bromo-cGMP rescues a sensory defect in both daf-11 and daf-21 mutants, supporting a role for DAF-11 guanylyl cyclase activity in this process
GO:0005524 ATP binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: InterPro-based ATP binding from the kinase-homology domain (residues 355-695). In receptor guanylyl cyclases this domain is a pseudokinase that may bind ATP as a regulator of cyclase activity; ATP binding has not been tested for DAF-11. Retained as a non-core, domain-based inference.
Supporting Evidence:
file:worm/daf-11/daf-11-uniprot.txt
DOMAIN 355..695
GO:0005886 plasma membrane
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: DAF-11 is a single-pass transmembrane protein, so plasma membrane is correct, but its functional pool is in the ciliary membrane of chemosensory neurons (see non-motile cilium IDA).
Supporting Evidence:
PMID:21124868
In wild-type animals, the DAF-11::GFP protein localized to the sensory cilia of the olfactory neuron pairs ASI, ASJ, ASK, AWB and AWC
GO:0005886 plasma membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: UniProt subcellular-location mapping (cell membrane, by sequence). Correct but less specific than the experimentally shown ciliary localization.
Supporting Evidence:
PMID:21124868
In wild-type animals, the DAF-11::GFP protein localized to the sensory cilia of the olfactory neuron pairs ASI, ASJ, ASK, AWB and AWC
IEA
GO_REF:0000044
ACCEPT
Summary: DAF-11::GFP localizes to the sensory cilia of ASI, ASJ, ASK, AWB and AWC; its ciliary targeting requires DAF-25. Correct core location (non-motile cilium is the more specific IDA term).
Supporting Evidence:
PMID:21124868
In wild-type animals, the DAF-11::GFP protein localized to the sensory cilia of the olfactory neuron pairs ASI, ASJ, ASK, AWB and AWC
GO:0006182 cGMP biosynthetic process
IBA
GO_REF:0000033
ACCEPT
Summary: cGMP biosynthesis is the direct process carried out by DAF-11 cyclase activity. Core.
Supporting Evidence:
PMID:10790386
We report that daf-11 encodes one of a large family of C. elegans transmembrane guanylyl cyclases (TM-GCs).
PMID:10790386
The cyclic GMP analogue 8-bromo-cGMP rescues a sensory defect in both daf-11 and daf-21 mutants, supporting a role for DAF-11 guanylyl cyclase activity in this process
GO:0006182 cGMP biosynthetic process
ISS
PMID:10790386
A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21)...
ACCEPT
Summary: ISS-based cGMP biosynthetic process, supported by cyclase-domain architecture and cGMP-analogue rescue of daf-11 sensory defects. Core.
Supporting Evidence:
PMID:10790386
The cyclic GMP analogue 8-bromo-cGMP rescues a sensory defect in both daf-11 and daf-21 mutants, supporting a role for DAF-11 guanylyl cyclase activity in this process
GO:0006935 chemotaxis
IGI
PMID:7828815
Multiple chemosensory defects in daf-11 and daf-21 mutants o...
ACCEPT
Summary: daf-11 mutants are defective in taxis to non-volatile attractants and to AWC-sensed volatile attractants; DAF-11 supplies cGMP for transduction in these neurons. Correct; core organismal role (positive chemotaxis/olfaction would be more specific).
Supporting Evidence:
PMID:7828815
both mutants are defective in taxis to volatile attractants detected primarily by the amphid neuron AWC
PMID:7828815
We propose that daf-11 and daf-21 mediate sensory transduction for both volatile and non-volatile compounds in specific amphid neurons.
GO:0007165 signal transduction
IMP
PMID:18832350
The EGL-4 PKG acts with KIN-29 salt-inducible kinase and pro...
KEEP AS NON CORE
Summary: Generic signal transduction term from the EGL-4/KIN-29 chemoreceptor-expression study. DAF-11 does act in cGMP sensory signalling, but this term is uninformative relative to receptor guanylyl cyclase signaling pathway.
Supporting Evidence:
PMID:18832350
Here we show that the cGMP-dependent protein kinase EGL-4 acts partly in parallel with KIN-29 to regulate CR gene expression.
GO:0007168 receptor guanylyl cyclase signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: IBA for receptor guanylyl cyclase signaling pathway. DAF-11 generates cGMP that gates the TAX-2/TAX-4 CNG channel and activates downstream effectors. The ligand-binding aspect of the term definition is not demonstrated for DAF-11, but the pathway-level term is appropriate.
Supporting Evidence:
PMID:1732156
These results suggest that daf-11 is directly involved in chemosensory transduction essential for dauer formation
GO:0007168 receptor guanylyl cyclase signaling pathway
IMP
PMID:18832350
The EGL-4 PKG acts with KIN-29 salt-inducible kinase and pro...
ACCEPT
Summary: Experimental (IMP) support that DAF-11 acts as a cGMP source upstream of the EGL-4 PKG in sensory neurons. Pathway-level term is appropriate.
Supporting Evidence:
PMID:18832350
Here we show that the cGMP-dependent protein kinase EGL-4 acts partly in parallel with KIN-29 to regulate CR gene expression.
GO:0007168 receptor guanylyl cyclase signaling pathway
ISS
PMID:10790386
A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21)...
ACCEPT
Summary: ISS from the DAF-11 cloning paper; DAF-11 is a transmembrane guanylyl cyclase whose cGMP output drives chemosensory signalling.
Supporting Evidence:
PMID:10790386
We report that daf-11 encodes one of a large family of C. elegans transmembrane guanylyl cyclases (TM-GCs).
PMID:10790386
The cyclic GMP analogue 8-bromo-cGMP rescues a sensory defect in both daf-11 and daf-21 mutants, supporting a role for DAF-11 guanylyl cyclase activity in this process
GO:0007602 phototransduction
IMP
PMID:20436480
C. elegans phototransduction requires a G protein-dependent ...
ACCEPT
Summary: daf-11 mutants lack LITE-1-dependent photocurrents in ASJ (and ASK, ASI); GTPgammaS fails to activate CNG channels in daf-11 ASJ. DAF-11 is the cyclase step of the G protein-cGMP phototransduction cascade, so it participates directly in phototransduction.
Supporting Evidence:
PMID:20436480
Two independent daf-11 mutant alleles, ks67 and m47, both lacked photocurrents in ASJ
PMID:20436480
Indeed, GTPΞ³S failed to stimulate CNG channels in ASJ of daf-11 mutant worms
GO:0008340 determination of adult lifespan
IGI
PMID:19489741
Endogenous cGMP regulates adult longevity via the insulin si...
KEEP AS NON CORE
Summary: Neuronal cGMP levels influence adult lifespan through insulin/TGF-beta signalling; daf-11 genetic interactions were used in this analysis. A real but indirect, systemic consequence of reduced sensory cGMP signalling.
Supporting Evidence:
PMID:19489741
Here it is shown that a suppressed neuronal cGMP level caused by GPA-3 activation leads to a significant increase (47.3%) in the mean lifespan of adult C. elegans
GO:0008340 determination of adult lifespan
IMP
PMID:19489741
Endogenous cGMP regulates adult longevity via the insulin si...
KEEP AS NON CORE
Summary: IMP version of the lifespan role (same study). Indirect, non-core.
Supporting Evidence:
PMID:19489741
Here it is shown that a suppressed neuronal cGMP level caused by GPA-3 activation leads to a significant increase (47.3%) in the mean lifespan of adult C. elegans
GO:0008340 determination of adult lifespan
IMP
PMID:24015261
The Receptor-Bound Guanylyl Cyclase DAF-11 Is the Mediator o...
KEEP AS NON CORE
Summary: daf-11 loss-of-function mutants are long-lived; Beckert et al. found the relation between cGMP and survival to be complex. Indirect, systemic, non-core.
Supporting Evidence:
PMID:24015261
mutants lacking the function of a specific receptor-bound guanylyl cyclase, DAF-11, have an increased life expectancy.
GO:0008355 olfactory learning
IMP
PMID:17251413
Caenorhabditis elegans integrates the signals of butanone an...
KEEP AS NON CORE
Summary: Butanone enhancement (an odour-food associative plasticity) requires the AWC-ON neuron, whose fate and function depend on DAF-11 and ODR-1; DAF-11 likely provides permissive cGMP signalling in AWC rather than a learning-specific function. Non-core.
Supporting Evidence:
PMID:17251413
whose fate is known to be determined by the NSY-1/ASK1 MAPKKK (mitogen-activated protein kinase kinase kinase) cascade as well as the DAF-11 and ODR-1 guanylyl cyclases
GO:0009190 cyclic nucleotide biosynthetic process
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: InterPro-derived parent of cGMP biosynthetic process; correct but less specific.
Supporting Evidence:
file:worm/daf-11/daf-11-uniprot.txt
Guanylate cyclase involved in the production of the second messenger cGMP
GO:0009266 response to temperature stimulus
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: ARBA electronic response to temperature stimulus.
Reason: There is no evidence that DAF-11 participates in thermosensation; thermosensory cGMP in AFD is produced by GCY-8/GCY-18/GCY-23. The temperature dependence of daf-11 dauer phenotypes reflects the temperature sensitivity of the dauer decision itself, not a DAF-11 role in sensing temperature.
Supporting Evidence:
PMID:1732156
These results suggest that daf-11 is directly involved in chemosensory transduction essential for dauer formation
GO:0009266 response to temperature stimulus
IMP
PMID:21124868
Localization of a guanylyl cyclase to chemosensory cilia req...
MARK AS OVER ANNOTATED
Summary: IMP from the DAF-25 study, presumably based on the temperature-sensitive dauer-constitutive phenotype of daf-11 mutants.
Reason: The temperature-sensitive Daf-c phenotype is an output of the dauer decision, which integrates pheromone, food and temperature; DAF-11 acts at the chemosensory transduction step in ASI/ASJ, not as a temperature-response component. The more appropriate annotation is regulation of dauer larval development, which this paper also supports.
Supporting Evidence:
PMID:21124868
Indeed the Daf-c phenotype of daf-25(m362) is very similar to that of daf-11(m84) at all temperatures tested
GO:0009581 detection of external stimulus
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: ARBA electronic term. DAF-11 is part of the transduction machinery converting external chemical and light stimuli into a cGMP signal in sensory neurons; broadly correct but generic.
Supporting Evidence:
PMID:7828815
We propose that daf-11 and daf-21 mediate sensory transduction for both volatile and non-volatile compounds in specific amphid neurons.
GO:0009582 detection of abiotic stimulus
IEA
GO_REF:0000117
MARK AS OVER ANNOTATED
Summary: ARBA electronic detection of abiotic stimulus.
Reason: The only abiotic stimulus for which DAF-11 is required is light, where the detecting molecule is the LITE-1 receptor and DAF-11 acts downstream as the cyclase; phototransduction (accepted separately) captures this more accurately. DAF-11 has no role in temperature or mechanical detection.
Supporting Evidence:
PMID:20436480
Two independent daf-11 mutant alleles, ks67 and m47, both lacked photocurrents in ASJ
GO:0010468 regulation of gene expression
IMP
PMID:24015261
The Receptor-Bound Guanylyl Cyclase DAF-11 Is the Mediator o...
KEEP AS NON CORE
Summary: DAF-11-dependent cGMP regulates transcript levels of pde-1 and pde-5 phosphodiesterases (UniProt, citing this paper). An indirect downstream effect of cGMP signalling; non-core.
Supporting Evidence:
file:worm/daf-11/daf-11-uniprot.txt
regulates cGMP levels by controlling the transcription of 3',5'-cyclic phosphodiesterase pde-1 and pde-5 mRNAs
GO:0010628 positive regulation of gene expression
IGI
PMID:19489741
Endogenous cGMP regulates adult longevity via the insulin si...
KEEP AS NON CORE
Summary: Genetic interaction evidence that neuronal cGMP from DAF-11 influences expression of insulin-like peptides (ins-7, daf-28) and pde genes. Indirect downstream effect; non-core.
Supporting Evidence:
PMID:19489741
cGMP, TGF-beta, and FOXO signaling interact to differentially produce the insulin-like molecules, ins-7 and daf-28
GO:0010628 positive regulation of gene expression
IMP
PMID:18832350
The EGL-4 PKG acts with KIN-29 salt-inducible kinase and pro...
KEEP AS NON CORE
Summary: DAF-11 acts upstream of EGL-4 PKG-dependent chemoreceptor gene expression (acts_upstream_of). Indirect; non-core.
Supporting Evidence:
PMID:18832350
Here we show that the cGMP-dependent protein kinase EGL-4 acts partly in parallel with KIN-29 to regulate CR gene expression.
GO:0010628 positive regulation of gene expression
IMP
PMID:19489741
Endogenous cGMP regulates adult longevity via the insulin si...
KEEP AS NON CORE
Summary: IGI/IMP evidence for a role of DAF-11 cGMP in promoting expression of insulin-like peptide genes. Indirect; non-core.
Supporting Evidence:
PMID:19489741
cGMP, TGF-beta, and FOXO signaling interact to differentially produce the insulin-like molecules, ins-7 and daf-28
GO:0010628 positive regulation of gene expression
IMP
PMID:19489741
Endogenous cGMP regulates adult longevity via the insulin si...
KEEP AS NON CORE
Summary: Duplicate of the preceding positive regulation of gene expression annotation from the same lifespan study. Indirect; non-core.
Supporting Evidence:
PMID:19489741
cGMP, TGF-beta, and FOXO signaling interact to differentially produce the insulin-like molecules, ins-7 and daf-28
GO:0010628 positive regulation of gene expression
IMP
PMID:25303524
Chemosensation of bacterial secondary metabolites modulates ...
KEEP AS NON CORE
Summary: daf-11 is required for normal daf-7 TGF-beta expression in ASI, including the induction of daf-7 by P. aeruginosa secondary metabolites. A well-supported but downstream transcriptional output of DAF-11 cGMP signalling; non-core.
Supporting Evidence:
PMID:25303524
consistent with daf-11, tax-2, and tax-4 acting upstream of daf-7 expression in all tissues
GO:0030425 dendrite
IDA
PMID:10790386
A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21)...
KEEP AS NON CORE
Summary: daf-11::GFP is seen along dendrites of expressing neurons; DAF-11 transits dendrites to the cilium, which is its site of action.
Supporting Evidence:
PMID:10790386
daf-11::gfp fusions are expressed in five identified pairs of chemosensory neurons in a pattern consistent with most daf-11 mutant phenotypes
GO:0030425 dendrite
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: UniProt subcellular-location mapping (dendrite). Correct but non-core relative to cilium.
Supporting Evidence:
file:worm/daf-11/daf-11-uniprot.txt
Cell projection, dendrite
GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway
IMP
PMID:11677050
DAF-7/TGF-beta expression required for the normal larval dev...
KEEP AS NON CORE
Summary: DAF-11 acts cell-autonomously in ASI to permit expression of the DAF-7 TGF-beta ligand, so it promotes TGF-beta pathway signalling indirectly by controlling ligand expression. Non-core downstream consequence of sensory cGMP signalling.
Supporting Evidence:
PMID:11677050
Expression of daf-11 cDNA by cell specific promoters suggests that daf-11 acts cell autonomously in ASI chemosensory neurons for daf-7 expression.
GO:0030516 regulation of axon extension
IMP
PMID:9486798
A cyclic nucleotide-gated channel inhibits sensory axon outg...
KEEP AS NON CORE
Summary: daf-11 mutants show late-onset sensory axon outgrowth defects similar to tax-2/tax-4 CNG channel mutants, implicating sensory cGMP signalling in maintaining axon structure. Real but peripheral role.
Supporting Evidence:
PMID:9486798
Animals mutant for the daf-11 gene have axon phenotypes that are similar to those of tax-2 and tax 4 mutants
GO:0035556 intracellular signal transduction
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: InterPro-derived intracellular signal transduction; correct in spirit (cGMP second messenger) but uninformative.
Supporting Evidence:
file:worm/daf-11/daf-11-uniprot.txt
Guanylate cyclase involved in the production of the second messenger cGMP
GO:0040014 regulation of multicellular organism growth
IGI
PMID:26434723
The Importance of cGMP Signaling in Sensory Cilia for Body S...
KEEP AS NON CORE
Summary: From the GCY-12 body-size study; the cached abstract attributes cGMP-dependent body-size control specifically to GCY-12 and does not name daf-11, so the daf-11 data are in the full text (not available here). Body-size control is a peripheral, EGL-4-dependent output; retained as non-core, deferring to the curator.
Supporting Evidence:
PMID:26434723
The large number of guanylyl cyclases encoded in the C. elegans genome suggests that EGL-4 exerts pleiotropic effects by partnering with different guanylyl cyclases for different downstream functions.
GO:0040024 dauer larval development
IGI
PMID:10625546
Targets of TGF-beta signaling in Caenorhabditis elegans daue...
MODIFY
Summary: IGI from the daf-14 Smad study, in which daf-11 Daf-c mutants were used in epistasis analysis.
Reason: DAF-11 does not carry out dauer larval development itself; loss of daf-11 causes constitutive dauer formation, so wild-type DAF-11 acts in sensory neurons to inhibit entry into dauer. negative regulation of dauer larval development describes this better.
Supporting Evidence:
PMID:10625546
Caenorhabditis elegans dauer formation is controlled by multiple environmental factors.
PMID:1732156
These results suggest that daf-11 is directly involved in chemosensory transduction essential for dauer formation
GO:0040024 dauer larval development
IGI
PMID:11677050
DAF-7/TGF-beta expression required for the normal larval dev...
MODIFY
Summary: IGI from the DAF-7 expression study placing daf-11 upstream of daf-7.
Reason: DAF-11 regulates (inhibits) dauer formation by permitting daf-7 expression in ASI; negative regulation of dauer larval development is more accurate.
Supporting Evidence:
PMID:11677050
Expression of daf-11 cDNA by cell specific promoters suggests that daf-11 acts cell autonomously in ASI chemosensory neurons for daf-7 expression.
GO:0040024 dauer larval development
IMP
PMID:10625546
Targets of TGF-beta signaling in Caenorhabditis elegans daue...
MODIFY
Summary: IMP version of the daf-14 study dauer annotation.
Reason: daf-11 mutants are dauer-constitutive, so DAF-11 negatively regulates dauer development; replace with the regulatory term.
Supporting Evidence:
PMID:1732156
These results suggest that daf-11 is directly involved in chemosensory transduction essential for dauer formation
GO:0040024 dauer larval development
IMP
PMID:10790386
A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21)...
MODIFY
Summary: IMP from the DAF-11 cloning paper (daf-11 mutants are dauer-constitutive and pheromone-hypersensitive).
Reason: DAF-11 is a regulator, not an executor, of dauer development: it acts in chemosensory neurons to repress dauer entry. Replace with negative regulation of dauer larval development.
Supporting Evidence:
PMID:7828815
We propose that daf-11 and daf-21 mediate sensory transduction for both volatile and non-volatile compounds in specific amphid neurons.
GO:0040024 dauer larval development
IMP
PMID:11677050
DAF-7/TGF-beta expression required for the normal larval dev...
MODIFY
Summary: IMP from the DAF-7 expression study (new daf-11 allele isolated as dauer-constitutive).
Reason: Replace with negative regulation of dauer larval development; DAF-11 inhibits dauer entry by sustaining daf-7 expression.
Supporting Evidence:
PMID:11677050
Expression of daf-11 cDNA by cell specific promoters suggests that daf-11 acts cell autonomously in ASI chemosensory neurons for daf-7 expression.
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: ARBA electronic taxis; correct parent of the experimentally supported chemotaxis annotation.
Supporting Evidence:
PMID:7828815
both mutants are defective in taxis to volatile attractants detected primarily by the amphid neuron AWC
GO:0042542 response to hydrogen peroxide
IMP
PMID:24015261
The Receptor-Bound Guanylyl Cyclase DAF-11 Is the Mediator o...
KEEP AS NON CORE
Summary: DAF-11 mediates the H2O2-induced rise in cGMP and affects oxidative-stress sensitivity (UniProt). A real but peripheral role; the cached record is abstract-only.
Supporting Evidence:
PMID:24015261
We also examined the influence of reactive oxygen species (ROS) on cyclic nucleotide metabolism and lifespan in C. elegans
file:worm/daf-11/daf-11-uniprot.txt
sensitivity to oxidative stress
GO:0043005 neuron projection
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: ARBA neuron projection; correct general parent (dendrite, cilium).
Supporting Evidence:
PMID:21124868
In wild-type animals, the DAF-11::GFP protein localized to the sensory cilia of the olfactory neuron pairs ASI, ASJ, ASK, AWB and AWC
GO:0043025 neuronal cell body
IDA
PMID:10790386
A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21)...
KEEP AS NON CORE
Summary: daf-11::GFP is also seen in neuronal cell bodies (perikaryon, UniProt). Correct; non-core site.
Supporting Evidence:
file:worm/daf-11/daf-11-uniprot.txt
Perikaryon
GO:0043204 perikaryon
EXP
PMID:10790386
A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21)...
KEEP AS NON CORE
Summary: Experimental perikaryal localization of daf-11::GFP. Non-core.
Supporting Evidence:
file:worm/daf-11/daf-11-uniprot.txt
Perikaryon
GO:0043204 perikaryon
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: UniProt subcellular-location mapping (perikaryon). Non-core.
Supporting Evidence:
file:worm/daf-11/daf-11-uniprot.txt
Perikaryon
GO:0050920 regulation of chemotaxis
IMP
PMID:7828815
Multiple chemosensory defects in daf-11 and daf-21 mutants o...
KEEP AS NON CORE
Summary: IMP regulation of chemotaxis. DAF-11 is better described as part of the transduction machinery for chemotaxis (accepted separately as chemotaxis) than as a regulator; retained as non-core.
Supporting Evidence:
PMID:7828815
We propose that daf-11 and daf-21 mediate sensory transduction for both volatile and non-volatile compounds in specific amphid neurons.
GO:0060271 cilium assembly
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
REMOVE
Summary: IGI cilium assembly derived from double-mutant epistasis between daf-11 and cilium-structure (che/osm/daf) mutants.
Reason: The cited paper shows that Daf-c mutations in daf-11 are suppressed by mutations in nine cilium-structure genes, i.e. daf-11 requires intact cilia to exert its effect; this epistasis places cilium formation upstream/permissive for DAF-11 signalling and does not show that DAF-11 builds cilia. daf-11 mutants have structurally normal, dye-filling amphid cilia. DAF-11 is a ciliary guanylyl cyclase, not a ciliogenesis factor. The IGI appears to reflect the cilium genes (WITH partners), not a function of DAF-11.
Supporting Evidence:
PMID:1732156
Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes.
PMID:21124868
By contrast, daf-11 and daf-21 mutants show wild-type dye filling
GO:0060271 cilium assembly
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
REMOVE
Summary: IGI cilium assembly derived from double-mutant epistasis between daf-11 and cilium-structure (che/osm/daf) mutants.
Reason: The cited paper shows that Daf-c mutations in daf-11 are suppressed by mutations in nine cilium-structure genes, i.e. daf-11 requires intact cilia to exert its effect; this epistasis places cilium formation upstream/permissive for DAF-11 signalling and does not show that DAF-11 builds cilia. daf-11 mutants have structurally normal, dye-filling amphid cilia. DAF-11 is a ciliary guanylyl cyclase, not a ciliogenesis factor. The IGI appears to reflect the cilium genes (WITH partners), not a function of DAF-11.
Supporting Evidence:
PMID:1732156
Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes.
PMID:21124868
By contrast, daf-11 and daf-21 mutants show wild-type dye filling
GO:0060271 cilium assembly
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
REMOVE
Summary: IGI cilium assembly derived from double-mutant epistasis between daf-11 and cilium-structure (che/osm/daf) mutants.
Reason: The cited paper shows that Daf-c mutations in daf-11 are suppressed by mutations in nine cilium-structure genes, i.e. daf-11 requires intact cilia to exert its effect; this epistasis places cilium formation upstream/permissive for DAF-11 signalling and does not show that DAF-11 builds cilia. daf-11 mutants have structurally normal, dye-filling amphid cilia. DAF-11 is a ciliary guanylyl cyclase, not a ciliogenesis factor. The IGI appears to reflect the cilium genes (WITH partners), not a function of DAF-11.
Supporting Evidence:
PMID:1732156
Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes.
PMID:21124868
By contrast, daf-11 and daf-21 mutants show wild-type dye filling
GO:0060271 cilium assembly
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
REMOVE
Summary: IGI cilium assembly derived from double-mutant epistasis between daf-11 and cilium-structure (che/osm/daf) mutants.
Reason: The cited paper shows that Daf-c mutations in daf-11 are suppressed by mutations in nine cilium-structure genes, i.e. daf-11 requires intact cilia to exert its effect; this epistasis places cilium formation upstream/permissive for DAF-11 signalling and does not show that DAF-11 builds cilia. daf-11 mutants have structurally normal, dye-filling amphid cilia. DAF-11 is a ciliary guanylyl cyclase, not a ciliogenesis factor. The IGI appears to reflect the cilium genes (WITH partners), not a function of DAF-11.
Supporting Evidence:
PMID:1732156
Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes.
PMID:21124868
By contrast, daf-11 and daf-21 mutants show wild-type dye filling
GO:0060271 cilium assembly
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
REMOVE
Summary: IGI cilium assembly derived from double-mutant epistasis between daf-11 and cilium-structure (che/osm/daf) mutants.
Reason: The cited paper shows that Daf-c mutations in daf-11 are suppressed by mutations in nine cilium-structure genes, i.e. daf-11 requires intact cilia to exert its effect; this epistasis places cilium formation upstream/permissive for DAF-11 signalling and does not show that DAF-11 builds cilia. daf-11 mutants have structurally normal, dye-filling amphid cilia. DAF-11 is a ciliary guanylyl cyclase, not a ciliogenesis factor. The IGI appears to reflect the cilium genes (WITH partners), not a function of DAF-11.
Supporting Evidence:
PMID:1732156
Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes.
PMID:21124868
By contrast, daf-11 and daf-21 mutants show wild-type dye filling
GO:0060271 cilium assembly
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
REMOVE
Summary: IGI cilium assembly derived from double-mutant epistasis between daf-11 and cilium-structure (che/osm/daf) mutants.
Reason: The cited paper shows that Daf-c mutations in daf-11 are suppressed by mutations in nine cilium-structure genes, i.e. daf-11 requires intact cilia to exert its effect; this epistasis places cilium formation upstream/permissive for DAF-11 signalling and does not show that DAF-11 builds cilia. daf-11 mutants have structurally normal, dye-filling amphid cilia. DAF-11 is a ciliary guanylyl cyclase, not a ciliogenesis factor. The IGI appears to reflect the cilium genes (WITH partners), not a function of DAF-11.
Supporting Evidence:
PMID:1732156
Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes.
PMID:21124868
By contrast, daf-11 and daf-21 mutants show wild-type dye filling
GO:0060271 cilium assembly
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
REMOVE
Summary: IGI cilium assembly derived from double-mutant epistasis between daf-11 and cilium-structure (che/osm/daf) mutants.
Reason: The cited paper shows that Daf-c mutations in daf-11 are suppressed by mutations in nine cilium-structure genes, i.e. daf-11 requires intact cilia to exert its effect; this epistasis places cilium formation upstream/permissive for DAF-11 signalling and does not show that DAF-11 builds cilia. daf-11 mutants have structurally normal, dye-filling amphid cilia. DAF-11 is a ciliary guanylyl cyclase, not a ciliogenesis factor. The IGI appears to reflect the cilium genes (WITH partners), not a function of DAF-11.
Supporting Evidence:
PMID:1732156
Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes.
PMID:21124868
By contrast, daf-11 and daf-21 mutants show wild-type dye filling
GO:0060271 cilium assembly
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
REMOVE
Summary: IGI cilium assembly derived from double-mutant epistasis between daf-11 and cilium-structure (che/osm/daf) mutants.
Reason: The cited paper shows that Daf-c mutations in daf-11 are suppressed by mutations in nine cilium-structure genes, i.e. daf-11 requires intact cilia to exert its effect; this epistasis places cilium formation upstream/permissive for DAF-11 signalling and does not show that DAF-11 builds cilia. daf-11 mutants have structurally normal, dye-filling amphid cilia. DAF-11 is a ciliary guanylyl cyclase, not a ciliogenesis factor. The IGI appears to reflect the cilium genes (WITH partners), not a function of DAF-11.
Supporting Evidence:
PMID:1732156
Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes.
PMID:21124868
By contrast, daf-11 and daf-21 mutants show wild-type dye filling
GO:0060271 cilium assembly
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
REMOVE
Summary: IGI cilium assembly derived from double-mutant epistasis between daf-11 and cilium-structure (che/osm/daf) mutants.
Reason: The cited paper shows that Daf-c mutations in daf-11 are suppressed by mutations in nine cilium-structure genes, i.e. daf-11 requires intact cilia to exert its effect; this epistasis places cilium formation upstream/permissive for DAF-11 signalling and does not show that DAF-11 builds cilia. daf-11 mutants have structurally normal, dye-filling amphid cilia. DAF-11 is a ciliary guanylyl cyclase, not a ciliogenesis factor. The IGI appears to reflect the cilium genes (WITH partners), not a function of DAF-11.
Supporting Evidence:
PMID:1732156
Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes.
PMID:21124868
By contrast, daf-11 and daf-21 mutants show wild-type dye filling
GO:0061065 regulation of dauer larval development
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
ACCEPT
Summary: IGI epistasis placing daf-11 at the chemosensory step controlling dauer formation. Regulation of dauer development is a core organismal role of DAF-11 cGMP signalling.
Supporting Evidence:
PMID:1732156
These results suggest that daf-11 is directly involved in chemosensory transduction essential for dauer formation
GO:0061065 regulation of dauer larval development
IGI
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
ACCEPT
Summary: IGI (same epistasis analysis). Core regulatory role in dauer decision.
Supporting Evidence:
PMID:1732156
Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes.
GO:0061065 regulation of dauer larval development
IMP
PMID:1732156
Genetic analysis of chemosensory control of dauer formation ...
ACCEPT
Summary: IMP: daf-11 mutants are dauer-constitutive. Core.
Supporting Evidence:
PMID:1732156
These results suggest that daf-11 is directly involved in chemosensory transduction essential for dauer formation
GO:0061065 regulation of dauer larval development
IMP
PMID:21124868
Localization of a guanylyl cyclase to chemosensory cilia req...
ACCEPT
Summary: IMP from the DAF-25 study: daf-25 mutants phenocopy daf-11 Daf-c and act at the same point in the pathway because DAF-25 is needed to localize DAF-11 to cilia.
Supporting Evidence:
PMID:21124868
This indicates that DAF-25 is required for the proper localization of DAF-11 to the cilia, providing a likely explanation for the similarities between the daf-11 and daf-25 mutant phenotypes.
GO:0061067 negative regulation of dauer larval development
IMP
PMID:6583682
A pheromone-induced developmental switch in Caenorhabditis e...
ACCEPT
Summary: Temperature-sensitive daf-11 Daf-c mutants form dauers under non-inducing conditions and over-respond to pheromone, showing that DAF-11 represses dauer entry. Core organismal role.
Supporting Evidence:
PMID:6583682
Temperature-sensitive (ts) dauer-constitutive mutants form dauer larvae at a restrictive temperature regardless of environmental stimuli.
GO:0061067 negative regulation of dauer larval development
IMP
PMID:8893028
Chemosensory neurons function in parallel to mediate a phero...
ACCEPT
Summary: Neuron-killing in Daf-c mutants shows DAF-11-pathway mutations disrupt dauer repression by ADF/ASI/ASG and activate ASJ-dependent dauer formation. Core.
Supporting Evidence:
PMID:8893028
Formation of the C. elegans dauer larva is repressed by the chemosensory neurons ADF, ASI, and ASG.
GO:0071321 cellular response to cGMP
IMP
PMID:19489741
Endogenous cGMP regulates adult longevity via the insulin si...
MARK AS OVER ANNOTATED
Summary: IMP cellular response to cGMP from the lifespan study.
Reason: DAF-11 produces cGMP; it is not a component of the cellular response to cGMP (effectors such as TAX-2/TAX-4, EGL-4 or PDEs fit that term). The phenotype is presumably that daf-11 mutant phenotypes respond to exogenous cGMP, which shows that cGMP is the relevant product, not that DAF-11 responds to cGMP. The abstract does not name daf-11; full text unavailable.
Supporting Evidence:
PMID:19489741
A reduced neuronal cGMP level was found to be caused by an increased cGMP-specific phosphodiesterase activity at the transcriptional level.
GO:0097730 non-motile cilium
IDA
PMID:10790386
A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21)...
ACCEPT
Summary: DAF-11 is enriched in the non-motile sensory cilia of ASI, ASJ, ASK, AWB and AWC, where it acts. Core location.
Supporting Evidence:
PMID:21124868
In wild-type animals, the DAF-11::GFP protein localized to the sensory cilia of the olfactory neuron pairs ASI, ASJ, ASK, AWB and AWC

Core Functions

Ciliary receptor-type guanylate cyclase: converts GTP to cGMP in the sensory cilia of ASI, ASJ, ASK, AWB and AWC chemosensory neurons, supplying the second messenger for cGMP-gated (TAX-2/TAX-4) transduction channels.

Supporting Evidence:
  • PMID:10790386
    We report that daf-11 encodes one of a large family of C. elegans transmembrane guanylyl cyclases (TM-GCs).
  • PMID:10790386
    The cyclic GMP analogue 8-bromo-cGMP rescues a sensory defect in both daf-11 and daf-21 mutants, supporting a role for DAF-11 guanylyl cyclase activity in this process
  • PMID:21124868
    In wild-type animals, the DAF-11::GFP protein localized to the sensory cilia of the olfactory neuron pairs ASI, ASJ, ASK, AWB and AWC

cGMP source for chemosensory and light transduction: DAF-11 is required for AWC-mediated chemotaxis to volatile odorants and for LITE-1-dependent photocurrents in ASJ, acting at the cyclase step between upstream receptors/G proteins and the CNG channel.

Molecular Function:
guanylate cyclase activity
Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • PMID:7828815
    both mutants are defective in taxis to volatile attractants detected primarily by the amphid neuron AWC
  • PMID:20436480
    Two independent daf-11 mutant alleles, ks67 and m47, both lacked photocurrents in ASJ

Sensory repression of dauer entry: cGMP signalling by DAF-11 in ASI/ASJ is required to keep larvae in reproductive development, partly by sustaining daf-7 TGF-beta expression in ASI.

Supporting Evidence:
  • PMID:1732156
    These results suggest that daf-11 is directly involved in chemosensory transduction essential for dauer formation
  • PMID:11677050
    Expression of daf-11 cDNA by cell specific promoters suggests that daf-11 acts cell autonomously in ASI chemosensory neurons for daf-7 expression.

References

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Suggested Questions for Experts

Q: What ligand or stimulus, if any, binds the DAF-11 extracellular domain, and is DAF-11 activity regulated directly by NO or other gases through its HNOBA region?

Q: Does DAF-11 form heterodimers with ODR-1 or other co-expressed receptor guanylyl cyclases in AWC/ASJ cilia, and is each partner catalytically competent?

Suggested Experiments

Experiment: Measure cyclase activity of recombinant DAF-11 (alone and co-expressed with ODR-1) in membranes, testing candidate ligands, NO donors and DAF-21/Hsp90 dependence.

Deep Research

WormBase

(daf-11-deep-research-wormbase.md)

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πŸ“š Additional Documentation

Notes

(daf-11-notes.md)

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