odr-1 (gcy-10) encodes a receptor-type (single-pass transmembrane) guanylyl cyclase of Caenorhabditis elegans. It has an extracellular periplasmic-binding- protein-like domain, a transmembrane helix, a cytoplasmic kinase-homology domain (predicted catalytically inactive), and a C-terminal guanylate cyclase catalytic domain that converts GTP to the second messenger cGMP (EC 4.6.1.2). ODR-1 is expressed in a defined set of ciliated sensory neurons (predominantly AWC, and also AWB, ASI, ASJ and ASK) and localizes to the sensory cilium and cell membrane. As a source of cGMP acting downstream of odorant receptors, ODR-1 is a shared signaling component required for AWC-mediated olfaction and odor discrimination and for AWB-mediated odor avoidance; the cGMP it produces gates the TAX-2/TAX-4 cyclic-nucleotide-gated channel. The same cGMP output is redeployed in other ciliated neurons, contributing to ASJ phototransduction, to bitter-tastant (quinine) sensitivity via non-cell-autonomous supply of cGMP to the EGL-4 PKG, and to maintenance of asymmetric olfactory-receptor (str-2) gene expression in AWC. No activating ligand for its extracellular domain has been identified.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004383 guanylate cyclase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Guanylate cyclase is the defining catalytic activity of ODR-1, supported by domain architecture (Pfam PF00211 cyclase domain 859-989), the E904A cyclase- domain mutant that abolishes activity and olfaction, and ISS transfer from orthologous receptor GCs. Correct and core. Supporting Evidence: PMID:10774726 the transmembrane guanylyl cyclase ODR-1 |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ODR-1 is a single-pass type I membrane protein. Its functionally relevant pool is in the sensory cilium (a specialized plasma-membrane compartment); plasma membrane is correct but less specific than the ciliary localization (see the IDA non-motile cilium annotation from PMID:10774726). Keep as a non-core supporting location. |
| GO:0006182 cGMP biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Production of the cGMP second messenger is the direct biological process of ODR-1's cyclase activity and is central to all of its downstream roles. Core. |
| GO:0007168 receptor guanylyl cyclase signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ODR-1 is a receptor-type GC and its cGMP output drives sensory signal transduction, so this term is apt at the pathway level. Note the strict GO definition invokes an extracellular ligand binding the GC receptor; no ligand for ODR-1's ectodomain is known, and ODR-1 acts downstream of odorant receptors as a shared component. Retain as a non-core signaling-pathway term. Supporting Evidence: PMID:10774726 ODR-1 appears to be a shared signaling component downstream of odorant receptors |
| GO:0001653 peptide receptor activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Phylogenetic (PANTHER) transfer from mammalian natriuretic-peptide-receptor guanylyl cyclases (NPR-A/NPR-B). C. elegans receptor GCs are orphan receptors with no demonstrated peptide ligand, and UniProt notes the ODR-1 extracellular domain may not be directly implicated in odorant detection. No experimental support for peptide-receptor activity in ODR-1; this is an over-annotation propagated from vertebrate paralogs. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: UniProtKB:P16066 · NPR1 (human natriuretic peptide receptor 1) SUPPORTS SOURCE BUT NOT TARGET Bona fide peptide (natriuretic peptide) receptor GC; ODR-1 is an orphan receptor GC with no known peptide ligand, so peptide-receptor activity does not transfer. UniProtKB:P20594 · NPR2 (human natriuretic peptide receptor 2) SUPPORTS SOURCE BUT NOT TARGET |
| GO:0004383 guanylate cyclase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated EC 4.6.1.2 / RHEA:13665 assignment of guanylate cyclase activity. Consistent with the catalytic domain and the manual ISS/IBA annotations. Core molecular function (duplicate of the manually supported term). |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro (IPR000719) inference from the kinase-homology domain; UniProt lists candidate ATP-binding residues (515-523, 534). However UniProt predicts this kinase domain to be catalytically inactive (pseudokinase), so nucleotide binding is uncertain and, if it occurs, is regulatory/structural rather than a core function. Retain as a weak, non-core electronic annotation. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt Subcellular Location mapping (SL-0039). Correct but subsumed by the more specific ciliary localization. Non-core supporting location. |
| GO:0005929 cilium | IEA GO_REF:0000044 | ACCEPT | Summary: Ciliary localization is experimentally established (IDA to non-motile cilium, GO:0097730, from PMID:10774726). This SubCell-derived cilium annotation is correct and captures the core location; the sibling IDA non-motile cilium term is the more specific, core cellular component. |
| GO:0007635 chemosensory behavior | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic annotation. odr-1's chemosensory role is well established experimentally (olfaction, quinine avoidance). This generic term is correct but less informative than the specific olfactory/chemotaxis terms; keep as a non-core parent. |
| GO:0009190 cyclic nucleotide biosynthetic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic parent of the specific, experimentally supported cGMP biosynthetic process (GO:0006182). Correct but redundant; keep as non-core. |
| GO:0035556 intracellular signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: High-level signal-transduction parent inferred from InterPro. Correct in spirit (cGMP second-messenger signaling) but uninformative relative to the specific receptor-GC-signaling / sensory-perception terms. Non-core. |
| GO:0050913 sensory perception of bitter taste | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic version of the experimentally supported quinine-sensitivity role (see IMP/IGI from PMID:23874221). odr-1 supplies cGMP non-cell- autonomously to EGL-4 in ASH; bitter-taste sensitivity is a peripheral, non-core role of odr-1. |
| GO:0004383 guanylate cyclase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Curator ISS transfer of guanylate cyclase activity from an orthologous receptor GC (UniProtKB:Q19187, gcy-12). Consistent with the catalytic domain and the E904A mutant phenotype. Core molecular function. |
| GO:0050767 regulation of neurogenesis | IMP PMID:31259686 The Caenorhabditis elegans Tubby homolog dynamically modulat... | KEEP AS NON CORE | Summary: From the Tubby (tub-1) study, in which odr-1 loss-of-function ("receptor guanylyl cyclase signaling mutants") causes expanded AWB ciliary membrane fans and altered ciliary lipid/protein content. This is a downstream, sensory-signaling-dependent developmental readout of reduced cGMP signaling, not a distinct activity of ODR-1; retain but as a non-core developmental role. Supporting Evidence: PMID:31259686 AWB cilia width is significantly increased in odr-1 receptor guanylyl cyclase signaling mutants |
| GO:0097499 protein localization to non-motile cilium | IMP PMID:31259686 The Caenorhabditis elegans Tubby homolog dynamically modulat... | KEEP AS NON CORE | Summary: odr-1 mutants show increased ciliary accumulation of TUB-1 and the PIP5-kinase PPK-1 in AWB cilia; loss of odr-1 sensory signaling thus alters ciliary protein localization. This is an indirect, non-cell-intrinsic consequence of reduced cGMP signaling rather than a direct trafficking function of ODR-1; keep as non-core. Supporting Evidence: PMID:31259686 we found that odr-1 mutants showed enrichment of a TUB-1 fusion protein in AWB cilia as compared to levels at the PCMC |
| 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: The cached abstract of PMID:18832350 describes EGL-4 PKG, KIN-29 and PKA regulating chemoreceptor gene expression and does not itself name odr-1; full text is unavailable. A role for odr-1 as an upstream cGMP source for EGL-4-dependent chemoreceptor-gene expression is plausible but cannot be verified from the abstract. Per curation policy the experimental annotation is not removed; treat as non-core and unverified from available text. |
| GO:0006182 cGMP biosynthetic process | ISS PMID:10774726 Olfaction and odor discrimination are mediated by the C. ele... | ACCEPT | Summary: cGMP biosynthesis is the direct process of ODR-1's cyclase activity, here transferred by similarity (WITH UniProtKB:P16066, a natriuretic-peptide- receptor GC) and anchored to the ODR-1 characterization paper. Core. Supporting Evidence: PMID:10774726 probably by overproduction of the shared second messenger cGMP |
| GO:0040015 negative regulation of multicellular organism growth | IGI PMID:26434723 The Importance of cGMP Signaling in Sensory Cilia for Body S... | KEEP AS NON CORE | Summary: Genetic-interaction annotation from the body-size study, whose abstract attributes cGMP-dependent body-size control specifically to gcy-12 (WITH UniProtKB:Q19187) and states EGL-4 partners with different GCs for different tasks. Body-size regulation is peripheral to odr-1's core sensory function. The experimental IGI is retained (full text not read) but marked non-core, and the reference is flagged as low relevance for odr-1. |
| 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: Parent of the negative-regulation term above; same body-size study (WITH UniProtKB:G5EGF0). Peripheral to odr-1's core function; retain as non-core. |
| GO:0007635 chemosensory behavior | IMP PMID:23874221 The C. elegans cGMP-dependent protein kinase EGL-4 regulates... | KEEP AS NON CORE | Summary: odr-1 loss causes behavioral hypersensitivity to dilute quinine, a chemosensory (bitter-tastant avoidance) phenotype mediated by cGMP supply to EGL-4. Correct; a generic chemosensory-behavior term for a peripheral (bitter/ nociceptive) role. Keep as non-core. Supporting Evidence: PMID:23874221 Loss-of-function mutations in the guanylyl cyclase genes odr-1, gcy-27, gcy-33 and gcy-34 resulted in behavioral hypersensitivity to dilute (1 mM) quinine |
| GO:0007635 chemosensory behavior | IGI PMID:23874221 The C. elegans cGMP-dependent protein kinase EGL-4 regulates... | KEEP AS NON CORE | Summary: Genetic-interaction version of the quinine-sensitivity chemosensory role (WITH UniProtKB:O76360). Same interpretation as the IMP above; non-core. Supporting Evidence: PMID:23874221 the cyclases may function in a non-cell-autonomous manner to provide cGMP to regulate EGL-4 function in ASH |
| GO:0050913 sensory perception of bitter taste | IMP PMID:23874221 The C. elegans cGMP-dependent protein kinase EGL-4 regulates... | KEEP AS NON CORE | Summary: Experimentally supported bitter-tastant (quinine) sensitivity role: odr-1(lof) animals are hypersensitive to dilute quinine and the defect is rescued by srb-6p::odr-1. A genuine but peripheral, non-cell-autonomous role of odr-1; non-core relative to olfaction. Supporting Evidence: PMID:23874221 The quinine hypersensitivity of odr-1(lof) animals was rescued by srb-6p::odr-1 expression (p<0.001), but not osm-10p::odr-1 expression (p>0.5). |
| GO:0050913 sensory perception of bitter taste | IGI PMID:23874221 The C. elegans cGMP-dependent protein kinase EGL-4 regulates... | KEEP AS NON CORE | Summary: Genetic-interaction version of the quinine bitter-taste role (WITH UniProtKB:O76360). Same interpretation; non-core. |
| GO:0007602 phototransduction | IMP PMID:20436480 C. elegans phototransduction requires a G protein-dependent ... | KEEP AS NON CORE | Summary: odr-1(n1936) mutants show a severe reduction in ASJ photocurrent density, demonstrating a requirement for membrane-associated GCs (odr-1, daf-11) in cGMP-dependent phototransduction. A genuine experimental role, but a redeployment of the same cGMP/CNG-channel machinery in a specialized context; peripheral to the core olfactory function, so non-core. Supporting Evidence: PMID:20436480 odr-1(n1936) mutant worms also showed a severe reduction in the density of photocurrents |
| GO:0010628 positive regulation of gene expression | IMP PMID:10571181 Lateral signaling mediated by axon contact and calcium entry... | KEEP AS NON CORE | Summary: A cGMP signaling pathway used in olfaction (odr-1-dependent) maintains asymmetric expression of the olfactory receptor gene str-2 in adult AWC. This is a real, cGMP-mediated effect on gene expression, but a specialized developmental/maintenance role downstream of odr-1's cyclase activity; non-core. Supporting Evidence: PMID:10571181 A cGMP signaling pathway that is used in olfaction maintains str-2 expression after the initial decision has been made. |
| GO:0042048 olfactory behavior | IMP PMID:8348618 Odorant-selective genes and neurons mediate olfaction in C. ... | ACCEPT | Summary: odr-1 was isolated as an odr (odorant-response-abnormal) gene; the G647D mutant (n1930) causes loss of chemotaxis to volatile odorants. Olfactory behavior is the core organismal role of odr-1. Accept as core. Supporting Evidence: PMID:8348618 Chemotaxis to subsets of volatile odorants is disrupted by mutations in the odr genes, which might be involved in odorant sensation or signal transduction. |
| GO:1990834 response to odorant | IMP PMID:8348618 Odorant-selective genes and neurons mediate olfaction in C. ... | ACCEPT | Summary: odr-1 mutants are defective in chemotaxis responses to volatile odorants; the gene is required for the organism's response to odorants. Core sensory role. Supporting Evidence: PMID:8348618 Chemotaxis to subsets of volatile odorants is disrupted by |
| GO:0097730 non-motile cilium | IDA PMID:10774726 Olfaction and odor discrimination are mediated by the C. ele... | ACCEPT | Summary: Direct experimental localization (IDA, WormBase) of ODR-1 to the sensory (non-motile) cilium, reported in the ODR-1 characterization paper. This is the core cellular component where ODR-1 functions. The localization datum is in the full text (not the cached abstract), so no verbatim quote is attached; accept and defer to the curator's IDA. |
| GO:0004383 guanylate cyclase activity | ISS PMID:10774726 Olfaction and odor discrimination are mediated by the C. ele... | ACCEPT | Summary: ISS assignment of guanylate cyclase activity anchored to the ODR-1 characterization paper (WITH UniProtKB:P16066). Core molecular function (duplicate of the other guanylate-cyclase annotations). Supporting Evidence: PMID:10774726 the transmembrane guanylyl cyclase ODR-1 |
| GO:0008355 olfactory learning | IMP PMID:10774726 Olfaction and odor discrimination are mediated by the C. ele... | KEEP AS NON CORE | Summary: ODR-1 influences odor adaptation/discrimination (overexpression disrupts butanone adaptation and olfactory discrimination), consistent with an olfactory-plasticity ("learning") role. A specialized aspect of odr-1's olfactory function; keep as non-core relative to the primary olfaction terms. Supporting Evidence: PMID:10774726 Olfactory discrimination is also disrupted by ODR-1 overexpression |
| GO:0008355 olfactory learning | IGI PMID:10774726 Olfaction and odor discrimination are mediated by the C. ele... | KEEP AS NON CORE | Summary: Genetic-interaction version of the olfactory-adaptation/learning role (WITH WB:WBGene00001664). Same interpretation as the IMP; non-core. Supporting Evidence: PMID:10774726 ODR-1 can influence odor discrimination and adaptation as well as olfaction |
| GO:0042048 olfactory behavior | IMP PMID:10774726 Olfaction and odor discrimination are mediated by the C. ele... | ACCEPT | Summary: ODR-1 is essential for responses to all AWC-sensed odorants; olfactory behavior is the core organismal function of odr-1. Accept as core. Supporting Evidence: PMID:10774726 ODR-1 is essential for responses to all AWC-sensed odorants |
| GO:0050918 positive chemotaxis | IMP PMID:10774726 Olfaction and odor discrimination are mediated by the C. ele... | ACCEPT | Summary: ODR-1 is required for AWC-mediated attraction (positive chemotaxis) to volatile odorants; ODR-1 is essential for responses to all AWC-sensed odorants. A specific, experimentally supported aspect of the core olfactory role. Accept. Supporting Evidence: PMID:10774726 ODR-1 is essential for responses to all AWC-sensed odorants |
| GO:0050919 negative chemotaxis | IMP PMID:10774726 Olfaction and odor discrimination are mediated by the C. ele... | ACCEPT | Summary: ODR-1 also acts in AWB, the sensory neuron pair that mediates avoidance (negative chemotaxis) of volatile odorants. Correct; a specific aspect of the core olfactory role. The AWB-avoidance datum is in the full text/UniProt FUNCTION rather than the cached abstract, so no verbatim quote is attached; accept and defer to the curator's IMP. |
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Download this section (compressed HTML)Q: What activates ODR-1's guanylate cyclase in vivo — is there a ligand for its extracellular domain, or is its output regulated purely by intracellular inputs (G-protein/Ca2+/phosphorylation) downstream of odorant receptors?
Suggested experts: L'Etoile ND, Bargmann CI
Q: Is ODR-1 a catalytically autonomous guanylyl cyclase, or does it act as a regulatory subunit / heterodimer with another GC (e.g. DAF-11) to produce cGMP in AWC/AWB and in ASJ photoreceptor neurons?
Suggested experts: Xu XZ
Experiment: Express and purify the ODR-1 cytoplasmic module (kinase-homology + cyclase domains) and assay GTP-to-cGMP conversion in vitro, comparing wild type with the E904A catalytic mutant and with co-expressed DAF-11 to test for heterodimeric activation.
Hypothesis: ODR-1 possesses guanylate cyclase activity that requires the cyclase domain (E904) and, like other receptor GCs, may need a partner GC (e.g. DAF-11) to form an active catalytic site.
Type: in vitro enzymatic assay
Experiment: Use a genetically encoded cGMP sensor in AWC to measure odorant-evoked cGMP transients in wild type versus odr-1(lof) and odr-1(E904A), and test epistasis with tax-2/tax-4 for the downstream calcium response.
Hypothesis: ODR-1-produced cGMP gates the TAX-2/TAX-4 CNG channel in AWC to drive odorant responses.
Type: in vivo cGMP/calcium imaging
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The activating ligand and the in vivo mechanism that regulates ODR-1's cyclase output are unknown. No peptide or small-molecule ligand has been identified for its extracellular periplasmic-binding-protein-like domain, and it is undetermined how odorant-receptor/G-protein input, Ca2+, or phosphorylation modulate ODR-1 cGMP production during sensory transduction.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: It is firmly established that ODR-1 is a transmembrane guanylyl cyclase producing cGMP that acts downstream of odorant receptors as a shared signaling component, that it is required for AWC/AWB olfaction, and that UniProt notes its extracellular domain "may not be directly implicated in the detection of volatile odorants." What is missing is the upstream activator/regulator of its enzymatic activity.
Significance: ODR-1 is the cGMP source for a canonical cGMP/CNG (TAX-2/TAX-4) sensory pathway; identifying what turns its cyclase on/off would define how olfactory-receptor signals are converted into second-messenger output in ciliated neurons.
What would resolve it: Biochemical/electrophysiological identification of an ODR-1 activator (candidate ligand screens on the ectodomain; epistasis with odorant receptors and G proteins; cGMP measurement in defined neurons upon odorant stimulation).
Provenance (the field's own admissions):
Gap: Whether ODR-1's guanylate cyclase domain is catalytically active on its own (a functional cyclase) versus a regulatory subunit that must partner with another guanylyl cyclase (e.g. DAF-11) to form an active enzyme has not been directly tested; ODR-1 cyclase activity has never been measured on purified protein.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: The E904A cyclase-domain mutant causes probable loss of cyclase activity and loss of chemotaxis, and ODR-1 and DAF-11 are co-expressed and jointly required in ASJ/ASK photoreceptor cells, indicating ODR-1 contributes to cGMP production; but no in vitro enzymology, dimerization state, or partner-dependence has been established. UniProt further predicts the adjacent kinase-homology domain to be catalytically inactive.
Significance: Several receptor guanylyl cyclases act as heterodimers or as regulatory (catalytically impaired) subunits; resolving ODR-1's catalytic autonomy would clarify whether the cGMP for AWC/AWB olfaction is made by ODR-1 itself or by an ODR-1-containing complex, and how much of odr-1 phenotypes reflect a non-catalytic/regulatory role.
What would resolve it: In vitro guanylate cyclase assays on purified/recombinant ODR-1 and defined catalytic-dead mutants; test ODR-1/DAF-11 heterodimerization and its contribution to neuronal cGMP.
Provenance (the field's own admissions):
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