id: B1Q257
gene_symbol: odr-1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: >-
  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.
alternative_products:
- name: b {ECO:0000312|WormBase:R01E6.1b}
  id: B1Q257-1
- name: a {ECO:0000312|WormBase:R01E6.1a}
  id: B1Q257-2
  sequence_note: VSP_057702, VSP_057703, VSP_057704
existing_annotations:
- term:
    id: GO:0004383
    label: guanylate cyclase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10774726
      supporting_text: "the transmembrane guanylyl cyclase ODR-1"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0006182
    label: cGMP biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
- term:
    id: GO:0007168
    label: receptor guanylyl cyclase signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:10774726
      supporting_text: "ODR-1 appears to be a shared signaling \ncomponent downstream of odorant receptors"
- term:
    id: GO:0001653
    label: peptide receptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - FUNCTIONAL_DIVERGENCE
      source_entities:
      - source_id: UniProtKB:P16066
        source_label: NPR1 (human natriuretic peptide receptor 1)
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: >-
          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.
      - source_id: UniProtKB:P20594
        source_label: NPR2 (human natriuretic peptide receptor 2)
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
- term:
    id: GO:0004383
    label: guanylate cyclase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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).
    action: ACCEPT
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      UniProt Subcellular Location mapping (SL-0039). Correct but subsumed by the
      more specific ciliary localization. Non-core supporting location.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0005929
    label: cilium
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
- term:
    id: GO:0007635
    label: chemosensory behavior
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0009190
    label: cyclic nucleotide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Generic parent of the specific, experimentally supported cGMP biosynthetic
      process (GO:0006182). Correct but redundant; keep as non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0050913
    label: sensory perception of bitter taste
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0004383
    label: guanylate cyclase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    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.
    action: ACCEPT
- term:
    id: GO:0050767
    label: regulation of neurogenesis
  evidence_type: IMP
  original_reference_id: PMID:31259686
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:31259686
      supporting_text: "AWB cilia width is significantly increased in odr-1 receptor guanylyl cyclase signaling mutants"
- term:
    id: GO:0097499
    label: protein localization to non-motile cilium
  evidence_type: IMP
  original_reference_id: PMID:31259686
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:31259686
      supporting_text: "we found that odr-1 mutants showed enrichment of a TUB-1 fusion protein in AWB cilia as compared to levels at the PCMC"
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:18832350
  qualifier: acts_upstream_of
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0006182
    label: cGMP biosynthetic process
  evidence_type: ISS
  original_reference_id: PMID:10774726
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10774726
      supporting_text: "probably by overproduction of the shared second messenger cGMP"
- term:
    id: GO:0040015
    label: negative regulation of multicellular organism growth
  evidence_type: IGI
  original_reference_id: PMID:26434723
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0040014
    label: regulation of multicellular organism growth
  evidence_type: IGI
  original_reference_id: PMID:26434723
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0007635
    label: chemosensory behavior
  evidence_type: IMP
  original_reference_id: PMID:23874221
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:23874221
      supporting_text: "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"
- term:
    id: GO:0007635
    label: chemosensory behavior
  evidence_type: IGI
  original_reference_id: PMID:23874221
  qualifier: involved_in
  review:
    summary: >-
      Genetic-interaction version of the quinine-sensitivity chemosensory role
      (WITH UniProtKB:O76360). Same interpretation as the IMP above; non-core.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:23874221
      supporting_text: "the cyclases may function in a non-cell-autonomous manner to provide cGMP to regulate EGL-4 function in ASH"
- term:
    id: GO:0050913
    label: sensory perception of bitter taste
  evidence_type: IMP
  original_reference_id: PMID:23874221
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:23874221
      supporting_text: "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)."
- term:
    id: GO:0050913
    label: sensory perception of bitter taste
  evidence_type: IGI
  original_reference_id: PMID:23874221
  qualifier: involved_in
  review:
    summary: >-
      Genetic-interaction version of the quinine bitter-taste role (WITH
      UniProtKB:O76360). Same interpretation; non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0007602
    label: phototransduction
  evidence_type: IMP
  original_reference_id: PMID:20436480
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:20436480
      supporting_text: "odr-1(n1936) mutant worms also showed a severe reduction in the density of photocurrents"
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:10571181
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:10571181
      supporting_text: "A cGMP signaling \npathway that is used in olfaction maintains str-2 expression after the initial \ndecision has been made."
- term:
    id: GO:0042048
    label: olfactory behavior
  evidence_type: IMP
  original_reference_id: PMID:8348618
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:8348618
      supporting_text: "Chemotaxis to subsets of volatile odorants is disrupted by \nmutations in the odr genes, which might be involved in odorant sensation or \nsignal transduction."
- term:
    id: GO:1990834
    label: response to odorant
  evidence_type: IMP
  original_reference_id: PMID:8348618
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:8348618
      supporting_text: "Chemotaxis to subsets of volatile odorants is disrupted by"
- term:
    id: GO:0097730
    label: non-motile cilium
  evidence_type: IDA
  original_reference_id: PMID:10774726
  qualifier: located_in
  review:
    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.
    action: ACCEPT
- term:
    id: GO:0004383
    label: guanylate cyclase activity
  evidence_type: ISS
  original_reference_id: PMID:10774726
  qualifier: enables
  review:
    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).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10774726
      supporting_text: "the transmembrane guanylyl cyclase ODR-1"
- term:
    id: GO:0008355
    label: olfactory learning
  evidence_type: IMP
  original_reference_id: PMID:10774726
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:10774726
      supporting_text: "Olfactory discrimination is also disrupted by ODR-1 \noverexpression"
- term:
    id: GO:0008355
    label: olfactory learning
  evidence_type: IGI
  original_reference_id: PMID:10774726
  qualifier: involved_in
  review:
    summary: >-
      Genetic-interaction version of the olfactory-adaptation/learning role
      (WITH WB:WBGene00001664). Same interpretation as the IMP; non-core.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:10774726
      supporting_text: "ODR-1 can influence odor discrimination and adaptation as well as \nolfaction"
- term:
    id: GO:0042048
    label: olfactory behavior
  evidence_type: IMP
  original_reference_id: PMID:10774726
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10774726
      supporting_text: "ODR-1 is essential for \nresponses to all AWC-sensed odorants"
- term:
    id: GO:0050918
    label: positive chemotaxis
  evidence_type: IMP
  original_reference_id: PMID:10774726
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10774726
      supporting_text: "ODR-1 is essential for \nresponses to all AWC-sensed odorants"
- term:
    id: GO:0050919
    label: negative chemotaxis
  evidence_type: IMP
  original_reference_id: PMID:10774726
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
core_functions:
- description: >-
    Receptor-type guanylate cyclase: catalyzes the conversion of GTP to the second
    messenger cGMP (EC 4.6.1.2) via its C-terminal cyclase domain, acting at the
    ciliary/plasma membrane of sensory neurons. The catalytic identity is supported
    by domain architecture and by the cyclase-domain E904A mutant that causes
    probable loss of cyclase activity and loss of odorant chemotaxis.
  molecular_function:
    id: GO:0004383
    label: guanylate cyclase activity
  directly_involved_in:
  - id: GO:0006182
    label: cGMP biosynthetic process
  locations:
  - id: GO:0060170
    label: ciliary membrane
  - id: GO:0097730
    label: non-motile cilium
  supported_by:
  - reference_id: PMID:10774726
    supporting_text: "the transmembrane guanylyl cyclase ODR-1"
- description: >-
    Shared cGMP-producing signaling component of AWC/AWB olfactory transduction:
    acting downstream of odorant receptors, ODR-1 generates the cGMP that gates the
    TAX-2/TAX-4 cyclic-nucleotide-gated channel, and is required for responses to
    all AWC-sensed odorants, for AWC attractive (positive) chemotaxis and AWB
    aversive (negative) chemotaxis, and for odor discrimination and adaptation.
  molecular_function:
    id: GO:0004383
    label: guanylate cyclase activity
  directly_involved_in:
  - id: GO:0042048
    label: olfactory behavior
  - id: GO:0007608
    label: sensory perception of smell
  locations:
  - id: GO:0097730
    label: non-motile cilium
  supported_by:
  - reference_id: PMID:10774726
    supporting_text: "ODR-1 appears to be a shared signaling \ncomponent downstream of odorant receptors"
  - reference_id: PMID:8348618
    supporting_text: "Chemotaxis to subsets of volatile odorants is disrupted by"
knowledge_gaps:
- gap_statement: >-
    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.
  boundary: >-
    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.
  gap_kind:
  - BIOLOGY
  dark_aspect: RESIDUAL_SUBGAP
  status: OPEN
  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.
  resolution: >-
    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:
  - reference_id: PMID:10774726
    supporting_text: "ODR-1 appears to be a shared signaling \ncomponent downstream of odorant receptors"
- gap_statement: >-
    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.
  boundary: >-
    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.
  gap_kind:
  - BIOLOGY
  dark_aspect: RESIDUAL_SUBGAP
  status: OPEN
  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.
  resolution: >-
    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:
  - reference_id: PMID:20436480
    supporting_text: "two membrane-associated GCs (daf-11 and odr-1) are expressed in C. elegans photoreceptor cells, including ASJ, ASK and AWB"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10571181
  title: Lateral signaling mediated by axon contact and calcium entry regulates asymmetric
    odorant receptor expression in C. elegans.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified (Troemel, Sagasti, Bargmann, Cell 1999). Supports the odr-1
      GO:0010628 (positive regulation of gene expression) annotation: a cGMP
      signaling pathway used in olfaction maintains adult AWC str-2 expression.
      Abstract-only in cache (full_text_available: false).
- id: PMID:10774726
  title: Olfaction and odor discrimination are mediated by the C. elegans guanylyl
    cyclase ODR-1.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified (L'Etoile & Bargmann, Neuron 2000). The founding
      characterization of ODR-1 as the transmembrane guanylyl cyclase required for
      AWC olfaction; source of the ciliary localization (IDA) and the E904A
      cyclase-domain mutant. Abstract-only in cache; multiple annotations trace here.
- id: PMID:18832350
  title: The EGL-4 PKG acts with KIN-29 salt-inducible kinase and protein kinase A
    to regulate chemoreceptor gene expression and sensory behaviors in Caenorhabditis
    elegans.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: >-
      PubMed-verified paper (van der Linden et al., Genetics 2008) about EGL-4/KIN-29/
      PKA control of chemoreceptor gene expression. The cached abstract does not name
      odr-1 and full text is unavailable, so odr-1's specific contribution to the
      GO:0010628 acts_upstream_of annotation cannot be confirmed from available text.
- id: PMID:20436480
  title: C. elegans phototransduction requires a G protein-dependent cGMP pathway
    and a taste receptor homolog.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified (Liu et al., Nat Neurosci 2010). Full text confirms odr-1(n1936)
      reduces ASJ photocurrents and that membrane GCs (odr-1, daf-11) supply cGMP to
      gate TAX-2/TAX-4 CNG channels downstream of LITE-1/Gi-o. Directly supports the
      phototransduction annotation.
- id: PMID:23874221
  title: The C. elegans cGMP-dependent protein kinase EGL-4 regulates nociceptive
    behavioral sensitivity.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified (Krzyzanowski et al., PLoS Genet 2013). Full text shows odr-1(lof)
      quinine hypersensitivity, cell-selective rescue by srb-6p::odr-1, and a model in
      which odr-1 supplies cGMP non-cell-autonomously to EGL-4 in ASH. Supports the
      bitter-taste / chemosensory-behavior annotations.
- id: PMID:26434723
  title: The Importance of cGMP Signaling in Sensory Cilia for Body Size Regulation
    in Caenorhabditis elegans.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified (Fujiwara et al., Genetics 2015). The abstract attributes cGMP-
      dependent body-size control specifically to gcy-12 (not odr-1) and notes EGL-4
      partners with different GCs for different tasks. odr-1's body-size IGI annotations
      are peripheral/non-core; abstract-only, full text not read.
- id: PMID:31259686
  title: The Caenorhabditis elegans Tubby homolog dynamically modulates olfactory
    cilia membrane morphogenesis and phospholipid composition.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified (DiTirro et al., eLife 2019). Full text uses odr-1 as a receptor-
      guanylyl-cyclase signaling mutant: odr-1 loss expands AWB ciliary fans and
      increases ciliary TUB-1, PPK-1 and PI(4,5)P2. Supports the (non-core) regulation
      of neurogenesis / protein localization to non-motile cilium annotations.
- id: PMID:8348618
  title: Odorant-selective genes and neurons mediate olfaction in C. elegans.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified (Bargmann, Hartwieg, Horvitz, Cell 1993). The founding odr-screen
      that isolated odr-1; source of the G647D (n1930) chemotaxis-loss mutant.
      Abstract-only in cache. Supports the olfactory-behavior / response-to-odorant
      annotations.
suggested_questions:
- question: >-
    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?
  experts:
  - L'Etoile ND
  - Bargmann CI
- question: >-
    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?
  experts:
  - Xu XZ
suggested_experiments:
- 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.
  description: >-
    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.
  experiment_type: in vitro enzymatic assay
- hypothesis: >-
    ODR-1-produced cGMP gates the TAX-2/TAX-4 CNG channel in AWC to drive odorant
    responses.
  description: >-
    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.
  experiment_type: in vivo cGMP/calcium imaging