odr-1 (gcy-10) research notes — C. elegans

UniProt: B1Q257 (GCY10_CAEEL). WormBase: WBGene00003848 / R01E6.1.
Gene symbol odr-1 (Odorant response abnormal), synonym gcy-10.
EC 4.6.1.2 (guanylate cyclase). Reference proteome protein B1Q257.

Identity / architecture (from UniProt B1Q257)

odr-1 encodes a receptor-type (transmembrane) guanylyl cyclase. Domain layout
(1067 aa, isoform b):
- Signal peptide 1–20; extracellular domain 21–438 (periplasmic-binding-protein-like
ligand-binding fold, InterPro IPR028082 / SSF53822).
- Single-pass type I transmembrane helix 439–459.
- Cytoplasmic 460–1067, containing:
- Protein-kinase-like (KHD) domain 509–791 — annotated by UniProt as predicted
catalytically inactive: "The protein kinase domain is predicted to be catalytically
inactive." (ECO:0000255|PROSITE-ProRule:PRU00159). This is the canonical
pseudokinase/kinase-homology domain of receptor guanylyl cyclases.
- Guanylate cyclase (catalytic) domain 859–989 (Pfam PF00211, PROSITE PS50125).
- N-glycosylation site (Asn411); glycoprotein.

Family: adenylyl cyclase class-4 / guanylyl cyclase family; PANTHER PTHR11920
(GUANYLYL CYCLASE), subfamily PTHR11920:SF355 (RECEPTOR-TYPE GUANYLATE CYCLASE
GCY-10-RELATED). C. elegans has ~27 receptor-type + 7 soluble GCs
PMID:23874221.

Catalytic activity (UniProt, EC 4.6.1.2): GTP = 3',5'-cyclic GMP + diphosphate
(Rhea:RHEA:13665). The specific EC/cyclase activity for odr-1 is by-similarity
(ECO:0000250|UniProtKB:Q19187 = gcy-12); there is no direct in-vitro enzymology on
purified ODR-1.

Subcellular location / expression

• Cell membrane / cilium. UniProt: "Cell membrane ... Single-pass type I membrane
  protein. Cell projection, cilium ... Localizes in cilium of sensory neurons"
  (ECO:0000269|PMID:10774726). GOA: non-motile cilium (GO:0097730, IDA, PMID:10774726,
  WormBase).
• Tissue specificity: "Expressed predominantly in AWC but also in AWB, ASI, ASJ and
  ASK sensory neurons and in I1 interneuron" (UniProt; PMID:10774726, PMID:9096403).
  PMID:20436480 corroborates AWB/ASJ/ASK expression: "two membrane-associated GCs
  (daf-11 and odr-1) are expressed in C. elegans photoreceptor cells, including ASJ, ASK
  and AWB".

KNOWN functions (well supported)

Molecular function: guanylate cyclase (cGMP synthesis)

• ODR-1 is a transmembrane guanylyl cyclase producing the second messenger cGMP. The
  cyclase identity is established by domain architecture and by the point mutant E904A
  in the cyclase domain: UniProt MUTAGEN 904 "E->A: Probable loss of cyclase activity.
  Loss of chemotaxis to some volatile odorants." (PMID:10774726). Note: activity is
  inferred (ISS/by-similarity), not measured on purified protein.
• Overexpression phenotype implicates cGMP overproduction:
  PMID:10774726

Biological process: olfaction / chemosensation (core)

• ODR-1 is essential for AWC-mediated olfaction and required for responses to all
  AWC-sensed odorants:
  PMID:10774726
• odr-1 was originally isolated as an odr (odorant-response-abnormal) gene in the
  founding olfaction screen: PMID:8348618. Mutagenesis G647D (in n1930): "loss of chemotaxis
  to volatile odorants" (UniProt, PMID:8348618).
• Acts in both attractive (AWC) and repulsive (AWB) odor pathways (UniProt FUNCTION,
  PMID:10774726, PMID:8348618): "Regulates chemotaxis responses toward volatile odorants
  in AWC sensory neurons and their avoidance in AWB sensory neurons."
• Role in odor discrimination and adaptation (overexpression disrupts both;
  PMID:10774726).

Phototransduction (ASJ) — non-image light sensing

• PMID:20436480 Model: LITE-1 → Gi/o (goa-1/gpa-3) →
  membrane GCs (daf-11, odr-1) → cGMP → CNG channel (tax-2/tax-4). This is the same
  cGMP→TAX-2/TAX-4 architecture as chemosensation, redeployed for light.

cGMP supply to EGL-4 (PKG) for bitter/quinine (nociceptive) sensitivity

• PMID:23874221 and the model that these GCs "function in a non-cell-autonomous manner to
  provide cGMP to regulate EGL-4 function in ASH" (odr-1 is not expressed in ASH).
  odr-1(lof) quinine hypersensitivity was rescued by srb-6p::odr-1 but not osm-10p::odr-1
  PMID:23874221.
  → supports GO:0050913 (sensory perception of bitter taste) and GO:0007635
  (chemosensory behavior).

Maintenance of asymmetric str-2 (olfactory receptor) expression in AWC

• PMID:10571181 odr-1 provides the cGMP;
  UniProt FUNCTION: "Required to maintain the expression of putative olfactory receptor
  str-2 in AWC neurons in adults (PubMed:10571181)." → supports GO:0010628 (positive
  regulation of gene expression), qualifier involved_in (WormBase, PMID:10571181).

AWB cilia membrane morphogenesis (developmental / non-cell-autonomous readout)

• In the Tubby paper, odr-1 is used as a "receptor guanylyl cyclase signaling mutant"
  whose reduced sensory signaling drives ciliary phenotypes:
  PMID:31259686, PMID:31259686,
  PMID:31259686. This is the basis of the GOA IMP annotations
  GO:0097499 (protein localization to non-motile cilium) and GO:0050767 (regulation of
  neurogenesis) attributed to PMID:31259686. These are downstream/developmental
  consequences of loss of odr-1 sensory-signaling, not a distinct biochemical activity of
  ODR-1; they are best treated as non-core.

Additional / peripheral GOA annotations reviewed

• GO:0010628 positive regulation of gene expression, acts_upstream_of, IMP,
  PMID:18832350. The cached abstract of PMID:18832350 is about EGL-4/KIN-29/PKA
  regulating chemoreceptor (CR) gene expression and does not name odr-1; full text
  unavailable. Consistent with odr-1 supplying cGMP upstream of EGL-4, but odr-1's
  specific role here cannot be verified from the abstract → treat cautiously
  (non-core / UNDECIDED-leaning; keep, defer to curator, flag reference).
• GO:0040015 / GO:0040014 regulation of multicellular organism growth (body size),
  IGI, PMID:26434723. The abstract of PMID:26434723 explicitly assigns body-size
  control to gcy-12 ("gcy-12 ... provide cGMP to the EGL-4 ... only for limited tasks
  including body size regulation") and states EGL-4 partners with different GCs for
  different functions. odr-1 is not named in the abstract; the annotation is an IGI
  (WITH gcy-12 = Q19187 and G5EGF0). Body-size regulation is clearly peripheral to odr-1
  and, per the paper's own model, is a gcy-12 task → non-core; keep (do not REMOVE an
  experimental IGI on abstract-only grounds), mark non-core, flag reference relevance LOW.
• GO:0001653 peptide receptor activity (IBA, GO_REF:0000033). This is a phylogenetic
  (PANTHER) inference from natriuretic-peptide-receptor GCs (mammalian NPR-A/NPR-B,
  UniProtKB:P16066/P20594). C. elegans receptor GCs are orphan receptors with no
  demonstrated peptide ligand; odr-1's extracellular domain is explicitly NOT implicated
  in odorant detection [UniProt DOMAIN "The extracellular domain may not be directly
  implicated in the detection of volatile odorants."]. "peptide receptor activity" is an
  over-annotation for odr-1 (no known peptide ligand) → MARK_AS_OVER_ANNOTATED / non-core.
• GO:0004672 protein kinase activity (IEA, InterPro) — NOTE: present in the UniProt DR
  block but NOT in the GOA TSV/seeded review (so not in existing_annotations). UniProt
  explicitly states the kinase (KHD) domain is predicted catalytically inactive; a
  protein-kinase-activity annotation would be a pseudokinase over-annotation. Documented
  here for completeness / knowledge_gaps.
• GO:0005524 ATP binding (IEA, InterPro:IPR000719). From the kinase-homology domain.
  UniProt lists ATP-binding residues (515–523, 534). Plausible structural nucleotide
  binding but the domain is a pseudokinase; keep as non-core (weak, IEA).
• GO:0009190 cyclic nucleotide biosynthetic process / GO:0035556 intracellular signal
  transduction (IEA, InterPro). Generic parents of the specific, well-supported
  cGMP-biosynthesis / receptor-GC-signaling terms; keep as non-core (redundant with the
  specific experimental terms).

NOT known / knowledge gaps (explicit)

1. Activating ligand / stimulus for ODR-1 is unknown. No peptide or small-molecule
   ligand has been identified for the extracellular domain, and UniProt states the
   extracellular domain "may not be directly implicated in the detection of volatile
   odorants" PMID:10774726. ODR-1 acts downstream of odorant receptors as a shared
   signaling component PMID:10774726, so what activates/regulates its cyclase output in
   vivo (Ca2+, phosphorylation, GPCR/G-protein input, an orphan-receptor ligand) is
   undetermined.
2. Direct catalytic activity of ODR-1 has never been measured biochemically. The
   cyclase activity is inferred (ISS from gcy-12/Q19187 and mammalian NPRs) and from the
   E904A "probable loss of cyclase activity" phenotype PMID:10774726; purified-protein
   enzymology is lacking. Whether ODR-1 homodimerizes or must heterodimerize with another
   GC (e.g. daf-11) to form an active catalytic unit is unresolved.
3. The kinase-homology domain: regulatory pseudokinase vs. active kinase. UniProt
   predicts it catalytically inactive (PRU00159). Whether it has any residual catalytic
   activity, and its regulatory role, are untested. (In this sense odr-1 is a candidate
   pseudokinase-containing, possibly regulatory-cyclase protein.)
4. Cell-autonomous vs non-cell-autonomous scope: for quinine/EGL-4, ODR-1 acts
   non-cell-autonomously to supply cGMP to ASH PMID:23874221; the diffusible-signal
   mechanism is not defined.

Core function synthesis (for core_functions)

1. Molecular function: guanylate cyclase activity (GO:0004383) producing cGMP from
   GTP — the catalytic identity of the protein. Location: ciliary membrane / plasma
   membrane of sensory neurons.
2. cGMP biosynthetic process (GO:0006182) / receptor guanylyl cyclase signaling
   pathway (GO:0007168): generation of the cGMP second messenger that gates the
   TAX-2/TAX-4 CNG channel.
3. Sensory perception / olfaction (GO:0042048 olfactory behavior; sensory perception
   of smell): the organismal role — required for AWC/AWB olfaction and odor
   discrimination.
4. Cellular location: non-motile cilium (GO:0097730) / ciliary membrane —
   experimentally localized (IDA, PMID:10774726).

Non-core (pleiotropic / downstream / genetic-tool readouts): phototransduction, bitter
taste/quinine (via EGL-4), body-size regulation (gcy-12-attributed), AWB cilia membrane
morphogenesis, str-2 maintenance, chemoreceptor-gene expression.

Deep research

Falcon deep-research launched (just deep-research-falcon worm odr-1 --fallback perplexity-lite). If it completes, its file is odr-1-deep-research-*.md. Review below
is grounded in primary cached literature (PMIDs above) and UniProt B1Q257, independent of
the deep-research summary.