Octopressin receptor (OPR) is a G protein-coupled receptor of the vasopressin/oxytocin receptor superfamily in Octopus vulgaris. It is specifically activated by octopressin (OP), one of two OT/VP superfamily peptides in octopus (the other being cephalotocin). OPR signals via calcium-mediated pathways (inositol phosphate/Ca2+ cascade) and is expressed in both the nervous system and peripheral tissues. Its physiological role is primarily to mediate contractile actions of octopressin on various tissues including rectum, oviduct, efferent branchial vessel, spermatophoric gland, and anterior aorta. OPR represents a novel evolutionary lineage distinct from vertebrate OT/VP receptors, with different ligand-binding residues compared to cephalotocin receptors (CTR1, CTR2).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004930 G protein-coupled receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: OPR is a member of the rhodopsin-type (class I) GPCR family, confirmed by sequence analysis and functional assay in Xenopus oocytes [PMID:15504101]. This IEA annotation is correct but too general; a more specific term (GO:0008528 G protein-coupled peptide receptor activity or GO:0005000 vasopressin receptor activity) is more appropriate for the specific function. Reason: While more specific terms exist (and are annotated separately), this broad GPCR annotation from combined IEA methods is technically correct and acceptable as a parent-level annotation. OPR contains domains and motifs typical of GPCRs, has 7TM architecture, and activates via G-protein signaling [PMID:15504101]. Supporting Evidence: PMID:15504101 Both CTR2 and OPR include domains and motifs typical of GPCRs, and the intron-exon structures are in accord with those of OT/VP receptor genes. |
| GO:0005000 vasopressin receptor activity | IEA GO_REF:0000120 | MODIFY | Summary: OPR belongs to the vasopressin/oxytocin receptor subfamily based on InterPro classification (IPR001817). While OPR is homologous to vertebrate vasopressin receptors, it does not bind vasopressin itself; it is specific for octopressin. The term GO:0005000 is defined in the context of vasopressin binding, and octopressin is a related but distinct neuropeptide. However, in GO, "vasopressin receptor activity" is the closest available child term in this lineage, and OPR is phylogenetically within this receptor family. The ligand-binding residues differ substantially from vertebrate VP receptors [PMID:15504101], and OPR is not activated by vertebrate OT/VP peptides. Reason: OPR is in the vasopressin/oxytocin receptor superfamily but does not bind vasopressin. The ligand-receptor binding mode for OP and OPR differs from other OT/VP superfamily peptides and receptors. Key binding residues conserved in vertebrate VP receptors are substituted in OPR. Since OPR binds octopressin (a neuropeptide) and signals via GPCR, a more accurate annotation would be GO:0008188 (neuropeptide receptor activity), which correctly captures its function without implying vasopressin specificity. Proposed replacements: neuropeptide receptor activity Supporting Evidence: PMID:15504101 Several regions and residues, which are requisite for binding of the vertebrate OT/VP receptor family with their ligands, are highly conserved in CTRs, but not in OPR. PMID:15504101 The substitution of amino acid residues suggests that the ligand-receptor binding mode for OP and OPR differs from other OT/VP superfamily peptides and receptors. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: OPR is a 7-transmembrane GPCR predicted to localize to the plasma membrane, consistent with the UniProt subcellular location annotation (Cell membrane, Multi-pass membrane protein). Reason: Plasma membrane localization is expected for a 7TM GPCR. UniProt annotates it as a cell membrane multi-pass membrane protein based on sequence features. The 7 transmembrane helices are predicted across positions 38-350 of the 419 AA protein. Supporting Evidence: PMID:15504101 Both CTR2 and OPR include domains and motifs typical of GPCRs, and the intron-exon structures are in accord with those of OT/VP receptor genes. |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: OPR signals through GPCR signaling, specifically activating the inositol phosphate/Ca2+ pathway. This was demonstrated by functional expression in Xenopus oocytes where OPR induced calcium-mediated inward chloride current upon octopressin stimulation [PMID:15504101]. This IEA annotation is correct but could be more specific. Reason: Correct annotation. OPR is a GPCR that mediates signal transduction via G-protein coupling. A more specific BP term (GO:0007218 neuropeptide signaling pathway) would be more informative, but this general term is acceptable as a parent-level annotation and is also supported by TAS evidence (see below). Supporting Evidence: PMID:15504101 CTR2 and OPR expressed in Xenopus oocytes induced calcium-mediated inward chloride current in a CT- and OP-specific manner respectively. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: OPR is an integral membrane protein with 7 transmembrane domains, inferred from InterPro domain matches (IPR000276, IPR001817, IPR017452). This is a very general CC term. Reason: This is correct but redundant with the more specific GO:0005886 (plasma membrane) annotation. However, as an IEA from InterPro2GO mapping, it is acceptable to retain. The protein has 7 predicted transmembrane helices and is clearly membrane-associated. |
| GO:0032870 cellular response to hormone stimulus | IEA GO_REF:0000118 | MODIFY | Summary: This TreeGrafter annotation suggests OPR is involved in cellular response to hormone stimulus. Octopressin is a neuropeptide hormone of the OT/VP superfamily, and OPR mediates the cellular response to octopressin. The term is reasonable but somewhat imprecise -- a neuropeptide signaling pathway term would be more specific. Reason: While octopressin can be considered a hormonal peptide, the more precise biological process is neuropeptide signaling. OPR mediates the physiological effects of octopressin in both nervous system and peripheral tissues. GO:0007218 (neuropeptide signaling pathway) is a more informative and specific term that better captures the biology. Proposed replacements: neuropeptide signaling pathway Supporting Evidence: PMID:15504101 OPR widely distributed in both the nervous systems and peripheral tissues ( Figure 4 C). The distribution of OPR in peripheral tissues is in agreement with our previous study, given that OP evoked rhythmic contractions with increased tonus in the rectum, oviduct, and efferent branchial vessel, rhythmic contractions in the spermatophoric gland, and tonic contractions in the ring slice of the anterior aorta in a previous study [ 12 ]. Therefore, a major physiological role for OP is contractile action of various tissues though OPR. |
| GO:0042277 peptide binding | IEA GO_REF:0000118 | MODIFY | Summary: This TreeGrafter annotation indicates peptide binding activity. OPR does bind octopressin, a neuropeptide. However, "peptide binding" is too vague for a receptor -- it does not capture the signaling function. The more informative term is GO:0008188 (neuropeptide receptor activity), which subsumes both binding and signaling. Reason: Peptide binding alone does not capture the receptor signaling function of OPR. The appropriate MF annotation is GO:0008188 (neuropeptide receptor activity), which encompasses both the binding of the neuropeptide ligand and the initiation of signaling. Simple "peptide binding" is uninformative for a signaling receptor. Proposed replacements: neuropeptide receptor activity Supporting Evidence: PMID:15504101 CTR2 and OPR expressed in Xenopus oocytes induced calcium-mediated inward chloride current in a CT- and OP-specific manner respectively. |
| GO:0004930 G protein-coupled receptor activity | TAS PMID:15504101 Novel evolutionary lineages of the invertebrate oxytocin/vas... | ACCEPT | Summary: TAS annotation based on Kanda et al. 2005, which cloned and functionally characterized OPR. The study demonstrated that OPR expressed in Xenopus oocytes activated calcium-mediated signaling upon octopressin stimulation, consistent with GPCR activity. OPR belongs to the rhodopsin-type GPCR family with characteristic 7TM architecture. Reason: Well-supported by the primary characterization study. OPR was cloned, expressed heterologously, and shown to activate calcium signaling in a ligand-specific manner. The receptor contains all hallmarks of a class I GPCR. This is a core function annotation. Supporting Evidence: PMID:15504101 Both CTR2 and OPR include domains and motifs typical of GPCRs, and the intron-exon structures are in accord with those of OT/VP receptor genes. CTR2 and OPR expressed in Xenopus oocytes induced calcium-mediated inward chloride current in a CT- and OP-specific manner respectively. |
| GO:0007186 G protein-coupled receptor signaling pathway | TAS PMID:15504101 Novel evolutionary lineages of the invertebrate oxytocin/vas... | ACCEPT | Summary: TAS annotation based on Kanda et al. 2005. OPR activates the inositol phosphate/Ca2+ signal transduction cascade, consistent with Gq/11-coupled GPCR signaling as seen in vertebrate OT/VP receptors (OxyR, V1aR, V1bR). The functional assay in Xenopus oocytes demonstrated calcium-mediated inward chloride current upon octopressin stimulation. Reason: Well-supported by functional data from the primary study. The calcium-mediated chloride current observed in Xenopus oocytes upon OP stimulation is characteristic of Gq/11-coupled GPCR signaling via the IP3/Ca2+ pathway, consistent with the signaling mode of vertebrate OT/VP receptors. Supporting Evidence: PMID:15504101 CTR2 and OPR expressed in Xenopus oocytes induced calcium-mediated inward chloride current in a CT- and OP-specific manner respectively. PMID:15504101 OxyR, V1aR and V1bR, coupled to Gq/11, activate the inositol 1,4,5-trisphosphate-calcium signal transduction cascade. |
| GO:0008188 neuropeptide receptor activity | TAS PMID:15504101 Novel evolutionary lineages of the invertebrate oxytocin/vas... | NEW | Summary: NEW annotation. OPR is a receptor for octopressin, a neuropeptide of the OT/VP superfamily. Functional assays demonstrated specific activation by octopressin but not by cephalotocin or vertebrate OT/VP peptides [PMID:15504101]. This is the most appropriate specific MF term for OPR, as GO:0005000 (vasopressin receptor activity) implies vasopressin-binding specificity that OPR does not possess. Reason: OPR is functionally characterized as a neuropeptide receptor specific for octopressin. GO:0008188 (neuropeptide receptor activity) correctly captures the molecular function without implying vasopressin specificity. This is supported by heterologous expression and functional assay data from Kanda et al. 2005. Supporting Evidence: PMID:15504101 CTR2 and OPR expressed in Xenopus oocytes induced calcium-mediated inward chloride current in a CT- and OP-specific manner respectively. PMID:15504101 These results lead to the conclusion that CTR2 and OPR are receptors specific for CT and OP respectively, and that these octopus receptors share a common ancestor with the vertebrate OT/VP receptors. |
| GO:0007218 neuropeptide signaling pathway | TAS PMID:15504101 Novel evolutionary lineages of the invertebrate oxytocin/vas... | NEW | Summary: NEW annotation. OPR mediates neuropeptide signaling by octopressin. Octopressin is expressed in the nervous system and peripheral tissues, and OPR mediates its contractile effects on rectum, oviduct, efferent branchial vessel, spermatophoric gland, and anterior aorta [PMID:15504101]. This is a more specific BP term than the existing GO:0007186 (GPCR signaling pathway). Reason: OPR is the receptor for octopressin, a neuropeptide. The signaling pathway it mediates is specifically neuropeptide signaling. This is more informative than the generic GPCR signaling pathway annotation and is directly supported by the functional and expression data in Kanda et al. 2005. Supporting Evidence: PMID:15504101 OPR widely distributed in both the nervous systems and peripheral tissues ( Figure 4 C). The distribution of OPR in peripheral tissues is in agreement with our previous study, given that OP evoked rhythmic contractions with increased tonus in the rectum, oviduct, and efferent branchial vessel, rhythmic contractions in the spermatophoric gland, and tonic contractions in the ring slice of the anterior aorta in a previous study [ 12 ]. Therefore, a major physiological role for OP is contractile action of various tissues though OPR. PMID:15504101 CTR2 and OPR expressed in Xenopus oocytes induced calcium-mediated inward chloride current in a CT- and OP-specific manner respectively. |
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