OPRM1 encodes the mu-type opioid receptor (MOR), a class A (rhodopsin-like) seven-transmembrane G protein-coupled receptor and the principal receptor for endogenous opioid peptides (beta-endorphin, endomorphins, enkephalins) and for morphine and most clinically used opioid analgesics (fentanyl, methadone, buprenorphine) and drugs of abuse (heroin). Located at the plasma membrane of neurons in the central and peripheral nervous system, agonist-bound MOR couples predominantly to pertussis toxin-sensitive Gi/o proteins: the Galpha(i/o) subunit inhibits adenylyl cyclase, while released G beta-gamma activates G protein-gated inwardly rectifying K+ (GIRK) channels and inhibits N- and L-type voltage-gated Ca2+ channels, hyperpolarizing neurons and suppressing presynaptic neurotransmitter release; MAPK/ERK and phospholipase C branches are also engaged. Activated MOR is phosphorylated by GRKs, binds beta-arrestins, and is internalized through clathrin-coated pits and recycled, processes that govern desensitization and tolerance. MOR is required for morphine analgesia, reward and physical dependence, and its signaling also underlies respiratory depression. The gene is extensively alternatively spliced; the common N40D (A118G) variant alters beta-endorphin binding and potency, and some isoforms (e.g. the 6TM MOR1K) have distinct coupling or act as dominant modulators of full-length receptor binding.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001965 G-protein alpha-subunit binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: MOR binds the alpha subunit of heterotrimeric Gi/o as part of its receptor activity; the DAMGO-MOR-Gi cryo-EM structure shows the receptor core engaging Galpha(i). Reason: Correct and phylogenetically sound (PAINT node). Binding of Galpha is a mechanistic component of the G protein-coupled opioid receptor activity captured by the core MF terms, so it is kept but not treated as a separate core function. Supporting Evidence: PMID:29899455 mediated by ΞΌOR signalling through the adenylyl cyclase-inhibiting heterotrimeric G protein Gi file:human/OPRM1/OPRM1-uniprot.txt predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins |
| GO:0001965 G-protein alpha-subunit binding | IDA PMID:20214800 Interaction of the mu-opioid receptor with GPR177 (Wntless) ... | KEEP AS NON CORE | Summary: IDA from the MOR/GPR177 (Wntless) interactor study. The cached full text centres on GPR177; the specific Galpha binding observation underlying this row could not be located in the cached text (it may be in a figure or table). Reason: Galpha(i/o) binding by MOR is well established (UniProt; MOR-Gi structure), so the claim is deferred to the curator and kept as non-core, consistent with the IBA row; the core function is captured by the opioid receptor activity terms. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins PMID:29899455 mediated by ΞΌOR signalling through the adenylyl cyclase-inhibiting heterotrimeric G protein Gi |
| GO:0004930 G protein-coupled receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: GPCR activity (InterPro mapping). Correct but general: MOR is an opioid receptor whose agonists include morphine and beta-endorphin. Reason: The term is true but less specific than the evidence supports. Human MOR binds opiates and opioid peptides and transduces through Gi/o; its documented ligands include morphine and beta-endorphin. Replace with the specific descendants morphine receptor activity (GO:0038047) and beta-endorphin receptor activity (GO:0004979), both already carried by this gene. Proposed replacements: morphine receptor activity beta-endorphin receptor activity Supporting Evidence: PMID:7905839 The expressed mu OR1 recognized tested opiate drugs and opioid peptides in a sodium- and GTP-sensitive fashion file:human/OPRM1/OPRM1-uniprot.txt Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone file:human/OPRM1/OPRM1-uniprot.txt Receptor for endogenous opioids such as beta-endorphin and endomorphin PMID:9689128 the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor |
| GO:0004930 G protein-coupled receptor activity | ISS GO_REF:0000024 | MODIFY | Summary: GPCR activity (ISS from rat Oprm1 (P33535)). Correct but general: MOR is an opioid receptor whose agonists include morphine and beta-endorphin. Reason: The term is true but less specific than the evidence supports. Human MOR binds opiates and opioid peptides and transduces through Gi/o; its documented ligands include morphine and beta-endorphin. Replace with the specific descendants morphine receptor activity (GO:0038047) and beta-endorphin receptor activity (GO:0004979), both already carried by this gene. Proposed replacements: morphine receptor activity beta-endorphin receptor activity Supporting Evidence: PMID:7905839 The expressed mu OR1 recognized tested opiate drugs and opioid peptides in a sodium- and GTP-sensitive fashion file:human/OPRM1/OPRM1-uniprot.txt Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone file:human/OPRM1/OPRM1-uniprot.txt Receptor for endogenous opioids such as beta-endorphin and endomorphin PMID:9689128 the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor |
| GO:0004979 beta-endorphin receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Beta-endorphin is a principal endogenous agonist of MOR; IBA from PAINT. Reason: Supported by direct human data (A118G variant alters beta-endorphin binding and potency) and UniProt. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Receptor for endogenous opioids such as beta-endorphin and endomorphin PMID:9689128 the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor |
| GO:0004979 beta-endorphin receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based assignment of beta-endorphin receptor activity (Mu_opioid_rcpt signature). Reason: Consistent with direct human data showing beta-endorphin binding and receptor activation. Supporting Evidence: PMID:9689128 the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor PMID:9689128 beta-endorphin is approximately three times more potent at the A118G variant receptor than at the most common allelic form in agonist-induced activation of G protein-coupled potassium channels |
| GO:0004979 beta-endorphin receptor activity | IMP PMID:9689128 Single-nucleotide polymorphism in the human mu opioid recept... | ACCEPT | Summary: Bond et al. showed that the N40D (A118G) variant binds beta-endorphin about three times more tightly and is about three times more responsive to it in GIRK activation assays. Reason: Direct evidence that human MOR binds beta-endorphin and transduces the signal through G protein-activated K+ channels; the variant comparison is a mutant phenotype supporting the IMP code. Supporting Evidence: PMID:9689128 the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor PMID:9689128 beta-endorphin is approximately three times more potent at the A118G variant receptor than at the most common allelic form in agonist-induced activation of G protein-coupled potassium channels |
| GO:0004985 G protein-coupled opioid receptor activity | IEA GO_REF:0000120 | ACCEPT | Summary: G protein-coupled opioid receptor activity (combined IEA). Reason: Accurate summary-level term: MOR responds to alkaloid opiates, synthetic opioids and several opioid peptide classes (endorphins, endomorphins, enkephalins). More specific ligand terms (morphine, beta-endorphin receptor activity) are also accepted; this parent remains informative as the family-level activity. Supporting Evidence: PMID:7905839 The expressed mu OR1 recognized tested opiate drugs and opioid peptides in a sodium- and GTP-sensitive fashion file:human/OPRM1/OPRM1-uniprot.txt Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone |
| GO:0005245 voltage-gated calcium channel activity | ISS GO_REF:0000024 | REMOVE | Summary: ISS transfer from rat Oprm1 (P33535) asserting voltage-gated calcium channel activity. Reason: MOR is a seven-transmembrane GPCR with no pore-forming channel domain. It inhibits N- and L-type voltage-gated calcium channels indirectly via Gi/o-released G beta-gamma; the effector channel activity belongs to CACNA1B/CACNA1C etc., not to the receptor. This is an effector-for-receptor error in the donor annotation. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels file:human/OPRM1/OPRM1-uniprot.txt OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level |
| GO:0005515 protein binding | IPI PMID:14573758 Interaction between the mu opioid receptor and filamin A is ... | REMOVE | Summary: Protein binding IPI with filamin A (FLNA). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:19788913 Regulation of mu opioid receptor internalization by the scaf... | REMOVE | Summary: Protein binding IPI with RanBPM (RANBP9). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:20214800 Interaction of the mu-opioid receptor with GPR177 (Wntless) ... | REMOVE | Summary: Protein binding IPI with GPR177/WLS. Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:23597562 Inhibition of tumor angiogenesis and growth by a small-molec... | MODIFY | Summary: Protein binding IPI with PENK, specifically the proenkephalin-A-derived opioid peptide chain (UniProtKB:P01210-PRO_0000008243), an endogenous MOR agonist; UniProt records this interaction with three experiments. Reason: Unlike the other protein-binding rows, the partner here is an endogenous opioid peptide ligand of the receptor, so the interaction supports a more informative molecular function. Replace generic protein binding with GO:0004985 G protein-coupled opioid receptor activity, already accepted on this gene. Proposed replacements: G protein-coupled opioid receptor activity Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt P35372; PRO_0000008243 [P01210]: PENK; NbExp=3 file:human/OPRM1/OPRM1-uniprot.txt Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe |
| GO:0005515 protein binding | IPI PMID:23840749 MOR is not enough: identification of novel mu-opioid recepto... | REMOVE | Summary: Protein binding IPI with candidate interactors from the MOR interactome study (Petko et al., "MOR is not enough"). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:23840749 MOR is not enough: identification of novel mu-opioid recepto... | REMOVE | Summary: Protein binding IPI with candidate interactors from the MOR interactome study (Petko et al., "MOR is not enough"). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:23840749 MOR is not enough: identification of novel mu-opioid recepto... | REMOVE | Summary: Protein binding IPI with candidate interactors from the MOR interactome study (Petko et al., "MOR is not enough"). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:23840749 MOR is not enough: identification of novel mu-opioid recepto... | REMOVE | Summary: Protein binding IPI with candidate interactors from the MOR interactome study (Petko et al., "MOR is not enough"). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:23840749 MOR is not enough: identification of novel mu-opioid recepto... | REMOVE | Summary: Protein binding IPI with candidate interactors from the MOR interactome study (Petko et al., "MOR is not enough"). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:23840749 MOR is not enough: identification of novel mu-opioid recepto... | REMOVE | Summary: Protein binding IPI with candidate interactors from the MOR interactome study (Petko et al., "MOR is not enough"). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:23840749 MOR is not enough: identification of novel mu-opioid recepto... | REMOVE | Summary: Protein binding IPI with candidate interactors from the MOR interactome study (Petko et al., "MOR is not enough"). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:23840749 MOR is not enough: identification of novel mu-opioid recepto... | REMOVE | Summary: Protein binding IPI with candidate interactors from the MOR interactome study (Petko et al., "MOR is not enough"). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:23840749 MOR is not enough: identification of novel mu-opioid recepto... | REMOVE | Summary: Protein binding IPI with candidate interactors from the MOR interactome study (Petko et al., "MOR is not enough"). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:23840749 MOR is not enough: identification of novel mu-opioid recepto... | REMOVE | Summary: Protein binding IPI with candidate interactors from the MOR interactome study (Petko et al., "MOR is not enough"). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:28298427 Systematic protein-protein interaction mapping for clinicall... | REMOVE | Summary: Protein binding IPI with partners from a systematic GPCR interactome screen. Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:28298427 Systematic protein-protein interaction mapping for clinicall... | REMOVE | Summary: Protein binding IPI with partners from a systematic GPCR interactome screen. Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:28298427 Systematic protein-protein interaction mapping for clinicall... | REMOVE | Summary: Protein binding IPI with partners from a systematic GPCR interactome screen. Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:28298427 Systematic protein-protein interaction mapping for clinicall... | REMOVE | Summary: Protein binding IPI with partners from a systematic GPCR interactome screen. Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:39083597 Multiplexed mapping of the interactome of GPCRs with recepto... | REMOVE | Summary: Protein binding IPI with RAMP proteins (multiplexed GPCR-RAMP interactome). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:39083597 Multiplexed mapping of the interactome of GPCRs with recepto... | REMOVE | Summary: Protein binding IPI with RAMP proteins (multiplexed GPCR-RAMP interactome). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005515 protein binding | IPI PMID:39083597 Multiplexed mapping of the interactome of GPCRs with recepto... | REMOVE | Summary: Protein binding IPI with RAMP proteins (multiplexed GPCR-RAMP interactome). Reason: Generic protein binding is uninformative about MOR function. The reported interaction is not disputed; removal reflects that the term carries no functional content and no more specific, evidence-backed MF is supported by the interaction data alone. |
| GO:0005737 cytoplasm | EXP P35372-12 PMID:20525224 A novel alternatively spliced isoform of the mu-opioid recep... | KEEP AS NON CORE | Summary: Gris et al. found that the 6TM MOR1K isoform (isoform 12) is retained intracellularly rather than at the cell surface. Reason: Applies to the MOR1K isoform, not to canonical MOR, which is at the plasma membrane. Kept as a non-core, isoform-specific location. Supporting Evidence: PMID:20525224 Overexpression of MOR1K in mammalian cells revealed that this 6TM receptor is not expressed at the cell membrane, but instead is retained in the intracellular compartment |
| GO:0005737 cytoplasm | IEA P35372-12 GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping of the isoform 12 (MOR1K) cytoplasm statement. Reason: Isoform-specific (MOR1K); not the location of canonical MOR. Non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: [Isoform 12]: Cytoplasm |
| GO:0005768 endosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Agonist-activated MOR is internalized via clathrin-coated pits and trafficked through endosomes before recycling. Reason: Correct trafficking location (UniProt subcellular-location mapping, by similarity to guinea pig MOR P97266; internalization is shown for human MOR in heterologous cells), but transient relative to the plasma membrane site of signaling. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Is rapidly internalized after agonist binding file:human/OPRM1/OPRM1-uniprot.txt The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits |
| GO:0005768 endosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Agonist-activated MOR is internalized via clathrin-coated pits and trafficked through endosomes before recycling. Reason: Correct trafficking location (by similarity to guinea pig MOR (P97266); internalization is shown for human MOR in heterologous cells), but transient relative to the plasma membrane site of signaling. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Is rapidly internalized after agonist binding file:human/OPRM1/OPRM1-uniprot.txt The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits |
| GO:0005783 endoplasmic reticulum | TAS PMID:9242668 Characterization of delta, kappa, and mu human opioid recept... | UNDECIDED | Summary: TAS for endoplasmic reticulum from a baculovirus/insect-cell overexpression study of human opioid receptors. Reason: Only the abstract is cached and it does not mention the endoplasmic reticulum. Passage through biosynthetic compartments is expected for any membrane receptor, but whether the paper observed or merely stated this cannot be checked. Left undecided rather than overruling the curator. |
| GO:0005794 Golgi apparatus | TAS PMID:9242668 Characterization of delta, kappa, and mu human opioid recept... | UNDECIDED | Summary: TAS for Golgi apparatus from a baculovirus/insect-cell overexpression study of human opioid receptors. Reason: Only the abstract is cached and it does not mention the Golgi apparatus. Passage through biosynthetic compartments is expected for any membrane receptor, but whether the paper observed or merely stated this cannot be checked. Left undecided rather than overruling the curator. |
| GO:0005886 plasma membrane | EXP PMID:10529478 Mutation of human mu opioid receptor extracellular "disulfid... | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: PMID:10529478 serine-for-cysteine substitutions were also observed to successfully reach the cell plasma membrane, as evidenced by electron microscopy |
| GO:0005886 plasma membrane | EXP PMID:12589820 Identification and characterization of two new human mu opio... | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location. The cited study characterized human MOR expressed in transfected cells; UniProt bases its Cell membrane location on this and related human studies, and electron microscopy and co-localization studies directly place human MOR at the plasma membrane. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:10529478 serine-for-cysteine substitutions were also observed to successfully reach the cell plasma membrane, as evidenced by electron microscopy PMID:16580639 MOR and SV protein co-localized at the cytoplasmic membrane |
| GO:0005886 plasma membrane | EXP PMID:16580639 The opioid ligand binding of human mu-opioid receptor is mod... | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: PMID:16580639 MOR and SV protein co-localized at the cytoplasmic membrane |
| GO:0005886 plasma membrane | EXP PMID:7891175 The human mu opioid receptor: modulation of functional desen... | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location. The cited study characterized human MOR expressed in transfected cells; UniProt bases its Cell membrane location on this and related human studies, and electron microscopy and co-localization studies directly place human MOR at the plasma membrane. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:10529478 serine-for-cysteine substitutions were also observed to successfully reach the cell plasma membrane, as evidenced by electron microscopy PMID:16580639 MOR and SV protein co-localized at the cytoplasmic membrane |
| GO:0005886 plasma membrane | EXP PMID:7957926 Expression of two variants of the human mu opioid receptor m... | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location. The cited study characterized human MOR expressed in transfected cells; UniProt bases its Cell membrane location on this and related human studies, and electron microscopy and co-localization studies directly place human MOR at the plasma membrane. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:10529478 serine-for-cysteine substitutions were also observed to successfully reach the cell plasma membrane, as evidenced by electron microscopy PMID:16580639 MOR and SV protein co-localized at the cytoplasmic membrane |
| GO:0005886 plasma membrane | EXP PMID:9689128 Single-nucleotide polymorphism in the human mu opioid recept... | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location. The cited study characterized human MOR expressed in transfected cells; UniProt bases its Cell membrane location on this and related human studies, and electron microscopy and co-localization studies directly place human MOR at the plasma membrane. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:10529478 serine-for-cysteine substitutions were also observed to successfully reach the cell plasma membrane, as evidenced by electron microscopy PMID:16580639 MOR and SV protein co-localized at the cytoplasmic membrane |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS PMID:7905839 Human mu opiate receptor. cDNA and genomic clones, pharmacol... | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS PMID:9242668 Characterization of delta, kappa, and mu human opioid recept... | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-112042 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-112271 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167408 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167419 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167427 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167429 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-374298 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-380073 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6793958 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749454 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-749456 | ACCEPT | Summary: MOR is an integral plasma membrane receptor where it binds extracellular opioids and couples to Gi/o. Reason: Core location, supported by multiple experimental studies on human MOR and UniProt (Cell membrane; multi-pass membrane protein). Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000002 | MODIFY | Summary: Generic GPCR signaling pathway (InterPro mapping). Reason: True but general. The pathway MOR initiates is the opioid receptor pathway, whose canonical arm is Gi/o-mediated adenylyl cyclase inhibition. Replace with GO:0031635 adenylate cyclase-inhibiting opioid receptor signaling pathway (is_a GO:0007193 and GO:0038003); GO:0038003 is already carried by this gene. Proposed replacements: adenylate cyclase-inhibiting opioid receptor signaling pathway Supporting Evidence: PMID:29899455 mediated by ΞΌOR signalling through the adenylyl cyclase-inhibiting heterotrimeric G protein Gi PMID:14573758 DAMGO inhibition of forskolin-stimulated adenylyl cyclase PMID:19788913 RanBPM had no effect on MOP-mediated inhibition of adenylyl cyclase |
| GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | TAS PMID:7905839 Human mu opiate receptor. cDNA and genomic clones, pharmacol... | MODIFY | Summary: Wang et al. reported that human MOR effects on cyclic AMP resemble those of the rat receptor. Reason: Correct but general; the cyclic-nucleotide coupling of MOR is inhibition of adenylyl cyclase via Gi/o. Replace with the specific descendant GO:0031635 adenylate cyclase-inhibiting opioid receptor signaling pathway. Proposed replacements: adenylate cyclase-inhibiting opioid receptor signaling pathway Supporting Evidence: PMID:7905839 Effects on cyclic AMP are similar to those noted for the rat mu opiate receptor PMID:14573758 DAMGO inhibition of forskolin-stimulated adenylyl cyclase |
| GO:0007197 adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway | ISS GO_REF:0000024 | MODIFY | Summary: ISS from rat Oprm1 asserting the acetylcholine-receptor-initiated adenylate cyclase-inhibiting pathway. Reason: The Gi/adenylyl cyclase-inhibiting arm is correct but the ligand class is wrong: MOR is activated by opioids, not acetylcholine. Lateral correction to GO:0031635 adenylate cyclase-inhibiting opioid receptor signaling pathway. Proposed replacements: adenylate cyclase-inhibiting opioid receptor signaling pathway Supporting Evidence: PMID:29899455 mediated by ΞΌOR signalling through the adenylyl cyclase-inhibiting heterotrimeric G protein Gi PMID:14573758 DAMGO inhibition of forskolin-stimulated adenylyl cyclase PMID:19788913 RanBPM had no effect on MOP-mediated inhibition of adenylyl cyclase |
| GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from rat: MOR activation can stimulate phospholipase C (via G beta-gamma). Reason: Listed by UniProt among downstream responses (by similarity). Real but secondary to the Gi/o adenylyl cyclase/ion channel arms; non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC) |
| GO:0007218 neuropeptide signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Neuropeptide signaling pathway (IBA): MOR is the receptor for the opioid neuropeptides beta-endorphin, endomorphins and enkephalins. Reason: Correct; beta-endorphin receptor activity is part_of this pathway in GO, and the IBA reflects conserved opioid peptide receptor function. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Receptor for endogenous opioids such as beta-endorphin and endomorphin PMID:9689128 the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor |
| GO:0007600 sensory perception | NAS PMID:9689128 Single-nucleotide polymorphism in the human mu opioid recept... | MODIFY | Summary: NAS "sensory perception" from the A118G variant paper, which discusses implications of MOR variation for physiology and opiate addiction. Reason: Too general. The sensory modality MOR acts on is nociception, so the replacement is GO:0019233 sensory perception of pain, matching the GO:0019233 rows (IBA/IEA/ISS) already kept on this gene. Knockout of MOR abolishes morphine analgesia. Proposed replacements: sensory perception of pain Supporting Evidence: PMID:8893006 a lack of mu receptors abolishes the analgesic effect of morphine, as well as place-preference activity and physical dependence |
| GO:0008285 negative regulation of cell population proliferation | TAS PMID:2159143 Opioid and nicotine receptors affect growth regulation of hu... | MARK AS OVER ANNOTATED | Summary: Maneckjee and Minna showed that mu, delta and kappa agonists inhibit growth of lung cancer cell lines expressing multiple opioid receptor types. Reason: The growth effect was obtained with agonists of all three opioid receptor classes in cell lines co-expressing them, so attribution to OPRM1 is indirect, and growth inhibition of tumour lines is not a physiological MOR function. Retained as over-annotation rather than removed. Supporting Evidence: PMID:2159143 mu, delta, and kappa opioid agonists at low concentrations (1-100 nM) inhibited lung cancer growth in vitro |
| GO:0008528 G protein-coupled peptide receptor activity | IEA GO_REF:0000117 | MODIFY | Summary: G protein-coupled peptide receptor activity (ARBA). Reason: Correct but general: MOR peptide ligands are the opioid peptides. Replace with the specific descendant beta-endorphin receptor activity (GO:0004979; is_a GO:0008528 via neuropeptide receptor activity, checked in OLS), already carried by this gene. Proposed replacements: beta-endorphin receptor activity Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Receptor for endogenous opioids such as beta-endorphin and endomorphin PMID:9689128 the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: Membrane (combined IEA). Reason: True but general; MOR is a plasma membrane receptor (many EXP rows). Replace with plasma membrane. Proposed replacements: plasma membrane Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0019226 transmission of nerve impulse | IEA GO_REF:0000107 | MODIFY | Summary: Transmission of nerve impulse, IEA transfer from mouse Oprm1. Reason: MOR does not carry out nerve impulse transmission; it modulates synaptic transmission, chiefly by presynaptic inhibition of transmitter release (Gbeta-gamma inhibition of voltage-gated calcium channels). Replace with GO:0099171 presynaptic modulation of chemical synaptic transmission, also carried by this gene. Proposed replacements: presynaptic modulation of chemical synaptic transmission Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level |
| GO:0019233 sensory perception of pain | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Sensory perception of pain (IBA). MOR is required for morphine analgesia and endogenous opioid control of nociception. Reason: Organismal process supported by knockout data (loss of morphine analgesia). MOR modulates rather than mediates pain sensation, and the organismal phenotype is downstream of its receptor activity, so it is kept as non-core. Supporting Evidence: PMID:8893006 a lack of mu receptors abolishes the analgesic effect of morphine, as well as place-preference activity and physical dependence file:human/OPRM1/OPRM1-uniprot.txt OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level |
| GO:0019233 sensory perception of pain | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sensory perception of pain (IEA from mouse). MOR is required for morphine analgesia and endogenous opioid control of nociception. Reason: Organismal process supported by knockout data (loss of morphine analgesia). MOR modulates rather than mediates pain sensation, and the organismal phenotype is downstream of its receptor activity, so it is kept as non-core. Supporting Evidence: PMID:8893006 a lack of mu receptors abolishes the analgesic effect of morphine, as well as place-preference activity and physical dependence file:human/OPRM1/OPRM1-uniprot.txt OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level |
| GO:0019233 sensory perception of pain | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sensory perception of pain (ISS from mouse). MOR is required for morphine analgesia and endogenous opioid control of nociception. Reason: Organismal process supported by knockout data (loss of morphine analgesia). MOR modulates rather than mediates pain sensation, and the organismal phenotype is downstream of its receptor activity, so it is kept as non-core. Supporting Evidence: PMID:8893006 a lack of mu receptors abolishes the analgesic effect of morphine, as well as place-preference activity and physical dependence file:human/OPRM1/OPRM1-uniprot.txt OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level |
| GO:0030424 axon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Axonal localization of MOR in neurons (UniProt subcellular-location mapping, by similarity to guinea pig OPRM1 P97266). Reason: Consistent with presynaptic actions of MOR; neuronal sub-location of the plasma membrane receptor, non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Cell projection, axon |
| GO:0030424 axon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Axonal localization of MOR in neurons (ISS from guinea pig OPRM1, P97266). Reason: Consistent with presynaptic actions of MOR; neuronal sub-location of the plasma membrane receptor, non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Cell projection, axon |
| GO:0030425 dendrite | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Dendritic localization of MOR in neurons (UniProt subcellular-location mapping, by similarity to guinea pig OPRM1 P97266). Reason: Plausible postsynaptic site (GIRK activation); neuronal sub-location of the plasma membrane receptor, non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Cell projection, dendrite |
| GO:0030425 dendrite | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Dendritic localization of MOR in neurons (ISS from guinea pig OPRM1, P97266). Reason: Plausible postsynaptic site (GIRK activation); neuronal sub-location of the plasma membrane receptor, non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Cell projection, dendrite |
| GO:0031681 G-protein beta-subunit binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: G-protein beta-subunit binding (IBA). Reason: MOR engages the heterotrimeric Gi/o (including G beta-gamma) during activation; mechanistic component of the receptor activity, kept as non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt interaction with a heterotrimeric complex containing GNAI1, GNB1 and GNG2 |
| GO:0038003 G protein-coupled opioid receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: G protein-coupled opioid receptor signaling pathway (IBA). Reason: Core process: MOR initiates opioid receptor signaling. The more specific Gi/o adenylyl cyclase-inhibiting arm (GO:0031635) is proposed via MODIFY rows; this parent remains accurate and also covers GIRK, calcium channel and MAPK branches. Supporting Evidence: PMID:7905839 The expressed mu OR1 recognized tested opiate drugs and opioid peptides in a sodium- and GTP-sensitive fashion PMID:29899455 mediated by ΞΌOR signalling through the adenylyl cyclase-inhibiting heterotrimeric G protein Gi |
| GO:0038003 G protein-coupled opioid receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: G protein-coupled opioid receptor signaling pathway (IEA from mouse). Reason: Core process: MOR initiates opioid receptor signaling. The more specific Gi/o adenylyl cyclase-inhibiting arm (GO:0031635) is proposed via MODIFY rows; this parent remains accurate and also covers GIRK, calcium channel and MAPK branches. Supporting Evidence: PMID:7905839 The expressed mu OR1 recognized tested opiate drugs and opioid peptides in a sodium- and GTP-sensitive fashion PMID:29899455 mediated by ΞΌOR signalling through the adenylyl cyclase-inhibiting heterotrimeric G protein Gi |
| GO:0038003 G protein-coupled opioid receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: G protein-coupled opioid receptor signaling pathway (ISS from guinea pig OPRM1, P97266). Reason: Core process: MOR initiates opioid receptor signaling. The more specific Gi/o adenylyl cyclase-inhibiting arm (GO:0031635) is proposed via MODIFY rows; this parent remains accurate and also covers GIRK, calcium channel and MAPK branches. Supporting Evidence: PMID:7905839 The expressed mu OR1 recognized tested opiate drugs and opioid peptides in a sodium- and GTP-sensitive fashion PMID:29899455 mediated by ΞΌOR signalling through the adenylyl cyclase-inhibiting heterotrimeric G protein Gi |
| GO:0038047 morphine receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Morphine receptor activity (IBA). Reason: Core: MOR is the molecular target of morphine; knockout abolishes morphine analgesia, reward and dependence. Supporting Evidence: PMID:8893006 the mu-opioid-receptor gene product is the molecular target of morphine in vivo file:human/OPRM1/OPRM1-uniprot.txt Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone |
| GO:0038047 morphine receptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: Morphine receptor activity (ISS from rat). Reason: Core; also supported by human receptor data and knockout evidence. Supporting Evidence: PMID:8893006 the mu-opioid-receptor gene product is the molecular target of morphine in vivo file:human/OPRM1/OPRM1-uniprot.txt Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone |
| GO:0042923 neuropeptide binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Neuropeptide binding (IBA): MOR binds opioid peptides. Reason: Correct; the binding step is subsumed by the accepted receptor-activity terms (beta-endorphin receptor activity), so it is kept as non-core. Supporting Evidence: PMID:9689128 the A118G variant receptor binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor |
| GO:0043005 neuron projection | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Neuron projection (IBA). Reason: Correct general neuronal sub-location (axons, dendrites); non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Cell projection, axon |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Perikaryon (UniProt subcellular-location mapping, by similarity to guinea pig OPRM1 P97266). Reason: Neuronal somatic localization of MOR; non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Perikaryon |
| GO:0043204 perikaryon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Perikaryon (ISS from guinea pig OPRM1, P97266). Reason: Neuronal somatic localization of MOR; non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt Perikaryon |
| GO:0048149 behavioral response to ethanol | IMP PMID:21039637 Stress-induced and cue-induced craving for alcohol in heavy ... | KEEP AS NON CORE | Summary: Behavioral response to ethanol (IMP, PMID:21039637: OPRM1 Asp40 allele associated with greater cue-induced alcohol craving in heavy drinkers). Reason: The cited human study is a preliminary genetic association, but the process assignment rests on mechanistic loss-of-function evidence: mu-opioid receptor knockout mice do not self-administer ethanol in operant or two-bottle paradigms and show ethanol aversion. MOR is therefore required for ethanol reinforcement. This is an organismal behavioural phenotype downstream of receptor signaling, so it is kept as non-core. Supporting Evidence: PMID:10869404 In no case did knockout mice show evidence of ethanol self-administration, and, in fact, these mice showed evidence of an aversion to ethanol under several experimental conditions. PMID:21039637 The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. |
| GO:0050769 positive regulation of neurogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of neurogenesis (IEA transfer from mouse Oprm1, P42866). The mouse annotation is an IMP from Rios et al., who studied neuritogenesis in mouse Neuro-2A cells on activation of mu opioid and CB1 cannabinoid receptors. Reason: The source examined neurite outgrowth (neuritogenesis) in a neuroblastoma cell line, which falls under neurogenesis in GO through neuron projection development, and found that receptor activation affects it and that co-activation of MOR and CB1 attenuates the response. The evidence is cell-line based and abstract-only here, and the effect is downstream of receptor signaling, so it is kept as non-core. Supporting Evidence: PMID:16682964 we examined the effect of receptor activation on the extent of Src and STAT3 phosphorylation and neuritogenesis in Neuro-2A cells PMID:16682964 implicating a role for receptor-receptor interactions in modulating neuritogenesis |
| GO:0050769 positive regulation of neurogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of neurogenesis (ISS from mouse Oprm1, P42866). The mouse annotation is an IMP from Rios et al., who studied neuritogenesis in mouse Neuro-2A cells on activation of mu opioid and CB1 cannabinoid receptors. Reason: The source examined neurite outgrowth (neuritogenesis) in a neuroblastoma cell line, which falls under neurogenesis in GO through neuron projection development, and found that receptor activation affects it and that co-activation of MOR and CB1 attenuates the response. The evidence is cell-line based and abstract-only here, and the effect is downstream of receptor signaling, so it is kept as non-core. Supporting Evidence: PMID:16682964 we examined the effect of receptor activation on the extent of Src and STAT3 phosphorylation and neuritogenesis in Neuro-2A cells PMID:16682964 implicating a role for receptor-receptor interactions in modulating neuritogenesis |
| GO:0061358 negative regulation of Wnt protein secretion | IMP PMID:20214800 Interaction of the mu-opioid receptor with GPR177 (Wntless) ... | KEEP AS NON CORE | Summary: Jin et al. found that morphine promotes MOR/GPR177 (Wntless) complexes in HEK293 cells, sequestering GPR177 and inhibiting Wnt secretion. Reason: MOR participates directly by binding and sequestering GPR177, so the process assignment is defensible, but the evidence is from overexpression in HEK293 cells and the in vivo significance is unestablished. Non-core. Supporting Evidence: PMID:20214800 morphine treatment promotes formation of MOR/GPR177 complexes. This in turn results in sequestration of GPR177 and inhibition of Wnt protein secretion. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of ERK1/2 cascade (ISS from rat). Reason: MOR activates ERK via G protein- or beta-arrestin-dependent routes (UniProt, by similarity). Real but secondary signaling branch; non-core. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt The activation of the ERK pathway occurs either in a G protein-dependent or a beta-arrestin-dependent manner |
| GO:0070588 calcium ion transmembrane transport | IEA GO_REF:0000108 | REMOVE | Summary: Calcium ion transmembrane transport, inferred (GO_REF:0000108) from the voltage-gated calcium channel activity annotation. Reason: Derived from the erroneous channel-activity MF (row removed above). MOR inhibits calcium channel currents via G beta-gamma; it does not transport calcium. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels |
| GO:0071315 cellular response to morphine | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Cellular response to morphine, inferred from morphine receptor activity. Reason: Logically entailed by the accepted morphine receptor activity and correct; kept as non-core since the receptor activity term already captures the function. Supporting Evidence: PMID:8893006 the mu-opioid-receptor gene product is the molecular target of morphine in vivo |
| GO:0080135 regulation of cellular response to stress | IMP PMID:21039637 Stress-induced and cue-induced craving for alcohol in heavy ... | UNDECIDED | Summary: IMP from a human genetic study of stress- and cue-induced alcohol craving. Reason: The cached abstract attributes moderation of stress-induced craving to a CRH-BP SNP, while the OPRM1 Asp40 allele is reported only for cue-induced craving. The full text, which may contain an OPRM1-by-stress analysis, is not available, so the annotation cannot be verified; the term (a cellular stress response) also fits poorly with a human craving phenotype. Supporting Evidence: PMID:21039637 a tag SNP of the CRH-BP gene (rs10055255) moderated stress-induced craving in this sample PMID:21039637 The Asp40 allele of the OPRM1 was associated with greater cue-induced alcohol craving following the neutral imagery condition. |
| GO:0098793 presynapse | IEA GO_REF:0000108 | ACCEPT | Summary: Presynapse (inferred from presynaptic modulation of chemical synaptic transmission). Reason: MOR acts on presynaptic terminals, where Gi/o-released G beta-gamma inhibits voltage-gated calcium channels and transmitter release. This is the cellular basis of spinal opioid analgesia and of MOR inhibition of GABA release from interneuron terminals, so the presynapse is a core site of MOR action alongside the plasma membrane in general. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level PMID:31818459 this release was attenuated by presynaptic mu opioid receptors (MORs) activation |
| GO:0098982 GABA-ergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GABA-ergic synapse (IEA transfer from mouse Oprm1, P42866). The mouse source is SynGO curation of Shao et al., where presynaptic MOR activation reduced GABA release from parvalbumin interneuron terminals onto CA1 pyramidal cells. Reason: Supported by rodent data placing MOR on presynaptic terminals of GABAergic interneurons, where it inhibits GABA release. A valid but context-specific synaptic location; non-core. Supporting Evidence: PMID:31818459 this release was attenuated by presynaptic mu opioid receptors (MORs) activation PMID:31818459 The data suggest that MORs specifically inhibit GABA release from PV terminals |
| GO:0099171 presynaptic modulation of chemical synaptic transmission | IEA GO_REF:0000107 | ACCEPT | Summary: Presynaptic modulation of chemical synaptic transmission (IEA from mouse). Reason: A principal neuronal output of MOR: G beta-gamma released by MOR-activated Gi/o inhibits presynaptic voltage-gated calcium channels and so transmitter release, the mechanism thought to underlie spinal analgesia. Supporting Evidence: file:human/OPRM1/OPRM1-uniprot.txt OPRM1-mediated inhibition of voltage-gated calcium channels on central presynaptic terminals of primary afferent nociceptors is thought to be one of the primary mechanisms mediating analgesia at the spinal level |
| GO:2000310 regulation of NMDA receptor activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of NMDA receptor activity (ISS from rat). Reason: MOR-NMDA receptor cross-talk (via PKC/HINT1 and related scaffolds) is described in rodents and relevant to tolerance, but it is an indirect, context-specific regulatory effect. Non-core. |
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Download this section (compressed HTML)Q: Do the uOR-Gi AHD-opening kinetics measured with mouse uOR (PMID:42870023) hold for human OPRM1 and for its N40D (A118G) variant, and do clinically used partial agonists such as buprenorphine differ between them?
Q: Is efficacy-dependent control of the Galpha alpha-helical domain opening also seen with Go and Gz, the other G proteins MOR couples to, and does it contribute to agonist-dependent G protein subtype selectivity?
Q: Should GO distinguish G protein-biased from beta-arrestin-dependent mu-opioid receptor signaling (for example separate process terms for G protein-mediated versus arrestin-scaffolded MOR signaling), given ligands such as PZM21 that activate Gi with minimal beta-arrestin-2 recruitment and the debated contribution of each arm to analgesia versus respiratory depression and tolerance?
Suggested experts: GO signaling editors, opioid receptor pharmacologists
Q: Which human OPRM1 splice isoforms are translated at physiologically meaningful levels in brain, and should isoform-specific annotations (e.g. Gs coupling and intracellular retention of 6TM MOR1K, binding-incompetent SV1/SV2) be propagated to the gene level?
Suggested experts: OPRM1 splicing researchers
Q: Is "regulation of cellular response to stress" (IMP, PMID:21039637) based on an OPRM1-by-stress analysis in the full text, given that the abstract attributes stress-induced craving to a different gene?
Suggested experts: OPRM1 curators
Experiment: Repeat the single-molecule FRET assay of Deutsch et al. (PMID:42870023) with purified human OPRM1 (and the N40D variant) coupled to human Gi1, across a graded agonist panel (DAMGO, morphine, buprenorphine, fentanyl), correlating low-FRET open-state occupancy with GTP turnover.
Hypothesis: Agonist efficacy at human OPRM1 is set by the rate of Gi alpha-helical domain opening, as shown for mouse uOR.
Type: single-molecule biophysics
Experiment: Compare Gi/o activation (GTP-gamma-S, cAMP inhibition, GIRK current) with beta-arrestin-2 recruitment and MOR internalization across a panel of balanced and biased agonists in matched human cell lines, and correlate each arm with downstream readouts.
Hypothesis: G protein-biased MOR agonists engage the Gi/adenylyl-cyclase-inhibiting arm while sparing the GRK/beta-arrestin desensitization arm.
Experiment: Express individual human OPRM1 splice isoforms (canonical MOR1, 6TM MOR1K, SV1/SV2) in a null background and measure ligand binding, G protein coupling (Gi/o versus Gs), surface versus intracellular localization, and dominant-negative effects on co-expressed MOR1.
Hypothesis: Specific OPRM1 isoforms diverge in coupling and trafficking and modulate canonical receptor function.
Experiment: Quantify presynaptic calcium current and evoked transmitter release at MOR-expressing terminals during MOR agonism with and without G beta-gamma scavengers or GIRK/Cav2.2 perturbation.
Hypothesis: MOR suppresses transmitter release chiefly through G beta-gamma inhibition of presynaptic voltage-gated calcium channels.
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