Oprm1
Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:11060299, PubMed:15944153, PubMed:16682964, PubMed:17384143, PubMed:17947509, PubMed:1846076, PubMed:18558479, PubMed:21292762, PubMed:7595566, PubMed:7678862, PubMed:8051154, PubMed:8240812, PubMed:8393525, PubMed:9224819, PubMed:9572309). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:11060299, PubMed:15944153, PubMed:16682964, PubMed:17384143, PubMed:17947509, PubMed:1846076, PubMed:18558479, PubMed:21292762, PubMed:7595566, PubMed:7678862, PubMed:8051154, PubMed:8240812, PubMed:8393525, PubMed:9224819, PubMed:9572309). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (PubMed:8624732). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:16682964, PubMed:9224819). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:9224819, PubMed:9572309). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (PubMed:15944153, PubMed:21292762, PubMed:7595566, PubMed:9572309). Also couples to adenylate cyclase stimulatory G alpha proteins (PubMed:7595566). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (PubMed:11060299, PubMed:17384143, PubMed:17947509, PubMed:18558479). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (PubMed:11278523, PubMed:11896051, PubMed:15944153). Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling (PubMed:11060299, PubMed:17384143, PubMed:17947509, PubMed:18558479). Endogenous ligands induce rapid desensitization, endocytosis and recycling. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (PubMed:16682964, PubMed:17384143).
Post-translational modifications
Phosphorylated. Differentially phosphorylated in basal and agonist-induced conditions. Agonist-mediated phosphorylation modulates receptor internalization. Phosphorylated by GRK2 in a agonist-dependent manner. Phosphorylation at Tyr-166 requires receptor activation, is dependent on non-receptor protein tyrosine kinase Src and results in a decrease in agonist efficacy by reducing G-protein coupling efficiency. Phosphorylated on tyrosine residues; the phosphorylation is involved in agonist-induced G-protein-independent receptor down-regulation. Phosphorylation at Ser-375 is involved in G-protein-dependent but not beta-arrestin-dependent activation of the ERK pathway.
Ubiquitinated. A basal ubiquitination seems not to be related to degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1 oligomers leading to proteasomal degradation; the ubiquitination is diminished by RTP4.
Sequence Similarities
Belongs to the G-protein coupled receptor 1 family.
Tissue Specificity
Brain. Is expressed in the cerebral cortex, caudate putamen, nucleus accumbens, septal nuclei, thalamus, hippocampus, and habenula. Not detected in cerebellum.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Cell projection
- Axon
- Perikaryon
- Cell projection
- Dendrite
- Endosome
- Is rapidly internalized after agonist binding.
Alternative names
Ror-b, Oprm1, Mu-type opioid receptor, M-OR-1, MOR-1, Opioid receptor B