ID:OPRM_HUMAN DESCRIPTION: RecName: Full=Mu-type opioid receptor; Short=M-OR-1; Short=MOR-1; AltName: Full=Mu opiate receptor; AltName: Full=Mu opioid receptor; Short=MOP; Short=hMOP; FUNCTION: Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. 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. 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 extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. 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. Also couples to adenylate cyclase stimulatory G alpha proteins. 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. 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. 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. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding- competent OPRM1 isoforms and reduce their ligand binding activity. SUBUNIT: Forms homooligomers and heterooligomers with other GPCRs, such as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably in dimeric forms). Interacts with PPL; the interaction disrupts agonist-mediated G-protein activation. Interacts (via C- terminus) with DNAJB4 (via C-terminus). Interacts with calmodulin; the interaction inhibits the constitutive activity of OPRM1; it abolishes basal and attenuates agonist-stimulated G-protein coupling. Interacts with FLNA, PLD2, RANBP9 and WLS. Interacts with GPM6A, RTP4, SYP, GNAS, RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1 (By similarity). INTERACTION: P21333:FLNA; NbExp=5; IntAct=EBI-2624570, EBI-350432; Q5T9L3:WLS; NbExp=7; IntAct=EBI-2624570, EBI-2868748; SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. SUBCELLULAR LOCATION: Isoform 12: Cytoplasm. TISSUE SPECIFICITY: Expressed in brain. Isoform 16 and isoform 17 are detected in brain. PTM: Phosphorylated. Differentially phosphorylated in basal and agonist-induced conditions. Agonist-mediated phosphorylation modulates receptor internalization. Phosphorylated by ADRBK1 in a agonist-dependent manner. Phosphorylation at Tyr-168 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 agoinist-induced G- protein-indepenedent receptor down-regulation. Phosphorylation at Ser-377 is involved in G-protein-dependent but not beta-arrestin- dependent activation of the ERK pathway (By similarity). PTM: 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 (By similarity). POLYMORPHISM: Variant Asp-40 does not show altered binding affinities for most opioid peptides and alkaloids tested, but it binds beta-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately 3 times more tightly than the most common allelic form. MISCELLANEOUS: OPRM1 is the main physiological target for most clinically important opioid analgesics. 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. Opioid-induced hyperalgesic responses are observed following both acute and chronic dosing associated with cellular excitation. SIMILARITY: Belongs to the G-protein coupled receptor 1 family. SEQUENCE CAUTION: Sequence=CAI20458.1; Type=Erroneous initiation; Sequence=EAW47705.1; Type=Erroneous initiation; WEB RESOURCE: Name=Wikipedia; Note=Mu opioid receptor entry; URL="http://en.wikipedia.org/wiki/Mu_opioid_receptor"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/oprm1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 81321 - Family A G protein-coupled receptor-like
ModBase Predicted Comparative 3D Structure on P35372
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
