Localization
Cell membrane,Cell projection,Axon,Perikaryon,Cell projection,Dendrite,Endosome;
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 extent 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. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis.
Gene Ontology
GO:0030424; GO:0005737; GO:0030425; GO:0032839; GO:0032590; GO:0005768; GO:0005925; GO:0005887; GO:0099055; GO:0099056; GO:0016020; GO:0045121; GO:0043204; GO:0097444; GO:0004979; GO:0031005; GO:0004930; GO:0001965; GO:0031681; GO:0038047; GO:0042923; GO:0042277; GO:0008022; GO:0019904; GO:0005245; GO:0002438; GO:0007191; GO:0007197; GO:0007193; GO:0031635; GO:0048149; GO:0042755; GO:0044849; GO:0060079; GO:0007186; GO:0006955; GO:0007626; GO:0106072; GO:0043951; GO:0051481; GO:0045019; GO:0061358; GO:0007218; GO:0038003; GO:0007200; GO:0032100; GO:0070374; GO:0050769; GO:0080135; GO:2000310; GO:0051930; GO:0042220; GO:0045471; GO:0032094; GO:0070848; GO:0032496; GO:0043278; GO:0009314; GO:0019233; GO:0042060