ID OPRM_CAVPO Reviewed; 98 AA. AC P97266; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 05-OCT-2016, entry version 97. DE RecName: Full=Mu-type opioid receptor; DE Short=M-OR-1; DE Short=MOR-1; DE Flags: Fragment; GN Name=OPRM1; OS Cavia porcellus (Guinea pig). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; OC Hystricognathi; Caviidae; Cavia. OX NCBI_TaxID=10141; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Ronnekleiv O.K., Bosch M.A., Cunningham M.J., Wagner E.J., RA Grandy D.K., Kelly M.J.; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. RN [2] RP SUBCELLULAR LOCATION, AND RECEPTOR INTERNALIZATION. RX PubMed=8799185; DOI=10.1073/pnas.93.17.9241; RA Sternini C., Spann M., Anton B., Keith D.E. Jr., Bunnett N.W., RA von Zastrow M., Evans C., Brecha N.C.; RT "Agonist-selective endocytosis of mu opioid receptor by neurons in RT vivo."; RL Proc. Natl. Acad. Sci. U.S.A. 93:9241-9246(1996). CC -!- FUNCTION: Receptor for endogenous opioids such as beta-endorphin CC and endomorphin. Agonist binding to the receptor induces coupling CC to an inactive GDP-bound heterotrimeric G-protein complex and CC subsequent exchange of GDP for GTP in the G-protein alpha subunit CC leading to dissociation of the G-protein complex with the free CC GTP-bound G-protein alpha and the G-protein beta-gamma dimer CC activating downstream cellular effectors. The agonist- and cell CC type-specific activity is predominantly coupled to pertussis CC toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, CC GNAI3 and GNAO1, and to a lesser extend to pertussis toxin- CC insensitive G alpha proteins GNAZ and GNA15. They mediate an array CC of downstream cellular responses, including inhibition of CC adenylate cyclase activity and both N-type and L-type calcium CC channels, activation of inward rectifying potassium channels, CC mitogen-activated protein kinase (MAPK), phospholipase C (PLC), CC phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase CC (PI3K) and regulation of NF-kappa-B. Also couples to adenylate CC cyclase stimulatory G alpha proteins. The selective temporal CC coupling to G-proteins and subsequent signaling can be regulated CC by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by CC members of the GPRK subfamily of Ser/Thr protein kinases and CC association with beta-arrestins is involved in short-term receptor CC desensitization. Beta-arrestins associate with the GPRK- CC phosphorylated receptor and uncouple it from the G-protein thus CC terminating signal transduction. The phosphorylated receptor is CC internalized through endocytosis via clathrin-coated pits which CC involves beta-arrestins. The activation of the ERK pathway occurs CC either in a G-protein-dependent or a beta-arrestin-dependent CC manner and is regulated by agonist-specific receptor CC phosphorylation. Acts as a class A G-protein coupled receptor CC (GPCR) which dissociates from beta-arrestin at or near the plasma CC membrane and undergoes rapid recycling. Receptor down-regulation CC pathways are varying with the agonist and occur dependent or CC independent of G-protein coupling. Endogenous ligands induce rapid CC desensitization, endocytosis and recycling. Heterooligomerization CC with other GPCRs can modulate agonist binding, signaling and CC trafficking properties. Involved in neurogenesis (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Forms homooligomers and heterooligomers with other GPCRs, CC such as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 CC (probably in dimeric forms). Interacts with PPL; the interaction CC disrupts agonist-mediated G-protein activation. Interacts (via C- CC terminus) with DNAJB4 (via C-terminus). Interacts with calmodulin; CC the interaction inhibits the constitutive activity of OPRM1; it CC abolishes basal and attenuates agonist-stimulated G-protein CC coupling. Interacts with RTP4, SYP, GNAS, RGS9, RGS17, RGS20, CC RGS4, PPP1R9B, HINT1, GPM6A, FLNA, PLD2, RANBP9 and WLS (By CC similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8799185}; CC Multi-pass membrane protein {ECO:0000269|PubMed:8799185}. CC -!- PTM: Phosphorylated. Differentially phosphorylated in basal and CC agonist-induced conditions. Agonist-mediated phosphorylation CC modulates receptor internalization. Phosphorylated by ADRBK1 in a CC agonist-dependent manner. Phosphorylated on tyrosine residues; the CC phosphorylation is involved in agonist-induced G-protein- CC independent receptor down-regulation (By similarity). CC {ECO:0000250}. CC -!- PTM: Ubiquitinated. A basal ubiquitination seems not to be related CC to degradation. Ubiquitination is increased upon formation of CC OPRM1:OPRD1 oligomers leading to proteasomal degradation; the CC ubiquitination is diminished by RTP4 (By similarity). CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U67928; AAB39617.1; -; Genomic_DNA. DR ProteinModelPortal; P97266; -. DR STRING; 10141.ENSCPOP00000017994; -. DR BindingDB; P97266; -. DR ChEMBL; CHEMBL4354; -. DR eggNOG; KOG3656; Eukaryota. DR eggNOG; ENOG410XRW9; LUCA. DR HOGENOM; HOG000230486; -. DR InParanoid; P97266; -. DR Proteomes; UP000005447; Unassembled WGS sequence. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB. DR GO; GO:0004930; F:G-protein coupled receptor activity; ISS:UniProtKB. DR GO; GO:0038047; F:morphine receptor activity; ISS:UniProtKB. DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB. DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; ISS:UniProtKB. DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISS:UniProtKB. DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISS:UniProtKB. DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; ISS:UniProtKB. DR GO; GO:0061358; P:negative regulation of Wnt protein secretion; ISS:UniProtKB. DR GO; GO:0007200; P:phospholipase C-activating G-protein coupled receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB. DR GO; GO:2000310; P:regulation of N-methyl-D-aspartate selective glutamate receptor activity; ISS:UniProtKB. DR GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR001418; Opioid_rcpt. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR00384; OPIOIDR. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. PE 3: Inferred from homology; KW Cell membrane; Complete proteome; G-protein coupled receptor; KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Transducer; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT CHAIN <1 >98 Mu-type opioid receptor. FT /FTId=PRO_0000069971. FT TOPO_DOM <1 9 Cytoplasmic. {ECO:0000250}. FT TRANSMEM 10 34 Helical; Name=2. {ECO:0000250}. FT TOPO_DOM 35 45 Extracellular. {ECO:0000250}. FT TRANSMEM 46 68 Helical; Name=3. {ECO:0000250}. FT TOPO_DOM 69 88 Cytoplasmic. {ECO:0000250}. FT TRANSMEM 89 >98 Helical; Name=4. {ECO:0000250}. FT MOD_RES 71 71 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P33535}. FT NON_TER 1 1 FT NON_TER 98 98 SQ SEQUENCE 98 AA; 11161 MW; BEDB096924E0B9BE CRC64; YTKMKTATNI YIFNLALADA LATSTLPFQS VNYLMGTWPF GTILCKIVIS IDYYNMFTSI FTLCTMSVDR YIAVCHPVKA LDFRTPRNAK TVNVCNWI //