OPRM_CAVPO
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 03-AUG-2022, entry version 116.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC 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., Grandy D.K.,
RA Kelly M.J.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP SUBCELLULAR LOCATION, RECEPTOR INTERNALIZATION, AND FUNCTION.
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 vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:9241-9246(1996).
CC -!- FUNCTION: Receptor for endogenous opioids such as beta-endorphin and
CC endomorphin. Receptor for natural and synthetic opioids including
CC morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and
CC methadone (PubMed:8799185). Also activated by enkephalin peptides, such
CC as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for
CC Met-enkephalin-Arg-Phe. Agonist binding to the receptor induces
CC coupling 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 GTP-
CC bound G-protein alpha and the G-protein beta-gamma dimer activating
CC downstream cellular effectors. The agonist- and cell type-specific
CC activity is predominantly coupled to pertussis toxin-sensitive G(i) and
CC G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1, and to a lesser
CC extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15.
CC They mediate an array of downstream cellular responses, including
CC inhibition of adenylate cyclase activity and both N-type and L-type
CC calcium channels, activation of inward rectifying potassium channels,
CC mitogen-activated protein kinase (MAPK), phospholipase C (PLC),
CC phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K)
CC and regulation of NF-kappa-B. Also couples to adenylate cyclase
CC stimulatory G alpha proteins. The selective temporal coupling to G-
CC proteins and subsequent signaling can be regulated by RGSZ proteins,
CC such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK
CC subfamily of Ser/Thr protein kinases and association with beta-
CC arrestins is involved in short-term receptor desensitization. Beta-
CC arrestins associate with the GPRK-phosphorylated receptor and uncouple
CC it from the G-protein thus terminating signal transduction. The
CC phosphorylated receptor is internalized through endocytosis via
CC clathrin-coated pits which involves beta-arrestins. The activation of
CC the ERK pathway occurs either in a G-protein-dependent or a beta-
CC arrestin-dependent manner and is regulated by agonist-specific receptor
CC phosphorylation. Acts as a class A G-protein coupled receptor (GPCR)
CC which dissociates from beta-arrestin at or near the plasma membrane and
CC undergoes rapid recycling. Receptor down-regulation pathways are
CC varying with the agonist and occur dependent or independent of G-
CC protein coupling. Endogenous ligands induce rapid desensitization,
CC endocytosis and recycling. Heterooligomerization with other GPCRs can
CC modulate agonist binding, signaling and trafficking properties.
CC Involved in neurogenesis (By similarity).
CC {ECO:0000250|UniProtKB:P33535, ECO:0000250|UniProtKB:P35372,
CC ECO:0000250|UniProtKB:P42866, ECO:0000269|PubMed:8799185}.
CC -!- SUBUNIT: Forms homooligomers and heterooligomers with other GPCRs, such
CC as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably
CC in dimeric forms). Interacts with heterotrimeric G proteins;
CC interaction with a heterotrimeric complex containing GNAI1, GNB1 and
CC GNG2 stabilizes the active conformation of the receptor and increases
CC its affinity for endomorphin-2, the synthetic opioid peptide DAMGO and
CC for morphinan agonists (By similarity). Interacts with PPL; the
CC interaction disrupts agonist-mediated G-protein activation. Interacts
CC (via C-terminus) with DNAJB4 (via C-terminus). Interacts with
CC calmodulin; the interaction inhibits the constitutive activity of
CC OPRM1; it abolishes basal and attenuates agonist-stimulated G-protein
CC coupling. Interacts with FLNA, PLD2, RANBP9 and WLS and GPM6A (By
CC similarity). Interacts with RTP4 (By similarity). Interacts with SYP
CC and GNAS (By similarity). Interacts with RGS9, RGS17, RGS20, RGS4,
CC PPP1R9B and HINT1. {ECO:0000250|UniProtKB:P33535,
CC ECO:0000250|UniProtKB:P35372, ECO:0000250|UniProtKB:P42866}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:8799185};
CC Multi-pass membrane protein {ECO:0000269|PubMed:8799185}. Cell
CC projection, axon {ECO:0000269|PubMed:8799185}. Perikaryon
CC {ECO:0000269|PubMed:8799185}. Cell projection, dendrite
CC {ECO:0000269|PubMed:8799185}. Endosome {ECO:0000269|PubMed:8799185}.
CC Note=Is rapidly internalized after agonist binding.
CC {ECO:0000269|PubMed:8799185}.
CC -!- PTM: Phosphorylated. Differentially phosphorylated in basal and
CC agonist-induced conditions. Agonist-mediated phosphorylation modulates
CC receptor internalization. Phosphorylated by GRK2 in a agonist-dependent
CC manner. Phosphorylated on tyrosine residues; the phosphorylation is
CC involved in agonist-induced G-protein-independent receptor down-
CC regulation (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated. Differentially phosphorylated in basal and
CC agonist-induced conditions. Agonist-mediated phosphorylation modulates
CC receptor internalization. Phosphorylated by GRK2 in a agonist-dependent
CC manner. Phosphorylated on tyrosine residues; the phosphorylation is
CC involved in agonist-induced G-protein-independent receptor down-
CC regulation. {ECO:0000250|UniProtKB:P33535}.
CC -!- PTM: Ubiquitinated. A basal ubiquitination seems not to be related to
CC degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1
CC oligomers leading to proteasomal degradation; the ubiquitination is
CC diminished by RTP4. {ECO:0000250|UniProtKB:P42866}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; U67928; AAB39617.1; -; Genomic_DNA.
DR AlphaFoldDB; P97266; -.
DR SMR; P97266; -.
DR STRING; 10141.ENSCPOP00000017994; -.
DR BindingDB; P97266; -.
DR ChEMBL; CHEMBL4354; -.
DR DrugCentral; P97266; -.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; P97266; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; 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:0007197; P:adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0038003; P:G protein-coupled opioid receptor signaling pathway; IDA: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 NMDA 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; Cell projection; Endosome; G-protein coupled receptor;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN <1..>98
FT /note="Mu-type opioid receptor"
FT /id="PRO_0000069971"
FT TOPO_DOM <1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TRANSMEM 10..34
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TOPO_DOM 35..45
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TRANSMEM 46..68
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TOPO_DOM 69..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TRANSMEM 89..>98
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT MOD_RES 71
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P33535"
FT NON_TER 1
FT NON_TER 98
SQ SEQUENCE 98 AA; 11161 MW; BEDB096924E0B9BE CRC64;
YTKMKTATNI YIFNLALADA LATSTLPFQS VNYLMGTWPF GTILCKIVIS IDYYNMFTSI
FTLCTMSVDR YIAVCHPVKA LDFRTPRNAK TVNVCNWI
