OPRM_BOVIN
ID OPRM_BOVIN Reviewed; 401 AA.
AC P79350;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Mu-type opioid receptor;
DE Short=M-OR-1;
DE Short=MOR-1;
GN Name=OPRM1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Corpus striatum;
RX PubMed=10581406; DOI=10.1016/s0169-328x(99)00249-1;
RA Onoprishvili I., Andria M.L., Vilim F.S., Hiller J.M., Simon E.J.;
RT "The bovine mu-opioid receptor: cloning of cDNA and pharmacological
RT characterization of the receptor expressed in mammalian cells.";
RL Brain Res. Mol. Brain Res. 73:129-137(1999).
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:10581406). Also activated by enkephalin peptides,
CC such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity
CC for 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:10581406}.
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:10581406};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P42866}. Cell
CC projection, axon {ECO:0000250|UniProtKB:P97266}. Perikaryon
CC {ECO:0000250|UniProtKB:P97266}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P97266}. Endosome
CC {ECO:0000250|UniProtKB:P97266}. Note=Is rapidly internalized after
CC agonist binding. {ECO:0000250|UniProtKB:P97266}.
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. Phosphorylation at Tyr-169 requires receptor activation, is
CC dependent on non-receptor protein tyrosine kinase Src and results in a
CC decrease in agonist efficacy by reducing G-protein coupling efficiency.
CC Phosphorylated on tyrosine residues; the phosphorylation is involved in
CC agonist-induced G-protein-independent receptor down-regulation.
CC Phosphorylation at Ser-378 is involved in G-protein-dependent but not
CC beta-arrestin-dependent activation of the ERK pathway (By similarity).
CC {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; U89677; AAB49477.2; -; mRNA.
DR RefSeq; NP_776833.1; NM_174408.2.
DR AlphaFoldDB; P79350; -.
DR SMR; P79350; -.
DR STRING; 9913.ENSBTAP00000026280; -.
DR BindingDB; P79350; -.
DR ChEMBL; CHEMBL3041; -.
DR DrugCentral; P79350; -.
DR PaxDb; P79350; -.
DR GeneID; 281958; -.
DR KEGG; bta:281958; -.
DR CTD; 4988; -.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; P79350; -.
DR OrthoDB; 1011272at2759; -.
DR PRO; PR:P79350; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISS: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; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0004979; F:beta-endorphin receptor activity; IEA:InterPro.
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; 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 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; IPR000105; Mu_opioid_rcpt.
DR InterPro; IPR001418; Opioid_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00537; MUOPIOIDR.
DR PRINTS; PR00384; OPIOIDR.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Disulfide bond; Endosome;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..401
FT /note="Mu-type opioid receptor"
FT /id="PRO_0000069970"
FT TOPO_DOM 1..69
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TRANSMEM 70..94
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TOPO_DOM 95..107
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TRANSMEM 108..132
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TOPO_DOM 133..143
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TRANSMEM 144..166
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TOPO_DOM 167..186
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TRANSMEM 187..208
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TOPO_DOM 209..231
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TRANSMEM 232..256
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TOPO_DOM 257..280
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TRANSMEM 281..307
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TOPO_DOM 308..315
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TRANSMEM 316..339
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT TOPO_DOM 340..401
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT REGION 365..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 335..339
FT /note="NPxxY; plays a role in stabilizing the activated
FT conformation of the receptor"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT MOD_RES 169
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P33535"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42866"
FT MOD_RES 373
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P33535"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P33535"
FT MOD_RES 397
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P33535"
FT LIPID 354
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 9
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 12
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 143..220
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 401 AA; 45028 MW; 6DA8592F29299C6E CRC64;
MDSGAVPTNA SNCTDPFTHP SSCSPAPSPS SWVNFSHLEG NLSDPCGPNR TELGGSDRLC
PSAGSPSMIT AIIIMALYSI VCVVGLFGNF LVMYVIVRYT KMKTATNIYI FNLALADALA
TSTLPFQSVN YLMGTWPFGT ILCKIVISID YYNMFTSIFT LCTMSVDRYI AVCHPVKALD
LRTPRNAKII NICNWILSSA IGLPVMFMAT TKYRQGSIDC TLTFSHPTWY WENLLKICVF
IFAFIMPILI ITVCYGLMIL RLKSVRMLSG SKEKDRNLRR ITRMVLVVVA VFIVCWTPIH
IYVIIKALIT IPETTFQTVS WHFCIALGYT NSCLNPVLYA FLDENFKRCF REFCIPTSST
IEQQNSTRIR QNTRDHPSTA NTVDRTNHQL ENLEAETTPL P
