OPRD_MOUSE
ID OPRD_MOUSE Reviewed; 372 AA.
AC P32300;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Delta-type opioid receptor;
DE Short=D-OR-1;
DE Short=DOR-1;
DE AltName: Full=K56;
DE AltName: Full=MSL-2;
GN Name=Oprd1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=1334555; DOI=10.1073/pnas.89.24.12048;
RA Kieffer B.L., Befort K., Gaveriaux-Ruff C., Hirth C.G.;
RT "The delta-opioid receptor: isolation of a cDNA by expression cloning and
RT pharmacological characterization.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:12048-12052(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=1335167; DOI=10.1126/science.1335167;
RA Evans C.J., Keith D.E. Jr., Morrison H., Magendzo K., Edwards R.H.;
RT "Cloning of a delta opioid receptor by functional expression.";
RL Science 258:1952-1955(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8393575; DOI=10.1073/pnas.90.14.6736;
RA Yasuda K., Raynor K., Kong H., Breder C.D., Takeda J., Reisine T.,
RA Bell G.I.;
RT "Cloning and functional comparison of kappa and delta opioid receptors from
RT mouse brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6736-6740(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8397421;
RA Keith D.E. Jr., Anton B., Evans C.J.;
RT "Characterization and mapping of a delta opioid receptor clone from NG108-
RT 15 cells.";
RL Proc. West. Pharmacol. Soc. 36:299-306(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-372.
RX PubMed=8415697; DOI=10.1073/pnas.90.20.9305;
RA Bzdega T., Chin H., Kim K., Jung H.H., Kozak C.A., Klee W.A.;
RT "Regional expression and chromosomal localization of the delta opiate
RT receptor gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:9305-9309(1993).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10677041; DOI=10.1016/s0896-6273(00)80836-3;
RA Zhu Y., King M.A., Schuller A.G., Nitsche J.F., Reidl M., Elde R.P.,
RA Unterwald E., Pasternak G.W., Pintar J.E.;
RT "Retention of supraspinal delta-like analgesia and loss of morphine
RT tolerance in delta opioid receptor knockout mice.";
RL Neuron 24:243-252(1999).
RN [7]
RP INTERACTION WITH OPRM1 AND RTP4, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=18836069; DOI=10.1073/pnas.0804106105;
RA Decaillot F.M., Rozenfeld R., Gupta A., Devi L.A.;
RT "Cell surface targeting of mu-delta opioid receptor heterodimers by RTP4.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:16045-16050(2008).
RN [8]
RP 3D-STRUCTURE MODELING.
RX PubMed=8844829; DOI=10.1093/protein/9.7.573;
RA Alkorta I., Loew G.H.;
RT "A 3D model of the delta opioid receptor and ligand-receptor complexes.";
RL Protein Eng. 9:573-583(1996).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 36-342 IN COMPLEX WITH
RP NALTRINDOLE, SUBCELLULAR LOCATION, DISULFIDE BOND, AND TOPOLOGY.
RX PubMed=22596164; DOI=10.1038/nature11111;
RA Granier S., Manglik A., Kruse A.C., Kobilka T.S., Thian F.S., Weis W.I.,
RA Kobilka B.K.;
RT "Structure of the delta-opioid receptor bound to naltrindole.";
RL Nature 485:400-404(2012).
CC -!- FUNCTION: G-protein coupled receptor that functions as receptor for
CC endogenous enkephalins and for a subset of other opioids. Ligand
CC binding causes a conformation change that triggers signaling via
CC guanine nucleotide-binding proteins (G proteins) and modulates the
CC activity of down-stream effectors, such as adenylate cyclase. Signaling
CC leads to the inhibition of adenylate cyclase activity. Inhibits
CC neurotransmitter release by reducing calcium ion currents and
CC increasing potassium ion conductance. Plays a role in the perception of
CC pain and in opiate-mediated analgesia. Plays a role in developing
CC analgesic tolerance to morphine. {ECO:0000269|PubMed:10677041,
CC ECO:0000269|PubMed:1334555, ECO:0000269|PubMed:1335167}.
CC -!- SUBUNIT: May form homooligomers. Forms a heterodimer with OPRM1
CC (PubMed:18836069). Interacts with GPRASP1 (By similarity). Interacts
CC with RTP4; the interaction promotes cell surface localization of the
CC OPRD1-OPRM1 heterodimer (PubMed:18836069).
CC {ECO:0000250|UniProtKB:P41143, ECO:0000269|PubMed:18836069}.
CC -!- INTERACTION:
CC P32300; Q9ER80: Rtp4; NbExp=2; IntAct=EBI-2615936, EBI-15731539;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10677041,
CC ECO:0000269|PubMed:1334555, ECO:0000269|PubMed:1335167,
CC ECO:0000269|PubMed:18836069, ECO:0000269|PubMed:22596164}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:10677041,
CC ECO:0000269|PubMed:1334555, ECO:0000269|PubMed:1335167,
CC ECO:0000269|PubMed:22596164}.
CC -!- TISSUE SPECIFICITY: Brain, with high concentrations in the basal
CC ganglia and limbic regions. {ECO:0000269|PubMed:10677041,
CC ECO:0000269|PubMed:1335167}.
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:0000269|PubMed:18836069}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate;
CC they show no obvious phenotype and are fertile. Mutant mice show
CC decreased analgesia in response to opioids, such as deltorphin-2. They
CC do not develop analgesic tolerance to morphine.
CC {ECO:0000269|PubMed:10677041}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; L06322; AAA37522.1; -; mRNA.
DR EMBL; L07271; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L11064; AAA37520.1; -; mRNA.
DR EMBL; S65335; AAA16009.1; -; mRNA.
DR EMBL; S66181; AAB28546.1; -; mRNA.
DR CCDS; CCDS18718.1; -.
DR PIR; B48227; B48227.
DR RefSeq; NP_038650.3; NM_013622.3.
DR PDB; 4EJ4; X-ray; 3.40 A; A=36-342.
DR PDBsum; 4EJ4; -.
DR AlphaFoldDB; P32300; -.
DR SMR; P32300; -.
DR DIP; DIP-46417N; -.
DR IntAct; P32300; 9.
DR STRING; 10090.ENSMUSP00000050077; -.
DR BindingDB; P32300; -.
DR ChEMBL; CHEMBL3222; -.
DR DrugCentral; P32300; -.
DR GuidetoPHARMACOLOGY; 317; -.
DR GlyGen; P32300; 2 sites.
DR iPTMnet; P32300; -.
DR PhosphoSitePlus; P32300; -.
DR EPD; P32300; -.
DR PaxDb; P32300; -.
DR PRIDE; P32300; -.
DR ProteomicsDB; 294201; -.
DR Antibodypedia; 2932; 445 antibodies from 36 providers.
DR DNASU; 18386; -.
DR Ensembl; ENSMUST00000056336; ENSMUSP00000050077; ENSMUSG00000050511.
DR GeneID; 18386; -.
DR KEGG; mmu:18386; -.
DR UCSC; uc008vap.1; mouse.
DR CTD; 4985; -.
DR MGI; MGI:97438; Oprd1.
DR VEuPathDB; HostDB:ENSMUSG00000050511; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000157669; -.
DR HOGENOM; CLU_009579_8_1_1; -.
DR InParanoid; P32300; -.
DR OMA; XALADAL; -.
DR OrthoDB; 1011272at2759; -.
DR PhylomeDB; P32300; -.
DR TreeFam; TF315737; -.
DR Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 18386; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Oprd1; mouse.
DR PRO; PR:P32300; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P32300; protein.
DR Bgee; ENSMUSG00000050511; Expressed in trophoblast giant cell and 51 other tissues.
DR ExpressionAtlas; P32300; baseline and differential.
DR Genevisible; P32300; MM.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0032590; C:dendrite membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0098992; C:neuronal dense core vesicle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
DR GO; GO:0097444; C:spine apparatus; ISO:MGI.
DR GO; GO:0031982; C:vesicle; ISO:MGI.
DR GO; GO:0038046; F:G protein-coupled enkephalin receptor activity; ISO:MGI.
DR GO; GO:0004985; F:G protein-coupled opioid receptor activity; IDA:MGI.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0033612; F:receptor serine/threonine kinase binding; ISO:MGI.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:MGI.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
DR GO; GO:0097237; P:cellular response to toxic substance; ISO:MGI.
DR GO; GO:0042755; P:eating behavior; ISO:MGI.
DR GO; GO:0038003; P:G protein-coupled opioid receptor signaling pathway; ISO:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:MGI.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0051924; P:regulation of calcium ion transport; ISO:MGI.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; ISO:MGI.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
DR InterPro; IPR000321; Delta_opi_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR001418; Opioid_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00525; DELTAOPIOIDR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00384; OPIOIDR.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..372
FT /note="Delta-type opioid receptor"
FT /id="PRO_0000069963"
FT TOPO_DOM 1..47
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22596164"
FT TRANSMEM 48..75
FT /note="Helical; Name=1"
FT TOPO_DOM 76..85
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22596164"
FT TRANSMEM 86..110
FT /note="Helical; Name=2"
FT TOPO_DOM 111..122
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22596164"
FT TRANSMEM 123..144
FT /note="Helical; Name=3"
FT TOPO_DOM 145..163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22596164"
FT TRANSMEM 164..186
FT /note="Helical; Name=4"
FT TOPO_DOM 187..206
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22596164"
FT TRANSMEM 207..238
FT /note="Helical; Name=5"
FT TOPO_DOM 239..261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22596164"
FT TRANSMEM 262..284
FT /note="Helical; Name=6"
FT TOPO_DOM 285..299
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:22596164"
FT TRANSMEM 300..321
FT /note="Helical; Name=7"
FT TOPO_DOM 322..372
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22596164"
FT REGION 340..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 333
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
FT CARBOHYD 18
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 33
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 121..198
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:22596164"
FT HELIX 42..76
FT /evidence="ECO:0007829|PDB:4EJ4"
FT HELIX 83..100
FT /evidence="ECO:0007829|PDB:4EJ4"
FT HELIX 102..111
FT /evidence="ECO:0007829|PDB:4EJ4"
FT HELIX 118..151
FT /evidence="ECO:0007829|PDB:4EJ4"
FT HELIX 153..159
FT /evidence="ECO:0007829|PDB:4EJ4"
FT HELIX 162..186
FT /evidence="ECO:0007829|PDB:4EJ4"
FT STRAND 187..192
FT /evidence="ECO:0007829|PDB:4EJ4"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:4EJ4"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:4EJ4"
FT HELIX 206..220
FT /evidence="ECO:0007829|PDB:4EJ4"
FT HELIX 223..238
FT /evidence="ECO:0007829|PDB:4EJ4"
FT HELIX 258..286
FT /evidence="ECO:0007829|PDB:4EJ4"
FT HELIX 294..321
FT /evidence="ECO:0007829|PDB:4EJ4"
FT HELIX 323..326
FT /evidence="ECO:0007829|PDB:4EJ4"
SQ SEQUENCE 372 AA; 40561 MW; BC3B3BBD2E52D3F9 CRC64;
MELVPSARAE LQSSPLVNLS DAFPSAFPSA GANASGSPGA RSASSLALAI AITALYSAVC
AVGLLGNVLV MFGIVRYTKL KTATNIYIFN LALADALATS TLPFQSAKYL METWPFGELL
CKAVLSIDYY NMFTSIFTLT MMSVDRYIAV CHPVKALDFR TPAKAKLINI CIWVLASGVG
VPIMVMAVTQ PRDGAVVCML QFPSPSWYWD TVTKICVFLF AFVVPILIIT VCYGLMLLRL
RSVRLLSGSK EKDRSLRRIT RMVLVVVGAF VVCWAPIHIF VIVWTLVDIN RRDPLVVAAL
HLCIALGYAN SSLNPVLYAF LDENFKRCFR QLCRTPCGRQ EPGSLRRPRQ ATTRERVTAC
TPSDGPGGGA AA
