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   27-MAR-2024, entry version 181.
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 a 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   GlyCosmos; P32300; 2 sites, No reported glycans.
DR   GlyGen; P32300; 2 sites.
DR   iPTMnet; P32300; -.
DR   PhosphoSitePlus; P32300; -.
DR   EPD; P32300; -.
DR   PaxDb; 10090-ENSMUSP00000050077; -.
DR   ProteomicsDB; 294201; -.
DR   Antibodypedia; 2932; 522 antibodies from 36 providers.
DR   DNASU; 18386; -.
DR   Ensembl; ENSMUST00000056336.2; ENSMUSP00000050077.2; ENSMUSG00000050511.2.
DR   GeneID; 18386; -.
DR   KEGG; mmu:18386; -.
DR   UCSC; uc008vap.1; mouse.
DR   AGR; MGI:97438; -.
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; SEARNKP; -.
DR   OrthoDB; 5393360at2759; -.
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 79 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 cell types or tissues.
DR   ExpressionAtlas; P32300; baseline and differential.
DR   GO; GO:0043679; C:axon terminus; ISO:MGI.
DR   GO; GO:0032590; C:dendrite membrane; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0098992; C:neuronal dense core vesicle; IDA:SynGO.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0098839; C:postsynaptic density membrane; ISO:MGI.
DR   GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
DR   GO; GO:0042734; C:presynaptic membrane; ISO:MGI.
DR   GO; GO:0097444; C:spine apparatus; ISO:MGI.
DR   GO; GO:0030672; C:synaptic vesicle membrane; 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:0042923; F:neuropeptide 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   CDD; cd15089; 7tmA_Delta_opioid_R; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000321; Delta_opi_rcpt.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR001418; Opioid_rcpt.
DR   PANTHER; PTHR24229:SF2; DELTA-TYPE OPIOID RECEPTOR; 1.
DR   PANTHER; PTHR24229; NEUROPEPTIDES RECEPTOR; 1.
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   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; P32300; MM.
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
//