ID   DRD3_RAT                Reviewed;         446 AA.
AC   P19020; P70647;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1990, sequence version 1.
DT   04-NOV-2026, entry version 203.
DE   RecName: Full=Dopamine receptor D3 {ECO:0000305};
DE   AltName: Full=Dopamine D3 receptor;
GN   Name=Drd3;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley;
RX   PubMed=1975644; DOI=10.1038/347146a0;
RA   Sokoloff P., Giros B., Martres M.-P., Bouthenet M.-L., Schwartz J.-C.;
RT   "Molecular cloning and characterization of a novel dopamine receptor (D3)
RT   as a target for neuroleptics.";
RL   Nature 347:146-151(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE SPLICING.
RX   PubMed=2039532; DOI=10.1016/0006-291x(91)90469-n;
RA   Giros B., Martres M.-P., Pilon C., Sokoloff P., Schwartz J.-C.;
RT   "Shorter variants of the D3 dopamine receptor produced through various
RT   patterns of alternative splicing.";
RL   Biochem. Biophys. Res. Commun. 176:1584-1592(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 71-106.
RX   PubMed=8333859; DOI=10.1006/bbrc.1993.1842;
RA   Pagliusi S., Chollet-Daemerius A., Losberger C., Mills A., Kawashima E.;
RT   "Characterization of a novel exon within the D3 receptor gene giving rise
RT   to an mRNA isoform expressed in rat brain.";
RL   Biochem. Biophys. Res. Commun. 194:465-471(1993).
RN   [4]
RP   INTERACTION WITH CLIC6.
RX   PubMed=14499480; DOI=10.1016/s0169-328x(03)00283-3;
RA   Griffon N., Jeanneteau F., Prieur F., Diaz J., Sokoloff P.;
RT   "CLIC6, a member of the intracellular chloride channel family, interacts
RT   with dopamine D(2)-like receptors.";
RL   Brain Res. Mol. Brain Res. 117:47-57(2003).
RN   [5]
RP   3D-STRUCTURE MODELING.
RC   TISSUE=Brain;
RX   PubMed=1358063; DOI=10.1042/bj2870277;
RA   Livingstone C.D., Strange P.G., Naylor L.H.;
RT   "Molecular modelling of D2-like dopamine receptors.";
RL   Biochem. J. 287:277-282(1992).
CC   -!- FUNCTION: G protein-coupled receptor for dopamine, a catecholamine
CC       neurotransmitter hormone that functions as the brain's 'reward
CC       chemical', driving motivation, reinforcement learning and pleasure
CC       (PubMed:1975644). Dopamine binding causes a conformation change that
CC       triggers signaling via guanine nucleotide-binding proteins (G proteins)
CC       and modulates the activity of downstream effectors, such as adenylate
CC       cyclase (PubMed:1975644). Dopamine receptors can be classified in two
CC       categories: (1) DRD3 (together with DRD2 and DRD4) is a D2-type
CC       receptor and is coupled to G(i)/G(o) G proteins, mediating inhibition
CC       of adenylate cyclase activity, while D1-type receptors (DRD1 and DRD5)
CC       are coupled to G(s) G proteins and promote activation of adenylate
CC       cyclase activity (PubMed:1975644). D1- and D2-type dopamine receptors
CC       have antagonistic effects, particularly in the brain's striatum, where
CC       they govern voluntary movement and reward: D1-type receptors generally
CC       stimulate neural activity and promotes action, while D2-type receptors
CC       tend to inhibit neural activity and suppress movement (By similarity).
CC       DRD3 is primarily expressed in limbic areas of the brain and is
CC       involved in the modulation of cognitive, emotional and motor functions:
CC       plays a key role in regulating neuronal signaling pathways associated
CC       with motivation, reward and behavior (By similarity). Involved in the
CC       incentive salience of drugs: controls responses to drug-related
CC       stimuli, making it a key target for reducing addiction to substances
CC       like cocaine, morphine, and alcohol (By similarity). Forms
CC       heterotetramers with DRD1 to potentiate beta-arrestin recruitment and
CC       mediate locomotor activity (By similarity). Also involved in autophagy
CC       regulation: receptor activation stimulates AMPK, which phosphorylates
CC       RPTOR and enhances its interaction with MTOR, thereby inhibiting mTORC1
CC       signaling and its downstream target RPS6KB1 (By similarity). This leads
CC       to activation of ULK1 and initiation of the autophagy cascade (By
CC       similarity). {ECO:0000250|UniProtKB:P30728,
CC       ECO:0000250|UniProtKB:P35462, ECO:0000269|PubMed:1975644}.
CC   -!- SUBUNIT: Interacts with CLIC6 (PubMed:14499480). Interacts with PALM.
CC       Interacts with FLNA (via filamin repeat 21); increases PKA-mediated
CC       phosphorylation of FLNA (By similarity). Interacts with DRD1 (By
CC       similarity). {ECO:0000250|UniProtKB:P30728,
CC       ECO:0000250|UniProtKB:P35462, ECO:0000269|PubMed:14499480}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P35462};
CC       Multi-pass membrane protein {ECO:0000250|UniProtKB:P35462}. Note=Both
CC       membrane-bound and scattered in the cytoplasm during basal conditions.
CC       Receptor stimulation results in the rapid internalization and
CC       sequestration of the receptors at the perinuclear area (5 and 15
CC       minutes), followed by the dispersal of the receptors to the membrane
CC       (30 minutes). DRD3 and GRK4 co-localize in lipid rafts of renal
CC       proximal tubule cells. {ECO:0000250|UniProtKB:P35462}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P19020-1; Sequence=Displayed;
CC       Name=D3(TM3-del);
CC         IsoId=P19020-2; Sequence=VSP_001874, VSP_001875;
CC       Name=D3(O2-DEL);
CC         IsoId=P19020-3; Sequence=VSP_001876;
CC   -!- TISSUE SPECIFICITY: Mainly in limbic areas of brain.
CC       {ECO:0000269|PubMed:1975644}.
CC   -!- PTM: Phosphorylated by GRK4 (GRK4-alpha and GRK4-gamma).
CC       {ECO:0000250|UniProtKB:P35462}.
CC   -!- PTM: Palmitoylated. {ECO:0000250|UniProtKB:P35462}.
CC   -!- SIMILARITY: Belongs to the G protein-coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; X53944; CAA37887.1; -; mRNA.
DR   EMBL; M69194; AAA41076.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; M69189; AAA41076.1; JOINED; Genomic_DNA.
DR   EMBL; M69190; AAA41076.1; JOINED; Genomic_DNA.
DR   EMBL; M69191; AAA41076.1; JOINED; Genomic_DNA.
DR   EMBL; M69192; AAA41076.1; JOINED; Genomic_DNA.
DR   EMBL; M69193; AAA41076.1; JOINED; Genomic_DNA.
DR   EMBL; S63847; AAB27545.1; -; Genomic_DNA.
DR   EMBL; S63846; AAB27545.1; JOINED; Genomic_DNA.
DR   PIR; S11565; DYRTD3.
DR   RefSeq; NP_058836.1; NM_017140.2. [P19020-1]
DR   AlphaFoldDB; P19020; -.
DR   SMR; P19020; -.
DR   CORUM; P19020; -.
DR   FunCoup; P19020; 204.
DR   STRING; 10116.ENSRNOP00000073117; -.
DR   BindingDB; P19020; -.
DR   ChEMBL; CHEMBL3138; -.
DR   DrugCentral; P19020; -.
DR   GuidetoPHARMACOLOGY; 216; -.
DR   GlyCosmos; P19020; 4 sites, No reported glycans.
DR   GlyGen; P19020; 4 sites.
DR   iPTMnet; P19020; -.
DR   PhosphoSitePlus; P19020; -.
DR   PaxDb; 10116-ENSRNOP00000073117; -.
DR   GeneID; 29238; -.
DR   KEGG; rno:29238; -.
DR   UCSC; RGD:2521; rat. [P19020-1]
DR   AGR; RGD:2521; -.
DR   CTD; 1814; -.
DR   RGD; 2521; Drd3.
DR   VEuPathDB; HostDB:ENSRNOG00000060806; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   HOGENOM; CLU_009579_11_1_1; -.
DR   InParanoid; P19020; -.
DR   OMA; ACDEQKS; -.
DR   OrthoDB; 42860at9989; -.
DR   PhylomeDB; P19020; -.
DR   Reactome; R-RNO-390651; Dopamine receptors.
DR   Reactome; R-RNO-418594; G alpha (i) signalling events.
DR   PRO; PR:P19020; -.
DR   Proteomes; UP000002494; Chromosome 11.
DR   Bgee; ENSRNOG00000060806; Expressed in Ammon's horn and 1 other cell type or tissue.
DR   GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR   GO; GO:0098691; C:dopaminergic synapse; ISO:RGD.
DR   GO; GO:0030139; C:endocytic vesicle; IDA:RGD.
DR   GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098839; C:postsynaptic density membrane; IDA:SynGO.
DR   GO; GO:0031748; F:D1 dopamine receptor binding; IPI:RGD.
DR   GO; GO:0004952; F:dopamine neurotransmitter receptor activity; TAS:RGD.
DR   GO; GO:0001591; F:dopamine neurotransmitter receptor activity, coupled via Gi/Go; IDA:BHF-UCL.
DR   GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR   GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR   GO; GO:0046717; P:acid secretion; IDA:BHF-UCL.
DR   GO; GO:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; ISO:RGD.
DR   GO; GO:0007195; P:adenylate cyclase-inhibiting dopamine receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0050482; P:arachidonate secretion; ISO:RGD.
DR   GO; GO:0006914; P:autophagy; IMP:RGD.
DR   GO; GO:0048148; P:behavioral response to cocaine; IMP:RGD.
DR   GO; GO:0032922; P:circadian regulation of gene expression; ISO:RGD.
DR   GO; GO:0007212; P:G protein-coupled dopamine receptor signaling pathway; TAS:RGD.
DR   GO; GO:0002031; P:G protein-coupled receptor internalization; IDA:RGD.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:RGD.
DR   GO; GO:0006874; P:intracellular calcium ion homeostasis; ISO:RGD.
DR   GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR   GO; GO:0050883; P:musculoskeletal movement, spinal reflex action; ISO:RGD.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IDA:RGD.
DR   GO; GO:0045776; P:negative regulation of blood pressure; ISO:RGD.
DR   GO; GO:0060160; P:negative regulation of dopamine receptor signaling pathway; ISO:RGD.
DR   GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; ISO:RGD.
DR   GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD.
DR   GO; GO:0050709; P:negative regulation of protein secretion; ISO:RGD.
DR   GO; GO:1903783; P:negative regulation of sodium ion import across plasma membrane; IMP:RGD.
DR   GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:RGD.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR   GO; GO:0032467; P:positive regulation of cytokinesis; ISO:RGD.
DR   GO; GO:0060161; P:positive regulation of dopamine receptor signaling pathway; ISO:RGD.
DR   GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:BHF-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR   GO; GO:0060134; P:prepulse inhibition; ISO:RGD.
DR   GO; GO:0002016; P:regulation of blood volume by renin-angiotensin; ISO:RGD.
DR   GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; IMP:RGD.
DR   GO; GO:0014059; P:regulation of dopamine secretion; IMP:RGD.
DR   GO; GO:0019216; P:regulation of lipid metabolic process; ISO:RGD.
DR   GO; GO:0090325; P:regulation of locomotion involved in locomotory behavior; IMP:RGD.
DR   GO; GO:0040014; P:regulation of multicellular organism growth; ISO:RGD.
DR   GO; GO:0051580; P:regulation of neurotransmitter uptake; ISO:RGD.
DR   GO; GO:0099149; P:regulation of postsynaptic neurotransmitter receptor internalization; IDA:SynGO.
DR   GO; GO:0001975; P:response to amphetamine; ISO:RGD.
DR   GO; GO:0042220; P:response to cocaine; ISO:RGD.
DR   GO; GO:0045471; P:response to ethanol; ISO:RGD.
DR   GO; GO:0034776; P:response to histamine; ISO:RGD.
DR   GO; GO:0043278; P:response to morphine; ISO:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IDA:BHF-UCL.
DR   GO; GO:0008542; P:visual learning; ISO:RGD.
DR   CDD; cd15310; 7tmA_D3_dopamine_R; 1.
DR   FunFam; 1.20.1070.10:FF:000424; D(3) dopamine receptor; 1.
DR   FunFam; 1.20.1070.10:FF:000287; Dopamine receptor D3; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 2.
DR   InterPro; IPR001620; Dopamine_D3_rcpt.
DR   InterPro; IPR000929; Dopamine_rcpt.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   PANTHER; PTHR24248; ADRENERGIC RECEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1.
DR   PANTHER; PTHR24248:SF154; D(3) DOPAMINE RECEPTOR; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00568; DOPAMINED3R.
DR   PRINTS; PR00242; DOPAMINER.
DR   PRINTS; PR00237; GPCRRHODOPSN.
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.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Disulfide bond;
KW   G protein-coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate;
KW   Receptor; Reference proteome; Transducer; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..446
FT                   /note="Dopamine receptor D3"
FT                   /id="PRO_0000069400"
FT   TOPO_DOM        1..32
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TRANSMEM        33..55
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TOPO_DOM        56..65
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TRANSMEM        66..88
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TOPO_DOM        89..104
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TRANSMEM        105..126
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TOPO_DOM        127..149
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TRANSMEM        150..170
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TOPO_DOM        171..187
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TRANSMEM        188..209
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TOPO_DOM        210..375
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TRANSMEM        376..397
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TOPO_DOM        398..412
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TRANSMEM        413..432
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   TOPO_DOM        433..446
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P35462"
FT   BINDING         110
FT                   /ligand="dopamine"
FT                   /ligand_id="ChEBI:CHEBI:59905"
FT                   /evidence="ECO:0000250|UniProtKB:P14416"
FT   BINDING         192
FT                   /ligand="dopamine"
FT                   /ligand_id="ChEBI:CHEBI:59905"
FT                   /evidence="ECO:0000250|UniProtKB:P14416"
FT   BINDING         196
FT                   /ligand="dopamine"
FT                   /ligand_id="ChEBI:CHEBI:59905"
FT                   /evidence="ECO:0000250|UniProtKB:P14416"
FT   BINDING         395
FT                   /ligand="dopamine"
FT                   /ligand_id="ChEBI:CHEBI:59905"
FT                   /evidence="ECO:0000250|UniProtKB:P14416"
FT   CARBOHYD        12
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        19
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        97
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        173
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        103..181
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   DISULFID        401..404
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   VAR_SEQ         92..100
FT                   /note="TGGVWNFSR -> HSGGHASSL (in isoform D3(TM3-del))"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001874"
FT   VAR_SEQ         101..446
FT                   /note="Missing (in isoform D3(TM3-del))"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001875"
FT   VAR_SEQ         176..193
FT                   /note="Missing (in isoform D3(O2-DEL))"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_001876"
FT   CONFLICT        71
FT                   /note="L -> M (in Ref. 3)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        139
FT                   /note="Q -> E (in Ref. 2; AAA41076)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   446 AA;  49516 MW;  180E36AFF217E9DB CRC64;
     MAPLSQISTH LNSTCGAENS TGVNRARPHA YYALSYCALI LAIIFGNGLV CAAVLRERAL
     QTTTNYLVVS LAVADLLVAT LVMPWVVYLE VTGGVWNFSR ICCDVFVTLD VMMCTASILN
     LCAISIDRYT AVVMPVHYQH GTGQSSCRRV ALMITAVWVL AFAVSCPLLF GFNTTGDPSI
     CSISNPDFVI YSSVVSFYVP FGVTVLVYAR IYIVLRQRQR KRILTRQNSQ CISIRPGFPQ
     QSSCLRLHPI RQFSIRARFL SDATGQMEHI EDKQYPQKCQ DPLLSHLQPP SPGQTHGGLK
     RYYSICQDTA LRHPSLEGGA GMSPVERTRN SLSPTMAPKL SLEVRKLSNG RLSTSLRLGP
     LQPRGVPLRE KKATQMVVIV LGAFIVCWLP FFLTHVLNTH CQACHVSPEL YRATTWLGYV
     NSALNPVIYT TFNVEFRKAF LKILSC
//