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Protein

D(2) dopamine receptor

Gene

Drd2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei114 – 1141AgonistBy similarity
Sitei194 – 1941Important for receptor activation
Sitei197 – 1971Important for receptor activation

GO - Molecular functioni

  • dopamine binding Source: RGD
  • dopamine neurotransmitter receptor activity Source: RGD
  • dopamine neurotransmitter receptor activity, coupled via Gi/Go Source: BHF-UCL
  • drug binding Source: BHF-UCL
  • ionotropic glutamate receptor binding Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD
  • receptor binding Source: RGD

GO - Biological processi

  • acid secretion Source: BHF-UCL
  • activation of protein kinase activity Source: RGD
  • adenohypophysis development Source: Ensembl
  • adenylate cyclase-inhibiting dopamine receptor signaling pathway Source: BHF-UCL
  • adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: RGD
  • adult walking behavior Source: Ensembl
  • arachidonic acid secretion Source: Ensembl
  • auditory behavior Source: RGD
  • axonogenesis Source: Ensembl
  • behavioral response to cocaine Source: GO_Central
  • behavioral response to ethanol Source: GO_Central
  • branching morphogenesis of a nerve Source: Ensembl
  • cellular potassium ion homeostasis Source: BHF-UCL
  • cerebral cortex GABAergic interneuron migration Source: Ensembl
  • circadian regulation of gene expression Source: Ensembl
  • dopamine metabolic process Source: Ensembl
  • dopamine receptor signaling pathway Source: RGD
  • feeding behavior Source: Ensembl
  • forebrain development Source: RGD
  • G-protein coupled receptor internalization Source: RGD
  • grooming behavior Source: Ensembl
  • intracellular signal transduction Source: Ensembl
  • locomotory behavior Source: RGD
  • long-term memory Source: RGD
  • negative regulation of adenylate cyclase activity Source: BHF-UCL
  • negative regulation of blood pressure Source: Ensembl
  • negative regulation of cell migration Source: Ensembl
  • negative regulation of cell proliferation Source: Ensembl
  • negative regulation of circadian sleep/wake cycle, sleep Source: RGD
  • negative regulation of cytosolic calcium ion concentration Source: RGD
  • negative regulation of dopamine receptor signaling pathway Source: Ensembl
  • negative regulation of dopamine secretion Source: RGD
  • negative regulation of innate immune response Source: Ensembl
  • negative regulation of insulin secretion Source: RGD
  • negative regulation of protein kinase B signaling Source: Ensembl
  • negative regulation of synaptic transmission, glutamatergic Source: GO_Central
  • negative regulation of voltage-gated calcium channel activity Source: BHF-UCL
  • neurological system process involved in regulation of systemic arterial blood pressure Source: Ensembl
  • orbitofrontal cortex development Source: RGD
  • peristalsis Source: Ensembl
  • phosphatidylinositol metabolic process Source: BHF-UCL
  • phospholipase C-activating dopamine receptor signaling pathway Source: GO_Central
  • pigmentation Source: Ensembl
  • positive regulation of cytokinesis Source: Ensembl
  • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: GO_Central
  • positive regulation of dopamine uptake involved in synaptic transmission Source: Ensembl
  • positive regulation of ERK1 and ERK2 cascade Source: RGD
  • positive regulation of glial cell line-derived neurotrophic factor secretion Source: Ensembl
  • positive regulation of G-protein coupled receptor protein signaling pathway Source: RGD
  • positive regulation of growth hormone secretion Source: Ensembl
  • positive regulation of long-term synaptic potentiation Source: RGD
  • positive regulation of mitotic nuclear division Source: BHF-UCL
  • positive regulation of multicellular organism growth Source: Ensembl
  • positive regulation of neuroblast proliferation Source: Ensembl
  • positive regulation of receptor internalization Source: RGD
  • positive regulation of renal sodium excretion Source: Ensembl
  • positive regulation of transcription from RNA polymerase II promoter Source: RGD
  • positive regulation of urine volume Source: Ensembl
  • prepulse inhibition Source: Ensembl
  • protein localization Source: Ensembl
  • regulation of heart rate Source: Ensembl
  • regulation of locomotion involved in locomotory behavior Source: RGD
  • regulation of long-term neuronal synaptic plasticity Source: Ensembl
  • regulation of MAPK cascade Source: RGD
  • regulation of phosphoprotein phosphatase activity Source: RGD
  • regulation of potassium ion transport Source: BHF-UCL
  • regulation of sodium ion transport Source: Ensembl
  • regulation of synapse structural plasticity Source: RGD
  • regulation of synaptic transmission Source: RGD
  • regulation of synaptic transmission, GABAergic Source: Ensembl
  • release of sequestered calcium ion into cytosol Source: BHF-UCL
  • response to amphetamine Source: RGD
  • response to axon injury Source: RGD
  • response to drug Source: BHF-UCL
  • response to ethanol Source: RGD
  • response to histamine Source: Ensembl
  • response to hypoxia Source: RGD
  • response to inactivity Source: RGD
  • response to iron ion Source: RGD
  • response to morphine Source: Ensembl
  • response to nicotine Source: RGD
  • response to toxic substance Source: RGD
  • sensory perception of smell Source: Ensembl
  • striatum development Source: RGD
  • synapse assembly Source: BHF-UCL
  • synaptic transmission, dopaminergic Source: RGD
  • temperature homeostasis Source: Ensembl
  • visual learning Source: Ensembl
  • Wnt signaling pathway Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_336766. Dopamine receptors.
REACT_339234. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
D(2) dopamine receptor
Alternative name(s):
Dopamine D2 receptor
Gene namesi
Name:Drd2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi2520. Drd2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3737ExtracellularBy similarityAdd
BLAST
Transmembranei38 – 6023Helical; Name=1By similarityAdd
BLAST
Topological domaini61 – 7010CytoplasmicBy similarity
Transmembranei71 – 9323Helical; Name=2By similarityAdd
BLAST
Topological domaini94 – 10815ExtracellularBy similarityAdd
BLAST
Transmembranei109 – 13022Helical; Name=3By similarityAdd
BLAST
Topological domaini131 – 15121CytoplasmicBy similarityAdd
BLAST
Transmembranei152 – 17221Helical; Name=4By similarityAdd
BLAST
Topological domaini173 – 18816ExtracellularBy similarityAdd
BLAST
Transmembranei189 – 21325Helical; Name=5By similarityAdd
BLAST
Topological domaini214 – 374161CytoplasmicBy similarityAdd
BLAST
Transmembranei375 – 39622Helical; Name=6By similarityAdd
BLAST
Topological domaini397 – 41014ExtracellularBy similarityAdd
BLAST
Transmembranei411 – 43222Helical; Name=7By similarityAdd
BLAST
Topological domaini433 – 44412CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  • acrosomal vesicle Source: RGD
  • axon Source: RGD
  • axon terminus Source: RGD
  • cytoplasmic vesicle Source: RGD
  • cytosol Source: GOC
  • dendrite Source: RGD
  • dendritic spine Source: RGD
  • endocytic vesicle Source: RGD
  • integral component of plasma membrane Source: GO_Central
  • intracellular Source: GOC
  • lateral plasma membrane Source: RGD
  • membrane Source: BHF-UCL
  • perikaryon Source: RGD
  • plasma membrane Source: RGD
  • postsynaptic density Source: RGD
  • sperm flagellum Source: RGD
  • synaptic vesicle membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi193 – 1931S → A: Moderate decrease in ligand binding. 200-fold reduction of agonist-mediated cAMP inhibition. 1 Publication
Mutagenesisi194 – 1941S → A: Small decrease in agonist binding. Complete loss of agonist-mediated cAMP inhibition. 1 Publication
Mutagenesisi197 – 1971S → A: Small decrease in agonist binding. 18-fold reduction of agonist-mediated cAMP inhibition. 1 Publication
Mutagenesisi420 – 4201S → A: Moderate decrease in ligand binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 444444D(2) dopamine receptorPRO_0000069390Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi5 – 51N-linked (GlcNAc...)Sequence Analysis
Glycosylationi17 – 171N-linked (GlcNAc...)Sequence Analysis
Glycosylationi23 – 231N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi107 ↔ 182PROSITE-ProRule annotation
Disulfide bondi400 ↔ 402PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP61169.

PTM databases

PhosphoSiteiP61169.

Expressioni

Gene expression databases

GenevisibleiP61169. RN.

Interactioni

Subunit structurei

Forms homo- and heterooligomers with DRD4. The interaction with DRD4 may modulate agonist-induced downstream signaling (By similarity). Interacts with HTR2A, GNAI1, CADPS and CADPS2 (By similarity). Interacts with KCNA2 (By similarity). Interacts with GPRASP1, PPP1R9B and CLIC6. Interacts with ARRB2.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ppp1r9bO352742EBI-80012,EBI-80022

Protein-protein interaction databases

BioGridi246498. 2 interactions.
DIPiDIP-30883N.
IntActiP61169. 3 interactions.
MINTiMINT-4792453.

Structurei

3D structure databases

ProteinModelPortaliP61169.
SMRiP61169. Positions 37-444.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni190 – 1978Agonist bindingBy similarity
Regioni211 – 374164Interaction with PPP1R9BAdd
BLAST
Regioni387 – 3959Agonist bindingBy similarity

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG309657.
GeneTreeiENSGT00760000118795.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP61169.
KOiK04145.
OMAiNSVKHSR.
OrthoDBiEOG769ZMG.
PhylomeDBiP61169.
TreeFamiTF334382.

Family and domain databases

InterProiIPR001922. Dopamine_D2_rcpt.
IPR000929. Dopamine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00567. DOPAMINED2R.
PR00242. DOPAMINER.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P61169-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDPLNLSWYD DDLERQNWSR PFNGSEGKAD RPHYNYYAML LTLLIFIIVF
60 70 80 90 100
GNVLVCMAVS REKALQTTTN YLIVSLAVAD LLVATLVMPW VVYLEVVGEW
110 120 130 140 150
KFSRIHCDIF VTLDVMMCTA SILNLCAISI DRYTAVAMPM LYNTRYSSKR
160 170 180 190 200
RVTVMIAIVW VLSFTISCPL LFGLNNTDQN ECIIANPAFV VYSSIVSFYV
210 220 230 240 250
PFIVTLLVYI KIYIVLRKRR KRVNTKRSSR AFRANLKTPL KGNCTHPEDM
260 270 280 290 300
KLCTVIMKSN GSFPVNRRRM DAARRAQELE MEMLSSTSPP ERTRYSPIPP
310 320 330 340 350
SHHQLTLPDP SHHGLHSNPD SPAKPEKNGH AKIVNPRIAK FFEIQTMPNG
360 370 380 390 400
KTRTSLKTMS RRKLSQQKEK KATQMLAIVL GVFIICWLPF FITHILNIHC
410 420 430 440
DCNIPPVLYS AFTWLGYVNS AVNPIIYTTF NIEFRKAFMK ILHC
Length:444
Mass (Da):50,904
Last modified:May 10, 2004 - v1
Checksum:i216E56CEE5CA32FB
GO
Isoform Short (identifier: P61169-2) [UniParc] [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     242-270: Missing.

Show »
Length:415
Mass (Da):47,599
Checksum:i2923089F3EDAC911
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti99 – 991E → D in CAA37373 (PubMed:2139615).Curated
Sequence conflicti173 – 1731G → R in CAA37373 (PubMed:2139615).Curated
Sequence conflicti180 – 1801N → G in CAA37373 (PubMed:2139615).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei242 – 27029Missing in isoform Short. 1 PublicationVSP_001871Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M36831 mRNA. Translation: AAA41075.1.
X53278 mRNA. Translation: CAA37373.1.
X56065 mRNA. Translation: CAA39543.1.
M32241 mRNA. Translation: AAA41074.1.
PIRiS08146.
RefSeqiNP_036679.1. NM_012547.1. [P61169-1]
XP_006243041.1. XM_006242979.2. [P61169-2]
UniGeneiRn.87299.

Genome annotation databases

EnsembliENSRNOT00000045944; ENSRNOP00000043759; ENSRNOG00000008428. [P61169-1]
ENSRNOT00000083419; ENSRNOP00000074235; ENSRNOG00000008428. [P61169-2]
GeneIDi24318.
KEGGirno:24318.
UCSCiRGD:2520. rat.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M36831 mRNA. Translation: AAA41075.1.
X53278 mRNA. Translation: CAA37373.1.
X56065 mRNA. Translation: CAA39543.1.
M32241 mRNA. Translation: AAA41074.1.
PIRiS08146.
RefSeqiNP_036679.1. NM_012547.1. [P61169-1]
XP_006243041.1. XM_006242979.2. [P61169-2]
UniGeneiRn.87299.

3D structure databases

ProteinModelPortaliP61169.
SMRiP61169. Positions 37-444.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246498. 2 interactions.
DIPiDIP-30883N.
IntActiP61169. 3 interactions.
MINTiMINT-4792453.

Chemistry

BindingDBiP61169.
ChEMBLiCHEMBL339.
GuidetoPHARMACOLOGYi215.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP61169.

Proteomic databases

PRIDEiP61169.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000045944; ENSRNOP00000043759; ENSRNOG00000008428. [P61169-1]
ENSRNOT00000083419; ENSRNOP00000074235; ENSRNOG00000008428. [P61169-2]
GeneIDi24318.
KEGGirno:24318.
UCSCiRGD:2520. rat.

Organism-specific databases

CTDi1813.
RGDi2520. Drd2.

Phylogenomic databases

eggNOGiNOG309657.
GeneTreeiENSGT00760000118795.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP61169.
KOiK04145.
OMAiNSVKHSR.
OrthoDBiEOG769ZMG.
PhylomeDBiP61169.
TreeFamiTF334382.

Enzyme and pathway databases

ReactomeiREACT_336766. Dopamine receptors.
REACT_339234. G alpha (i) signalling events.

Miscellaneous databases

NextBioi602973.
PROiP61169.

Gene expression databases

GenevisibleiP61169. RN.

Family and domain databases

InterProiIPR001922. Dopamine_D2_rcpt.
IPR000929. Dopamine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00567. DOPAMINED2R.
PR00242. DOPAMINER.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
    Tissue: Brain.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Alternative splicing directs the expression of two D2 dopamine receptor isoforms."
    Giros B., Sokoloff P., Martres M.-P., Riou J.-F., Emorine L.J., Schwartz J.-C.
    Nature 342:923-926(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "Multiple D2 dopamine receptors produced by alternative RNA splicing."
    Monsma F.J. Jr., McVittie L.D., Gerfen C.R., Mahan L.C., Sibley D.R.
    Nature 342:926-929(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. "Two forms of the rat D2 dopamine receptor as revealed by the polymerase chain reaction."
    Rao D.D., McKelvy J., Kebabian J., MacKenzie R.G.
    FEBS Lett. 263:18-22(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  6. "5'untranslated region of rat pituitary dopamine D2(B) receptor contains a putative CpG island."
    Taylor P.L., Inglis J.D., Eidne K.A.
    Submitted (OCT-1990) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
    Strain: Sprague-Dawley.
  7. "Identification by sequence analysis of a second rat brain cDNA encoding the dopamine (D2) receptor."
    Miller J.C., Wang Y., Filer D.
    Biochem. Biophys. Res. Commun. 166:109-112(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 242-270.
  8. "Cloning of two additional catecholamine receptors from rat brain."
    O'Dowd B.F., Nguyen T., Tirpak A., Jarvie K.R., Israel Y., Seeman P., Niznik H.B.
    FEBS Lett. 262:8-12(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 242-270.
  9. "Contributions of conserved serine residues to the interactions of ligands with dopamine D2 receptors."
    Cox B.A., Henningsen R.A., Spanoyannis A., Neve R.L., Neve K.A.
    J. Neurochem. 59:627-635(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF SER-193; SER-194; SER-197 AND SER-420.
  10. "Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein."
    Smith F.D., Oxford G.S., Milgram S.L.
    J. Biol. Chem. 274:19894-19900(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PPP1R9B.
  11. "CLIC6, a member of the intracellular chloride channel family, interacts with dopamine D(2)-like receptors."
    Griffon N., Jeanneteau F., Prieur F., Diaz J., Sokoloff P.
    Brain Res. Mol. Brain Res. 117:47-57(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CLIC6.
  12. Cited for: INTERACTION WITH GPRASP1.
  13. "G protein-coupled receptor kinase-mediated phosphorylation regulates post-endocytic trafficking of the D2 dopamine receptor."
    Namkung Y., Dipace C., Javitch J.A., Sibley D.R.
    J. Biol. Chem. 284:15038-15051(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARRB2.
  14. "Molecular modelling of D2-like dopamine receptors."
    Livingstone C.D., Strange P.G., Naylor L.H.
    Biochem. J. 287:277-282(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING.

Entry informationi

Entry nameiDRD2_RAT
AccessioniPrimary (citable) accession number: P61169
Secondary accession number(s): P13953
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: July 22, 2015
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.