P61169 (DRD2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
D(2) dopamine receptor

Alternative name(s):
Dopamine D2 receptor

Gene names

Name:

Drd2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	444 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Subunit structure	Forms homo- and heterooligomers with DRD4. The interaction with DRD4 may modulate agonist-induced downstream signaling By similarity. Interacts with GNAI1, CADPS and CADPS2 By similarity. Interacts with GPRASP1, PPP1R9B and CLIC6. Interacts with ARRB2. Ref.10 Ref.11 Ref.12 Ref.13
Subcellular location	Cell membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor internalization Inferred from direct assay PubMed 14617818. Source: RGD Wnt receptor signaling pathway Inferred from direct assay PubMed 17472703. Source: RGD acid secretion Inferred from direct assay PubMed 8302280. Source: BHF-UCL activation of protein kinase activity Inferred from direct assay PubMed 12086672. Source: RGD adenohypophysis development Inferred from electronic annotation. Source: Compara adenylate cyclase-inhibiting dopamine receptor signaling pathway Inferred from direct assay PubMed 2410769. Source: BHF-UCL adult walking behavior Inferred from electronic annotation. Source: Compara arachidonic acid secretion Inferred from electronic annotation. Source: Compara auditory behavior Inferred from mutant phenotype PubMed 17142301. Source: RGD axonogenesis Inferred from electronic annotation. Source: Compara behavioral response to cocaine Inferred from electronic annotation. Source: Compara behavioral response to ethanol Inferred from electronic annotation. Source: Compara branching morphogenesis of a nerve Inferred from electronic annotation. Source: Compara cellular potassium ion homeostasis Inferred by curator PubMed 2162345. Source: BHF-UCL cerebral cortex GABAergic interneuron migration Inferred from electronic annotation. Source: Compara circadian regulation of gene expression Inferred from electronic annotation. Source: Compara dopamine metabolic process Inferred from electronic annotation. Source: Compara elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Inferred from electronic annotation. Source: Compara feeding behavior Inferred from electronic annotation. Source: Compara forebrain development Inferred from mutant phenotype PubMed 17175142. Source: RGD grooming behavior Inferred from electronic annotation. Source: Compara intracellular protein kinase cascade Inferred from electronic annotation. Source: Compara locomotory behavior Inferred from mutant phenotype PubMed 16530737. Source: RGD long-term memory Inferred from mutant phenotype PubMed 17118678. Source: RGD negative regulation of adenylate cyclase activity Inferred from direct assay PubMed 2410769. Source: BHF-UCL negative regulation of blood pressure Inferred from electronic annotation. Source: Compara negative regulation of cell migration Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of circadian sleep/wake cycle, sleep Inferred from direct assay PubMed 12944496. Source: RGD negative regulation of dopamine receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of dopamine secretion Inferred from mutant phenotype PubMed 16490190. Source: RGD negative regulation of insulin secretion Inferred from mutant phenotype PubMed 18216393. Source: RGD negative regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara negative regulation of protein secretion Inferred from electronic annotation. Source: Compara negative regulation of synaptic transmission, glutamatergic Inferred from electronic annotation. Source: Compara negative regulation of voltage-gated calcium channel activity Inferred from direct assay PubMed 2162345. Source: BHF-UCL neurological system process involved in regulation of systemic arterial blood pressure Inferred from electronic annotation. Source: Compara peristalsis Inferred from electronic annotation. Source: Compara phosphatidylinositol metabolic process Inferred from direct assay PubMed 2162345. Source: BHF-UCL phospholipase C-activating dopamine receptor signaling pathway Inferred from electronic annotation. Source: Compara pigmentation Inferred from electronic annotation. Source: Compara positive regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype PubMed 18809670. Source: RGD positive regulation of G-protein coupled receptor protein signaling pathway Inferred from mutant phenotype PubMed 18809670. Source: RGD positive regulation of dopamine uptake involved in synaptic transmission Inferred from electronic annotation. Source: Compara positive regulation of growth hormone secretion Inferred from electronic annotation. Source: Compara positive regulation of long-term synaptic potentiation Inferred from mutant phenotype PubMed 20377617. Source: RGD positive regulation of mitosis Traceable author statement PubMed 8302280. Source: BHF-UCL positive regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara positive regulation of neuroblast proliferation Inferred from electronic annotation. Source: Compara positive regulation of receptor internalization Inferred from mutant phenotype PubMed 18809670. Source: RGD positive regulation of renal sodium excretion Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 12388421. Source: RGD positive regulation of urine volume Inferred from electronic annotation. Source: Compara prepulse inhibition Inferred from electronic annotation. Source: Compara protein localization Inferred from electronic annotation. Source: Compara reduction of cytosolic calcium ion concentration Inferred from mutant phenotype PubMed 15681393. Source: RGD regulation of heart rate Inferred from electronic annotation. Source: Compara regulation of locomotion involved in locomotory behavior Inferred from mutant phenotype PubMed 22394078. Source: RGD regulation of long-term neuronal synaptic plasticity Inferred from electronic annotation. Source: Compara regulation of phosphoprotein phosphatase activity Inferred from mutant phenotype PubMed 12435803. Source: RGD regulation of potassium ion transport Inferred from direct assay PubMed 2162345PubMed 8371717. Source: BHF-UCL regulation of sodium ion transport Inferred from electronic annotation. Source: Compara regulation of synapse structural plasticity Inferred from direct assay PubMed 22216301. Source: RGD regulation of synaptic transmission Inferred from direct assay PubMed 17314300. Source: RGD regulation of synaptic transmission, GABAergic Inferred from electronic annotation. Source: Compara release of sequestered calcium ion into cytosol Inferred from mutant phenotype PubMed 8371717. Source: BHF-UCL response to amphetamine Inferred from expression pattern PubMed 19145071. Source: RGD response to axon injury Inferred from expression pattern PubMed 19500946. Source: RGD response to drug Inferred from direct assay PubMed 1975644. Source: BHF-UCL response to ethanol Inferred from expression pattern PubMed 18536982. Source: RGD response to histamine Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from mutant phenotype PubMed 15681393. Source: RGD response to inactivity Inferred from expression pattern PubMed 17511973. Source: RGD response to iron ion Inferred from expression pattern PubMed 19022977. Source: RGD response to morphine Inferred from electronic annotation. Source: Compara response to nicotine Inferred from expression pattern PubMed 19406037. Source: RGD response to toxin Inferred from expression pattern PubMed 19576243. Source: RGD sensory perception of smell Inferred from electronic annotation. Source: Compara synapse assembly Inferred from expression pattern PubMed 10051231. Source: BHF-UCL synaptic transmission, dopaminergic Inferred from direct assay PubMed 17314300. Source: RGD temperature homeostasis Inferred from electronic annotation. Source: Compara visual learning Inferred from electronic annotation. Source: Compara
Cellular_component	acrosomal vesicle Inferred from direct assay PubMed 16924680. Source: RGD axon terminus Inferred from direct assay PubMed 7623147. Source: RGD endocytic vesicle Inferred from direct assay PubMed 14617818. Source: RGD integral to plasma membrane Inferred from electronic annotation. Source: Compara lateral plasma membrane Inferred from direct assay Ref.10. Source: RGD perikaryon Inferred from direct assay PubMed 12965226. Source: RGD postsynaptic density Inferred from direct assay PubMed 17145509. Source: RGD sperm flagellum Inferred from direct assay PubMed 16924680. Source: RGD synaptic vesicle membrane Inferred from direct assay PubMed 7623147. Source: RGD
Molecular_function	dopamine binding Inferred from mutant phenotype PubMed 17174299. Source: RGD dopamine neurotransmitter receptor activity, coupled via Gi/Go Inferred from direct assay PubMed 8302280. Source: BHF-UCL drug binding Inferred from direct assay PubMed 1975644. Source: BHF-UCL protein homodimerization activity Inferred from direct assay PubMed 20813060. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ppp1r9b	O35274	2	EBI-80012,EBI-80022

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P61169-1)

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.

Isoform Short (identifier: P61169-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 444	444	D(2) dopamine receptor		PRO_0000069390
Regions
	Topological domain	1 – 37	37	Extracellular By similarity
	Transmembrane	38 – 60	23	Helical; Name=1; By similarity
	Topological domain	61 – 70	10	Cytoplasmic By similarity
	Transmembrane	71 – 93	23	Helical; Name=2; By similarity
	Topological domain	94 – 108	15	Extracellular By similarity
	Transmembrane	109 – 130	22	Helical; Name=3; By similarity
	Topological domain	131 – 151	21	Cytoplasmic By similarity
	Transmembrane	152 – 172	21	Helical; Name=4; By similarity
	Topological domain	173 – 188	16	Extracellular By similarity
	Transmembrane	189 – 213	25	Helical; Name=5; By similarity
	Topological domain	214 – 374	161	Cytoplasmic By similarity
	Transmembrane	375 – 396	22	Helical; Name=6; By similarity
	Topological domain	397 – 410	14	Extracellular By similarity
	Transmembrane	411 – 432	22	Helical; Name=7; By similarity
	Topological domain	433 – 444	12	Cytoplasmic By similarity
	Region	190 – 197	8	Agonist binding By similarity
	Region	211 – 374	164	Interaction with PPP1R9B
	Region	387 – 395	9	Agonist binding By similarity
Sites
	Binding site	114	1	Agonist By similarity
	Site	194	1	Important for receptor activation
	Site	197	1	Important for receptor activation
Amino acid modifications
	Glycosylation	5	1	N-linked (GlcNAc...) Potential
	Glycosylation	17	1	N-linked (GlcNAc...) Potential
	Glycosylation	23	1	N-linked (GlcNAc...) Potential
	Disulfide bond	107 ↔ 182		By similarity
	Disulfide bond	400 ↔ 402		By similarity
Natural variations
	Alternative sequence	242 – 270	29	Missing in isoform Short.		VSP_001871
Experimental info
	Mutagenesis	193	1	S → A: Moderate decrease in ligand binding. 200-fold reduction of agonist-mediated cAMP inhibition. Ref.9
	Mutagenesis	194	1	S → A: Small decrease in agonist binding. Complete loss of agonist-mediated cAMP inhibition. Ref.9
	Mutagenesis	197	1	S → A: Small decrease in agonist binding. 18-fold reduction of agonist-mediated cAMP inhibition. Ref.9
	Mutagenesis	420	1	S → A: Moderate decrease in ligand binding. Ref.9
	Sequence conflict	99	1	E → D in CAA37373. Ref.5
	Sequence conflict	173	1	G → R in CAA37373. Ref.5
	Sequence conflict	180	1	N → G in CAA37373. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified May 10, 2004. Version 1. Checksum: 216E56CEE5CA32FB	FASTA	444	50,904
	10 20 30 40 50 60 MDPLNLSWYD DDLERQNWSR PFNGSEGKAD RPHYNYYAML LTLLIFIIVF GNVLVCMAVS 70 80 90 100 110 120 REKALQTTTN YLIVSLAVAD LLVATLVMPW VVYLEVVGEW KFSRIHCDIF VTLDVMMCTA 130 140 150 160 170 180 SILNLCAISI DRYTAVAMPM LYNTRYSSKR RVTVMIAIVW VLSFTISCPL LFGLNNTDQN 190 200 210 220 230 240 ECIIANPAFV VYSSIVSFYV PFIVTLLVYI KIYIVLRKRR KRVNTKRSSR AFRANLKTPL 250 260 270 280 290 300 KGNCTHPEDM KLCTVIMKSN GSFPVNRRRM DAARRAQELE MEMLSSTSPP ERTRYSPIPP 310 320 330 340 350 360 SHHQLTLPDP SHHGLHSNPD SPAKPEKNGH AKIVNPRIAK FFEIQTMPNG KTRTSLKTMS 370 380 390 400 410 420 RRKLSQQKEK KATQMLAIVL GVFIICWLPF FITHILNIHC DCNIPPVLYS AFTWLGYVNS 430 440 AVNPIIYTTF NIEFRKAFMK ILHC
	Isoform Short [UniParc] [UniParc]. Checksum: 2923089F3EDAC911	FASTA	415	47,599
	10 20 30 40 50 60 MDPLNLSWYD DDLERQNWSR PFNGSEGKAD RPHYNYYAML LTLLIFIIVF GNVLVCMAVS 70 80 90 100 110 120 REKALQTTTN YLIVSLAVAD LLVATLVMPW VVYLEVVGEW KFSRIHCDIF VTLDVMMCTA 130 140 150 160 170 180 SILNLCAISI DRYTAVAMPM LYNTRYSSKR RVTVMIAIVW VLSFTISCPL LFGLNNTDQN 190 200 210 220 230 240 ECIIANPAFV VYSSIVSFYV PFIVTLLVYI KIYIVLRKRR KRVNTKRSSR AFRANLKTPL 250 260 270 280 290 300 KDAARRAQEL EMEMLSSTSP PERTRYSPIP PSHHQLTLPD PSHHGLHSNP DSPAKPEKNG 310 320 330 340 350 360 HAKIVNPRIA KFFEIQTMPN GKTRTSLKTM SRRKLSQQKE KKATQMLAIV LGVFIICWLP 370 380 390 400 410 FFITHILNIH CDCNIPPVLY SAFTWLGYVN SAVNPIIYTT FNIEFRKAFM KILHC

References

[1]	"Cloning and expression of a rat D2 dopamine receptor cDNA." Bunzow J.R., van Tol H.H.M., Grandy D.K., Albert P., Salon J., Christie M., Machida C.A., Neve K.A., Civelli O. Nature 336:783-787(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). Tissue: Brain.
[2]	"D2 receptor, a missing exon." Eidne K.A., Taylor P.L., Zabavnik J., Saunders P.T.K., Inglis J.D. Nature 342:865-865(1989) [PubMed] [Europe PMC] [Abstract] 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]	"Dopamine responsiveness is regulated by targeted sorting of D2 receptors." Bartlett S.E., Enquist J., Hopf F.W., Lee J.H., Gladher F., Kharazia V., Waldhoer M., Mailliard W.S., Armstrong R., Bonci A., Whistler J.L. Proc. Natl. Acad. Sci. U.S.A. 102:11521-11526(2005) [PubMed] [Europe PMC] [Abstract] 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M36831 mRNA. Translation: AAA41075.1. X53278 mRNA. Translation: CAA37373.1. X56065 mRNA. Translation: CAA39543.1. M32241 mRNA. Translation: AAA41074.1.
IPI	IPI00231173. IPI00231514.
PIR	S08146.
RefSeq	NP_036679.1. NM_012547.1.
UniGene	Rn.87299.
3D structure databases
ProteinModelPortal	P61169.
SMR	P61169. Positions 37-444.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-30883N.
IntAct	P61169. 1 interaction.
MINT	MINT-4792453.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P61169.
Proteomic databases
PRIDE	P61169.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000045944; ENSRNOP00000043759; ENSRNOG00000008428.
GeneID	24318.
KEGG	rno:24318.
UCSC	RGD:2520. rat.
Organism-specific databases
CTD	1813.
RGD	2520. Drd2.
Phylogenomic databases
eggNOG	NOG309657.
GeneTree	ENSGT00700000104182.
HOGENOM	HOG000239242.
HOVERGEN	HBG106962.
InParanoid	P61169.
KO	K04145.
OrthoDB	EOG4MW865.
Gene expression databases
ArrayExpress	P61169.
Genevestigator	P61169.
GermOnline	ENSRNOG00000008428. Rattus norvegicus.
Family and domain databases
InterPro	IPR001922. Dopa_D2_rcpt. IPR000929. Dopamine_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00567. DOPAMINED2R. PR00242. DOPAMINER. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P61169.
ChEMBL	CHEMBL339.
NextBio	284001.

Entry information

Entry name

DRD2_RAT

Accession

Primary (citable) accession number: P61169
Secondary accession number(s): P13953

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	May 10, 2004
Last modified:	May 1, 2013
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program