P61168 (DRD2_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

Protein attributes

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

General annotation (Comments)

Function	Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase By similarity.
Subunit structure	Forms homo- and heterooligomers with DRD4. The interaction with DRD4 may modulate agonist-induced downstream signaling. Interacts with GPRASP1, PPP1R9B, CADPS, CADPS2 and CLIC6. Interacts with ARRB2 and GNAI1 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Isoform 1 and isoform 2 are expressed in the pituitary and brain. Isoform 1 is expressed seven times more than isoform 2 in the caudate nucleus.
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 electronic annotation. Source: Compara Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara activation of protein kinase activity Inferred from electronic annotation. Source: Compara adenohypophysis development Inferred from mutant phenotype PubMed 9140068. Source: MGI adenylate cyclase-inhibiting dopamine receptor signaling pathway Inferred from direct assay PubMed 12665504. Source: MGI adult walking behavior Inferred from mutant phenotype PubMed 7566118. Source: MGI arachidonic acid secretion Inferred from electronic annotation. Source: Compara auditory behavior Inferred from electronic annotation. Source: Compara axonogenesis Inferred from mutant phenotype PubMed 11438590. Source: MGI behavioral response to cocaine Inferred from mutant phenotype PubMed 17426149. Source: MGI behavioral response to ethanol Inferred from mutant phenotype PubMed 11105945PubMed 11166059PubMed 12837020. Source: MGI branching morphogenesis of a nerve Inferred from mutant phenotype PubMed 11438590. Source: MGI cerebral cortex GABAergic interneuron migration Inferred from mutant phenotype PubMed 17409246. Source: MGI circadian regulation of gene expression Inferred from mutant phenotype PubMed 16606840. Source: MGI dopamine metabolic process Inferred from mutant phenotype PubMed 7925842. Source: MGI 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 genetic interaction PubMed 15272078. Source: MGI grooming behavior Inferred from mutant phenotype PubMed 10698004. Source: MGI intracellular protein kinase cascade Inferred from electronic annotation. Source: Compara long-term memory Inferred from electronic annotation. Source: Compara negative regulation of adenylate cyclase activity Inferred from electronic annotation. Source: Compara negative regulation of blood pressure Inferred from mutant phenotype PubMed 11566895. Source: MGI negative regulation of cell migration Inferred from mutant phenotype PubMed 17409246. Source: MGI negative regulation of cell proliferation Inferred from mutant phenotype PubMed 10537166PubMed 9140068PubMed 9247267PubMed 9247268PubMed 9717839. Source: MGI negative regulation of circadian sleep/wake cycle, sleep Inferred from electronic annotation. Source: Compara negative regulation of dopamine receptor signaling pathway Inferred from mutant phenotype PubMed 11089973. Source: MGI negative regulation of insulin secretion Inferred from electronic annotation. Source: Compara negative regulation of protein kinase B signaling cascade Inferred from mutant phenotype PubMed 17251429. Source: MGI negative regulation of protein secretion Inferred from electronic annotation. Source: Compara negative regulation of synaptic transmission, glutamatergic Inferred from mutant phenotype PubMed 11160501PubMed 15489038. Source: MGI negative regulation of voltage-gated calcium channel activity Inferred from electronic annotation. Source: Compara neurological system process involved in regulation of systemic arterial blood pressure Inferred from mutant phenotype PubMed 11566895. Source: MGI neuron-neuron synaptic transmission Inferred from mutant phenotype PubMed 12084937. Source: MGI peristalsis Inferred from mutant phenotype PubMed 16525059. Source: MGI phosphatidylinositol metabolic process Inferred from electronic annotation. Source: Compara phospholipase C-activating dopamine receptor signaling pathway Inferred from direct assay PubMed 15016423. Source: MGI pigmentation Inferred from mutant phenotype PubMed 9140068. Source: MGI positive regulation of ERK1 and ERK2 cascade Inferred from electronic annotation. Source: Compara positive regulation of G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of dopamine uptake involved in synaptic transmission Inferred from mutant phenotype PubMed 9886065. Source: MGI positive regulation of growth hormone secretion Inferred from mutant phenotype PubMed 11897683. Source: MGI positive regulation of multicellular organism growth Inferred from mutant phenotype PubMed 11897683. Source: MGI positive regulation of neuroblast proliferation Inferred from direct assay PubMed 17426594. Source: MGI positive regulation of receptor internalization Inferred from electronic annotation. Source: Compara positive regulation of renal sodium excretion Inferred from mutant phenotype PubMed 11566895. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of urine volume Inferred from mutant phenotype PubMed 11566895. Source: MGI prepulse inhibition Inferred from mutant phenotype PubMed 10341260PubMed 12417685PubMed 12476322PubMed 17712281. Source: MGI protein localization Inferred from mutant phenotype PubMed 10828532. Source: MGI reduction of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara regulation of dopamine secretion Inferred from mutant phenotype PubMed 11943831. Source: MGI regulation of heart rate Inferred from mutant phenotype PubMed 11566895. Source: MGI regulation of long-term neuronal synaptic plasticity Inferred from mutant phenotype PubMed 9169514. Source: MGI regulation of phosphoprotein phosphatase activity Inferred from electronic annotation. Source: Compara regulation of potassium ion transport Inferred from mutant phenotype PubMed 11566895. Source: MGI regulation of sodium ion transport Inferred from mutant phenotype PubMed 11566895. Source: MGI regulation of synaptic transmission, GABAergic Inferred from mutant phenotype PubMed 15080900PubMed 15489038. Source: MGI release of sequestered calcium ion into cytosol Inferred from electronic annotation. Source: Compara response to amphetamine Inferred from mutant phenotype PubMed 12476322PubMed 18486343. Source: MGI response to axon injury Inferred from electronic annotation. Source: Compara response to drug Inferred from direct assay PubMed 7549459. Source: MGI response to histamine Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to inactivity Inferred from electronic annotation. Source: Compara response to iron ion Inferred from electronic annotation. Source: Compara response to morphine Inferred from mutant phenotype PubMed 11264672PubMed 11567069PubMed 11943831PubMed 12182883PubMed 9252189. Source: MGI response to nicotine Inferred from electronic annotation. Source: Compara response to toxin Inferred from electronic annotation. Source: Compara sensory perception of smell Inferred from mutant phenotype PubMed 16765459. Source: MGI synapse assembly Inferred from electronic annotation. Source: Compara synaptic transmission, dopaminergic Inferred from electronic annotation. Source: Compara temperature homeostasis Inferred from mutant phenotype PubMed 10471093PubMed 18486343. Source: MGI visual learning Inferred from mutant phenotype PubMed 12097513. Source: MGI
Cellular_component	acrosomal vesicle Inferred from electronic annotation. Source: Compara axon Inferred from direct assay PubMed 10051229. Source: MGI axon terminus Inferred from electronic annotation. Source: Compara dendrite Inferred from direct assay PubMed 10051229. Source: MGI endocytic vesicle Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred from electronic annotation. Source: Compara lateral plasma membrane Inferred from electronic annotation. Source: Compara membrane Inferred from direct assay PubMed 7706278. Source: MGI perikaryon Inferred from electronic annotation. Source: Compara postsynaptic density Inferred from electronic annotation. Source: Compara synaptic vesicle membrane Inferred from electronic annotation. Source: Compara
Molecular_function	dopamine binding Inferred from direct assay PubMed 15716360. Source: MGI dopamine neurotransmitter receptor activity, coupled via Gi/Go Inferred from direct assay PubMed 11015197PubMed 11069937PubMed 12476322PubMed 12930822PubMed 1980140Ref.1PubMed 7566118PubMed 7706278PubMed 8001143PubMed 8294904PubMed 8836575. Source: MGI drug binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P61168-1)

Also known as: Long;

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 2 (identifier: P61168-2)

Also known as: Short;

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_0000069388
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 By similarity
	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 2.		VSP_010241
Experimental info
	Sequence conflict	29	1	P → A in CAA39209. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 2EC8460CA11FC7F0	FASTA	444	50,930
	10 20 30 40 50 60 MDPLNLSWYD DDLERQNWSR PFNGSEGKPD 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 2 (Short) [UniParc] [UniParc]. Checksum: 645E7A47407FCFCD	FASTA	415	47,625
	10 20 30 40 50 60 MDPLNLSWYD DDLERQNWSR PFNGSEGKPD 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

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Differential expression of the mouse D2 dopamine receptor isoforms." Montmayeur J.P., Bausero P., Amlaiky N., Maroteaux L., Hen R., Borrelli E. FEBS Lett. 278:239-243(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[2]	"A second molecular form of D2 dopamine receptor in rat and bovine caudate nucleus." Chio C.L., Hess G.F., Graham R.S., Huff R.M. Nature 343:266-269(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"The dopamine D2 receptor: two molecular forms generated by alternative splicing." Dal-Toso R., Sommer B., Ewert M., Herb A., Pritchett D.B., Bach A., Shivers B.D., Seeburg P.H. EMBO J. 8:4025-4034(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 175-270 (ISOFORM 1).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X55674 mRNA. Translation: CAA39209.1. CH466522 Genomic DNA. Translation: EDL25723.1. BC105663 mRNA. Translation: AAI05664.1. BC105664 mRNA. Translation: AAI05665.1. BC105665 mRNA. Translation: AAI05666.1. BC105666 mRNA. Translation: AAI05667.1.
IPI	IPI00229964. IPI00469269.
PIR	DYMSD2. S13921.
RefSeq	NP_034207.2. NM_010077.2.
UniGene	Mm.41970.
3D structure databases
ProteinModelPortal	P61168.
SMR	P61168. Positions 27-444.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000075170.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P61168.
Proteomic databases
PRIDE	P61168.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000075764; ENSMUSP00000075170; ENSMUSG00000032259.
GeneID	13489.
KEGG	mmu:13489.
Organism-specific databases
CTD	1813.
MGI	MGI:94924. Drd2.
Phylogenomic databases
eggNOG	NOG309657.
GeneTree	ENSGT00700000104182.
HOGENOM	HOG000239242.
HOVERGEN	HBG106962.
InParanoid	Q0VGH9.
KO	K04145.
OMA	WYDDDLE.
OrthoDB	EOG4MW865.
Gene expression databases
Bgee	P61168.
CleanEx	MM_DRD2.
Genevestigator	P61168.
GermOnline	ENSMUSG00000032259. Mus musculus.
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	P61168.
ChEMBL	CHEMBL3427.
NextBio	284001.
SOURCE	Search...

Entry information

Entry name

DRD2_MOUSE

Accession

Primary (citable) accession number: P61168
Secondary accession number(s): P13953, Q0VGH9

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program