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Protein

D(2) dopamine receptor

Gene

DRD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Binding sitei114AgonistBy similarity1
Sitei194Important for receptor activationBy similarity1
Sitei197Important for receptor activationBy similarity1

GO - Molecular functioni

  • dopamine binding Source: GO_Central
  • dopamine neurotransmitter receptor activity, coupled via Gi/Go Source: BHF-UCL
  • drug binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • potassium channel regulator activity Source: BHF-UCL
  • protein homodimerization activity Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-390651 Dopamine receptors
R-HSA-418594 G alpha (i) signalling events
SignaLinkiP14416
SIGNORiP14416

Protein family/group databases

TCDBi9.A.14.3.10 the g-protein-coupled receptor (gpcr) family

Names & Taxonomyi

Protein namesi
Recommended name:
D(2) dopamine receptor
Alternative name(s):
Dopamine D2 receptor
Gene namesi
Name:DRD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000149295.13
HGNCiHGNC:3023 DRD2
MIMi126450 gene
neXtProtiNX_P14416

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 37ExtracellularBy similarityAdd BLAST37
Transmembranei38 – 60Helical; Name=1By similarityAdd BLAST23
Topological domaini61 – 70CytoplasmicBy similarity10
Transmembranei71 – 93Helical; Name=2By similarityAdd BLAST23
Topological domaini94 – 108ExtracellularBy similarityAdd BLAST15
Transmembranei109 – 130Helical; Name=3By similarityAdd BLAST22
Topological domaini131 – 151CytoplasmicBy similarityAdd BLAST21
Transmembranei152 – 172Helical; Name=4By similarityAdd BLAST21
Topological domaini173 – 188ExtracellularBy similarityAdd BLAST16
Transmembranei189 – 213Helical; Name=5By similarityAdd BLAST25
Topological domaini214 – 373CytoplasmicBy similarityAdd BLAST160
Transmembranei374 – 395Helical; Name=6By similarityAdd BLAST22
Topological domaini396 – 409ExtracellularBy similarityAdd BLAST14
Transmembranei410 – 431Helical; Name=7By similarityAdd BLAST22
Topological domaini432 – 443CytoplasmicBy similarityAdd BLAST12

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1813
MalaCardsiDRD2
MIMi103780 phenotype
OpenTargetsiENSG00000149295
Orphaneti36899 Myoclonus-dystonia syndrome
PharmGKBiPA27478

Chemistry databases

ChEMBLiCHEMBL217
DrugBankiDB01614 Acepromazine
DB01063 Acetophenazine
DB05766 ACP-104
DB01425 Alizapride
DB00915 Amantadine
DB06288 Amisulpride
DB00543 Amoxapine
DB00182 Amphetamine
DB04599 Aniracetam
DB00714 Apomorphine
DB01238 Aripiprazole
DB09207 AS-8112
DB06216 Asenapine
DB04889 Bicifadine
DB04888 Bifeprunox
DB05687 BL-1020
DB04857 Brasofensine
DB09128 Brexpiprazole
DB01200 Bromocriptine
DB09018 Bromopride
DB00490 Buspirone
DB00248 Cabergoline
DB06016 Cariprazine
DB01038 Carphenazine
DB00477 Chlorpromazine
DB01239 Chlorprothixene
DB00568 Cinnarizine
DB00363 Clozapine
DB01151 Desipramine
DB01184 Domperidone
DB00988 Dopamine
DB01142 Doxepin
DB00450 Droperidol
DB01049 Ergoloid mesylate
DB00696 Ergotamine
DB00875 Flupentixol
DB00623 Fluphenazine
DB04842 Fluspirilene
DB00502 Haloperidol
DB04946 Iloperidone
DB00458 Imipramine
DB05816 intranasal apomorphine
DB04924 Itopride
DB01221 Ketamine
DB01235 Levodopa
DB00589 Lisuride
DB00408 Loxapine
DB06077 Lumateperone
DB08815 Lurasidone
DB00934 Maprotiline
DB01043 Memantine
DB00933 Mesoridazine
DB01403 Methotrimeprazine
DB01233 Metoclopramide
DB06148 Mianserin
DB00805 Minaprine
DB00370 Mirtazapine
DB01618 Molindone
DB00540 Nortriptyline
DB00334 Olanzapine
DB01267 Paliperidone
DB01186 Pergolide
DB00850 Perphenazine
DB05316 Pimavanserin
DB01100 Pimozide
DB01621 Pipotiazine
DB00413 Pramipexole
DB00433 Prochlorperazine
DB00420 Promazine
DB01069 Promethazine
DB00777 Propiomazine
DB01224 Quetiapine
DB00409 Remoxipride
DB00734 Risperidone
DB01549 Rolicyclidine
DB00268 Ropinirole
DB05271 Rotigotine
DB06144 Sertindole
DB05280 SLV 308
DB00391 Sulpiride
DB04844 Tetrabenazine
DB00372 Thiethylperazine
DB01622 Thioproperazine
DB00679 Thioridazine
DB01623 Thiothixene
DB13025 Tiapride
DB00831 Trifluoperazine
DB00508 Triflupromazine
DB00726 Trimipramine
DB01392 Yohimbine
DB00246 Ziprasidone
DB01624 Zuclopenthixol
GuidetoPHARMACOLOGYi215

Polymorphism and mutation databases

BioMutaiDRD2
DMDMi118206

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000693871 – 443D(2) dopamine receptorAdd BLAST443

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi5N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi17N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi23N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi107 ↔ 182PROSITE-ProRule annotation
Disulfide bondi399 ↔ 401PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP14416
PeptideAtlasiP14416
PRIDEiP14416

PTM databases

iPTMnetiP14416
PhosphoSitePlusiP14416
SwissPalmiP14416

Expressioni

Gene expression databases

BgeeiENSG00000149295
CleanExiHS_DRD2
ExpressionAtlasiP14416 baseline and differential
GenevisibleiP14416 HS

Organism-specific databases

HPAiHPA015691

Interactioni

Subunit structurei

Forms homo- and heterooligomers with DRD4. The interaction with DRD4 may modulate agonist-induced downstream signaling. Interacts with GPRASP1, PPP1R9B and CLIC6 (By similarity). Interacts with CADPS and CADPS2. Interacts with ARRB2 (By similarity). Interacts with KCNA2 (By similarity). Interacts with GNAI2 isoform sGi2, the interaction allows the creation of an intracellular pool of DRD2 that can be released to cell surface upon agonist stimulation. Interacts with HTR2A.By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: Ensembl

Protein-protein interaction databases

BioGridi108147, 18 interactors
DIPiDIP-5977N
IntActiP14416, 6 interactors
MINTiP14416
STRINGi9606.ENSP00000354859

Chemistry databases

BindingDBiP14416

Structurei

Secondary structure

1443
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi36 – 61Combined sources26
Helixi63 – 65Combined sources3
Helixi68 – 86Combined sources19
Helixi88 – 97Combined sources10
Helixi104 – 137Combined sources34
Helixi147 – 167Combined sources21
Helixi168 – 175Combined sources8
Helixi183 – 185Combined sources3
Helixi189 – 195Combined sources7
Turni196 – 198Combined sources3
Helixi199 – 222Combined sources24
Helixi369 – 398Combined sources30
Helixi405 – 417Combined sources13
Helixi418 – 420Combined sources3
Helixi422 – 429Combined sources8
Helixi431 – 442Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1I15model-A34-58[»]
B72-97[»]
C108-129[»]
D153-172[»]
E190-210[»]
F371-396[»]
G403-426[»]
5AERX-ray2.19B/C430-443[»]
6CM4X-ray2.87A35-222[»]
A363-443[»]
ProteinModelPortaliP14416
SMRiP14416
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP14416

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni190 – 197Agonist bindingBy similarity8
Regioni211 – 373Interaction with PPP1R9BBy similarityAdd BLAST163
Regioni386 – 394Agonist bindingBy similarity9

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00890000139331
HOVERGENiHBG106962
InParanoidiP14416
KOiK04145
OMAiRNWSRPF
OrthoDBiEOG091G06VI
PhylomeDBiP14416
TreeFamiTF334382

Family and domain databases

InterProiView protein in InterPro
IPR001922 Dopamine_D2_rcpt
IPR000929 Dopamine_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00567 DOPAMINED2R
PR00242 DOPAMINER
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P14416-1) [UniParc]FASTAAdd to basket
Also known as: D2(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.

« Hide

        10         20         30         40         50
MDPLNLSWYD DDLERQNWSR PFNGSDGKAD RPHYNYYATL LTLLIAVIVF
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
RVTVMISIVW VLSFTISCPL LFGLNNADQN ECIIANPAFV VYSSIVSFYV
210 220 230 240 250
PFIVTLLVYI KIYIVLRRRR KRVNTKRSSR AFRAHLRAPL KGNCTHPEDM
260 270 280 290 300
KLCTVIMKSN GSFPVNRRRV EAARRAQELE MEMLSSTSPP ERTRYSPIPP
310 320 330 340 350
SHHQLTLPDP SHHGLHSTPD SPAKPEKNGH AKDHPKIAKI FEIQTMPNGK
360 370 380 390 400
TRTSLKTMSR RKLSQQKEKK ATQMLAIVLG VFIICWLPFF ITHILNIHCD
410 420 430 440
CNIPPVLYSA FTWLGYVNSA VNPIIYTTFN IEFRKAFLKI LHC
Length:443
Mass (Da):50,619
Last modified:April 1, 1990 - v2
Checksum:i9BF8EA36C988A2E2
GO
Isoform 2 (identifier: P14416-2) [UniParc]FASTAAdd to basket
Also known as: D2(Short)

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

Show »
Length:414
Mass (Da):47,347
Checksum:iBFC25AC601DFDC7F
GO
Isoform 3 (identifier: P14416-3) [UniParc]FASTAAdd to basket
Also known as: D2(Longer)

The sequence of this isoform differs from the canonical sequence as follows:
     270-270: V → VVQ

Show »
Length:445
Mass (Da):50,847
Checksum:i111674E96E087FD6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti40L → R in AAB26819 (PubMed:1363862).Curated1

Polymorphismi

Genetic variations in DRD2 may determine the genetic susceptibility to alcoholism [MIMi:103780]. Genetic variations in DRD2 might be a protective factor against the development of withdrawal symptoms but might also be a risk factor in a highly burdened subgroup of alcoholics with a paternal and grandpaternal history of alcoholism and might contribute to suicide risk in alcoholics.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017143154V → I Found in patients with alcohol-responsive myoclonus-dystonia; unknown pathological significance; the mutation does not affect functional properties. 2 PublicationsCorresponds to variant dbSNP:rs104894220EnsemblClinVar.1
Natural variantiVAR_014674310P → S. Corresponds to variant dbSNP:rs1800496EnsemblClinVar.1
Natural variantiVAR_003462311S → C May be associated with a higher risk for schizophrenia. 1 PublicationCorresponds to variant dbSNP:rs1801028EnsemblClinVar.1
Natural variantiVAR_064579327K → E1 PublicationCorresponds to variant dbSNP:rs71653614EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001870242 – 270Missing in isoform 2. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_026455270V → VVQ in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M30625 mRNA Translation: AAA88024.1
X51645 mRNA Translation: CAB56463.1
X51646 Genomic DNA Translation: CAB37869.1
X51362 mRNA Translation: CAA35746.1
M29066 mRNA Translation: AAA52761.1
S62137 mRNA Translation: AAB26819.1
S69899 mRNA Translation: AAB20571.1
S58589
, S58577, S58584, S58586, S58588 Genomic DNA Translation: AAB26274.1
AF176812 mRNA Translation: AAF61479.1
AB065860 Genomic DNA Translation: BAC06078.1
AF050737 Genomic DNA Translation: AAC78779.1
BC021195 mRNA Translation: AAH21195.1
CCDSiCCDS8361.1 [P14416-1]
CCDS8362.1 [P14416-2]
PIRiS08417 DYHUD2
RefSeqiNP_000786.1, NM_000795.3 [P14416-1]
NP_057658.2, NM_016574.3 [P14416-2]
XP_016872785.1, XM_017017296.1 [P14416-1]
UniGeneiHs.73893

Genome annotation databases

EnsembliENST00000346454; ENSP00000278597; ENSG00000149295 [P14416-2]
ENST00000362072; ENSP00000354859; ENSG00000149295 [P14416-1]
ENST00000538967; ENSP00000438215; ENSG00000149295 [P14416-3]
ENST00000542968; ENSP00000442172; ENSG00000149295 [P14416-1]
GeneIDi1813
KEGGihsa:1813
UCSCiuc001pnz.4 human [P14416-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDRD2_HUMAN
AccessioniPrimary (citable) accession number: P14416
Secondary accession number(s): Q9NZR3, Q9UPA9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: April 1, 1990
Last modified: May 23, 2018
This is version 210 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health