D(2) dopamine receptor

Details

Name
D(2) dopamine receptor
Synonyms
  • Dopamine D2 receptor
Gene Name
DRD2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001508|D(2) dopamine receptor
MDPLNLSWYDDDLERQNWSRPFNGSDGKADRPHYNYYATLLTLLIAVIVFGNVLVCMAVS
REKALQTTTNYLIVSLAVADLLVATLVMPWVVYLEVVGEWKFSRIHCDIFVTLDVMMCTA
SILNLCAISIDRYTAVAMPMLYNTRYSSKRRVTVMISIVWVLSFTISCPLLFGLNNADQN
ECIIANPAFVVYSSIVSFYVPFIVTLLVYIKIYIVLRRRRKRVNTKRSSRAFRAHLRAPL
KGNCTHPEDMKLCTVIMKSNGSFPVNRRRVEAARRAQELEMEMLSSTSPPERTRYSPIPP
SHHQLTLPDPSHHGLHSTPDSPAKPEKNGHAKDHPKIAKIFEIQTMPNGKTRTSLKTMSR
RKLSQQKEKKATQMLAIVLGVFIICWLPFFITHILNIHCDCNIPPVLYSAFTWLGYVNSA
VNPIIYTTFNIEFRKAFLKILHC
Number of residues
443
Molecular Weight
50618.91
Theoretical pI
9.85
GO Classification
Functions
dopamine binding / dopamine neurotransmitter receptor activity, coupled via Gi/Go / drug binding / identical protein binding / potassium channel regulator activity
Processes
activation of protein kinase activity / adenohypophysis development / adenylate cyclase-inhibiting dopamine receptor signaling pathway / adult walking behavior / arachidonic acid secretion / associative learning / auditory behavior / axonogenesis / behavioral response to cocaine / behavioral response to ethanol / branching morphogenesis of a nerve / cellular calcium ion homeostasis / cerebral cortex GABAergic interneuron migration / circadian regulation of gene expression / dopamine metabolic process / feeding behavior / G-protein coupled receptor internalization / grooming behavior / intracellular signal transduction / locomotory behavior / long-term memory / negative regulation of adenylate cyclase activity / negative regulation of blood pressure / negative regulation of cell migration / negative regulation of cell proliferation / negative regulation of circadian sleep/wake cycle, sleep / negative regulation of cytosolic calcium ion concentration / negative regulation of dopamine receptor signaling pathway / negative regulation of dopamine secretion / negative regulation of innate immune response / negative regulation of insulin secretion / negative regulation of protein kinase B signaling / negative regulation of protein secretion / negative regulation of synaptic transmission, glutamatergic / negative regulation of voltage-gated calcium channel activity / neurological system process involved in regulation of systemic arterial blood pressure / neuron-neuron synaptic transmission / orbitofrontal cortex development / peristalsis / phosphatidylinositol metabolic process / phospholipase C-activating dopamine receptor signaling pathway / pigmentation / positive regulation of cytokinesis / positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway / positive regulation of dopamine uptake involved in synaptic transmission / positive regulation of ERK1 and ERK2 cascade / positive regulation of G-protein coupled receptor protein signaling pathway / positive regulation of glial cell-derived neurotrophic factor secretion / positive regulation of growth hormone secretion / positive regulation of long-term synaptic potentiation / positive regulation of multicellular organism growth / positive regulation of neuroblast proliferation / positive regulation of receptor internalization / positive regulation of renal sodium excretion / positive regulation of transcription from RNA polymerase II promoter / positive regulation of urine volume / prepulse inhibition / protein localization / regulation of cAMP metabolic process / regulation of dopamine secretion / regulation of dopamine uptake involved in synaptic transmission / regulation of heart rate / regulation of locomotion involved in locomotory behavior / regulation of long-term neuronal synaptic plasticity / regulation of phosphoprotein phosphatase activity / regulation of potassium ion transport / regulation of sodium ion transport / regulation of synapse structural plasticity / regulation of synaptic transmission, GABAergic / release of sequestered calcium ion into cytosol / response to amphetamine / response to axon injury / response to cocaine / response to drug / response to histamine / response to hypoxia / response to inactivity / response to iron ion / response to light stimulus / response to morphine / response to nicotine / response to toxic substance / sensory perception of smell / striatum development / synapse assembly / synaptic transmission, dopaminergic / temperature homeostasis / visual learning / Wnt signaling pathway
Components
acrosomal vesicle / axon / axon terminus / ciliary membrane / cytosol / dendrite / dendritic spine / endocytic vesicle / integral component of plasma membrane / intracellular / lateral plasma membrane / nonmotile primary cilium / perikaryon / plasma membrane / postsynaptic density / sperm flagellum / synaptic vesicle membrane
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Pfam Domain Function
Transmembrane Regions
38-60 71-93 109-130 152-172 189-213 374-395 410-431
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0021274|D(2) dopamine receptor (DRD2)
ATGGATCCACTGAATCTGTCCTGGTATGATGATGATCTGGAGAGGCAGAACTGGAGCCGG
CCCTTCAACGGGTCAGACGGGAAGGCGGACAGACCCCACTACAACTACTATGCCACACTG
CTCACCCTGCTCATCGCTGTCATCGTCTTCGGCAACGTGCTGGTGTGCATGGCTGTGTCC
CGCGAGAAGGCGCTGCAGACCACCACCAACTACCTGATCGTCAGCCTCGCAGTGGCCGAC
CTCCTCGTCGCCACACTGGTCATGCCCTGGGTTGTCTACCTGGAGGTGGTAGGTGAGTGG
AAATTCAGCAGGATTCACTGTGACATCTTCGTCACTCTGGACGTCATGATGTGCACGGCG
AGCATCCTGAACTTGTGTGCCATCAGCATCGACAGGTACACAGCTGTGGCCATGCCCATG
CTGTACAATACGCGCTACAGCTCCAAGCGCCGGGTCACCGTCATGATCTCCATCGTCTGG
GTCCTGTCCTTCACCATCTCCTGCCCACTCCTCTTCGGACTCAATAACGCAGACCAGAAC
GAGTGCATCATTGCCAACCCGGCCTTCGTGGTCTACTCCTCCATCGTCTCCTTCTACGTG
CCCTTCATTGTCACCCTGCTGGTCTACATCAAGATCTACATTGTCCTCCGCAGACGCCGC
AAGCGAGTCAACACCAAACGCAGCAGCCGAGCTTTCAGGGCCCACCTGAGGGCTCCACTA
AAGGGCAACTGTACTCACCCCGAGGACATGAAACTCTGCACCGTTATCATGAAGTCTAAT
GGGAGTTTCCCAGTGAACAGGCGGAGAGTGGAGGCTGCCCGGCGAGCCCAGGAGCTGGAG
ATGGAGATGCTCTCCAGCACCAGCCCACCCGAGAGGACCCGGTACAGCCCCATCCCACCC
AGCCACCACCAGCTGACTCTCCCCGACCCGTCCCACCATGGTCTCCACAGCACTCCCGAC
AGCCCCGCCAAACCAGAGAAGAATGGGCATGCCAAAGACCACCCCAAGATTGCCAAGATC
TTTGAGATCCAGACCATGCCCAATGGCAAAACCCGGACCTCCCTCAAGACCATGAGCCGT
AGGAAGCTCTCCCAGCAGAAGGAGAAGAAAGCCACTCAGATGCTCGCCATTGTTCTCGGC
GTGTTCATCATCTGCTGGCTGCCCTTCTTCATCACACACATCCTGAACATACACTGTGAC
TGCAACATCCCGCCTGTCCTGTACAGCGCCTTCACGTGGCTGGGCTATGTCAACAGCGCC
GTGAACCCCATCATCTACACCACCTTCAACATTGAGTTCCGCAAGGCCTTCCTGAAGATC
CTCCACTGCTGA
Chromosome Location
11
Locus
11q23
External Identifiers
ResourceLink
UniProtKB IDP14416
UniProtKB Entry NameDRD2_HUMAN
GenBank Protein ID181432
GenBank Gene IDM30625
GenAtlas IDDRD2
HGNC IDHGNC:3023
General References
  1. Selbie LA, Hayes G, Shine J: The major dopamine D2 receptor: molecular analysis of the human D2A subtype. DNA. 1989 Nov;8(9):683-9. [PubMed:2533064]
  2. Dal Toso R, Sommer B, Ewert M, Herb A, Pritchett DB, Bach A, Shivers BD, Seeburg PH: The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J. 1989 Dec 20;8(13):4025-34. [PubMed:2531656]
  3. Robakis NK, Mohamadi M, Fu DY, Sambamurti K, Refolo LM: Human retina D2 receptor cDNAs have multiple polyadenylation sites and differ from a pituitary clone at the 5' non-coding region. Nucleic Acids Res. 1990 Mar 11;18(5):1299. [PubMed:2138729]
  4. Grandy DK, Marchionni MA, Makam H, Stofko RE, Alfano M, Frothingham L, Fischer JB, Burke-Howie KJ, Bunzow JR, Server AC, et al.: Cloning of the cDNA and gene for a human D2 dopamine receptor. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9762-6. [PubMed:2532362]
  5. Stormann TM, Gdula DC, Weiner DM, Brann MR: Molecular cloning and expression of a dopamine D2 receptor from human retina. Mol Pharmacol. 1990 Jan;37(1):1-6. [PubMed:2137193]
  6. Selbie LA, Hayes G, Shine J: DNA homology screening: isolation and characterization of the human D2A dopamine receptor subtype. Adv Second Messenger Phosphoprotein Res. 1990;24:9-14. [PubMed:2144985]
  7. Araki K, Kuwano R, Morii K, Hayashi S, Minoshima S, Shimizu N, Katagiri T, Usui H, Kumanishi T, Takahashi Y: Structure and expression of human and rat D2 dopamine receptor genes. Neurochem Int. 1992 Jul;21(1):91-8. [PubMed:1363862]
  8. Dearry A, Falardeau P, Shores C, Caron MG: D2 dopamine receptors in the human retina: cloning of cDNA and localization of mRNA. Cell Mol Neurobiol. 1991 Oct;11(5):437-53. [PubMed:1835903]
  9. Seeman P, Ohara K, Ulpian C, Seeman MV, Jellinger K, Van Tol HH, Niznik HB: Schizophrenia: normal sequence in the dopamine D2 receptor region that couples to G-proteins. DNA polymorphisms in D2. Neuropsychopharmacology. 1993 Feb;8(2):137-42. [PubMed:8471125]
  10. Seeman P, Nam D, Ulpian C, Liu IS, Tallerico T: New dopamine receptor, D2(Longer), with unique TG splice site, in human brain. Brain Res Mol Brain Res. 2000 Mar 10;76(1):132-41. [PubMed:10719223]
  11. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  12. Binda AV, Kabbani N, Levenson R: Regulation of dense core vesicle release from PC12 cells by interaction between the D2 dopamine receptor and calcium-dependent activator protein for secretion (CAPS). Biochem Pharmacol. 2005 May 15;69(10):1451-61. [PubMed:15857609]
  13. Lopez-Aranda MF, Acevedo MJ, Gutierrez A, Koulen P, Khan ZU: Role of a Galphai2 protein splice variant in the formation of an intracellular dopamine D2 receptor pool. J Cell Sci. 2007 Jul 1;120(Pt 13):2171-8. Epub 2007 Jun 5. [PubMed:17550964]
  14. Borroto-Escuela DO, Van Craenenbroeck K, Romero-Fernandez W, Guidolin D, Woods AS, Rivera A, Haegeman G, Agnati LF, Tarakanov AO, Fuxe K: Dopamine D2 and D4 receptor heteromerization and its allosteric receptor-receptor interactions. Biochem Biophys Res Commun. 2011 Jan 28;404(4):928-34. doi: 10.1016/j.bbrc.2010.12.083. Epub 2010 Dec 22. [PubMed:21184734]
  15. Albizu L, Holloway T, Gonzalez-Maeso J, Sealfon SC: Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology. 2011 Sep;61(4):770-7. doi: 10.1016/j.neuropharm.2011.05.023. Epub 2011 May 27. [PubMed:21645528]
  16. Johnston CA, Siderovski DP: Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30. [PubMed:17264214]
  17. Johnston CA, Siderovski DP: Retraction for Johnston and Siderovski. Structural basis for nucleotide exchange on Galphai subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1808. [PubMed:22408789]
  18. Itokawa M, Arinami T, Futamura N, Hamaguchi H, Toru M: A structural polymorphism of human dopamine D2 receptor, D2(Ser311-->Cys). Biochem Biophys Res Commun. 1993 Nov 15;196(3):1369-75. [PubMed:7902708]
  19. Klein C, Brin MF, Kramer P, Sena-Esteves M, de Leon D, Doheny D, Bressman S, Fahn S, Breakefield XO, Ozelius LJ: Association of a missense change in the D2 dopamine receptor with myoclonus dystonia. Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5173-6. [PubMed:10220438]
  20. Johann M, Putzhammer A, Eichhammer P, Wodarz N: Association of the -141C Del variant of the dopamine D2 receptor (DRD2) with positive family history and suicidality in German alcoholics. Am J Med Genet B Neuropsychiatr Genet. 2005 Jan 5;132B(1):46-9. [PubMed:15389757]
  21. Klein C, Gurvich N, Sena-Esteves M, Bressman S, Brin MF, Ebersole BJ, Fink S, Forsgren L, Friedman J, Grimes D, Holmgren G, Kyllerman M, Lang AE, de Leon D, Leung J, Prioleau C, Raymond D, Sanner G, Saunders-Pullman R, Vieregge P, Wahlstrom J, Breakefield XO, Kramer PL, Ozelius LJ, Sealfon SC: Evaluation of the role of the D2 dopamine receptor in myoclonus dystonia. Ann Neurol. 2000 Mar;47(3):369-73. [PubMed:10716258]
  22. Bevilacqua L, Doly S, Kaprio J, Yuan Q, Tikkanen R, Paunio T, Zhou Z, Wedenoja J, Maroteaux L, Diaz S, Belmer A, Hodgkinson CA, Dell'osso L, Suvisaari J, Coccaro E, Rose RJ, Peltonen L, Virkkunen M, Goldman D: A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature. 2010 Dec 23;468(7327):1061-6. doi: 10.1038/nature09629. [PubMed:21179162]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00248CabergolineapprovedyesagonistDetails
DB00268Ropiniroleapproved, investigationalyesagonistDetails
DB00391Sulpirideapproved, investigationalyesantagonistDetails
DB00420Promazineapproved, vet_approvedyesantagonistDetails
DB00433Prochlorperazineapproved, vet_approvedyesantagonistDetails
DB00450Droperidolapproved, vet_approvedyesantagonistDetails
DB00477Chlorpromazineapproved, investigational, vet_approvedyesantagonistDetails
DB00502HaloperidolapprovedyesantagonistDetails
DB00623FluphenazineapprovedyesantagonistDetails
DB00714Apomorphineapproved, investigationalyesagonistDetails
DB00831Trifluoperazineapproved, investigationalyesantagonistDetails
DB00915AmantadineapprovedyesagonistDetails
DB00933Mesoridazineapproved, investigationalyesantagonistDetails
DB01063AcetophenazineapprovedyesantagonistDetails
DB01069Promethazineapproved, investigationalunknownantagonistDetails
DB01100PimozideapprovedyesantagonistDetails
DB01184Domperidoneapproved, investigational, vet_approvedyesantagonistDetails
DB01186Pergolideapproved, investigational, vet_approved, withdrawnyesagonistDetails
DB01200Bromocriptineapproved, investigationalyesagonistDetails
DB01238Aripiprazoleapproved, investigationalyesantagonistpartial agonistDetails
DB00246ZiprasidoneapprovedyesantagonistDetails
DB00334Olanzapineapproved, investigationalyesantagonistDetails
DB00363ClozapineapprovedyesantagonistDetails
DB00372Thiethylperazineapproved, withdrawnunknownantagonistDetails
DB00490Buspironeapproved, investigationalyesantagonistDetails
DB00508Triflupromazineapproved, vet_approvedyesantagonistDetails
DB00568Cinnarizineapproved, investigationalnoother/unknownDetails
DB00679Thioridazineapproved, withdrawnyesantagonistDetails
DB00734Risperidoneapproved, investigationalyesantagonistDetails
DB00777PropiomazineapprovedunknownantagonistDetails
DB00805MinaprineapprovedunknownagonistDetails
DB00850PerphenazineapprovedyesantagonistDetails
DB00875Flupentixolapproved, investigational, withdrawnyesantagonistDetails
DB01224QuetiapineapprovedyesantagonistDetails
DB01233Metoclopramideapproved, investigationalyesantagonistDetails
DB01235LevodopaapprovedyesagonistDetails
DB01239Chlorprothixeneexperimental, investigational, withdrawnyesantagonistDetails
DB01267PaliperidoneapprovedyesantagonistDetails
DB01624Zuclopenthixolapproved, investigationalyesantagonistDetails
DB01618MolindoneapprovedyesantagonistDetails
DB04842Fluspirileneapproved, investigationalyesantagonistDetails
DB00589Lisurideapproved, investigationalyesagonistDetails
DB00408LoxapineapprovedyesantagonistDetails
DB00413Pramipexoleapproved, investigationalyesagonistDetails
DB00409Remoxiprideapproved, withdrawnyesantagonistDetails
DB00696ErgotamineapprovedunknownagonistDetails
DB04857BrasofensineinvestigationalunknownDetails
DB04888BifeprunoxinvestigationalunknownDetails
DB04889BicifadineinvestigationalunknownDetails
DB06144Sertindoleapproved, investigational, withdrawnyesantagonistDetails
DB12061PardoprunoxinvestigationalunknownDetails
DB04924ItoprideinvestigationalunknownDetails
DB05316Pimavanserinapproved, investigationalunknownDetails
DB04946IloperidoneapprovedyesantagonistDetails
DB01038CarphenazinewithdrawnyesantagonistDetails
DB05687BL-1020investigationalunknownDetails
DB05766ACP-104investigationalunknownDetails
DB06077LumateperoneinvestigationalunknownDetails
DB05964AmitifadineinvestigationalunknownDetails
DB06016Cariprazineapproved, investigationalyesagonistpartial agonistDetails
DB06216AsenapineapprovedyesantagonistDetails
DB06229OcaperidoneinvestigationalunknownDetails
DB06477SumaniroleinvestigationalunknownDetails
DB04599AniracetamexperimentalunknownDetails
DB06288Amisulprideapproved, investigationalyesantagonistDetails
DB05271RotigotineapprovedyesagonistDetails
DB01403Methotrimeprazineapproved, investigationalyesantagonistDetails
DB01549Rolicyclidineexperimental, illicitunknownDetails
DB00543AmoxapineapprovedunknownantagonistDetails
DB00726Trimipramineapprovedunknownother/unknownDetails
DB01392Yohimbineapproved, investigational, vet_approvedunknownantagonistDetails
DB01221Ketamineapproved, vet_approvedunknownagonistpartial agonistDetails
DB00988DopamineapprovedyesagonistDetails
DB01614Acepromazineexperimental, vet_approvedyesantagonistDetails
DB01621Pipotiazineapproved, investigationalyesantagonistDetails
DB01622ThioproperazineexperimentalyesantagonistDetails
DB01623ThiothixeneapprovedyesantagonistDetails
DB01425AlizaprideinvestigationalyesantagonistDetails
DB08815Lurasidoneapproved, investigationalyesantagonistDetails
DB04844Tetrabenazineapproved, investigationalunknowninhibitorDetails
DB00370MirtazapineapprovedunknowninhibitorbinderDetails
DB00182Amphetamineapproved, illicit, investigationalunknownbinderDetails
DB00458ImipramineapprovedunknownbinderDetails
DB00540NortriptylineapprovedunknownantagonistDetails
DB01043Memantineapproved, investigationalunknownantagonistagonistDetails
DB00934Maprotilineapproved, investigationalunknownbinderDetails
DB01151Desipramineapproved, investigationalunknownbinderDetails
DB06148Mianserinapproved, investigationalunknownantagonistDetails
DB09018BromoprideinvestigationalyesantagonistDetails
DB09207AS-8112experimentalunknownantagonistDetails
DB09128Brexpiprazoleapproved, investigationalyesagonistpartial agonistDetails
DB13025TiaprideinvestigationalyesblockerDetails
DB08922PerospironeexperimentalyesantagonistDetails
DB09097Quinagolideapproved, investigationalunknownagonistDetails
DB12478PiribedilinvestigationalunknownDetails
DB06454Sarizotaninvestigationalunknownpartial agonistDetails
DB12518RacloprideinvestigationalunknownantagonistDetails
DB12093TetrahydropalmatineinvestigationalunknownantagonistDetails
DB09194EtoperidonewithdrawnunknownantagonistDetails
DB09223BlonanserininvestigationalyesantagonistDetails
DB00555Lamotrigineapproved, investigationalunknowninhibitorDetails
DB09225Zotepineapproved, investigational, withdrawnyesantagonistDetails
DB09224MelperoneinvestigationalyesantagonistDetails
DB09286PipamperoneinvestigationalunknownantagonistDetails
DB11274Dihydro-alpha-ergocryptineapprovedyesagonistDetails
DB12579JNJ-37822681investigationalyesantagonistDetails
DB14185Aripiprazole lauroxilapproved, investigationalyespartial agonistDetails
DB13345Dihydroergocristineapproved, experimentalyesantagonistagonistDetails
DB01049Ergoloid mesylateapprovedyesantagonistagonistDetails
DB11275EpicriptineapprovedyesagonistDetails