D(2) dopamine receptor

NameD(2) dopamine receptor
Synonyms
  • Dopamine D2 receptor
Gene NameDRD2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001508|D(2) dopamine receptor
MDPLNLSWYDDDLERQNWSRPFNGSDGKADRPHYNYYATLLTLLIAVIVFGNVLVCMAVS
REKALQTTTNYLIVSLAVADLLVATLVMPWVVYLEVVGEWKFSRIHCDIFVTLDVMMCTA
SILNLCAISIDRYTAVAMPMLYNTRYSSKRRVTVMISIVWVLSFTISCPLLFGLNNADQN
ECIIANPAFVVYSSIVSFYVPFIVTLLVYIKIYIVLRRRRKRVNTKRSSRAFRAHLRAPL
KGNCTHPEDMKLCTVIMKSNGSFPVNRRRVEAARRAQELEMEMLSSTSPPERTRYSPIPP
SHHQLTLPDPSHHGLHSTPDSPAKPEKNGHAKDHPKIAKIFEIQTMPNGKTRTSLKTMSR
RKLSQQKEKKATQMLAIVLGVFIICWLPFFITHILNIHCDCNIPPVLYSAFTWLGYVNSA
VNPIIYTTFNIEFRKAFLKILHC
Number of residues443
Molecular Weight50618.91
Theoretical pI9.85
GO Classification
Functions
  • identical protein binding
  • dopamine binding
  • dopamine neurotransmitter receptor activity, coupled via Gi/Go
  • drug binding
  • potassium channel regulator activity
Processes
  • activation of protein kinase activity
  • grooming behavior
  • adult walking behavior
  • orbitofrontal cortex development
  • response to cocaine
  • adenylate cyclase-inhibiting dopamine receptor signaling pathway
  • positive regulation of G-protein coupled receptor protein signaling pathway
  • locomotory behavior
  • long-term memory
  • regulation of dopamine secretion
  • response to drug
  • synaptic transmission, dopaminergic
  • arachidonic acid secretion
  • regulation of long-term neuronal synaptic plasticity
  • response to amphetamine
  • visual learning
  • circadian regulation of gene expression
  • negative regulation of adenylate cyclase activity
  • behavioral response to ethanol
  • negative regulation of protein secretion
  • regulation of synapse structural plasticity
  • striatum development
  • response to iron ion
  • positive regulation of neuroblast proliferation
  • response to light stimulus
  • positive regulation of renal sodium excretion
  • negative regulation of voltage-gated calcium channel activity
  • positive regulation of urine volume
  • regulation of heart rate
  • positive regulation of dopamine uptake involved in synaptic transmission
  • regulation of cAMP metabolic process
  • negative regulation of dopamine secretion
  • positive regulation of receptor internalization
  • phosphatidylinositol metabolic process
  • response to histamine
  • cerebral cortex GABAergic interneuron migration
  • response to toxic substance
  • regulation of synaptic transmission, GABAergic
  • G-protein coupled receptor internalization
  • positive regulation of ERK1 and ERK2 cascade
  • positive regulation of cytokinesis
  • positive regulation of growth hormone secretion
  • response to morphine
  • neurological system process involved in regulation of systemic arterial blood pressure
  • negative regulation of cell proliferation
  • positive regulation of transcription from RNA polymerase II promoter
  • response to axon injury
  • feeding behavior
  • positive regulation of long-term synaptic potentiation
  • axonogenesis
  • protein localization
  • auditory behavior
  • response to hypoxia
  • negative regulation of cell migration
  • regulation of potassium ion transport
  • negative regulation of circadian sleep/wake cycle, sleep
  • positive regulation of multicellular organism growth
  • regulation of phosphoprotein phosphatase activity
  • response to nicotine
  • release of sequestered calcium ion into cytosol
  • regulation of dopamine uptake involved in synaptic transmission
  • negative regulation of insulin secretion
  • adenohypophysis development
  • negative regulation of dopamine receptor signaling pathway
  • behavioral response to cocaine
  • negative regulation of protein kinase B signaling
  • response to inactivity
  • prepulse inhibition
  • regulation of locomotion involved in locomotory behavior
  • associative learning
  • negative regulation of cytosolic calcium ion concentration
  • pigmentation
  • intracellular signal transduction
  • negative regulation of synaptic transmission, glutamatergic
  • sensory perception of smell
  • cellular calcium ion homeostasis
  • synapse assembly
  • peristalsis
  • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway
  • temperature homeostasis
  • Wnt signaling pathway
  • positive regulation of glial cell-derived neurotrophic factor secretion
  • negative regulation of blood pressure
  • neuron-neuron synaptic transmission
  • dopamine metabolic process
  • regulation of sodium ion transport
  • branching morphogenesis of a nerve
  • phospholipase C-activating dopamine receptor signaling pathway
  • negative regulation of innate immune response
Components
  • intracellular
  • plasma membrane
  • lateral plasma membrane
  • sperm flagellum
  • postsynaptic density
  • axon
  • cytosol
  • perikaryon
  • integral component of plasma membrane
  • endocytic vesicle
  • ciliary membrane
  • axon terminus
  • nonmotile primary cilium
  • synaptic vesicle membrane
  • acrosomal vesicle
  • dendrite
  • dendritic spine
General FunctionPotassium channel regulator activity
Specific FunctionDopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Pfam Domain Function
Transmembrane Regions38-60 71-93 109-130 152-172 189-213 374-395 410-431
GenBank Protein ID181432
UniProtKB IDP14416
UniProtKB Entry NameDRD2_HUMAN
Cellular LocationCell 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
GenBank Gene IDM30625
GeneCard IDNot Available
GenAtlas IDDRD2
HGNC IDHGNC:3023
Chromosome Location11
Locus11q23
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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 21179162