D(4) dopamine receptor

Details

Name
D(4) dopamine receptor
Synonyms
  • D(2C) dopamine receptor
  • Dopamine D4 receptor
Gene Name
DRD4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000775|D(4) dopamine receptor
MGNRSTADADGLLAGRGPAAGASAGASAGLAGQGAAALVGGVLLIGAVLAGNSLVCVSVA
TERALQTPTNSFIVSLAAADLLLALLVLPLFVYSEVQGGAWLLSPRLCDALMAMDVMLCT
ASIFNLCAISVDRFVAVAVPLRYNRQGGSRRQLLLIGATWLLSAAVAAPVLCGLNDVRGR
DPAVCRLEDRDYVVYSSVCSFFLPCPLMLLLYWATFRGLQRWEVARRAKLHGRAPRRPSG
PGPPSPTPPAPRLPQDPCGPDCAPPAPGLPRGPCGPDCAPAAPGLPPDPCGPDCAPPAPG
LPQDPCGPDCAPPAPGLPRGPCGPDCAPPAPGLPQDPCGPDCAPPAPGLPPDPCGSNCAP
PDAVRAAALPPQTPPQTRRRRRAKITGRERKAMRVLPVVVGAFLLCWTPFFVVHITQALC
PACSVPPRLVSAVTWLGYVNSALNPVIYTVFNAEFRNVFRKALRACC
Number of residues
467
Molecular Weight
48359.86
Theoretical pI
8.37
GO Classification
Functions
dopamine binding / dopamine neurotransmitter receptor activity / dopamine neurotransmitter receptor activity, coupled via Gi/Go / drug binding / G-protein coupled amine receptor activity / identical protein binding / potassium channel regulator activity / SH3 domain binding
Processes
activation of MAPK activity / adenylate cyclase-inhibiting dopamine receptor signaling pathway / adult locomotory behavior / arachidonic acid secretion / behavioral fear response / behavioral response to cocaine / behavioral response to ethanol / cellular calcium ion homeostasis / circadian rhythm / dopamine metabolic process / dopamine receptor signaling pathway / fear response / inhibitory postsynaptic potential / negative regulation of adenylate cyclase activity / negative regulation of cAMP biosynthetic process / negative regulation of protein secretion / negative regulation of voltage-gated calcium channel activity / olfactory learning / photoperiodism / positive regulation of dopamine uptake involved in synaptic transmission / positive regulation of excitatory postsynaptic potential / positive regulation of kinase activity / positive regulation of penile erection / positive regulation of sodium / regulation of calcium-mediated signaling / regulation of circadian rhythm / regulation of dopamine metabolic process / regulation of neurotransmitter secretion / response to amphetamine / response to histamine / response to steroid hormone / retina development in camera-type eye / sensory perception of chemical stimulus / short-term memory / social behavior / synaptic transmission / synaptic transmission, dopaminergic
Components
cell cortex / dendritic spine / integral component of plasma membrane / membrane / neuronal cell body / plasma membrane / terminal bouton / vesicle membrane
General Function
Sh3 domain binding
Specific Function
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
Pfam Domain Function
Transmembrane Regions
38-60 71-93 110-131 152-175 192-213 395-417 427-449
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010271|D(4) dopamine receptor (DRD4)
ATGGGGAACCGCAGCACCGCGGACGCGGACGGGCTGCTGGCTGGGCGCGGGCCGGCCGCG
GGGGCATCTGCGGGGGCATCTGCGGGGCTGGCTGGGCAGGGCGCGGCGGCGCTGGTGGGG
GGCGTGCTGCTCATCGGCGCGGTGCTCGCGGGGAACTCGCTCGTGTGCGTGAGCGTGGCC
ACCGAGCGCGCCCTGCAGACGCCCACCAACTCCTTCATCGTGAGCCTGGCGGCCGCCGAC
CTCCTCCTCGCTCTCCTGGTGCTGCCGCTCTTCGTCTACTCCGAGGTCCAGGGTGGCGCG
TGGCTGCTGAGCCCCCGCCTGTGCGACGCCCTCATGGCCATGGACGTCATGCTGTGCACC
GCCTCCATCTTCAACCTGTGCGCCATCAGCGTGGACAGGTTCGTGGCCGTGGCCGTGCCG
CTGCGCTACAACCGGCAGGGTGGGAGCCGCCGGCAGCTGCTGCTCATCGGCGCCACGTGG
CTGCTGTCCGCGGCGGTGGCGGCGCCCGTACTGTGCGGCCTCAACGACGTGCGCGGCCGC
GACCCCGCCGTGTGCCGCCTGGAGGACCGCGACTACGTGGTCTACTCGTCCGTGTGCTCC
TTCTTCCTACCCTGCCCGCTCATGCTGCTGCTCTACTGGGCCACGTTCCGCGGCCTGCAG
CGCTGGGAGGTGGCACGTCGCGCCAAGCTGCACGGCCGCGCGCCCCGCCGACCCAGCGGC
CCTGGCCCGCCTTCCCCCACGCCACCCGCGCCCCGCCTCCCCCAGGACCCCTGCGGCCCC
GACTGTGCGCCCCCCGCGCCCGGCCTTCCCCGGGGTCCCTGCGGCCCCGACTGTGCGCCC
GCCGCGCCCAGCCTCCCCCAGGACCCCTGCGGCCCCGACTGTGCGCCCCCCGCGCCCGGC
CTCCCCCCGGACCCCTGCGGCTCCAACTGTGCTCCCCCCGACGCCGTCAGAGCCGCCGCG
CTCCCACCCCAGACTCCACCGCAGACCCGCAGGAGGCGGCGTGCCAAGATCACCGGCCGG
GAGCGCAAGGCCATGAGGGTCCTGCCGGTGGTGGTCGGGGCCTTCCTGCTGTGCTGGACG
CCCTTCTTCGTGGTGCACATCACGCAGGCGCTGTGTCCTGCCTGCTCCGTGCCCCCGCGG
CTGGTCAGCGCCGTCACCTGGCTGGGCTACGTCAACAGCGCCCTCAACCCCGTCATCTAC
ACTGTCTTCAACGCCGAGTTCCGCAACGTCTTCCGCAAGGCCCTGCGTGCCTGCTGCTGA
Chromosome Location
11
Locus
11p15.5
External Identifiers
ResourceLink
UniProtKB IDP21917
UniProtKB Entry NameDRD4_HUMAN
GenBank Protein ID291946
GenBank Gene IDL12398
GenAtlas IDDRD4
HGNC IDHGNC:3025
General References
  1. Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O, Kennedy J, Seeman P, Niznik HB, Jovanovic V: Multiple dopamine D4 receptor variants in the human population. Nature. 1992 Jul 9;358(6382):149-52. [PubMed:1319557]
  2. Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O: Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature. 1991 Apr 18;350(6319):610-4. [PubMed:1840645]
  3. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [PubMed:16554811]
  4. Lichter JB, Barr CL, Kennedy JL, Van Tol HH, Kidd KK, Livak KJ: A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Hum Mol Genet. 1993 Jun;2(6):767-73. [PubMed:8353495]
  5. Asghari V, Schoots O, van Kats S, Ohara K, Jovanovic V, Guan HC, Bunzow JR, Petronis A, Van Tol HH: Dopamine D4 receptor repeat: analysis of different native and mutant forms of the human and rat genes. Mol Pharmacol. 1994 Aug;46(2):364-73. [PubMed:8078498]
  6. Whistler JL, Enquist J, Marley A, Fong J, Gladher F, Tsuruda P, Murray SR, Von Zastrow M: Modulation of postendocytic sorting of G protein-coupled receptors. Science. 2002 Jul 26;297(5581):615-20. [PubMed:12142540]
  7. Rondou P, Haegeman G, Vanhoenacker P, Van Craenenbroeck K: BTB Protein KLHL12 targets the dopamine D4 receptor for ubiquitination by a Cul3-based E3 ligase. J Biol Chem. 2008 Apr 25;283(17):11083-96. doi: 10.1074/jbc.M708473200. Epub 2008 Feb 26. [PubMed:18303015]
  8. Woods AS: The dopamine D(4) receptor, the ultimate disordered protein. J Recept Signal Transduct Res. 2010 Oct;30(5):331-6. doi: 10.3109/10799893.2010.513842. [PubMed:20836733]
  9. Rondou P, Skieterska K, Packeu A, Lintermans B, Vanhoenacker P, Vauquelin G, Haegeman G, Van Craenenbroeck K: KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target the receptor for degradation. Cell Signal. 2010 Jun;22(6):900-13. doi: 10.1016/j.cellsig.2010.01.014. Epub 2010 Jan 25. [PubMed:20100572]
  10. 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]
  11. Livingstone CD, Strange PG, Naylor LH: Molecular modelling of D2-like dopamine receptors. Biochem J. 1992 Oct 1;287 ( Pt 1):277-82. [PubMed:1358063]
  12. Seeman P, Ulpian C, Chouinard G, Van Tol HH, Dwosh H, Lieberman JA, Siminovitch K, Liu IS, Waye J, Voruganti P, et al.: Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: no association with schizophrenia. Am J Med Genet. 1994 Dec 15;54(4):384-90. [PubMed:7726213]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00363ClozapineapprovedunknownantagonistDetails
DB00246ZiprasidoneapprovedunknownantagonistDetails
DB00334Olanzapineapproved, investigationalunknownantagonistDetails
DB00372Thiethylperazineapproved, withdrawnunknownantagonistDetails
DB00420Promazineapproved, vet_approvedunknownantagonistDetails
DB00714Apomorphineapproved, investigationalyesagonistDetails
DB00777PropiomazineapprovedunknownantagonistDetails
DB00413Pramipexoleapproved, investigationalyesagonistDetails
DB00268Ropiniroleapproved, investigationalunknownagonistDetails
DB04908Flibanserinapproved, investigationalyesantagonistagonistDetails
DB12061PardoprunoxinvestigationalunknownDetails
DB06216AsenapineapprovedunknownantagonistDetails
DB06477SumaniroleinvestigationalunknownDetails
DB01186Pergolideapproved, investigational, vet_approved, withdrawnunknownagonistDetails
DB01200Bromocriptineapproved, investigationalunknownantagonistDetails
DB00589Lisurideapproved, investigationalyesagonistDetails
DB00248CabergolineapprovedunknownagonistDetails
DB05271RotigotineapprovedyesagonistDetails
DB01267PaliperidoneapprovedyesantagonistDetails
DB00734Risperidoneapproved, investigationalunknownantagonistDetails
DB01238Aripiprazoleapproved, investigationalunknownantagonistpartial agonistDetails
DB01224QuetiapineapprovedunknownligandDetails
DB01403Methotrimeprazineapproved, investigationalunknownantagonistDetails
DB00409Remoxiprideapproved, withdrawnunknownantagonistDetails
DB00988DopamineapprovedyesagonistDetails
DB01235LevodopaapprovedyesagonistDetails
DB04946IloperidoneapprovedunknownantagonistDetails
DB00477Chlorpromazineapproved, investigational, vet_approvedunknownbinderDetails
DB00408LoxapineapprovedunknownbinderDetails
DB00543AmoxapineapprovedunknownantagonistDetails
DB08922PerospironeexperimentalunknownantagonistDetails
DB09286PipamperoneinvestigationalunknownantagonistDetails
DB14185Aripiprazole lauroxilapproved, investigationalunknownDetails
DB00490Buspironeapproved, investigationalunknownantagonistDetails
DB13345Dihydroergocristineapproved, experimentalyesantagonistagonistDetails
DB01049Ergoloid mesylateapprovedyesantagonistagonistDetails
DB11275EpicriptineapprovedyesagonistDetails