D(4) dopamine receptor

NameD(4) dopamine receptor
Synonyms
  • D(2C) dopamine receptor
  • Dopamine D4 receptor
Gene NameDRD4
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000775|D(4) dopamine receptor
MGNRSTADADGLLAGRGPAAGASAGASAGLAGQGAAALVGGVLLIGAVLAGNSLVCVSVA
TERALQTPTNSFIVSLAAADLLLALLVLPLFVYSEVQGGAWLLSPRLCDALMAMDVMLCT
ASIFNLCAISVDRFVAVAVPLRYNRQGGSRRQLLLIGATWLLSAAVAAPVLCGLNDVRGR
DPAVCRLEDRDYVVYSSVCSFFLPCPLMLLLYWATFRGLQRWEVARRAKLHGRAPRRPSG
PGPPSPTPPAPRLPQDPCGPDCAPPAPGLPRGPCGPDCAPAAPGLPPDPCGPDCAPPAPG
LPQDPCGPDCAPPAPGLPRGPCGPDCAPPAPGLPQDPCGPDCAPPAPGLPPDPCGSNCAP
PDAVRAAALPPQTPPQTRRRRRAKITGRERKAMRVLPVVVGAFLLCWTPFFVVHITQALC
PACSVPPRLVSAVTWLGYVNSALNPVIYTVFNAEFRNVFRKALRACC
Number of residues467
Molecular Weight48359.86
Theoretical pI8.37
GO Classification
Functions
  • drug binding
  • SH3 domain binding
  • identical protein binding
  • dopamine binding
  • dopamine neurotransmitter receptor activity
  • G-protein coupled amine receptor activity
  • dopamine neurotransmitter receptor activity, coupled via Gi/Go
  • potassium channel regulator activity
Processes
  • synaptic transmission, dopaminergic
  • regulation of dopamine metabolic process
  • adenylate cyclase-inhibiting dopamine receptor signaling pathway
  • negative regulation of adenylate cyclase activity
  • regulation of neurotransmitter secretion
  • adult locomotory behavior
  • social behavior
  • response to histamine
  • arachidonic acid secretion
  • response to steroid hormone
  • dopamine receptor signaling pathway
  • behavioral fear response
  • activation of MAPK activity
  • short-term memory
  • synaptic transmission
  • behavioral response to ethanol
  • retina development in camera-type eye
  • negative regulation of cAMP biosynthetic process
  • negative regulation of protein secretion
  • negative regulation of voltage-gated calcium channel activity
  • sensory perception of chemical stimulus
  • olfactory learning
  • photoperiodism
  • fear response
  • dopamine metabolic process
  • positive regulation of dopamine uptake involved in synaptic transmission
  • behavioral response to cocaine
  • response to amphetamine
  • positive regulation of excitatory postsynaptic potential
  • regulation of circadian rhythm
  • circadian rhythm
  • positive regulation of kinase activity
  • inhibitory postsynaptic potential
  • positive regulation of penile erection
  • positive regulation of sodium
  • cellular calcium ion homeostasis
  • regulation of calcium-mediated signaling
Components
  • membrane
  • plasma membrane
  • neuronal cell body
  • dendritic spine
  • integral component of plasma membrane
  • terminal bouton
  • vesicle membrane
  • cell cortex
General FunctionSh3 domain binding
Specific FunctionDopamine 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 Regions38-60 71-93 110-131 152-175 192-213 395-417 427-449
GenBank Protein ID291946
UniProtKB IDP21917
UniProtKB Entry NameDRD4_HUMAN
Cellular LocationCell 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
GenBank Gene IDL12398
GeneCard IDNot Available
GenAtlas IDDRD4
HGNC IDHGNC:3025
Chromosome Location11
Locus11p15.5
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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 7726213