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Protein

D(4) dopamine receptor

Gene

Drd4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs (By similarity). Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:10832611). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi77SodiumBy similarity1
Binding sitei112AgonistBy similarity1
Metal bindingi119SodiumBy similarity1

GO - Molecular functioni

  • dopamine binding Source: RGD
  • dopamine neurotransmitter receptor activity, coupled via Gi/Go Source: RGD
  • drug binding Source: RGD
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • adenylate cyclase-inhibiting dopamine receptor signaling pathway Source: UniProtKB
  • associative learning Source: RGD
  • behavioral fear response Source: RGD
  • circadian rhythm Source: RGD
  • dopamine receptor signaling pathway Source: RGD
  • locomotory behavior Source: RGD
  • modulation of chemical synaptic transmission Source: RGD
  • negative regulation of vascular associated smooth muscle cell migration Source: RGD
  • negative regulation of vascular smooth muscle cell proliferation Source: RGD
  • olfactory learning Source: RGD
  • photoperiodism Source: RGD
  • positive regulation of excitatory postsynaptic potential Source: RGD
  • positive regulation of penile erection Source: RGD
  • regulation of calcium-mediated signaling Source: RGD
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of neurotransmitter secretion Source: RGD
  • response to steroid hormone Source: RGD
  • retina development in camera-type eye Source: RGD
  • short-term memory Source: RGD
  • synaptic transmission, dopaminergic Source: RGD

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processBiological rhythms
LigandMetal-binding, Sodium

Names & Taxonomyi

Protein namesi
Recommended name:
D(4) dopamine receptor
Alternative name(s):
D(2C) dopamine receptor
Dopamine D4 receptor
Gene namesi
Name:Drd4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2522 Drd4

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 – 34ExtracellularBy similarityAdd BLAST34
Transmembranei35 – 57Helical; Name=1By similarityAdd BLAST23
Topological domaini58 – 67CytoplasmicBy similarity10
Transmembranei68 – 90Helical; Name=2By similarityAdd BLAST23
Topological domaini91 – 106ExtracellularBy similarityAdd BLAST16
Transmembranei107 – 128Helical; Name=3By similarityAdd BLAST22
Topological domaini129 – 146CytoplasmicBy similarityAdd BLAST18
Transmembranei147 – 170Helical; Name=4By similarityAdd BLAST24
Topological domaini171 – 186ExtracellularBy similarityAdd BLAST16
Transmembranei187 – 208Helical; Name=5By similarityAdd BLAST22
Topological domaini209 – 314CytoplasmicBy similarityAdd BLAST106
Transmembranei315 – 337Helical; Name=6By similarityAdd BLAST23
Topological domaini338 – 346ExtracellularBy similarity9
Transmembranei347 – 369Helical; Name=7By similarityAdd BLAST23
Topological domaini370 – 387CytoplasmicBy similarityAdd BLAST18

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3361
GuidetoPHARMACOLOGYi217

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000694031 – 387D(4) dopamine receptorAdd BLAST387

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi3N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi105 ↔ 180PROSITE-ProRule annotation
Disulfide bondi340 ↔ 343By similarity
Lipidationi387S-palmitoyl cysteineBy similarity1

Post-translational modificationi

Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex: polyubiquitination does not lead to degradation of DRD4 protein.By similarity
Palmitoylated. Palmitoylation of the C-terminal Cys is important for normal expression at the cell membrane.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Ubl conjugation

Proteomic databases

PaxDbiP30729

PTM databases

PhosphoSitePlusiP30729

Expressioni

Tissue specificityi

Central nervous system: hypothalamus, thalamus, olfactory bulb, and frontal cortex.

Interactioni

Subunit structurei

Forms homo- and heterooligomers with DRD2. D4.7 allele exhibits higher affinity for homodimers compared to DRD2 heterodimers, while alleles D42. and 4.4 have similar affinities for both. The interaction with DRD2 may modulate agonist-induced downstream signaling (By similarity). Interacts with CLIC6 (PubMed:14499480). Interacts with GPRASP1. May interact with ADORA2A. Interacts with KLHL12 (By similarity).By similarity1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

DIPiDIP-59866N
IntActiP30729, 2 interactors
STRINGi10116.ENSRNOP00000024137

Chemistry databases

BindingDBiP30729

Structurei

3D structure databases

ProteinModelPortaliP30729
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

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
HOGENOMiHOG000239242
HOVERGENiHBG106962
InParanoidiP30729
PhylomeDBiP30729

Family and domain databases

InterProiView protein in InterPro
IPR002185 Dopamine_D4_rcpt
IPR000929 Dopamine_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR44250:SF1 PTHR44250:SF1, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00569 DOPAMINED4R
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

Sequencei

Sequence statusi: Complete.

P30729-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGNSSATGDG GLLAGRGPES LGTGTGLGGA GAAALVGGVL LIGMVLAGNS
60 70 80 90 100
LVCVSVASER ILQTPTNYFI VSLAAADLLL AVLVLPLFVY SEVQGGVWLL
110 120 130 140 150
SPRLCDTLMA MDVMLCTASI FNLCAISVDR FVAVTVPLRY NQQGQCQLLL
160 170 180 190 200
IAATWLLSAA VAAPVVCGLN DVPGRDPTVC CLEDRDYVVY SSICSFFLPC
210 220 230 240 250
PLMLLLYWAT FRGLRRWEAA RHTKLHSRAP RRPSGPGPPV SDPTQGPLFS
260 270 280 290 300
DCPPPSPSLR TSPTVSSRPE SDLSQSPCSP GCLLPDAALA QPPAPSSRRK
310 320 330 340 350
RGAKITGRER KAMRVLPVVV GAFLMCWTPF FVVHITRALC PACFVSPRLV
360 370 380
SAVTWLGYVN SALNPIIYTI FNAEFRSVFR KTLRLRC
Length:387
Mass (Da):41,294
Last modified:May 30, 2000 - v2
Checksum:i1E0A5D74524F5050
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti93 – 94Missing in AAA96716 (PubMed:1554689).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84009 mRNA Translation: AAA96716.1
U03551 Genomic DNA Translation: AAA18588.1
AC118351 Genomic DNA No translation available.
UniGeneiRn.10159

Similar proteinsi

Entry informationi

Entry nameiDRD4_RAT
AccessioniPrimary (citable) accession number: P30729
Secondary accession number(s): Q62610
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: May 30, 2000
Last modified: May 23, 2018
This is version 140 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

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