Human Gene DRD4 (ENST00000176183.6_4) from GENCODE V47lift37
  Description: dopamine receptor D4 (from RefSeq NM_000797.4)
Gencode Transcript: ENST00000176183.6_4
Gencode Gene: ENSG00000069696.7_7
Transcript (Including UTRs)
   Position: hg19 chr11:637,269-640,706 Size: 3,438 Total Exon Count: 4 Strand: +
Coding Region
   Position: hg19 chr11:637,305-640,603 Size: 3,299 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:637,269-640,706)mRNA (may differ from genome)Protein (419 aa)
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-  Comments and Description Text from UniProtKB
  ID: DRD4_HUMAN
DESCRIPTION: RecName: Full=D(4) dopamine receptor; AltName: Full=D(2C) dopamine receptor; AltName: Full=Dopamine D4 receptor;
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.
SUBUNIT: 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. Interacts with CLIC6 (By similarity) and GPRASP1. May interact with ADORA2A. Interacts with KLHL12.
SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
PTM: Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex: polyubiquitination does not lead to degradation of DRD4 protein.
POLYMORPHISM: The number of repeats of 16 amino acids in the third cytoplasmic loop is highly polymorphic and varies among different alleles. Alleles corresponding in size to a 2 (D4.2), 3 (D4.3), 4 (D4.4), 5 (D4.5), 6 (D4.6), 7 (D4.7) and 9 (D4.9) repeats have been described. The sequence shown is that of allele D4.7. The polymorphic repeat sequence has little influence on DRD4-binding profiles and might not be essential for G protein interaction.
SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
SEQUENCE CAUTION: Sequence=AAL58637.1; Type=Erroneous gene model prediction;

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: DRD4
Diseases sorted by gene-association score: attention deficit-hyperactivity disorder* (608), autonomic nervous system disease* (400), attention deficit-hyperactivity disorder susceptibility, drd4-related* (100), oppositional defiant disorder (30), pathological gambling (25), tic disorder (24), chronic tic disorder (24), separation anxiety disorder (22), conduct disorder (22), dependent personality disorder (17), gilles de la tourette syndrome (17), personality disorder (13), substance abuse (12), heroin dependence (12), mood disorder (11), drug addiction (11), obsessive-compulsive disorder (10), specific developmental disorder (9), schizophrenia (7), delusional disorder (7), impulse control disorder (7), major depressive disorder and accelerated response to antidepressant drug treatment (7), alcohol dependence (7), alcohol abuse (7), psychotic disorder (6), disease of mental health (5), early-onset schizophrenia (4), anxiety disorder (3), substance dependence (3), autism spectrum disorder (2), migraine with or without aura 1 (2), parkinson disease, late-onset (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 3.62 RPKM in Pituitary
Total median expression: 52.62 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -14.0036-0.389 Picture PostScript Text
3' UTR -38.10103-0.370 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000276 - 7TM_GPCR_Rhodpsn
IPR002185 - Dopa_D4_rcpt
IPR000929 - Dopamine_rcpt
IPR017452 - GPCR_Rhodpsn_supfam

Pfam Domains:
PF00001 - 7 transmembrane receptor (rhodopsin family)
PF10320 - Serpentine type 7TM GPCR chemoreceptor Srsx

SCOP Domains:
81321 - Family A G protein-coupled receptor-like

ModBase Predicted Comparative 3D Structure on P21917
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001591 dopamine neurotransmitter receptor activity, coupled via Gi/Go
GO:0004871 signal transducer activity
GO:0004930 G-protein coupled receptor activity
GO:0004952 dopamine neurotransmitter receptor activity
GO:0005515 protein binding
GO:0008144 drug binding
GO:0015459 potassium channel regulator activity
GO:0017124 SH3 domain binding
GO:0035240 dopamine binding
GO:0042802 identical protein binding
GO:0046872 metal ion binding
GO:0051379 epinephrine binding
GO:0051380 norepinephrine binding

Biological Process:
GO:0000187 activation of MAPK activity
GO:0001662 behavioral fear response
GO:0001975 response to amphetamine
GO:0006874 cellular calcium ion homeostasis
GO:0007165 signal transduction
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007195 adenylate cyclase-inhibiting dopamine receptor signaling pathway
GO:0007212 dopamine receptor signaling pathway
GO:0008344 adult locomotory behavior
GO:0032417 positive regulation of sodium:proton antiporter activity
GO:0033674 positive regulation of kinase activity
GO:0034776 response to histamine
GO:0035176 social behavior
GO:0042053 regulation of dopamine metabolic process
GO:0042417 dopamine metabolic process
GO:0042596 fear response
GO:0042752 regulation of circadian rhythm
GO:0048148 behavioral response to cocaine
GO:0048149 behavioral response to ethanol
GO:0048511 rhythmic process
GO:0050482 arachidonic acid secretion
GO:0050709 negative regulation of protein secretion
GO:0051586 positive regulation of dopamine uptake involved in synaptic transmission
GO:0060080 inhibitory postsynaptic potential
GO:1901386 negative regulation of voltage-gated calcium channel activity

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0098794 postsynapse


-  Descriptions from all associated GenBank mRNAs
  BC172267 - Synthetic construct Homo sapiens clone IMAGE:100068961, MGC:198972 dopamine receptor D4 (DRD4) mRNA, encodes complete protein.
S76942 - dopamine D4 receptor {exon 1} [human, brain tumor tissue, mRNA Partial Mutant, 386 nt].
EU432112 - Homo sapiens dopamine receptor D4 (DRD4) mRNA, complete cds.
L12398 - Homo sapiens dopamine receptor D4 (DRD4) mRNA, complete cds.
JD450300 - Sequence 431324 from Patent EP1572962.
JD192706 - Sequence 173730 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P21917 (Reactome details) participates in the following event(s):

R-HSA-390846 D2-like dopamine receptors bind to dopamine
R-HSA-749454 The Ligand:GPCR:Gi complex dissociates
R-HSA-749456 Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi
R-HSA-380073 Liganded Gi-activating GPCR acts as a GEF for Gi
R-HSA-390651 Dopamine receptors
R-HSA-418594 G alpha (i) signalling events
R-HSA-375280 Amine ligand-binding receptors
R-HSA-388396 GPCR downstream signalling
R-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-372790 Signaling by GPCR
R-HSA-500792 GPCR ligand binding
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: B0M0J7, DRD4_HUMAN, ENST00000176183.1, ENST00000176183.2, ENST00000176183.3, ENST00000176183.4, ENST00000176183.5, NM_000797, P21917, Q7Z7Q5, Q8NGM5, uc317ceq.1, uc317ceq.2
UCSC ID: ENST00000176183.6_4
RefSeq Accession: NM_000797.4
Protein: P21917 (aka DRD4_HUMAN or D4DR_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.