DRD4

Protein identityUniProt · HPA

UniProt accession

P21917

Gene

DRD4

Ensembl

ENSG00000069696

Chromosome

11

Canonical length

419 aa

Protein class

FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted membrane proteins

Subcellular location

Plasma membrane,Centrosome

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes the D4 subtype of the dopamine receptor. The D4 subtype is a G-protein coupled receptor which inhibits adenylyl cyclase. It is a target for drugs which treat schizophrenia and Parkinson disease. Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder, and the personality trait of novelty seeking. This gene contains a polymorphic number (2-10 copies) of tandem 48 nt repeats; the sequence shown contains four repeats. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

419 residues, UniProt reviewed canonical sequence.

>P21917|DRD4
     1  MGNRSTADAD GLLAGRGPAA GASAGASAGL AGQGAAALVG GVLLIGAVLA GNSLVCVSVA
    61  TERALQTPTN SFIVSLAAAD LLLALLVLPL FVYSEVQGGA WLLSPRLCDA LMAMDVMLCT
   121  ASIFNLCAIS VDRFVAVAVP LRYNRQGGSR RQLLLIGATW LLSAAVAAPV LCGLNDVRGR
   181  DPAVCRLEDR DYVVYSSVCS FFLPCPLMLL LYWATFRGLQ RWEVARRAKL HGRAPRRPSG
   241  PGPPSPTPPA PRLPQDPCGP DCAPPAPGLP RGPCGPDCAP AAPSLPQDPC GPDCAPPAPG
   301  LPPDPCGSNC APPDAVRAAA LPPQTPPQTR RRRRAKITGR ERKAMRVLPV VVGAFLLCWT
   361  PFFVVHITQA LCPACSVPPR LVSAVTWLGY VNSALNPVIY TVFNAEFRNV FRKALRACC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DRD4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.42

Highest tissue expression

3.9 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DRD4.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 208 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary attention deficit-hyperactivity disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.86

gnomAD pLI

0

gnomAD missense Z

-2

DepMap mean gene effect

0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-inhibiting dopamine receptor signaling pathway
• adenylate cyclase-modulating G protein-coupled receptor signaling pathway
• adult locomotory behavior
• arachidonate secretion
• behavioral fear response
• behavioral response to cocaine
• behavioral response to ethanol
• chemical synaptic transmission
• fear response
• G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• inhibitory postsynaptic potential
• intracellular calcium ion homeostasis
• negative regulation of protein secretion
• phospholipase C-activating dopamine receptor signaling pathway
• positive regulation of dopamine uptake involved in synaptic transmission
• positive regulation of MAPK cascade
• regulation of circadian rhythm
• regulation of dopamine metabolic process
• regulation of postsynaptic neurotransmitter receptor internalization
• response to amphetamine
• response to histamine
• rhythmic process
• social behavior

Molecular functions

• dopamine binding
• dopamine neurotransmitter receptor activity
• dopamine neurotransmitter receptor activity, coupled via Gi/Go
• epinephrine binding
• G protein-coupled serotonin receptor activity
• identical protein binding
• metal ion binding
• neurotransmitter receptor activity
• norepinephrine binding
• potassium channel regulator activity
• SH3 domain binding

Cellular components

• centrosome
• dendrite
• glutamatergic synapse
• membrane
• plasma membrane
• postsynapse

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Dopamine receptor family
• GPCR, rhodopsin-like, 7TM
• 7 transmembrane receptor (rhodopsin family)
• Dopamine D4 receptor

KeywordsUniProt

• Biological rhythms
• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Lipoprotein
• Membrane
• Metal-binding
• Palmitate
• Receptor
• Repeat
• Sodium
• Transducer
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of DRD4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLIC6
• GPRASP1
• KLHL12