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dopamine D2 receptor (DRD2)
Function:
- one of the five types of dopamine receptor
- activity is mediated by G proteins which inhibit adenylyl cyclase
- forms homo- & heterooligomers with DRD4
- interacts with GNAI2 isoform sGi2 allowing creation of an intracellular pool of DRD2 that can be released to cell surface upon agonist stimulation
- interacts with GPRASP1, PPP1R9B & CLIC6
- interacts with CADPS & CADPS2
- interacts with ARRB2, KCNA2. HTR2A
- linked to Gi in medium spiny neurons of striatum
Structure: belongs to the G-protein coupled receptor 1 family
Compartment:
- cell membrane
- dopamine-D1 & D2 receptors colocalize in 60-80% of medium spiny neurons of striatum (GABAergic neurons?)
Alternative splicing: named isoforms=3
Expression:
- medium spiny neurons of striatum
Polymorphism:
- genetic variations in DRD2 may determine the genetic susceptibility to alcoholism
- genetic variations in DRD2 might be a protective factor against the development of withdrawal symptoms but might also be a risk factor in a highly burdened subgroup of alcoholics with a paternal & grandpaternal history of alcoholism & might contribute to suicide risk in alcoholics
Pathology:
- it has been suggested that DRD2 is involved in psychiatric disorders; especially in schizophrenia
- overstimulation of dopamine D2 receptor may be involved in schizophrenia
- defects in DRD2 are associated with myoclonus dystonia
- anti-dopamine D2 receptor Ab implicated in autoimmune movement & psychiatric disorders [4,5]
Pharmacology:
- dopamine D2 receptor agonists ropinirole & bromocryptine used for treatment of Parkinson's disease (see dopamine receptor agonist)
Interactions
molecular events
Related
anti-dopamine D2 receptor Ab
General
dopamine receptor
Properties
SIZE: entity length = 443 aa
MW = 51 kD
COMPARTMENT: synaptic membrane
CELL: neuron
MOTIF: exoplasmic domain {1-37}
MOTIF: N-glycosylation site {N5}
N-glycosylation site {N17}
N-glycosylation site {N23}
transmembrane domain {38-60}
cytoplasmic loop {61-71}
transmembrane domain {72-97}
exoplasmic loop {98-108}
MOTIF: cysteine residue {C107}
MODIFICATION: cysteine residue {C182}
transmembrane domain {109-130}
cytoplasmic loop {131-151}
transmembrane domain {152-174}
exoplasmic loop {175-186}
MOTIF: cysteine residue {C182}
MODIFICATION: cysteine residue {C107}
transmembrane domain {187-210}
MOTIF: serine residue {193}
serine residue {194}
serine residue {197}
cytoplasmic loop {211-373}
MOTIF: PPP1R9B interaction {211-373}
transmembrane domain {374-397}
exoplasmic loop {398-405}
transmembrane domain {406-429}
cytoplasmic domain {430-443}
Database Correlations
OMIM correlations
UniProt P14416
Pfam PF00001
Entrez Gene 1813
Kegg hsa:1813
References
- UniProt :accession P14416
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=DRD2
- Surmeier DJ, Reiner A, Levine MS, Ariano MA.
Are neostriatal dopamine receptors co-localized?
Trends Neurosci. 1993 Aug;16(8):299-305. Review.
PMID: 7691003
- Dale RC, Merheb V, Pillai S et al
Antibodies to surface dopamine-2 receptor in autoimmune movement
and psychiatric disorders.
Brain. 2012 Nov;135(Pt 11):3453-68.
PMID: 23065479 Free Article
- Pathmanandavel K, Starling J, Merheb V et al
Antibodies to surface dopamine-2 receptor and N-methyl-D-
aspartate receptor in the first episode of acute psychosis in
children.
Biol Psychiatry. 2015 Mar 15;77(6):537-47.
PMID: 25168608