Contents

Search


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

  1. UniProt :accession P14416
  2. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=DRD2
  3. 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
  4. 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
  5. 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