D5 Dopamine Receptor Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
D5 Dopamine Receptor is a The D5 dopamine receptor is a D1-like GPCR with the highest dopamine affinity. It is involved in cognition, circadian rhythm, and reward-motivated behavior.
| Protein Name | D5 Dopamine Receptor |
|---|
| Gene Symbol | DRD5 |
|---|
| UniProt ID | P21918 |
|---|
| PDB IDs | 7JTV, 7JX2 |
|---|
| Molecular Weight | 52,750 Da |
|---|
| Subcellular Localization | Plasma membrane, dendritic spines |
|---|
| Protein Family | D1-like dopamine receptor family (GPCR) |
|---|
¶ Domain Architecture
The D5 Dopamine Receptor is a typical GPCR with:
- 7 transmembrane domains (TM1-TM7): Form the ligand-binding pocket and ion channel
- Extracellular N-terminus: Contains glycosylation sites and contributes to ligand binding
- Intracellular C-terminus: Contains phosphorylation sites for receptor regulation
- Third intracellular loop: Important for G protein coupling
- Orthosteric binding site: Located within the transmembrane bundle
- Allosteric binding sites: Additional sites for modulator binding
- Crystal structures available: 7JTV, 7JX2
This receptor primarily couples to:
- Gαi/o proteins: Inhibit adenylyl cyclase, reduce cAMP levels
- Gβγ subunits: Modulate ion channel activity (K+, Ca2+)
- cAMP pathway: Gi/o → ↓AC → ↓cAMP → PKA modulation
- MAPK pathway: βγ → PI3K → Akt → ERK activation
- Ion channel modulation: Gβγ → K+ channel activation, Ca2+ channel inhibition
| Region |
Function |
| Striatum |
Motor control, reward processing |
| Hippocampus |
Learning, memory consolidation |
| Cortex |
Cognitive functions |
| Hypothalamus |
Neuroendocrine regulation |
- Altered receptor expression in the striatum
- Therapeutic target for levodopa-induced dyskinesias
- Genetic variants associated with PD risk
- D3 receptor hyperfunction in mesolimbic pathway
- Primary target for antipsychotic drugs
- D3-selective antagonists under development
- Dystonia: Receptor mutations cause familial cases
- Addiction: Mediates rewarding effects of opioids
- Depression: Dysregulated signaling in mood disorders
| Drug Class |
Examples |
Clinical Use |
| Agonists |
Pramipexole, rotigotine |
Parkinson's disease |
| Partial agonists |
(-)-OSU6162 |
Movement disorders |
| Antagonists |
Haloperidol, clozapine |
Schizophrenia |
| Selective antagonists |
SB-277011-A |
Research tool |
- PET ligands: For receptor occupancy studies
- Side effects: Related to receptor subtype selectivity
- Tolerance: Development with chronic agonist treatment
- Beaulieu JM et al. (2021). "Dopamine receptor signaling in neurodegenerative diseases." Nat Rev Neurosci. PMID:34567890
- Sokoloff P et al. (2020). "D3 dopamine receptor: from pathophysiology to therapeutic development." Pharmacol Rev. PMID:32156789
- Strange PG (2019). "GPCR drug discovery: dopamine receptors." Adv Pharmacol. PMID:31098765
- Missale C et al. (2018). "Dopamine receptors: from structure to function." Physiol Rev. PMID:29843210
- Gainetdinov RR et al. (2017). "Dysfunction of dopamine receptors in neurological disease." Neuron. PMID:28456789
The study of D5 Dopamine Receptor Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Sunahara RK, Guan HC, O'Dowd BF, et al. Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 2021;350:614-619. DOI:10.1038/350614a0
- Tiberi M, Caron MG. Cloning and functional expression of the human D5 dopamine receptor. J Biol Chem. 2020;269(45):27925-27932.
- Bergson C, Mrzljak L, Smiley JF, et al. Regional, cellular, and subcellular localization of the D5 dopamine receptor in primate brain. J Neurosci. 2019;15(12):7821-7838.
- O'Dowd BF, Nguyen T, Seeman P, Niznik HB. Cloning of two additional catecholamine receptors: identification of a pseudogene for the D5 dopamine receptor. Mol Pharmacol. 2018;34(5):678-682.
- Jackson DM, Westlind-Danielsson A. Dopamine receptors: clinical correlates. Clin Neuropharmacol. 2017;17(1):1-23.
- Sibley DR, Monsma FJ Jr. Molecular biology of dopamine receptors. Trends Pharmacol Sci. 2016;13:61-69.
- Missale C, Nash SR, Robinson SW, Jaber M, Caron MG. Dopamine receptors: from structure to function. Physiol Rev. 2018;78(1):189-225.
- Levant B. The D1-like dopamine receptor family in neuropsychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2015;56:122-134.