D5 Dopamine Receptor Protein

D5 Dopamine Receptor Protein

Introduction

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.

Overview

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. [@tiberi2020]

Protein Information

D5 Dopamine Receptor Protein

Introduction

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.

Overview

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. [@tiberi2020]

Protein Information

<div class="infobox infobox-protein"> [@bergson2019]
<table> [@odowd2018]
<tr><th>Protein Name</th><td>D5 Dopamine Receptor</td></tr> [@jackson2017]
<tr><th>Gene Symbol</th><td>[DRD5](/genes/dr5)</td></tr> [@sibley2016]
<tr><th>UniProt ID</th><td>[P21918](https://www.uniprot.org/uniprot/P21918)</td></tr> [@missale2018]
<tr><th>PDB IDs</th><td>7JTV, 7JX2</td></tr> [@levant2015]
<tr><th>Molecular Weight</th><td>52,750 Da</td></tr>
<tr><th>Subcellular Localization</th><td>Plasma membrane, [dendritic spines](/mechanisms/dendritic-spines)</td></tr>
<tr><th>Protein Family</th><td>D1-like dopamine receptor family (GPCR)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/breast-cancer" style="color:#ef9a9a">Breast Cancer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/lymphoma" style="color:#ef9a9a">Lymphoma</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">72 edges</a></td>
</tr>
</table>
</div>

Structure

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

Structural Features

• Orthosteric binding site: Located within the transmembrane bundle
• Allosteric binding sites: Additional sites for modulator binding
• Crystal structures available: 7JTV, 7JX2

Normal Function

G Protein Coupling

This receptor primarily couples to:

• Gαi/o proteins: Inhibit adenylyl cyclase, reduce cAMP levels
• Gβγ subunits: Modulate ion channel activity (K+, Ca2+)

Signaling Pathways

Physiological Roles

| Region | Function |
|--------|----------|
| Striatum | Motor control, reward processing |
| [Hippocampus](/brain-regions/hippocampus) | Learning, memory consolidation |
| [Cortex](/brain-regions/cortex) | Cognitive functions |
| Hypothalamus | Neuroendocrine regulation |

Role in Disease

Parkinson's Disease

• Altered receptor expression in the striatum
• Therapeutic target for levodopa-induced dyskinesias
• Genetic variants associated with PD risk

Schizophrenia

• D3 receptor hyperfunction in mesolimbic pathway
• Primary target for antipsychotic drugs
• D3-selective antagonists under development

Other Neurological Conditions

• Dystonia: Receptor mutations cause familial cases
• Addiction: Mediates rewarding effects of opioids
• Depression: Dysregulated signaling in mood disorders

Therapeutic Targeting

Drug Classes

| 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 |

Clinical Considerations

• PET ligands: For receptor occupancy studies
• Side effects: Related to receptor subtype selectivity
• Tolerance: Development with chronic agonist treatment

Key Publications

Background

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.

See Also

• [DRD3 Gene](/genes/drd3)
• [DRD5 Gene](/genes/drd5)
• [OPRM1 Gene](/mechanisms/dopaminergic-neuron-vulnerability)
• [OPRK1 Gene](/mechanisms/dopaminergic-neuron-vulnerability)
• [OPRD1 Gene](/mechanisms/dopaminergic-neuron-vulnerability)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Schizophrenia](/diseases/schizophrenia)
• [GPCR](/mechanisms/dopaminergic-neuron-vulnerability)
• [Dopamine Signaling](/mechanisms/dopaminergic-signaling-neurodegeneration)
• [Opioid Signaling](/mechanisms/dopaminergic-neuron-vulnerability)

External Links

• [UniProt](https://www.uniprot.org/uniprot/P21918)
• [PDB](https://www.rcsb.org/structures/7JTV)
• [IUPHAR/BPS Guide to Pharmacology](https://www.guidetopharmacology.org/GRAC/ObjectDetailsForward?name=DRD5&objectClass=receptor)
• [Human Protein Atlas](https://www.proteinatlas.org/search/DRD5)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving D5 Dopamine Receptor Protein discovered through SciDEX knowledge graph analysis: