α2δ-1 Calcium Channel Subunit

α2δ-1 Calcium Channel Subunit

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">α2δ-1 Calcium Channel Subunit</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>α2δ-1 Calcium Channel Subunit</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>CACNA2D1</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O95198</td>
</tr>
<tr>
<td class="label">PDB IDs</td>
<td>6WONY, 7MX3</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~140 kDa (precursor)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, Synaptic vesicles</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Voltage-gated calcium channel auxiliary subunits</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Gabapentin</td>
<td>α2δ-1 antagonist</td>
</tr>
<tr>
<td class="label">Pregabalin</td>
<td>α2δ-1 antagonist</td>
</tr>
<tr>
<td class="label">Mirogabalin</td>
<td>α2δ-1 antagonist</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Α2Δ 1 Calcium Channel Subunit 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

α2δ-1 Calcium Channel Subunit

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">α2δ-1 Calcium Channel Subunit</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>α2δ-1 Calcium Channel Subunit</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>CACNA2D1</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O95198</td>
</tr>
<tr>
<td class="label">PDB IDs</td>
<td>6WONY, 7MX3</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~140 kDa (precursor)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, Synaptic vesicles</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Voltage-gated calcium channel auxiliary subunits</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Gabapentin</td>
<td>α2δ-1 antagonist</td>
</tr>
<tr>
<td class="label">Pregabalin</td>
<td>α2δ-1 antagonist</td>
</tr>
<tr>
<td class="label">Mirogabalin</td>
<td>α2δ-1 antagonist</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Α2Δ 1 Calcium Channel Subunit 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

α2δ-1 (CACNA2D1) is an auxiliary subunit of voltage-gated calcium channels that plays crucial roles in channel trafficking, localization, and modulation. It is the primary target of gabapentinoid analgesics. [@role]

This protein is involved in: [@calcium]

• Calcium channel trafficking: Essential for proper channel localization
• Synaptic transmission: Modulates neurotransmitter release
• Pain signaling: Mediates neuropathic pain mechanisms
• Cardiac function: Modulates cardiac calcium channels

Protein Overview

Protein Structure

The α2δ-1 protein is synthesized as a precursor that undergoes post-translational cleavage:

• α2 subunit: Large extracellular domain with multiple binding sites
• δ subunit: Single transmembrane segment
• Disulfide bond: α2 and δ are linked by disulfide bond
• Gabapentin binding site: Located on the α2 domain
• VGCC interaction domain: Critical for channel association

Normal Function

• Channel Trafficking: Facilitates proper localization of Cav1.2, Cav2.1, Cav2.2
• Synaptic Plasticity: Modulates neurotransmitter release probability
• Excitability: Influences neuronal firing properties
• Development: Important for synaptogenesis

Role in Disease

Neuropathic Pain

• Mechanism: α2δ-1 is upregulated in dorsal root ganglion after nerve injury
• Target: Gabapentin and pregabalin bind α2δ-1 to reduce pain
• Efficacy: Effective for diabetic neuropathy, postherpetic neuralgia

Epilepsy

• Altered expression: α2δ-1 dysregulation affects calcium influx
• Synaptic dysfunction: Contributes to hyperexcitability

Autism Spectrum Disorder

• Genetic variants: Rare de novo mutations in ASD patients
• Synaptic function: Disrupts excitatory/inhibitory balance

Therapeutic Targeting

Key Publications

See Also

• [CACNA2D1 Gene](/genes/cacna2d1)
• [Voltage-Gated Calcium Channels](/mechanisms/calcium-channel-dysfunction)
• [Cav2.1 Protein](/proteins/cav2-1-protein)

Background

The study of Α2Δ 1 Calcium Channel Subunit 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.

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References