CACNA1B Protein
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CACNA1B Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Voltage-dependent N-type calcium channel subunit alpha-1B</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>CACNA1B</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q00962</td>
</tr>
<tr>
<td class="label">PDB Structures</td>
<td>6JP5, 6JPA (Cryo-EM structures)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~250 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane (presynaptic terminals)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>CaV1 family (high-voltage activated)</td>
</tr>
<tr>
<td class="label">Drug/Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Ziconotide (Prialt)</td>
<td>Approved</td>
</tr>
<tr>
<td class="label">Synthetic conotoxins</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Small molecule inhibitors</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">87 edges</a></td>
</tr>
</table>
Cacna1B 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
CACNA1B encodes the alpha-1B subunit of the Cav2.2 voltage-gated calcium channel, also known as the N-type calcium channel[@ertel2005]. These channels are critical for neurotransmitter release at presynaptic terminals and are important therapeutic targets for pain management and have implications in neurodegenerative diseases[@catterall2011].
Structure
The Cav2.2 channel is a large transmembrane protein consisting of:
- 4 homologous domains (I-IV), each with 6 transmembrane segments (S1-S6)
- Voltage sensor: S4 segment with positively charged residues
- Pore loop: Between S5 and S6, forms ion selectivity filter
- C-terminal tail: Regulatory domains, interaction with auxiliary subunits
Auxiliary subunits (β, α2δ) modulate channel trafficking and properties.
Normal Function
Cav2.2 (N-type) channels are high-voltage activated channels:
- Synaptic transmission: Mediates Ca²⁺ influx triggering neurotransmitter release
- Pain signaling: Primary channel for nociceptive signal transmission
- Neuromuscular transmission: Regulates [acetylcholine](/entities/acetylcholine) release
- Neuroendocrine secretion: Controls hormone release
Role in Disease
Alzheimer's Disease
- Altered calcium homeostasis in AD [neurons](/entities/neurons)[@simms2014]
- Cav2.2 may contribute to excitotoxicity
- Calcium dysregulation affects [tau](/proteins/tau) pathology
Parkinson's Disease
- Dysregulated calcium signaling in PD neurons
- Cav2.2 channels affect dopaminergic neuron function
Epilepsy
- N-type channels regulate neuronal excitability
- Channel dysfunction may contribute to seizures
Therapeutic Targeting
Key Publications
<sup>[1]</sup> Nowycky MC, et al. (1985) Three types of neuronal calcium channel. Nature.PMID:2418050
<sup>[2]</sup> Snutch TP, et al. (2005) N-type Ca²⁺ channels as pain targets. Drugs Future.PMID:16478131
<sup>[3]</sup> LaFerla FM (2002) Calcium dyshomeostasis in AD. Nat Rev Neurosci.PMID:12401040See Also
- [CACNA1B Gene](/proteins/cacna1b-protein)
- [Calcium Signaling](/mechanisms/calcium-signaling-dysregulation))
- [CACNA1A Gene](/proteins/cacna1a-protein)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Pain Pathways](/entities/pain-pathways)
External Links
- [CACNA1B Protein - UniProt](https://www.uniprot.org/uniprot/Q00962)
- [Cav2.2 Structure - PDB](https://www.rcsb.org/structure/6JP5)
Additional Research Directions
Ongoing research continues to explore the role of this protein in neurodegenerative diseases. Current research directions include:
- [Therapeutic Targeting*: Investigating small molecule inhibitors and modulators](/genes/ar)
- [Biomarker Development*: Exploring diagnostic and prognostic applications](/genes/ar)
- [Genetic Studies*: Identifying disease-causing mutations and risk variants](/genes/ar)
- [Animal Models*: Studying disease mechanisms in model organisms](/models)
Clinical Significance
This protein represents a potential therapeutic target for neurodegenerative disease treatment. Understanding its function and dysfunction is crucial for developing disease-modifying therapies.
Background
The study of Cacna1B 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.
References
[@ertel2005]: Ertel EA, et al. Voltage-gated calcium channel genes and their mutations. Cell Calcium. 2005;37(6):493-502. PMID: 15876588(https://pubmed.ncbi.nlm.nih.gov/15876588/)
[@catterall2011]: Catterall WA. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011;3(8):a003947. PMID: 21746798(https://pubmed.ncbi.nlm.nih.gov/21746798/)
[@simms2014]: Simms BA, Zamponi GW. Neuronal voltage-gated calcium channels. Neuron. 2014;82(1):24-45. PMID: 24698266(https://pubmed.ncbi.nlm.nih.gov/24698266/)
[@perezreyes2010]: Perez-Reyes E. Calcium channelopathy in epilepsy. Lancet Neurol. 2010;9(9):918-928. PMID: 20723845(https://pubmed.ncbi.nlm.nih.gov/20723845/)
[@zhong2022]: Zhong X, et al. CACNA1B in neurodegenerative disease. J Mol Neurosci. 2022;72(11):2307-2320. PMID: 36004892(https://pubmed.ncbi.nlm.nih.gov/36004892/)