STXBP2 Protein (Munc18-2)

STXBP2 Protein (Munc18-2)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">STXBP2 Protein (Munc18-2)</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Munc18-2 (STXBP2)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>STXBP2</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O00139</td>
</tr>
<tr>
<td class="label">PDB ID</td>
<td>3C85</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>66.2 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytosolic (presynaptic terminal)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Munc18/syntaxin binding family</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Target</td>
</tr>
<tr>
<td class="label">Small molecule modulators</td>
<td>STXBP2-syntaxin interaction</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>AAV-STXBP2 for synaptic disorders</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/hemophagocytic-lymphohistiocytosis" style="color:#ef9a9a">Hemophagocytic Lymphohistiocytosis</a>, <a href="/wiki/microvillus-inclusion-disease" style="color:#ef9a9a">Microvillus Inclusion Disease</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">30 edges</a></td>
</tr>
</table>

Introduction

...

STXBP2 Protein (Munc18-2)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">STXBP2 Protein (Munc18-2)</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Munc18-2 (STXBP2)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>STXBP2</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O00139</td>
</tr>
<tr>
<td class="label">PDB ID</td>
<td>3C85</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>66.2 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytosolic (presynaptic terminal)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Munc18/syntaxin binding family</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Target</td>
</tr>
<tr>
<td class="label">Small molecule modulators</td>
<td>STXBP2-syntaxin interaction</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>AAV-STXBP2 for synaptic disorders</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/hemophagocytic-lymphohistiocytosis" style="color:#ef9a9a">Hemophagocytic Lymphohistiocytosis</a>, <a href="/wiki/microvillus-inclusion-disease" style="color:#ef9a9a">Microvillus Inclusion Disease</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">30 edges</a></td>
</tr>
</table>

Introduction

Stxbp2 Protein (Munc18 2) 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

STXBP2 (Syntaxin Binding Protein 2), also known as Munc18-2, is a 590-amino acid neuronal protein that regulates synaptic vesicle release by binding syntaxin and facilitating SNARE complex formation. [@sdhof2013]

Protein Information

Structure

STXBP2 has a characteristic Munc18 fold:

• Domain 1: Syntaxin binding
• Domain 2: Interdomain contacts
• Domain 3: Syntaxin binding pocket

Binds to syntaxin in a closed conformation, preventing SNARE assembly until primed.

Normal Function

STXBP2 is essential for neurotransmitter release:

• Syntaxin Stabilization: Binds and stabilizes syntaxin 1 in closed conformation
• SNARE Assembly: Facilitates SNARE complex formation
• Vesicle Priming: Essential for synaptic vesicle priming
• Fusion Regulation: Acts as both a clamp and facilitator of fusion
• Dual Role: Regulates both excitatory and inhibitory transmission

Role in Disease

Alzheimer's Disease

• Altered Munc18 function affects synaptic vesicle release
• May contribute to synaptic dysfunction

Parkinson's Disease

• Impaired vesicle release affects dopaminergic signaling
• May contribute to neurodegeneration

Epilepsy (EIEE)

• Recessive mutations cause early infantile epileptic encephalopathy 15 (EIEE15)
• Affects syntaxin binding and SNARE assembly
• Severe seizures, developmental regression

Familial Hemophagocytic Lymphohistiocytosis 5 (FHL5)

• Biallelic mutations cause immune dysregulation
• Affects cytotoxic T cell and NK cell function

Therapeutic Targeting

Key Publications

Munc18-2 structure - Nat Struct Mol Biol (2009) - PMID: 19339982(https://pubmed.ncbi.nlm.nih.gov/19339982/)

STXBP2 mutations in epilepsy - Nat Genet (2011) - PMID: 21892160(https://pubmed.ncbi.nlm.nih.gov/21892160/)

Munc18 and vesicle priming - Cell (2010) - PMID: 20620956(https://pubmed.ncbi.nlm.nih.gov/20620956/)

STXBP2 in immune cells - Nat Immunol (2010) - PMID: 20118930(https://pubmed.ncbi.nlm.nih.gov/20118930/)

Background

The study of Stxbp2 Protein (Munc18 2) 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

• STXBP2 Gene
• STXBP1 Gene
• [STX1A Protein](/proteins/stx1a-protein)
• [SNAP25 Protein](/proteins/snap25-protein)
• [Synaptic Vesicle Cycle](/mechanisms/synaptic-vesicle-cycle)

External Links

• [UniProt: STXBP2](https://www.uniprot.org/uniprot/O00139)
• [PDB: STXBP2](https://www.rcsb.org/structure/3C85)
• [GeneCards: STXBP2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=STXBP2)
• [OMIM: STXBP2](https://www.omim.org/entry/601717)

Molecular Mechanisms

STXBP2 (Syntaxin Binding Protein 2), also known as Munc18-2, is a member of the Sec1/Munc18 (SM) protein family:

• Syntaxin binding: Binds to syntaxin-1, -2, -3 forming binary complexes
• Vesicle priming: Essential for synaptic vesicle priming
• Exocytosis: Regulates SNARE complex assembly
• Localization: Cytosolic and membrane-associated

Munc18-2 is critical for:

• Neurotransmitter release: Regulates vesicle fusion
• Immune function: Required for cytotoxic T cell granule release
• Cellular secretion: General exocytic pathways

Role in Neurodegeneration

• Alzheimer's disease: Alters synaptic vesicle dynamics
• Parkinson's disease: Affects dopamine release
• Therapeutic targeting: Modulating Munc18 levels for neuroprotection

References

[Rizo J, et al, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29689794/)

[Unknown, Südhof TC (2013). 'Neurotransmitter release: binding of Munc18.' Nature (2013)](https://pubmed.ncbi.nlm.nih.gov/24335912/)

[Shen J, et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28615472/)

[Zhou P, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30625633/)

[Heeroma SJ, et al, (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19126551/)

[Stork T, et al, (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/24550301/)

[Martin S, et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/23319571/)

[Toonen RF, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/31982548/)