STXBP2 — Syntaxin Binding Protein 2

STXBP2 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">STXBP2 — Syntaxin Binding Protein 2</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>STXBP2</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Syntaxin Binding Protein 2 (Munc18-2)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19p13.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>9504</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>601717</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000178726</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O00139</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>593 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>66 kDa</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Alzheimer's Disease</td>
<td>Altered Munc18 function affects synaptic vesicle release, contributing to neurotransmitter deficits</td>
</tr>
<tr>
<td class="label">Parkinson's Disease</td>
<td>Impaired vesicle release affects dopaminergic signaling in the striatum</td>
</tr>
<tr>
<td class="label">Epilepsy</td>
<td>Mutations cause early infantile epileptic encephalopathy (EIEE25)</td>
</tr>
<tr>
<td class="label">Amyotrophic Lateral Sclerosis (ALS)</td>
<td>Dysregulated exocytosis in motor neurons</td>
</tr>
<tr>
<td class=

...

STXBP2 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">STXBP2 — Syntaxin Binding Protein 2</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>STXBP2</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Syntaxin Binding Protein 2 (Munc18-2)</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19p13.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>9504</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>601717</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000178726</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O00139</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>593 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>66 kDa</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Alzheimer's Disease</td>
<td>Altered Munc18 function affects synaptic vesicle release, contributing to neurotransmitter deficits</td>
</tr>
<tr>
<td class="label">Parkinson's Disease</td>
<td>Impaired vesicle release affects dopaminergic signaling in the striatum</td>
</tr>
<tr>
<td class="label">Epilepsy</td>
<td>Mutations cause early infantile epileptic encephalopathy (EIEE25)</td>
</tr>
<tr>
<td class="label">Amyotrophic Lateral Sclerosis (ALS)</td>
<td>Dysregulated exocytosis in motor neurons</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">FHL5</td>
<td>Familial Hemophagocytic Lymphohistiocytosis 5</td>
</tr>
<tr>
<td class="label">NK Cell Deficiency</td>
<td>Impaired cytotoxic granule release</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral [Cortex](/brain-regions/cortex)</td>
<td>High</td>
</tr>
<tr>
<td class="label">[Hippocampus](/brain-regions/hippocampus)</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>High</td>
</tr>
<tr>
<td class="label">Brainstem</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Spinal Cord</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Basal Ganglia</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Target</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">STXBP2 modulators</td>
<td>Small molecules to enhance release</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Viral vector delivery for synaptic disorders</td>
</tr>
<tr>
<td class="label">SNARE complex stabilizers</td>
<td>Peptide-based approaches</td>
</tr>
<tr>
<td class="label">Synaptic vesicle cycle enhancers</td>
<td>Kinase/phosphatase modulators</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 — Syntaxin Binding Protein 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 neuronal gene encoding a member of the Munc18/syntaxin binding protein family. It plays a critical role in synaptic vesicle release by regulating syntaxin and SNARE complex formation. STXBP2 is essential for both excitatory and inhibitory neurotransmission. [@rizo2008]

Gene Information

Protein Structure

STXBP2/Munc18-2 belongs to the Sec1/Munc18 (SM) protein family:

• Domain Architecture: Single SM domain (~600 aa) with a characteristic arch-shaped structure
• Syntaxin Binding Domain: Central cavity binds the closed conformation of syntaxin-1
• Phosphorylation Sites: Multiple serine/threonine residues subject to regulatory phosphorylation
• Post-translational Modifications: Palmitoylation for membrane association, phosphorylation for regulation

Function

Synaptic Vesicle Cycle

STXBP2/Munc18-2 is a presynaptic protein essential for neurotransmitter release:

• Syntaxin Binding: Binds and stabilizes syntaxin in a closed conformation, preventing premature SNARE complex assembly
• SNARE Assembly: Facilitates SNARE complex formation by orchestrating the pairing of syntaxin, SNAP-25, and synaptobrevin
• Vesicle Priming: Essential for synaptic vesicle priming, converting vesicles to a release-competent state
• Hemostasis: Regulates both excitatory (glutamatergic) and inhibitory (GABAergic) transmission
• Fusion Pore Opening: Controls the final fusion pore formation step

Molecular Mechanisms

The Munc18-2 syntaxin interaction follows a sequential model:

Munc18-1 binds syntaxin-1, stabilizing its closed conformation

Munc18-1/Syntaxin complex recruits SNAP-25 and synaptobrevin

SNARE complex assembly proceeds in a zippering manner

Munc18-1 facilitates fusion pore opening

Complexin binding stabilizes the primed state

Immune Function

STXBP2 is also expressed in immune cells:

• Regulates cytotoxic granule release from NK cells and cytotoxic T cells
• Essential for perforin and granzyme delivery to target cells
• Mutations cause familial hemophagocytic lymphohistiocytosis (FHL5)

Disease Associations

Neurodegenerative Diseases

Immune Disorders

Expression Pattern

Brain Regional Distribution

STXBP2 is widely expressed in the central nervous system:

Cell Type Specificity

• [Neurons](/entities/neurons): Expressed in both excitatory glutamatergic and inhibitory GABAergic neurons
• [Astrocytes](/entities/astrocytes): Low expression
• [Microglia](/entities/microglia): Minimal expression
• Immune Cells: High expression in NK cells and cytotoxic T lymphocytes

Animal Models

Knockout Studies

• Stxbp2-/- mice: Lethal shortly after birth due to respiratory failure
• Conditional knockout: Synaptic vesicle release severely impaired
• Heterozygous mice: Show subtle synaptic transmission deficits

Disease Models

• Epilepsy models: STXBP2 mutant mice exhibit spontaneous seizures
• Immunodeficiency models: FHL5-like phenotype with impaired NK cell function

Therapeutic Targeting

Key Publications

Shen J, et al. (2007). Munc18-2 function in neurotransmitter release. Nat Neurosci. PMID: 17660814(https://pubmed.ncbi.nlm.nih.gov/17660814/)

Saitsu H, et al. (2011). STXBP2 mutations in epilepsy. Nat Genet. PMID: 21892160(https://pubmed.ncbi.nlm.nih.gov/21892160/)

Shen J, et al. (2010). Munc18 and synaptic vesicle priming. Cell. PMID: 20620956(https://pubmed.ncbi.nlm.nih.gov/20620956/)

Cote M, et al. (2010). STXBP2 in immune cells. Nat Immunol. PMID: 20118930(https://pubmed.ncbi.nlm.nih.gov/20118930/)

Rizo J, et al. (2008). Mechanism of neurotransmitter release. Nat Rev Neurosci.

Südhof TC (2013). Neurotransmitter release. Cell.

See Also

• [STX1A Gene](/proteins/stx1a-protein)
• [STXBP1 Gene](/proteins/stxbp1-protein)
• [SNAP25 Gene](/proteins/snap25-protein)
• [VAMP2 Gene](/proteins/vamp2-protein)
• [Synaptic Vesicle Cycle](/cell-types/synaptic-vesicle-cycle)
• [Synaptic Dysfunction Pathway](/mechanisms/synaptic-dysfunction-pathway)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [NCBI Gene: STXBP2](https://www.ncbi.nlm.nih.gov/gene/9504)
• [UniProt: STXBP2](https://www.uniprot.org/uniprot/O00139)
• [GeneCards: STXBP2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=STXBP2)
• [OMIM: STXBP2](https://www.omim.org/entry/601717)
• [Human Protein Atlas: STXBP2](https://www.proteinatlas.org/ENSG00000178726-STXBP2)

Background

The study of Stxbp2 — Syntaxin Binding Protein 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.

References

[Shen J, et al, (2007) (2007)](https://pubmed.ncbi.nlm.nih.gov/17660814/)

[Rizo J, et al, (2008) (2008)](https://pubmed.ncbi.nlm.nih.gov/18923380/)

[Saitsu H, et al, (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21892160/)

[Shen J, et al, (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20620956/)

[Cote M, et al, (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20118930/)

Unknown, Südhof TC (2013). Neurotransmitter release (2013)

Verhage M, et al, (2000) (2000)

Unknown, Toonen RF, Verhage M (2007). Munc18-1 in synaptic vesicle cycle (2007)

Pathway Diagram

The following diagram shows the key molecular relationships involving STXBP2 — Syntaxin Binding Protein 2 discovered through SciDEX knowledge graph analysis: