VAPB Protein

<div class="infobox infobox-protein">
<div class="infobox-header">VAPB Protein</div>
<div class="infobox-image">
<p style="font-size: 48px;">🧬</p>
</div> [@kabashi2010]
<table class="infobox-table">
<tr><th>Gene</th><td>[VAPB](/genes/vapb)</td></tr>
<tr><th>Protein</th><td>VAPB (Vesicle-Associated Membrane Protein-Associated Protein B)</td></tr>
<tr><th>UniProt</th><td><a href="https://www.uniprot.org/uniprot/O95255" target="_blank">O95255</a></td></tr>
<tr><th>Molecular Weight</th><td>~33 kDa</td></tr>
<tr><th>Localization</th><td>ER membrane</td></tr>
<tr><th>Protein Family</th><td>VAP family</td></tr>
<tr><th>Associated Diseases</th><td>[ALS8](/diseases/als), [ALS](/diseases/als)</td></tr>
</table>
</div>

VAPB Protein (Vesicle-Associated Membrane Protein-Associated Protein B/C)

Introduction

Vapb 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.

VAPB is an ER-resident protein involved in lipid metabolism, calcium homeostasis, and ER homeostasis. Dominant mutations cause a form of ALS, while the protein plays important roles in neurodegeneration broadly.

Overview

...

<div class="infobox infobox-protein">
<div class="infobox-header">VAPB Protein</div>
<div class="infobox-image">
<p style="font-size: 48px;">🧬</p>
</div> [@kabashi2010]
<table class="infobox-table">
<tr><th>Gene</th><td>[VAPB](/genes/vapb)</td></tr>
<tr><th>Protein</th><td>VAPB (Vesicle-Associated Membrane Protein-Associated Protein B)</td></tr>
<tr><th>UniProt</th><td><a href="https://www.uniprot.org/uniprot/O95255" target="_blank">O95255</a></td></tr>
<tr><th>Molecular Weight</th><td>~33 kDa</td></tr>
<tr><th>Localization</th><td>ER membrane</td></tr>
<tr><th>Protein Family</th><td>VAP family</td></tr>
<tr><th>Associated Diseases</th><td>[ALS8](/diseases/als), [ALS](/diseases/als)</td></tr>
</table>
</div>

VAPB Protein (Vesicle-Associated Membrane Protein-Associated Protein B/C)

Introduction

Vapb 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.

VAPB is an ER-resident protein involved in lipid metabolism, calcium homeostasis, and ER homeostasis. Dominant mutations cause a form of ALS, while the protein plays important roles in neurodegeneration broadly.

Overview

VAPB (Vesicle-associated membrane protein-associated protein B) is an ER-resident protein involved in lipid metabolism, ER homeostasis, and intracellular trafficking. Dominant VAPB mutations cause ALS (ALS8), characterized by atypical cytoplasmic inclusions and ER stress. VAPB dysfunction leads to impaired lipid exchange between ER and other organelles, contributing to neurodegeneration in ALS and FTD.

Structure

VAPB is a type III ER transmembrane protein:

• N-terminal major sperm protein (MSP) domain (extracellular/lumenal)
• Coiled-coil domain (homo-oligomerization)
• Transmembrane anchor (C-terminal)
• Phosphorylation sites (Ser/Thr)

| Property | Value |
|----------|-------|
| Gene | VAPB |
| Protein | VAPB (Vesicle-Associated Membrane Protein-Associated Protein B) |
| UniProt | O95255 |
| Molecular Weight | ~33 kDa |
| Subcellular Localization | ER membrane |
| Protein Family | VAP family (VAPA, VAPB) |

Normal Function

VAPB participates in multiple cellular processes:

ER-PM contact sites: Forms tethers between ER and plasma membrane

Lipid metabolism: Interacts with lipid transfer proteins (OSBPs, CERT)

Calcium homeostasis: Regulates store-operated calcium entry (SOCE)

ER stress response: Modulates [UPR](/entities/unfolded-protein-response) signaling

[Autophagy](/entities/autophagy) regulation: Affects autophagosome formation

The MSP domain can be cleaved and secreted to regulate:

• Neuronal morphogenesis
• Axon guidance
• Cytoskeleton dynamics

Role in Disease

ALS8 (ALS Type 8)

Dominant VAPB mutations (P56S, Δ56-63) cause familial ALS8:

• P56S mutation is a proline-to-serine change
• Leads to ER stress and impaired ER-PM contacts
• Reduces lipid transfer function
• Causes mitochondrial dysfunction

Amyotrophic Lateral Sclerosis

• VAPB aggregates found in sporadic ALS motor [neurons](/entities/neurons)
• Impaired lipid metabolism contributes to membrane defects
• ER stress and calcium dysregulation are pathogenic mechanisms
• Interacts with [TDP-43](/proteins/tdp-43) pathology

Pathogenic Mechanisms

| Mechanism | Effect |
|-----------|--------|
| ER stress | Upregulation of CHOP, activation of caspases |
| Lipid dysregulation | Altered membrane composition |
| Calcium dyshomeostasis | Excitotoxicity, mitochondrial dysfunction |
| Autophagy impairment | Protein aggregate accumulation |

Therapeutic Targeting

| Approach | Target | Status |
|----------|--------|--------|
| ER stress modulators | Reduce UPR activation | Research |
| Lipid metabolism enhancers | Restore membrane function | Research |
| Calcium stabilizers | Prevent excitotoxicity | Research |

See Also

• [VAPB Gene](/proteins/vapb-protein)
• [Amyotrophic Lateral Sclerosis](/diseases/als)
• [ER Stress Pathway](/mechanisms/endoplasmic-reticulum-stress)
• [Lipid Metabolism in Neurodegeneration](/mechanisms/sphingolipid-metabolism-neurodegeneration)
• [TDP-43 Protein](/proteins/tdp-43)

Brain Atlas Resources

The following resources from the Allen Brain Atlas provide expression and connectivity data for this protein/gene:

• [Allen Human Brain Atlas - Gene Expression](https://human.brain-map.org/microarray/search/show?search_term=VAPB): Searchable gene expression database from adult human brain
• [Allen Brain Atlas - RNA Sequencing](https://human.brain-map.org/rnasearch): RNA sequencing data across brain regions
• [Allen Cell Type Atlas](https://celltypes.brain-map.org/): Single-cell transcriptomic data for cell type classification
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/): Comprehensive mouse brain gene expression database
• [BrainSpan Atlas of the Developing Human Brain](https://www.brainspan.org/): Developmental expression data across brain regions and ages

External Links

• [Gene - NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/)
• [Protein - UniProt](https://www.uniprot.org/uniprot/)
• [Structure - PDB](https://www.rcsb.org/)

Background

The study of Vapb 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

[Nishimura AL, et al, (2004) (2004)](https://pubmed.ncbi.nlm.nih.gov/15372380/)

[Gkogkas C, et al, (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20659558/)

[Zhou Y, et al, (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/21028957/)

[Chen HC, et al, (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22138087/)

[Kabashi E, et al, (2010) (2010)](https://pubmed.ncbi.nlm.nih.gov/20142614/)