Hsp110 Protein

Hsp110 Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Hsp110 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Hsp110 / Hsp70-4</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>HSPA4</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P34932</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>94 kDa</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>N-terminal ATPase domain, C-terminal substrate-binding domain</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Ubiquitous, high in brain, heart, testis</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, nucleus, organelles</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/colorectal-cancer" style="color:#ef9a9a">Colorectal Cancer</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">40 edges</a></td>
</tr>
</table>

Hsp110 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.

Hsp110 Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Hsp110 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Hsp110 / Hsp70-4</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>HSPA4</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P34932</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>94 kDa</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>N-terminal ATPase domain, C-terminal substrate-binding domain</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Ubiquitous, high in brain, heart, testis</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, nucleus, organelles</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/colorectal-cancer" style="color:#ef9a9a">Colorectal Cancer</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">40 edges</a></td>
</tr>
</table>

Hsp110 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.

Hsp110 (encoded by the HSPA4 gene) is a member of the Hsp70 family of molecular chaperones. It is also known as Hsp110, Hsp70-4, or APG-2. Hsp110 is one of the most abundant [heat shock proteins](/entities/heat-shock-proteins) and plays essential roles in protein quality control. [@mattoo2017]

Overview

Normal Function

Hsp110 is a key component of the cellular protein quality control network:

Molecular Mechanisms

Hsp110 operates through sophisticated mechanisms:

• ATP-Dependent Cycling: N-terminal ATPase domain regulates substrate binding
• Hsp70/Hsp40 Collaboration: Forms functional complexes with Hsp70 and Hsp40
• Disaggregationase Activity: Can extract proteins from pre-formed aggregates
• Co-chaperone Interactions: Binds J-domain proteins for substrate delivery
• Nuclear Import/Export: Facilitates nuclear-cytoplasmic transport of proteins

Disease Associations

Neurodegenerative Diseases

• Alzheimer's Disease: Hsp110 may aid in clearing [Aβ](/proteins/amyloid-beta) and [tau](/proteins/tau) aggregates
• Parkinson's Disease: Protects against [α-synuclein](/proteins/alpha-synuclein) toxicity
• Amyotrophic Lateral Sclerosis: Modifies SOD1 and [TDP-43](/proteins/tdp-43) aggregation
• Huntington's Disease: Helps clear mutant [huntingtin](/proteins/huntingtin-protein) aggregates

Cancer

• Overexpressed in many cancers
• Confers resistance to chemotherapy
• Anti-apoptotic function through protein quality control

Metabolic Disorders

• Linked to insulin signaling and metabolic homeostasis
• May affect diabetes complications

Therapeutic Targeting

• Hsp110 agonists: Activate chaperone function for neurodegeneration
• Hsp110 antagonists: Inhibit in cancer therapy to sensitize tumors
• Gene therapy: AAV-HSPA4 for neuroprotection
• Combination approaches: With Hsp70/Hsp40 modulators

Animal Models

• HSPA4 knockout mice: Embryonic lethal in some backgrounds
• Transgenic overexpression: Protects against protein aggregation
• Drosophila models: Loss causes neurodegeneration
• C. elegans: Used for aggregation studies

Research Directions

• Developing small molecule modulators of Hsp110
• Understanding disaggregase mechanism
• Biomarker development
• Gene therapy optimization
• Structure-function studies

See Also

• [HSPA4 Gene](/proteins/hspa4-protein)
• [HSP70 Family](/entities/hsp70-family)
• [Protein Quality Control Pathway](/mechanisms/protein-quality-control-network))
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Autophagy-Lysosomal Pathway](/mechanisms/autophagy-lysosomal-pathway)

External Links

• [UniProt: P34932](https://www.uniprot.org/uniprot/P34932)
• [NCBI Gene: HSPA4](https://www.ncbi.nlm.nih.gov/gene/3309)
• [OMIM: HSPA4](https://www.omim.org/entry/140100)
• [PDB: Hsp110 Structure](https://www.rcsb.org/structure/4J7L)

Background

The study of Hsp110 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