G3BP2 Protein - Ras-GTPase-Activating Protein-Binding Protein 2

G3BP2 Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">G3BP2 Protein - Ras-GTPase-Activating Protein-Binding Protein 2</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Ras-GTPase-Activating Protein-Binding Protein 2</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>G3BP2</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UHW2</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>56.4 kDa</td>
</tr>
<tr>
<td class="label">Length</td>
<td>497 amino acids</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, stress granules, nucleus (shuttles)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>G3BP family (G3BP1, G3BP2, G3BP3)</td>
</tr>
<tr>
<td class="label">RNA-Binding Classification</td>
<td>Prion-like, intrinsically disordered regions</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Stress Granule Modulators</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Kinase Inhibitors</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Autophagy Enhancers</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Antisense Oligonucleotides</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atheros

...

G3BP2 Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">G3BP2 Protein - Ras-GTPase-Activating Protein-Binding Protein 2</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Ras-GTPase-Activating Protein-Binding Protein 2</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>G3BP2</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UHW2</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>56.4 kDa</td>
</tr>
<tr>
<td class="label">Length</td>
<td>497 amino acids</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, stress granules, nucleus (shuttles)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>G3BP family (G3BP1, G3BP2, G3BP3)</td>
</tr>
<tr>
<td class="label">RNA-Binding Classification</td>
<td>Prion-like, intrinsically disordered regions</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Stress Granule Modulators</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Kinase Inhibitors</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Autophagy Enhancers</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Antisense Oligonucleotides</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/cardiac" style="color:#ef9a9a">Cardiac</a>, <a href="/wiki/tumor" style="color:#ef9a9a">Tumor</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">16 edges</a></td>
</tr>
</table>

Introduction

G3Bp2 Protein Ras Gtpase Activating Protein 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

G3BP2 (Ras-GTPase-Activating Protein-Binding Protein 2) is a multifunctional RNA-binding protein that serves as a critical scaffold for stress granule assembly and a key regulator of mRNA translation. Originally identified as a protein that binds Ras-GAP, G3BP2 has evolved to be recognized as a central player in cellular stress responses and RNA metabolism. [@buchan2011]

Protein Information

Structure

G3BP2 contains multiple functional domains:

N-Terminal Domain

• NTF2-like Domain: Dimerization, nuclear export signal (NES) binding
• PxxP Proline-Rich Region: Protein-protein interactions, SH3 domain binding

Central Region

• RRM1 (RNA Recognition Motif): RNA binding, ~90 aa
• RRM2: Accessory RNA binding
• RGG (Arg-Gly-Gly) Repeats: RNA binding, prion-like properties
• Acid-Rich Region: Regulatory functions

C-Terminal Domain

• C-terminal Acidic Tail: Autoinhibition, protein interactions

Normal Function

Stress Granule Assembly

• Primary nucleator of stress granules
• G3BP2 condensation drives liquid-liquid phase separation (LLPS)
• Recruits mRNA and translation factors
• Forms stress granule core with G3BP1

mRNA Translation Regulation

• Represses translation initiation
• Sequesters translation machinery during stress
• Controls mRNA stability
• Regulates specific mRNA subsets

Signal Transduction

• Originally characterized as Ras-GAP SH3 domain interactor
• Modulates MAPK/ERK signaling
• Integrates stress signals with translation

Autophagy Regulation

• Links stress granules to autophagy
• Selective autophagy of stress granules
• G3BP2 clearance via autophagy

RNA Metabolism

• Processes specific mRNA targets
• AUF1/HNRNP D competition
• circRNA regulation

Role in Disease

Amyotrophic Lateral Sclerosis (ALS)

• Stress Granule Pathology: G3BP2 positive granules accumulate in ALS
• Mutations: G3BP2 mutations are rare but pathogenic
• Impaired Clearance: Defective autophagy leads to persistence
• Aggregation: Sequestration of [TDP-43](/proteins/tdp-43), FUS in granules
• Therapeutic: Stress granule-disrupting compounds in trials

Frontotemporal Dementia (FTD)

• [TDP-43](/mechanisms/tdp-43-proteinopathy) Pathology: G3BP2 colocalizes with inclusions
• Stress Granule Connection: Similar to ALS mechanisms
• RNA Metabolism: Dysregulated mRNA processing

Alzheimer's Disease

• Translational Dysregulation: G3BP2 affects [APP](/entities/app-protein) translation
• Stress Response: Chronic stress leads to granule accumulation
• [Tau](/proteins/tau) Pathology: Stress granule-[tau](/proteins/tau) interactions

Parkinson's Disease

• [Alpha-Synuclein](/mechanisms/alpha-synuclein): G3BP2 may affect aggregation
• ER Stress: Links to PD-relevant stress pathways
• [Autophagy](/entities/autophagy): Clearance mechanisms impaired

Cancer

• Translation Control: Supports tumor growth under stress
• Metastasis: Promotes epithelial-mesenchymal transition
• Therapeutic Target: G3BP2 inhibitors in development

Therapeutic Targeting

Key Publications

Matsuki H et al. (2013). "G3BP2 in stress granule formation and neurodegeneration." Cell Death Differ. PMID: 23175186(https://pubmed.ncbi.nlm.nih.gov/23175186/)

Protter DSW et al. (2016). "Stress granules: the center of translation regulation." Cell. PMID: 27984723(https://pubmed.ncbi.nlm.nih.gov/27984723/)

Tourrière H et al. (2003). "Ras-GAP-derived fragments drive the formation of stress granules." J Cell Biol. PMID: 14581454(https://pubmed.ncbi.nlm.nih.gov/14581454/)

Kedersha N et al. (2016). "G3BP-Caprin1-USP10 complexes mediate stress granule dynamics." J Cell Biol. PMID: 27325790(https://pubmed.ncbi.nlm.nih.gov/27325790/)

Background

The study of G3Bp2 Protein Ras Gtpase Activating Protein 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.

See Also

• [G3BP2 Gene](/genes/g3bp2)
• [ALS](/diseases/amyotrophic-lateral-sclerosis)
• [Frontotemporal Dementia](/diseases/frontotemporal-dementia)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Stress Granules Pathway](/genes/ran)
• [RNA Metabolism Pathway](/genes/th)
• [Protein Aggregation Pathway](/genes/th)

External Links

• [UniProt: Q9UHW2](https://www.uniprot.org/uniprot/Q9UHW2)
• [GeneCards: G3BP2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=G3BP2)
• [PDB: Available structures](https://www.ebi.ac.uk/pdbe/)

References

[Anderson P, et al, (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25620003/)

[Buchan JR, et al, (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21233337/)

[Gilks N, et al, (2004) (2004)](https://pubmed.ncbi.nlm.nih.gov/15471484/)

[Reineke LC, et al, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29553832/)

[Advani VM, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30681757/)

[Van Treeck B, et al, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29438767/)

[Wolozin B, et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28641066/)

[Aulas A, et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28159608/)