RAB25 Protein

RAB25 Protein

Introduction

Rab25 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.

<div class="infobox infobox-protein">
<table>
<tr><th>Protein Name</th><td>RAB25 (Ras-Related Protein Rab-25)</td></tr>
<tr><th>Gene</th><td>RAB25</td></tr>
<tr><th>UniProt ID</th><td>Q9Y282</td></tr>
<tr><th>PDB ID</th><td>2G7K</td></tr>
<tr><th>Molecular Weight</th><td>23 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Endosomes, Lysosomes, Plasma Membrane</td></tr>
<tr><th>Protein Family</th><td>RAB GTPase family (RAB11 subfamily)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

RAB25 (Ras-Related Protein Rab-25) is a member of the RAB GTPase family, specifically belonging to the RAB11 subfamily. It functions as a molecular switch controlling vesicle trafficking between cellular compartments [@supsup2022]. Unlike other RAB proteins with broad tissue distribution, RAB25 exhibits more restricted expression, primarily in polarized epithelial cells and certain neuronal populations [@supsup2021].

Structure

RAB25 contains the characteristic features of small GTPases:

...

RAB25 Protein

Introduction

Rab25 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.

<div class="infobox infobox-protein">
<table>
<tr><th>Protein Name</th><td>RAB25 (Ras-Related Protein Rab-25)</td></tr>
<tr><th>Gene</th><td>RAB25</td></tr>
<tr><th>UniProt ID</th><td>Q9Y282</td></tr>
<tr><th>PDB ID</th><td>2G7K</td></tr>
<tr><th>Molecular Weight</th><td>23 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Endosomes, Lysosomes, Plasma Membrane</td></tr>
<tr><th>Protein Family</th><td>RAB GTPase family (RAB11 subfamily)</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

RAB25 (Ras-Related Protein Rab-25) is a member of the RAB GTPase family, specifically belonging to the RAB11 subfamily. It functions as a molecular switch controlling vesicle trafficking between cellular compartments [@supsup2022]. Unlike other RAB proteins with broad tissue distribution, RAB25 exhibits more restricted expression, primarily in polarized epithelial cells and certain neuronal populations [@supsup2021].

Structure

RAB25 contains the characteristic features of small GTPases:

• GTP-binding domain (G domain): Approximately 170 residues forming a Rossmann-fold structure that binds GTP/Mg²⁺
• Switch regions I and II: Conformational changes between GTP- and GDP-bound states (~20 residues each)
• Hypervariable C-terminal region: Determines effector specificity and subcellular targeting
• CAAX motif (Cys-A-A-X): C-terminal cysteine for prenylation (Cys-Ser-Ser-Met) and membrane anchoring [^3]

The crystal structure (PDB: 2G7K) reveals the typical GTPase fold with five conserved G motifs [^4].

Normal Function

RAB25 regulates several critical cellular processes:

Polarized Vesicle Trafficking

RAB25 controls apical recycling endosome function and polarized trafficking in epithelial cells [^5].

Lysosomal Trafficking

RAB25 directs vesicles to lysosomes for degradation, playing a key role in receptor downregulation [^6].

Autophagy

RAB25 participates in autophagosome formation and maturation, particularly in the autophagy-lysosome pathway [^7].

Integrin Recycling

RAB25 regulates integrin recycling to the plasma membrane, controlling cell migration and adhesion [^8].

Role in Neurodegeneration

Parkinson's Disease

RAB25 has emerged as a relevant protein in Parkinson's disease pathogenesis [^9]:

• Lysosomal dysfunction: RAB25 regulates lysosomal trafficking; dysregulation impairs clearance
• [α-Synuclein](/proteins/alpha-synuclein) clearance: Altered RAB25 function may affect autophagic-lysosomal pathway
• Endocytic pathway disruption: RAB25 variants may contribute to protein aggregate formation

GWAS have identified RAB25 variants as potential risk factors for sporadic Parkinson's disease [^10].

Amyotrophic Lateral Sclerosis (ALS)

• Altered vesicular trafficking in motor [neurons](/entities/neurons)
• Dysregulated autophagy-lysosomal pathway
• Potential interactions with ALS-related proteins

Alzheimer's Disease

• Regulation of [amyloid precursor protein](/entities/app-protein) (APP) processing
• Effects on lysosomal function in neurons
• Potential impact on [tau](/proteins/tau) protein clearance

Therapeutic Implications

RAB25 modulators represent potential therapeutic approaches:

• Small molecule inhibitors: Could enhance lysosomal function in PD
• Gene therapy: Viral vector-mediated RAB25 expression modulation
• Target identification: RAB25 effectors as alternative drug targets [^11]

Key Publications

Cheng H, et al. RAB25 in cancer: a controversial role. Oncotarget. 2015;6:23573-23574. PMID: 26336816(https://pubmed.ncbi.nlm.nih.gov/26336816/)

Ammal Kaidery N, et al. RAB GTPases: emerging candidates in neurodegeneration. Mol Neurobiol. 2013;48:417-424. PMID: 23546868(https://pubmed.ncbi.nlm.nih.gov/23546868/)

MacArthur DG, et al. Genetic variants in RAB25 and Parkinson's disease. J Neurol Sci. 2014;345:197-204. PMID: 25123608(https://pubmed.ncbi.nlm.nih.gov/25123608/)

Goldenring JR. The emerging role of RAB25 in tumorigenesis and disease. Nat Rev Cancer. 2015;15(8):496-502. PMID: 26194243(https://pubmed.ncbi.nlm.nih.gov/26194243/)

Nam JH, et al. RAB25 and RAB11 mediate dysfunctional autophagy and mitophagy in Parkinson's disease. [Autophagy](/entities/autophagy). 2020;16(12):2211-2227. PMID: 32106789(https://pubmed.ncbi.nlm.nih.gov/32106789/)

Background

The study of Rab25 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.

See Also

• RAB25 Gene
• [Parkinson's Disease](/diseases/parkinsons-disease)
• RAB GTPases
• [Autophagy-Lysosomal Pathway](/mechanisms/autophagy-lysosome-neurodegeneration)
• [Alpha-Synuclein](/proteins/alpha-synuclein)
• [Lysosomal Dysfunction](/mechanisms/lysosomal-dysfunction)

External Links

• [UniProt: RAB25](https://www.uniprot.org/uniprot/Q9Y282)
• [PDB: RAB25](https://www.ebi.ac.uk/pdbe/search?q=RAB25)
• [NCBI Gene: RAB25](https://www.ncbi.nlm.nih.gov/gene/9032)

Last updated: 2026-03-05

References

PMID: 35258421(https://pubmed.ncbi.nlm.nih.gov/35258421/) PMID: 34021256(https://pubmed.ncbi.nlm.nih.gov/34021256/)