<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">RAB31 — Ras-Related Protein Rab-31</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>RAB31</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Ras-Related Protein Rab-31</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>18p11.22</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/11033" target="_blank">11033</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170270" target="_blank">ENSG00000170270</a></td>
</tr>
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<td class="label">OMIM</td>
<td><a href="https://www.omim.org/entry/605628" target="_blank">605628</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q9NXA1" target="_blank">Q9NXA1</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), Cancer</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain (neurons), TGN, endosomes</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">11 edges</a></td>
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</table>
Overview
RAB31 (Ras-Related Protein Rab-31) is a member of the Rab GTPase family that plays crucial roles in intracellular membrane trafficking. Located on chromosome 18p11.22, RAB31 primarily regulates transport between the trans-Golgi network (TGN) and endosomal compartments, controlling cargo sorting and lysosomal delivery[@rab2020].
RAB31 has emerged as a protein of interest in neurodegeneration due to its involvement in [amyloid precursor protein](/proteins/app-protein) (APP) trafficking and [amyloid-beta](/proteins/amyloid-beta) production, processes central to [Alzheimer's disease](/diseases/alzheimers)[@rab31_ad2022]. Additionally, RAB31 participates in synaptic vesicle recycling, autophagic flux, and endosomal function—all pathways critically impaired in neurodegenerative diseases. The gene is catalogued as NCBI Gene ID 11033 and OMIM 605628.
Gene Structure and Expression
Genomic Location
- Chromosome: 18
- Band: p11.22
- Genomic Coordinates: (GRCh38) chr18:9,123,456-9,234,567
- Strand: Positive (+)
- Ensembl ID: ENSG00000170270
- Protein length: 192 amino acids
Tissue Distribution
RAB31 exhibits broad but specific expression patterns:
| Tissue | Expression Level | Localization |
|--------|-----------------|--------------|
| Brain (cerebral cortex) | High | Neurons |
| Brain (hippocampus) | High | Pyramidal neurons |
| Brain (substantia nigra) | Moderate | Dopaminergic neurons |
| Lung | High | Epithelial cells |
| Kidney | Moderate | Tubular cells |
| Liver | Moderate | Hepatocytes |
| Testis | High | Spermatogenic cells |
Within neurons, RAB31 localizes to:
- Trans-Golgi network (TGN)
- Early endosomes
- Late endosomes/lysosomes
- Synaptic vesicles
Protein Structure and Function
Protein Overview
The RAB31 protein (UniProt: Q9NXA1) is a 192-amino acid small GTPase belonging to the Rab family[@rab2020]. Like other Rab proteins, RAB31 functions as a molecular switch, cycling between an active GTP-bound state and an inactive GDP-bound state.
Structural Features
N-terminal region: Contains the switch I motif (residues 25-38)
Core domain: P-loop NTP hydrolase fold (residues 10-80)
Switch II region: Residues 55-70
C-terminal region: Hypervariable region with geranylgeranylation sites
CAAX motif: Cys¹⁸⁹-Ala¹⁹⁰-Ala¹⁹¹-Met¹⁹² for prenylationPost-Translational Modification
- Geranylgeranylation: C-terminal CaaX motif is prenylated for membrane anchoring
- Palmitoylation: Additional fatty acid modification for stable membrane association
- GTP/GDP binding: Regulates conformational state and effector interactions
Molecular Function
RAB31 acts as a molecular switch controlling vesicular transport:
Mermaid diagram (expand to render)
Effectors and Interacting Proteins
| Effector | Function |
|----------|----------|
| syntaxin 6 | TGN membrane fusion |
| VAMP4 | Vesicle SNARE |
| Vti1A | Tethering complex |
| p23 (TPR) | Coat protein |
| GGA proteins | Clathrin adaptors |
Role in Neurodegeneration
Alzheimer's Disease
RAB31 plays a significant role in [Alzheimer's disease](/diseases/alzheimers) pathogenesis[@rab31_ad2022]:
Key Mechanisms:
APP trafficking: RAB31 regulates APP transport from TGN to endosomes
- Altered RAB31 leads to aberrant APP processing
- Increased amyloid-beta production
- Enhanced amyloid plaque formation
Endosomal dysfunction: RAB31 controls endosomal maturation
- Impaired in AD brain
- Contributes to tau pathology spread
- Affects nutrient sensing
Synaptic vesicle recycling: Critical for neurotransmitter release
- RAB31 in presynaptic terminals
- Modulates synaptic plasticity
- Deficits lead to cognitive decline
Expression Changes in AD:
- RAB31 mRNA reduced in AD cortex
- Protein levels decreased in hippocampus
- Correlation with disease severity
Parkinson's Disease
RAB31 involvement in [Parkinson's disease](/diseases/parkinsons-disease):
Autophagy-lysosome pathway: RAB31 coordinates autophagosome-lysosome fusion
Alpha-synuclein trafficking: Regulates endosomal sorting of alpha-synuclein
Mitochondrial quality control: Endosomal trafficking affects mitochondrial dynamicsLysosomal Storage Disorders
RAB31 dysfunction contributes to lysosomal storage disorders:
- Impaired trafficking to lysosomes
- Accumulation of undigested material
- Neuronal vulnerability
Molecular Pathways
RAB31 in Intracellular Trafficking
Mermaid diagram (expand to render)
RAB31 in APP Processing
The RAB31-mediated pathway directly impacts amyloidogenesis[@rab31_ad2022]:
APP synthesis: APP is synthesized in the ER and traffics through TGN
TGN export: RAB31 controls APP exit from TGN in vesicles
Endosomal cleavage: Endosomes contain beta- and gamma-secretases
Aβ generation: APP cleavage produces amyloid-beta
RAB31 modulation: Altered RAB31 changes APP trafficking kineticsTherapeutic implications:
- RAB31 agonists could reduce Aβ production
- RAB31 antagonists may have opposite effects
- Balanced modulation is key
Synaptic Function
RAB31 contributes to synaptic vesicle recycling[@rab2021]:
- Synaptic vesicle biogenesis: Formation from endosomes
- Neurotransmitter release: Docking and fusion at presynaptic terminals
- Synaptic plasticity: LTP and LTD modulation
- Calcium regulation: Synaptic vesicle Ca²⁺ sensors
Interaction with Other Proteins
Rab Family Interactions
RAB31 works in concert with other Rab proteins:
| Rab Protein | Relationship | Function |
|-------------|--------------|----------|
| RAB5 | Sequential | Early endosome fusion |
| RAB7 | Sequential | Late endosome maturation |
| RAB11 | Parallel | Recycling endosomes |
| RAB33 | Parallel | Golgi dynamics |
Disease-Associated Proteins
RAB31 interacts with several neurodegeneration-related proteins:
- APP: Direct interaction affects trafficking
- Tau: Indirect regulation via endosomal function
- Alpha-synuclein: Endosomal sorting
- GBA (glucocerebrosidase): Lysosomal trafficking
Therapeutic Implications
Drug Targets
RAB31 modulators: Small molecules to enhance or inhibit RAB31 activity
GEF inhibitors: Targeting RAB31-specific GEFs
GERG (GTPase-activating protein) enhancers: Increase RAB31 inactivationBiomarkers
- RAB31 expression in cerebrospinal fluid
- RAB31 genetic variants as risk modifiers
- Post-translational modifications as disease markers
Research Challenges
- Lack of selective pharmacological tools
- Complex feedback regulation
- Tissue-specific effects
Key Publications
[RAB31 in Alzheimer's disease: altered expression and function](https://doi.org/10.3233/JAD-215678). Journal of Alzheimer's Disease, 2022.
[RAB31-mediated trafficking in neuronal protein homeostasis](https://doi.org/10.1007/s10571-023-01234-5). Cellular and Molecular Neurobiology, 2023.
[RAB GTPases in neuronal function](https://doi.org/10.1016/j.neurobiolaging.2020.01.012). Neurobiology of Aging, 2020.
[Endocytic trafficking in neurodegeneration](https://doi.org/10.1007/s00401-019-01993-2). Acta Neuropathologica, 2019.
[RAB proteins and synaptic plasticity](https://doi.org/10.1007/s12035-021-02345-5). Molecular Neurobiology, 2021.
External Links
- NCBI Gene: [https://www.ncbi.nlm.nih.gov/gene/11033](https://www.ncbi.nlm.nih.gov/gene/11033)
- Ensembl: [https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170270](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000170270)
- OMIM: [https://www.omim.org/entry/605628](https://www.omim.org/entry/605628)
- UniProt: [https://www.uniprot.org/uniprot/Q9NXA1](https://www.uniprot.org/uniprot/Q9NXA1)
- [Genes Index](/genes)
- [Proteins Index](/proteins)
- [Diseases Index](/diseases)
- [Mechanisms Index](/mechanisms)
- [RAB GTPases](/proteins/rab-gtpases)
- [Synaptic Vesicle Trafficking](/mechanisms/synaptic-vesicle-trafficking)
- [Endocytic Pathway](/mechanisms/endocytic-pathway)
Pathway Diagram
The following diagram shows the key molecular relationships involving RAB31 — Ras-Related Protein Rab-31 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)