RAB31 — Ras-Related Protein Rab-31

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RAB31 — Ras-Related Protein Rab-31

<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>
<tr>
<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>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">11 edges</a></td>
</tr>
</table>

RAB31 — Ras-Related Protein Rab-31

Overview

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RAB31 — Ras-Related Protein Rab-31

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 prenylation

Post-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 dynamics

Lysosomal 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 kinetics

Therapeutic 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 inactivation

Biomarkers

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)

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