RAB27B Protein
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">RAB27B Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>RAB27B</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>RAB27B</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NPF4</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>24.8 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Secretory vesicles, plasma membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Rab GTPase family</td>
</tr>
<tr>
<td class="label">PDB Structure</td>
<td>5EBM</td>
</tr>
<tr>
<td class="label">Process</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Vesicle docking</td>
<td>Direct effector interactions</td>
</tr>
<tr>
<td class="label">Peripheral transport</td>
<td>Actin-myosin based movement</td>
</tr>
<tr>
<td class="label">Fusion competence</td>
<td>Munc13-4 mediated priming</td>
</tr>
<tr>
<td class="label">Cargo sorting</td>
<td>Selective packaging into RAB27B vesicles</td>
</tr>
<tr>
<td class="label">Effector</td>
<td>Primary Function</td>
</tr>
<tr>
<td class="label">Slac2-a/MyRIP</td>
<td>Actin-based transport</td>
</tr>
<tr>
<td class="label">Munc13-4</td>
<td>Vesicle priming</td>
</tr>
<tr>
<td class="label">Synaptotagmin-like proteins</td>
<td>Calcium regulation</td>
</tr>
<tr>
<td class="label">Granuphilin</td>
<td>Docking to plasma membrane</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <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">42 edges</a></td>
</tr>
</table>
Rab27B 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.
Overview
RAB27B is a member of the Rab GTPase family that plays a critical role in regulated exocytosis and intracellular vesicle trafficking. Rab27B is particularly important in controlling the transport and release of secretory granules in various cell types, including neuroendocrine cells, platelets, and melanocytes. The protein functions as a molecular switch cycling between active (GTP-bound) and inactive (GDP-bound) states, interacting with a variety of effector proteins to mediate specific trafficking events[^1][^2].
Structure
Domain Organization
RAB27B contains several key structural features:
GTP-binding domain: Core switch regions that alternate between active/inactive states
Switch I region: Interacts with effectors when GTP-bound (residues 32-40)
Switch II region: Conformational change on GTP hydrolysis (residues 56-66)
Hypervariable C-terminal region: Determines membrane association and effector specificity
Prenylation site: CaaX motif (Cys-Ser-Ser-Met) for geranylgeranylationEffector-Binding Surfaces
RAB27B has distinct binding surfaces for its effector proteins:
- Slac2-a/MyRIP: Links to actin cytoskeleton for peripheral transport
- Munc13-4: Facilitates priming and exocytosis of secretory granules
- Synaptotagmin-like proteins: Calcium-dependent regulation of exocytosis
Normal Function
Regulated Secretion
RAB27B controls several key secretion pathways:
Neuroendocrine secretion: Regulates dense-core granule release in [neurons](/entities/neurons) and neuroendocrine cells
Platelet activation: Controls alpha-granule secretion during clot formation
Melanocyte function: Regulates melanosome transport and distribution
Salivary gland secretion: Controls amylase release
Lung surfactant secretion: Regulates secretion from type II pneumocytesCellular Transport
Effector Proteins
Role in Disease
Alzheimer's Disease
- Altered RAB27B expression in AD brains
- May affect [amyloid precursor protein](/entities/app-protein) (APP) processing
- Potential role in synaptic vesicle dynamics and neurotransmitter release
- Dysregulated exocytosis contributes to synaptic dysfunction
- RAB27B interactions with amyloid pathology under investigation[^3]
Parkinson's Disease
- Dysregulated in dopaminergic neurons
- May contribute to protein aggregation through altered trafficking
- Altered exocytosis affects neurotransmission
- RAB27B-lysosomal pathway connections relevant to [alpha-synuclein](/mechanisms/alpha-synuclein) clearance
Cancer
- Overexpressed in several cancers (breast, colorectal, gastric)
- Promotes tumor cell invasion and metastasis
- May affect secretory pathway in cancer cells
- Potential biomarker for certain malignancies
- Therapeutic target under investigation
Bleeding Disorders
- RAB27B mutations affect platelet secretion
- Contributes to bleeding diatheses
- May interact with other bleeding disorder genes
Therapeutic Implications
Drug Development
- Targeting RAB27B interaction interfaces with effector proteins
- Small molecule inhibitors under development
- Antisense oligonucleotides for expression modulation
- Potential for combination therapies in cancer
Research Directions
- Understanding RAB27B effector specificity
- Developing specific inhibitors
- Exploring therapeutic applications in neurodegeneration
- RAB27B-based biomarkers for disease progression
Animal Models
Knockout Studies
- RAB27B knockout mice show:
- Impaired platelet secretion
- Altered melanocyte function
- Neurosecretory deficits
- Variable effects on fertility
Transgenic Models
- Overexpression studies reveal:
- Enhanced tumor progression in cancer models
- Altered synaptic function
- Effects on metabolic parameters
Key Publications
<sup>[1]</sup> Fukuda, M. et al. (2002). Slac2-c (Synaptotagmin-like protein homology 4-c)/granuphilin directly regulates insulin granule exocytosis and binding to the exocyst. Journal of Biological Chemistry, 277(42), 39673-39678.
<sup>[2]</sup> Desnos, C. et al. (2003). Munc13-4 functions as a Ca2+ and Ptid-dependent secretory vesicle docking protein. Journal of Cell Biology, 162(4), 587-597.
<sup>[3]</sup>参考文献: Bendor, J. et al. (2013). The function of [alpha-synuclein](/proteins/alpha-synuclein). Neuron, 79(6), 1044-1068.See Also
- [RAB27B Gene](/proteins/rab27b-protein)
- [Rab GTPases](/entities/rab-gtpases)
- [Exocytosis](/mechanisms/exocytosis)
- [Vesicle trafficking](/mechanisms/synaptic-vesicle-trafficking)
- [Synaptic transmission](/mechanisms/synaptic-transmission)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [UniProt: RAB27B](https://www.uniprot.org/uniprot/Q9NPF4)
- [NCBI Protein: RAB27B](https://www.ncbi.nlm.nih.gov/protein/NP_004254)
- [GeneCards: RAB27B](https://www.genecards.org/cgi-bin/carddisp.pl?gene=RAB27B)
- [RAB27B pathway in disease](https://pubmed.ncbi.nlm.nih.gov/)
Background
The study of Rab27B 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
<sup>[1]</sup> Fukuda, M. et al. (2002). Slac2-c (Synaptotagmin-like protein homology 4-c)/granuphilin directly regulates insulin granule exocytosis and binding to the exocyst. Journal of Biological Chemistry, 277(42), 39673-39678. PMID: 12414904(https://pubmed.ncbi.nlm.nih.gov/12414904/)
<sup>[2]</sup> Desnos, C. et al. (2003). Munc13-4 functions as a Ca2+ and Ptid-dependent secretory vesicle docking protein. Journal of Cell Biology, 162(4), 587-597. PMID: 12952945(https://pubmed.ncbi.nlm.nih.gov/12952945/)
<sup>[3]</sup> Bendor, J. et al. (2013). The function of alpha-synuclein. Neuron, 79(6), 1044-1068. PMID: 24065793(https://pubmed.ncbi.nlm.nih.gov/24065793/)
Note: This page is part of the NeuroWiki protein database. Last updated: 2026-03-04
[^1]: [Reference missing - citation needed]
[^2]: [Reference missing - citation needed]
[^3]: [Reference missing - citation needed]