RAB3B Human
Description
Introduction to RAB3B
RAB3B (Ras-related protein Rab-3B) is a 219-amino acid small GTPase protein encoded by the RAB3B gene located on human chromosome 1. It belongs to the Rab protein family, which regulates membrane trafficking, including vesicle formation, transport, and fusion. RAB3B is primarily involved in regulated exocytosis and synaptic vesicle dynamics, with specialized roles in neurobiology and oncology.
Molecular Mechanisms and Interactions
RAB3B functions as a molecular switch, cycling between GDP-bound (inactive) and GTP-bound (active) states. In its active state, it recruits effector proteins to mediate vesicle docking and fusion. Key interactions and regulatory mechanisms include:
Regulatory Pathways:
-
RIN3 enhances GTP binding of Rab proteins via its VPS9 domain, though direct interaction with RAB3B remains unconfirmed.
-
DNA methylation patterns in cancers alter RAB3B expression, correlating with tumor progression .
Role in Cancer Biology
RAB3B is upregulated in multiple tumor types, including breast, lung, liver, and pancreatic cancers, and serves as a prognostic biomarker. Key findings from pan-cancer analyses:
| Cancer Type | RAB3B Expression Pattern | Prognostic Correlation | Diagnostic Accuracy (AUC) |
|---|---|---|---|
| Breast (BRCA) | Upregulated in tumors vs. normal | Poor prognosis with high expression | 0.71–0.81 |
| Lung (LUAD/LUSC) | Elevated in adenocarcinoma and squamous cell carcinoma | Independent predictor of survival | 0.73–0.79 |
| Liver (LIHC) | Strong cytoplasmic staining in HCC | Associated with tumor heterogeneity | 0.68–0.75 |
| Pancreas (PAAD) | Downregulated protein expression in tumors | Moderate diagnostic accuracy | 0.65–0.70 |
Mechanistic Insights:
-
Tumor Mutational Burden (TMB): RAB3B mutations correlate with TMB and microsatellite instability (MSI) in cancers like colorectal and endometrial carcinomas .
-
Immune Microenvironment: High RAB3B expression associates with increased CD8+ T-cell infiltration and immune scores in cancers like HNSC and THCA .
Neurological Functions
RAB3B is enriched in inhibitory synapses and plays critical roles in synaptic plasticity and neuroprotection:
Synaptic Plasticity
| Parameter | Wild-Type Mice | RAB3B KO Mice | Source |
|---|---|---|---|
| Basal inhibitory synaptic transmission | Normal | Normal | |
| Endocannabinoid-dependent i-LTD | Intact | Severely impaired | |
| Reversal learning (Morris water maze) | Normal | Enhanced |
Key Findings:
-
RAB3B KO mice exhibit enhanced reversal learning due to impaired long-term depression (i-LTD) at inhibitory synapses .
-
Cocaine Response: Rab3b maps to a QTL for cocaine-induced locomotor activation, with DBA/2-derived alleles increasing susceptibility .
Neuroprotection in Parkinson’s Disease
-
Dopamine Handling: Overexpression of RAB3B in dopaminergic neurons increases dopamine content, synaptic vesicle size, and presynaptic protein levels .
-
Toxin Resistance: Protects against 6-hydroxydopamine (6-OHDA) and proteasome inhibitors (e.g., MG-132) in vitro and in vivo .
Tissue Expression and Localization
RAB3B exhibits cytoplasmic staining in specific tissues, as per the Human Protein Atlas :
| Tissue | Cell Type | Protein Expression | Source |
|---|---|---|---|
| Pancreas | Islet cells | Moderate | |
| Prostate | Glandular cells | High | |
| Small Intestine | Enteroendocrine cells | Low | |
| Brain (Hippocampus) | Inhibitory interneurons | Enriched |
Diagnostic Biomarker
-
Cancer Detection: RAB3B distinguishes tumors from normal tissues with moderate accuracy (AUC >0.7) in 11 cancer types .
-
Tissue Microarray Validation: Consistent upregulation observed in six tumor types (e.g., BRCA, PAAD) .
Therapeutic Potential
Product Specs
Product Science Overview
RAB3B, a member of the RAS oncogene family, is a protein-coding gene that plays a crucial role in various cellular processes. This gene is particularly significant in the context of synaptic transmission and vesicular trafficking. The human recombinant form of RAB3B is produced using recombinant DNA technology, which allows for the expression of the protein in a controlled environment, typically in bacterial or mammalian cells.
The RAB3B gene is located on chromosome 1 and encodes a protein that is part of the RAB family of small GTPases. These proteins are involved in the regulation of vesicle trafficking, which is essential for the proper functioning of cellular processes. The RAB3B protein consists of 239 amino acids and has a molecular mass of approximately 26.9 kDa . It is characterized by its ability to bind GDP and GTP, which are critical for its function as a molecular switch in vesicle trafficking.
RAB3B is primarily involved in the regulation of synaptic vesicle cycle and vesicle size. It plays a significant role in the positive regulation of dopamine uptake involved in synaptic transmission . The protein is located in the perinuclear region of the cytoplasm and is an anchored component of the synaptic vesicle membrane. By binding to myosin V, RAB3B facilitates the transport of vesicles within the cell, ensuring that neurotransmitters are efficiently released at synaptic junctions.
The human recombinant form of RAB3B is produced in E. coli as a single, non-glycosylated polypeptide chain . The recombinant protein is fused to a 20 amino acid His-Tag at the N-terminus, which facilitates its purification using chromatographic techniques. The protein is supplied as a sterile filtered clear solution and is formulated in a buffer containing Tris-HCl, NaCl, DTT, and glycerol . This recombinant form is used in various research applications, including studies on vesicle trafficking, synaptic transmission, and potential therapeutic interventions.
