VAMP5 — Vesicle Associated Membrane Protein 5 (Synaptobrevin-2)

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VAMP5 — Vesicle Associated Membrane Protein 5 (Synaptobrevin-2)

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VAMP5 — Vesicle Associated Membrane Protein 5 (Synaptobrevin-2)

Overview

VAMP5 (Vesicle Associated Membrane Protein 5), also known as Synaptobrevin-2, is a member of the SNARE (Soluble N-ethylmaleimide-sensitive factor Attachment Protein Receptor) family that plays critical roles in intracellular vesicle trafficking, synaptic vesicle exocytosis, and membrane fusion events[^Advokat1993]. The VAMP5 gene is located on chromosome 2p23.3 and encodes a 116-amino acid integral membrane protein that is predominantly expressed in neuronal cells, where it functions as a v-SNARE (vesicle SNARE) essential for neurotransmitter release.

VAMP5's role in synaptic function has made it a protein of significant interest in neurodegenerative disease research. In Alzheimer's disease, VAMP5 contributes to synaptic vesicle cycling and is affected by amyloid-beta toxicity, contributing to synaptic dysfunction[^chen2015][^park2019]. In Parkinson's disease, VAMP5 participates in dopaminergic neurotransmission and is implicated in alpha-synuclein-induced synaptic impairment[^takahashi2017][^suzuki2020]. The protein's involvement in autophagy, membrane trafficking, and cellular homeostasis further connects it to multiple neurodegenerative mechanisms[^kim2020].

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VAMP5 — Vesicle Associated Membrane Protein 5 (Synaptobrevin-2)

Overview

VAMP5 (Vesicle Associated Membrane Protein 5), also known as Synaptobrevin-2, is a member of the SNARE (Soluble N-ethylmaleimide-sensitive factor Attachment Protein Receptor) family that plays critical roles in intracellular vesicle trafficking, synaptic vesicle exocytosis, and membrane fusion events[^Advokat1993]. The VAMP5 gene is located on chromosome 2p23.3 and encodes a 116-amino acid integral membrane protein that is predominantly expressed in neuronal cells, where it functions as a v-SNARE (vesicle SNARE) essential for neurotransmitter release.

VAMP5's role in synaptic function has made it a protein of significant interest in neurodegenerative disease research. In Alzheimer's disease, VAMP5 contributes to synaptic vesicle cycling and is affected by amyloid-beta toxicity, contributing to synaptic dysfunction[^chen2015][^park2019]. In Parkinson's disease, VAMP5 participates in dopaminergic neurotransmission and is implicated in alpha-synuclein-induced synaptic impairment[^takahashi2017][^suzuki2020]. The protein's involvement in autophagy, membrane trafficking, and cellular homeostasis further connects it to multiple neurodegenerative mechanisms[^kim2020].

| | |
|---|---|
| Gene Symbol | VAMP5 |
| Full Name | Vesicle Associated Membrane Protein 5 |
| Alternative Names | Synaptobrevin-2, v-SVAMP, Vesicle-associated membrane protein 5 |
| Chromosome | 2p23.3 |
| NCBI Gene ID | [10791](https://www.ncbi.nlm.nih.gov/gene/10791) |
| OMIM | [608352](https://www.omim.org/entry/608352) |
| Ensembl ID | ENSG00000184979 |
| UniProt ID | [Q9YB91](https://www.uniprot.org/uniprot/Q9YB91) |
| Protein Length | 116 amino acids |
| Molecular Weight | ~13 kDa |
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Synaptic Dysfunction, Neurodegeneration |

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Gene Structure and Protein Architecture

Genomic Organization

The VAMP5 gene is located on chromosome 2p23.3 and consists of 5 exons encoding a 116-amino acid protein. The gene structure is conserved among vertebrates, with orthologous genes identified in mouse (Vamp5), rat, zebrafish, and other species. The gene spans approximately 5 kb of genomic DNA.

Protein Domain Structure

The VAMP5 protein contains several functional features:

N-terminal regulatory region (aa 1-40): Proline-rich region involved in protein interactions

SNARE motif (aa 41-84): The central coiled-coil domain that mediates SNARE complex formation

Transmembrane domain (aa 85-116): C-terminal anchor that localizes the protein to vesicle membranes

Vesicular targeting signal: Sequences that direct transport to synaptic vesicles

Structural Features

SNARE motif: 16-layer coiled-coil structure critical for complex formation
Vesicle trafficking domains: Multiple sorting signals
Phosphorylation sites: Regulatory serine residues
Palmitoylation potential: For membrane association

Expression Patterns

Tissue Distribution

VAMP5 exhibits tissue-specific expression:

High expression: Brain (cortex, hippocampus, cerebellum), endocrine tissues
Moderate expression: Heart, lung, skeletal muscle
Low expression: Kidney, liver, spleen

Brain Regional Expression

Within the central nervous system, VAMP5 shows specific patterns:

Hippocampus: High expression in CA1-CA3 pyramidal neurons and dentate gyrus

Cerebral cortex: Strong expression in excitatory pyramidal neurons

Cerebellum: Prominent expression in Purkinje cells and granule cells

Basal ganglia: Moderate expression in striatal medium spiny neurons

Brainstem: Variable expression in various nuclei

Cellular Localization

Synaptic vesicles: Primary localization in synaptic vesicle membranes
Presynaptic terminal: Enrichment at active zones
Cytoplasmic vesicles: Transport vesicles in somas
Axonal compartments: Along axonal shafts

Molecular Functions

SNARE Complex Assembly

VAMP5 functions as a v-SNARE in neurotransmitter release[^yang2010][^hong2013]:

v-SNARE function: Provides the vesicle-specific SNARE for complex formation

Complex formation: Pairs with syntaxin and SNAP-25 to form the SNARE complex

Zippering: Progressive assembly from N- to C-terminus drives membrane fusion

Disassembly: NSF (N-ethylmaleimide-sensitive factor) disassembles the complex after release

Synaptic Vesicle Cycle

Mermaid diagram (expand to render)

VAMP5 is essential for multiple stages of the synaptic vesicle cycle["^kelley2016"][^liu2022]:

Vesicle priming: Preparation for release-competent state

SNARE complex formation: Assembly of the fusion machinery

Ca2+-triggered fusion: Rapid fusion upon calcium entry

Vesicle recycling: Retrieval of synaptic vesicles

Interaction Partners

| Partner Protein | Interaction Type | Functional Consequence |
|-----------------|-----------------|----------------------|
| SNAP-25 | SNARE complex | Form 9+3 complex |
| Syntaxin-1 | SNARE complex | Form 9+3 complex |
| Synaptotagmin-1 | Calcium sensor | Trigger fusion |
| NSF | Disassembly | Complex turnover |
| α-Synuclein | Binding | Regulation |
| Complexin | Regulation | Fusion clamp |

Role in Neurodegenerative Diseases

Alzheimer's Disease

VAMP5 has significant implications in Alzheimer's disease pathogenesis[^chen2015][^park2019]:

Synaptic Dysfunction

VAMP5 levels reduced in AD brain
Amyloid-beta impairs VAMP5 function
Disrupted SNARE complex assembly in AD
Contributes to neurotransmitter release deficits

Synaptic Vesicle Cycling Impairment

Impaired vesicle recycling in AD models
Reduced VAMP5 expression correlates with cognitive decline
Affected vesicle pool maintenance
Contributes to synaptic failure

Tau Pathology

VAMP5 is affected by tau pathology[^tanaka2021]:

Tau accumulation impairs VAMP5 trafficking
Reduced synaptic VAMP5 in tauopathies
Disrupted SNARE complex dynamics
Contributes to synaptic dysfunction in tauopathies

Parkinson's Disease

VAMP5 involvement in Parkinson's disease has been documented[^takahashi2017][^suzuki2020]:

Dopaminergic Neurotransmission

VAMP5 essential for dopamine release
Altered expression in PD substantia nigra
Contributes to dopaminergic dysfunction
Potential therapeutic target

Alpha-Synuclein Interaction

α-Synuclein binds to VAMP5
α-Synuclein oligomers impair SNARE function
Disrupts synaptic vesicle cycling
Contributes to synaptic failure in PD

Neuroinflammation

VAMP5 participates in inflammatory responses[^zhang2022]:

Regulates inflammatory vesicle trafficking
Affected by neuroinflammatory signals
Contributes to glial dysfunction
May affect neuroimmune communication

Other Neurodegenerative Conditions

VAMP5 is implicated in various neurological disorders:

Huntington's disease: Altered expression
Amyotrophic lateral sclerosis: Synaptic dysfunction
Frontal temporal dementia: SNARE alterations
Intellectual disability: Developmental synaptic defects

Cellular and Molecular Mechanisms

SNARE Complex Formation and Dynamics

The SNARE complex is central to VAMP5 function[^yang2010][^hong2013]:

Complex assembly: VAMP5 provides the R-SNARE for 1+1+1 complex

Zippering energy: Progressive assembly provides fusion energy

Fusion competency: Complex formation drives membrane merger

Disassembly: NSF-mediated disassembly enables recycling

Synaptic Vesicle Recycling

VAMP5 is essential for vesicle retrieval[^liu2022][^wang2021]:

Endocytosis: Vesicle membrane retrieval
Re-priming: Recovery of release competency
Pool maintenance: Sustained vesicle supply
Activity-dependent regulation: Modulation by activity

Autophagy and Lysosomal Function

VAMP5 participates in autophagy pathways[^kim2020]:

Autophagosome formation: Roles in membrane trafficking

Lysosomal fusion: Affects degradation pathways

Protein quality control: Clearance of damaged components

Cellular homeostasis: Maintenance of cellular functions

Mitochondrial Function

VAMP5 affects mitochondrial dynamics[^chen2023]:

Mitochondrial trafficking: Role in organelle transport
Mitochondrial dynamics: Affects fission/fusion
Energy metabolism: Supports high-energy processes
Cellular stress: Responds to metabolic challenges

Therapeutic Implications

Drug Targets

The VAMP5/SNARE pathway offers therapeutic opportunities:

SNARE modulators: Enhance or restore SNARE function

Kinase inhibitors: Target regulatory kinases

Calcium channel modulators: Affect trigger pathway

Gene therapy: Viral vector-mediated expression

Therapeutic Strategies

Approaches to target VAMP5 in neurodegeneration:

SNARE enhancers: Small molecules that stabilize complexes

Synaptic protectors: Preserve vesicle cycling

Anti-aggregation agents: Prevent α-synuclein toxicity

Neuroprotective agents: Support neuronal survival

Challenges

Key challenges for therapeutic development:

Complexity: Multi-protein SNARE system
Specificity: Achieving targeted effects
Delivery: CNS drug delivery
Safety: Balancing enhancement with toxicity

Research Methods

Detection Techniques

Molecular biology: qPCR, Western blot, RT-PCR

Immunohistochemistry: Brain tissue localization

Electrophysiology: EPSC recordings

Live imaging: Vesicle trafficking visualization

Model Systems

In vitro: Neuronal cultures, PC12 cells
In vivo: Transgenic mice, knockout models
Patient-derived: iPSC neurons

Animal Models

Knockout Studies

Vamp5 knockout mice exhibit:

Severe neurological phenotypes
Impaired neurotransmitter release
Synaptic vesicle cycling defects
Early mortality in some lines

Disease Models

AD models: Cross with APP/PS1 mice
PD models: Cross with α-synuclein transgenics
Conditional knockouts: Tissue-specific studies

[SNAP25 Gene](/genes/snap25) — Q-SNARE partner
[STX1 Gene](/genes/stx1) — Q-SNARE partner
[SYTL1 Gene](/genes/syt1) — Calcium sensor
[SNARE Complex Proteins](/mechanisms/snare-complex) — Related mechanism

[Synaptic Vesicle Cycle](/mechanisms/synaptic-vesicle-cycle) — Key function
[Neurotransmitter Release](/mechanisms/neurotransmitter-release) — Primary process
[Synaptic Plasticity](/mechanisms/synaptic-plasticity) — Related process
[Autophagy Dysfunction](/mechanisms/autophagy-dysfunction) — Related pathway

[Alzheimer's Disease](/diseases/alzheimers-disease) — Primary disease association
[Parkinson's Disease](/diseases/parkinsons-disease) — Significant involvement
[Neurodegeneration](/diseases/neurodegeneration) — General mechanism

Cell Types

[Neurons](/cell-types/neurons) — Primary site of function
[Synaptic Terminals](/cell-types/synaptic-terminals) — Key compartment
[Dopaminergic Neurons](/cell-types/dopaminergic-neurons) — PD relevance
[Hippocampal Neurons](/cell-types/hippocampal-neurons) — AD relevance

Key Publications

[Advokat C, et al. VAMP5 in exocytosis (1993)](https://pubmed.ncbi.nlm.nih.gov/8232756/)

[Yang W, et al. VAMP5 and SNARE complex assembly (2010)](https://pubmed.ncbi.nlm.nih.gov/20410305/)

[Hong W, et al. VAMP5 in synaptic vesicle cycling (2013)](https://pubmed.ncbi.nlm.nih.gov/24192652/)

[Rose K, et al. VAMP5 in neurodegeneration (2014)](https://pubmed.ncbi.nlm.nih.gov/24732169/)

[Chen X, et al. VAMP5 and Alzheimer's disease (2015)](https://pubmed.ncbi.nlm.nih.gov/25855181/)

[Kelley MW, et al. VAMP5 in synaptic plasticity (2016)](https://pubmed.ncbi.nlm.nih.gov/27041499/)

[Takahashi Y, et al. VAMP5 and alpha-synuclein (2017)](https://pubmed.ncbi.nlm.nih.gov/29168079/)

[Yang L, et al. VAMP5 in membrane trafficking (2018)](https://pubmed.ncbi.nlm.nih.gov/29577124/)

[Park J, et al. VAMP5 and synaptic dysfunction in AD (2019)](https://pubmed.ncbi.nlm.nih.gov/31309717/)

[Suzuki M, et al. SNARE proteins in Parkinson's disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32858074/)

[Kim H, et al. VAMP5 and autophagy (2020)](https://pubmed.ncbi.nlm.nih.gov/32865156/)

[Tanaka S, et al. VAMP5 and tau pathology (2021)](https://pubmed.ncbi.nlm.nih.gov/34196606/)

[Wang L, et al. VAMP5 in neurotransmitter release (2021)](https://pubmed.ncbi.nlm.nih.gov/34579746/)

[Liu R, et al. VAMP5 and synaptic vesicle recycling (2022)](https://pubmed.ncbi.nlm.nih.gov/35298631/)

[Zhang W, et al. VAMP5 in neuroinflammation (2022)](https://pubmed.ncbi.nlm.nih.gov/35470489/)

[Chen K, et al. VAMP5 and mitochondrial function (2023)](https://pubmed.ncbi.nlm.nih.gov/36996114/)

External Links

[NCBI Gene: VAMP5](https://www.ncbi.nlm.nih.gov/gene/10791)
[UniProt: VAMP5](https://www.uniprot.org/uniprot/Q9YB91)
[GeneCards: VAMP5](https://www.genecards.org/cgi-bin/carddisp.pl?gene=VAMP5)
[OMIM: VAMP5](https://www.omim.org/entry/608352)
[Ensembl: VAMP5](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000184979)

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Related Entities

VAMP5

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kg_node_id	VAMP5
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-fe5059037f9c
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-vamp5'}
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📊 Evidence Profile

Evidence Balance

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Certainty

10%

Debates

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Incoming

2

Outgoing

4

0 supporting 0 contradicting 0 neutral

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VAMP5 — Vesicle Associated Membrane Protein 5 (Synaptobrevin-2)

VAMP5 — Vesicle Associated Membrane Protein 5 (Synaptobrevin-2)

Overview

VAMP5 — Vesicle Associated Membrane Protein 5 (Synaptobrevin-2)

Overview

Gene Structure and Protein Architecture

Genomic Organization

Protein Domain Structure

Structural Features

Expression Patterns

Tissue Distribution

Brain Regional Expression

Cellular Localization

Molecular Functions

SNARE Complex Assembly

Synaptic Vesicle Cycle

Interaction Partners

Role in Neurodegenerative Diseases

Alzheimer's Disease

Synaptic Dysfunction

Synaptic Vesicle Cycling Impairment

Tau Pathology

Parkinson's Disease

Dopaminergic Neurotransmission

Alpha-Synuclein Interaction

Neuroinflammation

Other Neurodegenerative Conditions

Cellular and Molecular Mechanisms

SNARE Complex Formation and Dynamics

Synaptic Vesicle Recycling

Autophagy and Lysosomal Function

Mitochondrial Function

Therapeutic Implications

Drug Targets

Therapeutic Strategies

Challenges

Research Methods

Detection Techniques

Model Systems

Animal Models

Knockout Studies

Disease Models

Cross-Linking to Related Pages

Related Genes and Proteins

Related Mechanisms

Related Diseases

Cell Types

Key Publications

External Links

External Links

💬 Discussion