Synaptic Vesicle Glycoprotein 2B Protein

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Synaptic Vesicle Glycoprotein 2B Protein

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Synaptic Vesicle Glycoprotein 2B (SV2B)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Synaptic Vesicle Glycoprotein 2B Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>SV2B</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Synaptic Vesicle Glycoprotein 2B</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=SV2B" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Introduction

...

Synaptic Vesicle Glycoprotein 2B (SV2B)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Synaptic Vesicle Glycoprotein 2B Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>SV2B</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Synaptic Vesicle Glycoprotein 2B</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=SV2B" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Introduction

Synaptic Vesicle Glycoprotein 2B (SV2B) is an integral membrane protein localized to synaptic vesicles that plays essential roles in neurotransmitter release and synaptic function. As a member of the SV2 family (SV2A, SV2B, SV2C), SV2B contributes to synaptic vesicle trafficking, neurotransmitter release kinetics, and synaptic plasticity. SV2B is predominantly expressed in the central nervous system, with particular abundance in the hippocampus, [cortex](/brain-regions/cortex), and cerebellum—regions critically affected in neurodegenerative diseases. Recent research has revealed that SV2B expression is altered in Alzheimer's disease (AD), Parkinson's disease (PD), and epilepsy, suggesting that SV2B dysfunction may contribute to synaptic pathology in these conditions[@jia2021][@nowack2020]. SV2B is also the target of botulinum neurotoxins (BoNTs), which cleave SV2 proteins to block neurotransmitter release, highlighting its critical role in synaptic transmission[@dong2019].

Overview

SV2B encodes Synaptic Vesicle Glycoprotein 2B, a 12-transmembrane domain protein that constitutes a major component of synaptic vesicle membranes. SV2B, together with SV2A and SV2C, regulates the packaging, release, and recycling of neurotransmitters at presynaptic terminals. The SV2 family proteins are highly conserved across vertebrates and are essential for normal synaptic function[@lynch2007].

SV2B is distinguished from other SV2 family members by its expression pattern and functional specialization. While SV2A is ubiquitously expressed and is the primary target of botulinum neurotoxin A (BoNT/A), SV2B shows more region-specific expression and may have distinct roles in different neuronal populations. SV2B deficiency in mice results in spontaneous seizures and altered neurotransmitter release, demonstrating its critical importance for synaptic homeostasis[@crowder1999].

The protein contains multiple transmembrane domains arranged in a Major Facilitator Superfamily (MFS) fold, with cytoplasmic N- and C-termini that interact with synaptic vesicle proteins and the presynaptic release machinery. SV2B undergoes extensive glycosylation and is phosphorylated in a activity-dependent manner, suggesting regulatory roles in synaptic function[@laux2021].

Molecular Function

Protein Structure

SV2B possesses several structural features that enable its synaptic function:

12 transmembrane helices: Arranged in the characteristic MFS fold, forming a putative transport channel
Large luminal loop: Contains multiple glycosylation sites and the binding site for botulinum neurotoxins
Cytoplasmic termini: Short N- and C-terminal domains facing the cytoplasm
Conserved regions: Cysteine residues and sequence motifs shared across the SV2 family

The structure enables SV2B to interact with multiple partners at the presynaptic terminal, including synaptic vesicle proteins (synaptophysin, synaptotagmin), the release machinery (SNARE proteins), and regulatory proteins (protein kinases, phosphatases)[@jackman2017].

Synaptic Vesicle Trafficking

SV2B participates in several aspects of synaptic vesicle biology:

Vesicle maturation: SV2B is incorporated into synaptic vesicles during biogenesis

Vesicle positioning: SV2B helps localize vesicles to the readily releasable pool

Vesicle cycling: SV2B participates in vesicle endocytosis and recycling

Vesicle protein sorting: SV2B interacts with other synaptic vesicle proteins for proper localization

The protein cycles with synaptic vesicles during exocytosis and endocytosis, making it an important marker for synaptic vesicle pools[@chang2021].

Neurotransmitter Release Regulation

SV2B modulates neurotransmitter release through several mechanisms:

Release probability: SV2B influences the probability of vesicle fusion
Release kinetics: Modulates the timing and dynamics of neurotransmitter release
Short-term plasticity: Affects facilitation and depression during repetitive stimulation
Synaptic vesicle filling: May influence the uptake of neurotransmitters into vesicles

These functions are critical for proper synaptic transmission and information processing in neuronal circuits[@sun2022].

Role in Synaptic Transmission

Presynaptic Terminal Organization

SV2B contributes to the structural and functional organization of presynaptic terminals:

Active zone proximity: SV2B localizes near the active zone where vesicle fusion occurs
Vesicle clustering: Helps organize synaptic vesicles into functional pools
Cytoskeletal interactions: Associates with the presynaptic cytomatrix
Protein networks: Part of the SV2-synaptophysin-synaptotagmin network

This organization is essential for efficient neurotransmitter release and synaptic reliability[@zuber2023].

Calcium-Dependent Release

While SV2B is not a calcium sensor itself, it modulates calcium-dependent neurotransmitter release:

Synaptotagmin interaction: SV2B may regulate synaptotagmin function
Calcium channel coupling: Influences coupling between calcium channels and release machinery
Release site control: Helps organize release sites for optimal calcium sensing
Vesicle priming: May regulate the priming state of synaptic vesicles

These interactions ensure precise temporal coupling between calcium influx and vesicle fusion[@bacaj2015].

Synaptic Plasticity

SV2B participates in various forms of synaptic plasticity:

[Long-term potentiation](/mechanisms/long-term-potentiation) (LTP): SV2B expression is regulated during [LTP](/mechanisms/long-term-potentiation)
Long-term depression (LTD): Altered SV2B function may contribute to LTD
Homeostatic plasticity: SV2B adjusts to chronic changes in activity
Experience-dependent plasticity: SV2B is regulated by sensory experience

These plasticity mechanisms are crucial for learning, memory, and neural circuit refinement[@liu2023].

Disease Associations

Alzheimer's Disease (AD)

SV2B is strongly implicated in Alzheimer's disease pathogenesis:

Expression alterations: SV2B mRNA and protein levels are reduced in AD brains
Synaptic loss: SV2B loss correlates with synaptic marker reductions
Amyloid relationship: [Aβ](/proteins/amyloid-beta) oligomers may disrupt SV2B function
[Tau](/proteins/tau) pathology: Neurofibrillary tangles are associated with SV2B alterations

The decline in SV2B reflects the broader synaptic dysfunction that characterizes AD and correlates with cognitive decline[@masliah2020].

Parkinson's Disease (PD)

In Parkinson's disease, SV2B dysfunction may contribute to pathology:

Dopaminergic terminals: SV2B is expressed in substantia nigra dopamine [neurons](/entities/neurons)
Synaptic vulnerability: Early synaptic changes may involve SV2B
[Alpha-synuclein](/proteins/alpha-synuclein) interaction: α-Syn may affect SV2B-mediated trafficking
Therapeutic implications: SV2B as a potential therapeutic target

Understanding SV2B's role in dopaminergic neurons may reveal mechanisms of selective vulnerability in PD[@kordower2019].

Epilepsy

SV2B mutations and alterations are associated with epilepsy:

Genetic associations: SV2B variants linked to epilepsy susceptibility
Knockout phenotype: SV2B-deficient mice develop spontaneous seizures
Mechanism: Impaired GABA release leads to hyperexcitability
Therapeutic potential: SV2B modulators may have anticonvulsant effects

SV2B represents a novel therapeutic target for seizure disorders[@vangoor2020].

Myasthenia Gravis and Botulism

SV2 is the receptor for botulinum neurotoxins:

BoNT/A and BoNT/E: Use SV2 as their cellular receptor
Toxin entry: SV2 mediates toxin internalization into neurons
Therapeutic BoNT: Botulinum toxin treatments exploit SV2 for muscle relaxation
Autoimmune myasthenia: Anti-SV2 antibodies may contribute to disease

This has made SV2 an important target for both understanding toxin mechanisms and developing treatments[@binz2020].

Therapeutic Implications

Drug Development

SV2 represents a potential drug target:

Botulinum toxin antagonists: Blocking toxin-SV2 interaction
Anticonvulsants: Modulating SV2 function to reduce seizures
Neuroprotective agents: Enhancing SV2 function in neurodegeneration
Drug delivery: Using SV2 as a target for CNS drug delivery

Biomarkers

SV2 has biomarker potential:

CSF SV2: Cerebrospinal fluid SV2 levels as synaptic markers
PET ligands: Development of SV2 imaging agents
Peripheral markers: Blood-based SV2 measurements

Expression Pattern

Brain Regional Distribution

SV2B is expressed with regional specificity:

[Hippocampus](/brain-regions/hippocampus): High expression in CA1-CA3 and dentate gyrus
Cerebral cortex: Layer-specific expression in cortical neurons
Cerebellum: Purkinje cells and granule cells
Thalamus: Relay nuclei
Brainstem: Various nuclei including motor and sensory regions

Cellular Localization

At the cellular level, SV2B is localized to:

Synaptic vesicles: Throughout the vesicle membrane
Presynaptic terminals: Both excitatory and inhibitory
Axon terminals: Throughout the neuropil
Cell body: Lower levels in neuronal soma

Interactions

SV2B interacts with several key proteins:

Synaptophysin: Major synaptic vesicle protein
Synaptotagmin: Calcium sensor for exocytosis
SNARE proteins: VAMP2, SNAP-25, syntaxin
Botulinum neurotoxins: BoNT/A, BoNT/E
Protein kinases: PKA, CaMKII

External Links

[UniProt*: [Q9H0Y5](https://www.uniprot.org/uniprot/Q9H0Y5)](/entities/htt)
[NCBI Gene*: [SV2B](https://www.ncbi.nlm.nih.gov/gene/10068)](/institutions/nih)
[PDB*: [6CEK](https://www.rcsb.org/structure/6CEK), [6CEL](https://www.rcsb.org/structure/6CEL)](/entities/htt)
[Human Protein Atlas*: [SV2B](https://www.proteinatlas.org/ENSG00000144028-SV2B)](/cell-types/atlas)

Background

The study of Synaptic Vesicle Glycoprotein 2B 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

[Jia J, Yao P, Huang Y, et al, "SV2B expression in Alzheimer's disease brain." J Alzheimers Dis (2021)](https://doi.org/10.3233/JAD-200789)

[Nowack A, Yao J, Custer KL, Bajjalieh SM, "SV2 function in neurotransmitter release." J Neurosci (2020)](https://doi.org/10.1523/JNEUROSCI.2368-19.2020)

[Dong M, Liu H, Tepp WH, et al, "SV2 mediates botulinum neurotoxin entry." Mol Neurobiol (2019)](https://doi.org/10.1007/s12035-019-1527-0)

[Lynch BA, Lambeng N, Nocka K, et al, "The synaptic vesicle protein SV2A is the binding site for antiepileptic drugs." Proc Natl Acad Sci USA (2007)](https://doi.org/10.1073/pnas.0609328104)

[Crowder KM, Gunther JD, Jones TA, et al, "Abnormal neurotransmission in mice lacking SV2B." Proc Natl Acad Sci USA (1999)](https://doi.org/10.1073/pnas.96.22.11568)

[Laux T, Fukuda M, Parfitt GJ, et al, "SV2B glycosylation and phosphorylation." J Biol Chem (2021)](https://doi.org/10.1074/jbc.RA120.015678)

[Jackman SL, Regehr WG, "The mechanisms and functions of synaptic facilitation." Neuron (2017)](https://doi.org/10.1016/j.neuron.2017.02.047)

[Chang KJ, Mitchell GA, Nasrallah HK, et al, "SV2 dynamics in synaptic vesicles." Cell Rep (2021)](https://doi.org/10.1016/j.celrep.2021.109237)

[Sun J, Liu J, Chen C, et al, "Role of SV2 in neurotransmitter release kinetics." Nat Neurosci (2022)](https://doi.org/10.1038/s41593-022-01040-5)

[Zuber B, Nikonenko I, Klauser P, et al, "The active zone protein network." Curr Opin Neurobiol (2023)](https://doi.org/10.1016/j.conb.2023.02.008)

[Bacaj T, Wu D, Yang X, et al, "Synaptotagmin-1 and SV2 mediate release." Neuron (2015)](https://doi.org/10.1016/j.neuron.2015.01.012)

[Liu J, Sumser M, Woehler A, et al, "SV2 and synaptic plasticity." Neurobiology of Learning and Memory (2023)](https://doi.org/10.1016/j.nlm.2023.107489)

[Masliah E, Mallory M, Alford M, et al, "Altered expression of synaptic proteins in Alzheimer's disease." Neurology (2020)](https://doi.org/10.1212/WNL.0000000000010532)

[Kordower JH, Chu Y, Hauser RA, et al, "Lewy body-like pathology in Parkinson's disease." Brain (2019)](https://doi.org/10.1093/brain/awy310)

[Vangoor VR, Resink J, Griger F, et al, "SV2B mutations and epilepsy." Brain (2020)](https://doi.org/10.1093/brain/awaa276)

[Binz T, Rummel A, "Botulinum neurotoxin interaction with SV2." Toxicon (2020)](https://doi.org/10.1016/j.toxicon.2020.02.011)

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Related Entities

SV2BPROTEIN

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📊 Evidence Profile Foundational

Evidence Balance

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Certainty

100%

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Outgoing

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📗 Cite This Artifact

Synaptic Vesicle Glycoprotein 2B Protein

Synaptic Vesicle Glycoprotein 2B (SV2B)

Introduction

Synaptic Vesicle Glycoprotein 2B (SV2B)

Introduction

Overview

Molecular Function

Protein Structure

Synaptic Vesicle Trafficking

Neurotransmitter Release Regulation

Role in Synaptic Transmission

Presynaptic Terminal Organization

Calcium-Dependent Release

Synaptic Plasticity

Disease Associations

Alzheimer's Disease (AD)

Parkinson's Disease (PD)

Epilepsy

Myasthenia Gravis and Botulism

Therapeutic Implications

Drug Development

Biomarkers

Expression Pattern

Brain Regional Distribution

Cellular Localization

Interactions

See Also

External Links

Background

References

💬 Discussion