synaptic vesicle glycoprotein 2A | Atypical SLC22B subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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synaptic vesicle glycoprotein 2A

Target not currently curated in GtoImmuPdb

Target id: 2634

Nomenclature: synaptic vesicle glycoprotein 2A

Systematic Nomenclature: SLC22B1

Family: Atypical SLC22B subfamily

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 742 1q21.2 SV2A synaptic vesicle glycoprotein 2A
Mouse - 742 3 F2 Sv2a synaptic vesicle glycoprotein 2 a
Rat - 742 2q34 Sv2a synaptic vesicle glycoprotein 2a
Previous and Unofficial Names
SV2
Database Links
Specialist databases
Bioparadigms SLC Tables SLC22B1 (Hs)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
Galactose N/A - - 5

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Parameter Reference
levetiracetam Rn Inhibition 5.8 pKi 8
pKi 5.8 (Ki 1.58x10-6 M) [8]
brivaracetam Rn Inhibition 7.0 pIC50 2
pIC50 7.0 (IC50 1x10-7 M) [2]
Description: In vitro inhibitory activity against [3H](2S)-2-[4-(3-azidophenyl)-2-oxopyrrolidin-1-yl]butanamide binding to levetiracetam binding site, in rat brain homogenate.
levetiracetam Rn Inhibition 6.1 pIC50 2
pIC50 6.1 (IC50 7.94x10-7 M) [2]
Description: In vitro inhibitory activity against [3H](2S)-2-[4-(3-azidophenyl)-2-oxopyrrolidin-1-yl]butanamide binding to levetiracetam binding site, in rat brain homogenate
Tissue Distribution
Brain: highest in basal ganglia and thalamus. Located on subcellular membranes in transfected COS cells (by Western blot and immunohistochemistry).
Species:  Rat
Technique:  Northern blot
References:  1
Clinically-Relevant Mutations and Pathophysiology
Disease:  Epilepsy
Role: 
Drugs: 
References:  6,9-10
General Comments
SV2A (SCL22B1) has been identified as the brain binding-site for the antiepileptic drugs levetiracetam [3-4] and brivaracetam [7].

References

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1. Bajjalieh SM, Peterson K, Linial M, Scheller RH. (1993) Brain contains two forms of synaptic vesicle protein 2. Proc. Natl. Acad. Sci. U.S.A., 90 (6): 2150-4. [PMID:7681585]

2. Kenda BM, Matagne AC, Talaga PE, Pasau PM, Differding E, Lallemand BI, Frycia AM, Moureau FG, Klitgaard HV, Gillard MR et al.. (2004) Discovery of 4-substituted pyrrolidone butanamides as new agents with significant antiepileptic activity. J. Med. Chem., 47 (3): 530-49. [PMID:14736235]

3. Klitgaard H, Verdru P. (2007) Levetiracetam: the first SV2A ligand for the treatment of epilepsy. Expert Opin Drug Discov, 2 (11): 1537-45. [PMID:23484603]

4. Löscher W, Gillard M, Sands ZA, Kaminski RM, Klitgaard H. (2016) Synaptic Vesicle Glycoprotein 2A Ligands in the Treatment of Epilepsy and Beyond. CNS Drugs, 30 (11): 1055-1077. [PMID:27752944]

5. Madeo M, Kovács AD, Pearce DA. (2014) The human synaptic vesicle protein, SV2A, functions as a galactose transporter in Saccharomyces cerevisiae. J. Biol. Chem., 289 (48): 33066-71. [PMID:25326386]

6. Mendoza-Torreblanca JG, Vanoye-Carlo A, Phillips-Farfán BV, Carmona-Aparicio L, Gómez-Lira G. (2013) Synaptic vesicle protein 2A: basic facts and role in synaptic function. Eur. J. Neurosci., 38 (11): 3529-39. [PMID:24102679]

7. Nicolas JM, Hannestad J, Holden D, Kervyn S, Nabulsi N, Tytgat D, Huang Y, Chanteux H, Staelens L, Matagne A et al.. (2016) Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia, 57 (2): 201-9. [PMID:26663401]

8. Noyer M, Gillard M, Matagne A, Hénichart JP, Wülfert E. (1995) The novel antiepileptic drug levetiracetam (ucb L059) appears to act via a specific binding site in CNS membranes. Eur. J. Pharmacol., 286 (2): 137-46. [PMID:8605950]

9. Vogl C, Tanifuji S, Danis B, Daniels V, Foerch P, Wolff C, Whalley BJ, Mochida S, Stephens GJ. (2015) Synaptic vesicle glycoprotein 2A modulates vesicular release and calcium channel function at peripheral sympathetic synapses. Eur. J. Neurosci., 41 (4): 398-409. [PMID:25484265]

10. von Rosenstiel P. (2007) Brivaracetam (UCB 34714). Neurotherapeutics, 4 (1): 84-7. [PMID:17199019]

How to cite this page

Atypical SLC22B subfamily: synaptic vesicle glycoprotein 2A. Last modified on 27/11/2018. Accessed on 19/03/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2634.