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synaptic vesicle glycoprotein 2A

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Target id: 2634

Nomenclature: synaptic vesicle glycoprotein 2A

Systematic Nomenclature: SLC22B1

Family: Atypical SLC22B subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 12 742 1q21.2 SV2A synaptic vesicle glycoprotein 2A
Mouse 12 742 3 F2.1 Sv2a synaptic vesicle glycoprotein 2a
Rat 12 742 2q34 Sv2a synaptic vesicle glycoprotein 2a
Previous and Unofficial Names Click here for help
SV2 | synaptic vesicle glycoprotein 2 a
Database Links Click here for help
Specialist databases
Bioparadigms SLC Tables SLC22B1 (Hs)
RESOLUTE SV2A (Hs)
Other databases
Alphafold Q7L0J3 (Hs), Q9JIS5 (Mm), Q02563 (Rn)
ChEMBL Target CHEMBL1998 (Hs), CHEMBL4381 (Rn)
DrugBank Target Q7L0J3 (Hs)
Ensembl Gene ENSG00000159164 (Hs), ENSMUSG00000038486 (Mm), ENSRNOG00000021182 (Rn)
Entrez Gene 9900 (Hs), 64051 (Mm), 117559 (Rn)
Human Protein Atlas ENSG00000159164 (Hs)
KEGG Gene hsa:9900 (Hs), mmu:64051 (Mm), rno:117559 (Rn)
OMIM 185860 (Hs)
Pharos Q7L0J3 (Hs)
RefSeq Nucleotide NM_014849 (Hs), NM_022030 (Mm), NM_057210 (Rn)
RefSeq Protein NP_055664 (Hs), NP_071313 (Mm), NP_476558 (Rn)
UniProtKB Q7L0J3 (Hs), Q9JIS5 (Mm), Q02563 (Rn)
Wikipedia SV2A (Hs)
Substrates and Reaction Kinetics Click here for help
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 Value Parameter Reference
levetiracetam Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Rn Inhibition 5.8 pKi 8
⤷ pKi 5.8 (Ki 1.58x10-6 M) [8]
brivaracetam Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure 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 Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure 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 Click here for help
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 Click here for help
Disease:  Epilepsy
Role:  SV2A is a widely distributed CNS protein believed to be involved in the abnormal coordination of synaptic vesicle exocytosis and neurotransmitter release underlying pathological brain activity in epileptic seizure. The exact mechanism has yet to be defined.
Drugs:  levetiracetam and brivaracetam
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 USA, 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]

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