This family of transporters has previously been classified as part of the atypical major facilitator superfamily (MSF) protein superfamily [1,8-11]. The atypical SLCs share sequence similarities and phylogenetic ancestry with other SLCs, and they have historically been classified in to subfamilies (also referred to as atypical MFS transporter families (AMTF1-15)) based on phylogenetic, sequence and structural analyses [9].

There are three human synaptic vesicle glycoprotein 2 family members, SV2A, SV2B and SV2C. They have transmembrane transporter activity and can be classified in to the SLC superfamily of solute carriers in subfamily SLC22, as SCL22B1, B2 and B3 respectively. SV2A (SCL22B1) has been identified as the brain binding-site for the antiepileptic drugs levetiracetam [3-4] and brivaracetam [6].

* Key recommended reading is highlighted with an asterisk

* 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]

* 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]

Perland E, Bagchi S, Klaesson A, Fredriksson R. (2017) Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression. Open Biol, 7 (9). [PMID:28878041]

1. Alexander SPH, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL et al.. (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters. Br J Pharmacol, 176 Suppl 1: S397-S493. [PMID:31710713]

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. 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]

7. 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]

8. Pao SS, Paulsen IT, Saier Jr MH. (1998) Major facilitator superfamily. Microbiol Mol Biol Rev, 62 (1): 1-34. [PMID:9529885]

9. Perland E, Bagchi S, Klaesson A, Fredriksson R. (2017) Characteristics of 29 novel atypical solute carriers of major facilitator superfamily type: evolutionary conservation, predicted structure and neuronal co-expression. Open Biol, 7 (9). [PMID:28878041]

10. Perland E, Fredriksson R. (2017) Classification Systems of Secondary Active Transporters. Trends Pharmacol Sci, 38 (3): 305-315. [PMID:27939446]

11. Reddy VS, Shlykov MA, Castillo R, Sun EI, Saier Jr MH. (2012) The major facilitator superfamily (MFS) revisited. FEBS J, 279 (11): 2022-35. [PMID:22458847]