Synaptic vesicle glycoprotein 2A of the Major Facilitator Superfamily of transporters
Synaptic vesicle glycoprotein 2 (SV2) is a transporter-like integral membrane glycoprotein, with 12 transmembrane regions, expressed in vertebrates and is localized to synaptic and endocrine secretory vesicles. Three isoforms have been identified, SV2A, SV2B, and SV2C. SV2A and SV2B are widely expressed in the brain, while SV2C is more restricted to evolutionarily older brain. SV2 isoforms have been shown to be critical for the proper function of the central nervous system. SV2 serves as the receptor for botulinum neurotoxin A (BoNT/A), one of seven neurotoxins produced by the bacterium Clostridium botulinum. BoNT/A blocks neurotransmitter release by cleaving synaptosome-associated protein of 25 kD (SNAP-25) within presynaptic nerve terminals. It is unclear how SV2A is involved in correct SV function, but it has been suggested to either act as a transporter or a regulator of exocytosis by mediating Ca2+ dynamics. SV2A has been identified as the molecular target of the antiepileptic drug levetiracetam (LEV). Its expression is decreased in patients with epilepsy and in epileptic animal models. SV2A belongs to the Metazoan Synaptic Vesicle Glycoprotein 2 (SV2) and related small molecule transporter family (SV2-like) of the Major Facilitator Superfamily (MFS) of membrane transport proteins. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
Feature 1:putative chemical substrate binding pocket [chemical binding site]
Evidence:
Comment:based on the structures of MFS transporters with bound substrates, substrate analogs, and/or inhibitors
Comment:since MFS proteins facilitate the transport of many different substrates including ions, sugar phosphates, drugs, neurotransmitters, nucleosides, amino acids, and peptides, the residues involved in substrate binding may not be strictly conserved among superfamily members
Comment:the substrate binding site or translocation pore has access to both sides of the membrane in an alternating fashion through a conformational change of the MFS transporter
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