Synaptic vesicle glycoprotein 2C (SV2C) is an N-glycosylated protein encoded by human SV2C gene. Homologous to the synaptic vesicle proteins SV2A and SV2B, SV2C is a new isoform of the synaptic vesicle 2 protein superfamily. SV2C is a receptor for botulinum neurotoxin A that is only concentrated on a small subset of synaptic vesicles in phylogenetically old brain areas. It is significant in the regulation of neurotransmitter release and synaptic transmission in the basal ganglia.
Basic Information of SV2C | |
Protein Name | Synaptic vesicle glycoprotein 2C |
Gene Name | SV2C |
Aliases | Synaptic Vesicle Glycoprotein 2C, Synaptic Vesicle Protein 2C |
Organism | Homo sapiens (Human) |
UniProt ID | Q496J9 |
Transmembrane Times | 12 |
Length (aa) | 727 |
Sequence | MEDSYKDRTSLMKGAKDIAREVKKQTVKKVNQAVDRAQDEYTQRSYSRFQDEEDDDDYYPAGETYNGEANDDEGSSEATEGHDEDDEIYEGEYQGIPSMNQAKDSIVSVGQPKGDEYKDRRELESERRADEEELAQQYELIIQECGHGRFQWALFFVLGMALMADGVEVFVVGFVLPSAETDLCIPNSGSGWLGSIVYLGMMVGAFFWGGLADKVGRKQSLLICMSVNGFFAFLSSFVQGYGFFLFCRLLSGFGIGGAIPTVFSYFAEVLAREKRGEHLSWLCMFWMIGGIYASAMAWAIIPHYGWSFSMGSAYQFHSWRVFVIVCALPCVSSVVALTFMPESPRFLLEVGKHDEAWMILKLIHDTNMRARGQPEKVFTVNKIKTPKQIDELIEIESDTGTWYRRCFVRIRTELYGIWLTFMRCFNYPVRDNTIKLTIVWFTLSFGYYGLSVWFPDVIKPLQSDEYALLTRNVERDKYANFTINFTMENQIHTGMEYDNGRFIGVKFKSVTFKDSVFKSCTFEDVTSVNTYFKNCTFIDTVFDNTDFEPYKFIDSEFKNCSFFHNKTGCQITFDDDYSAYWIYFVNFLGTLAVLPGNIVSALLMDRIGRLTMLGGSMVLSGISCFFLWFGTSESMMIGMLCLYNGLTISAWNSLDVVTVELYPTDRRATGFGFLNALCKAAAVLGNLIFGSLVSITKSIPILLASTVLVCGGLVGLCLPDTRTQVLM |
SV2C plays an important role in regulating secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. It regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles. It mainly has an influence on the diseases related to the nervous system including epilepsy, Parkinson's disease and schizophrenia, which related to dopaminergic dysfunction caused by disruption of SV2C. It serves as a receptor for botulinum neurotoxin/A (BoNT/A), regulating glucose-evoked granule recruitment and dopamine release. Another important role has been found for SV2C in the regulating of Ca2+ and catecholamines, which indicated that SV2C was associated with several non-nervous diseases such as hypertension, venous thromboembolism, and coagulation pathways.
Fig.1 Secondary structure of SV2C.
This article reviewed the function of Synaptic vesicle 2C. They systematically introduced three highly homologous isoforms of SV2 protein: SV2A, SV2B and SV2C, and mainly summarized important functions that have been reported. SV2C improved psychosis through regulating dopamine release and affects hypertension, venous thromboembolism, and coagulation pathways. However, specific mechanisms of these effects were needed to be investigated and elucidated.
The researchers identified SV2C as a mediator of dopamine homeostasis and disruption of SV2C could lead to Parkinson disease. But, expression of SV2C was significantly altered in postmortem brain tissue from Parkinson disease cases but not in Alzheimer disease.
This article confirmed the distribution of SV2C in the substantia nigra, ventral tegmental area, dorsal striatum, pallidum, and nucleus accumbens of rodent, rhesus macaque, and human by using a custom SV2C-specific antiserum. And SV2C was closely related to dopamine and basal ganglia function.
This article indicated that glycosylated human SV2C was the neuronal receptor of the BoNT/A1, and the neuronal tropism of BoNT/A1 did not exist without recognition of both the peptide moiety and an N-linked glycan on SV2.
This article reported that knock-out of SV2C could lead to significant increase expression of tyrosine hydroxylase mRNA and decrease expression of enkephalin mRNA. They draw a conclusion that SV2C was important in the basal ganglia network.
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