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synaptic vesicle glycoprotein 2A (SV2A, KIAA0736, PSEC0174)
Function:
1) control of regulated secretion in neural & endocrine cell
- selectively enhances low-frequency neurotransmission
2) positively regulates vesicle fusion
- maintains readily releasable pool of secretory vesicles
3) interacts with SYT1/synaptotagmin-1 (Ca+2-dependent)
4) binds adapter protein complex AP-2
5) phosphorylation by CK1 of the N-terminal cytoplasmic domain regulates interaction with SYT1
6) N-glycosylated
7) brain binding-site for the antiepileptic drug levetiracetam
Compartment:
- cytoplasmic vesicle, secretory vesicle, synaptic vesicle, synaptic vesicle membrane
- enriched in chromaffin granules
- not present in adrenal microsomes
- associated with both insulin granules & synaptic-like microvesicles in insulin-secreting cells of the pancreas
Alternative splicing: named isoforms=2
Expression:
- neurons: expressed in virtually all synapses [2]
Radiology:
- 11C-UCB-J-PET imaging (SV2A) may provide a direct measure of synaptic density [2]
* 11C-UCB-J-PET apparently an SV2A analog [2]
Related
levetiracetam (Keppra, Etiracetam, Spritam)
General
phosphoprotein
transmembrane 12 protein
Properties
SIZE: MW = 83 kD
entity length = 742 aa
COMPARTMENT: cytoplasm
MOTIF: cytoplasmic domain {1-169}
MOTIF: binding site
SITE: 1-57
FOR-BINDING-OF: synaptotagmin-1
Ser phosphorylation site {S127}
transmembrane domain {170-190}
exoplasmic loop {191-205}
transmembrane domain {206-226}
cytoplasmic loop {227-233}
transmembrane domain {234-254}
exoplasmic loop {255-262}
transmembrane domain {263-283}
cytoplasmic loop {284-294}
transmembrane domain {295-315}
exoplasmic loop {316-334}
transmembrane domain {335-355}
cytoplasmic loop {356-447}
transmembrane domain {448-468}
exoplasmic loop {469-598}
MOTIF: N-glycosylation site {N498}
N-glycosylation site {N548}
N-glycosylation site {N573}
transmembrane domain {599-619}
cytoplasmic loop {620-626}
transmembrane domain {627-647}
exoplasmic loop {648-651}
transmembrane domain {652-672}
cytoplasmic loop {673-685}
transmembrane domain {686-708}
exoplasmic loop {709-712}
transmembrane domain {713-731}
cytoplasmic domain {732-742}
Database Correlations
OMIM 185860
UniProt Q7L0J3
Pfam PF07690
References
- UniProt :accession Q7L0J3
- Chen MK, Mecca AP, Naganawa M et al
Assessing Synaptic Density in Alzheimer Disease With Synaptic
Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging.
JAMA Neurol. Published online July 16, 2018.
PMID: 30014145
https://jamanetwork.com/journals/jamaneurology/fullarticle/2687472
- Mormino EC, Jagust WJ.
A New Tool for Clinical Neuroscience - Synaptic Imaging.
JAMA Neurol. Published online July 16, 2018
PMID: 30014142
https://jamanetwork.com/journals/jamaneurology/fullarticle/2687466