UniProtKB - Q02563 (SV2A_RAT)
Protein
Synaptic vesicle glycoprotein 2A
Gene
Sv2a
Organism
Rattus norvegicus (Rat)
Status
Functioni
Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles.
(Microbial infection) Receptor for C.botulinum neurotoxin type A (BoNT/A, botA); the toxin binds via extracellular loop 4 (PubMed:16543415). Restores uptake of BoNT/A in mouse cells that are deleted for SV2 receptor (PubMed:16543415, PubMed:18815274). Glycosylation of Asn-573 is not essential for receptor activity, but enhances uptake (PubMed:18815274, PubMed:19650874). Also serves as a receptor for the closely related C.botulinum neurotoxin type A2; glycosylation is not essential but enhances the interaction (PubMed:29649119).4 Publications
Possible receptor for C.botulinum neurotoxin type D (BoNT/D, botD); BoNT/D does not bind to extracellular loop 4 as do BoNT/A and BoNT/E, nor to loop 1 or loop 3 (PubMed:21483489). Another group does not find a convincing interaction with SV2 (PubMed:21632541).2 Publications
(Microbial infection) Receptor for C.botulinum neurotoxin type E (BoNT/E); the toxin probably binds via extracellular loop 4 and requires glycosylation of Asn-573 (PubMed:18815274, PubMed:19650874). Restores uptake of BoNT/E in mouse cells that are deleted for SV2 receptor (PubMed:18815274).2 Publications
(Microbial infection) Receptor for C.botulinum neurotoxin type F (BoNT/F) (PubMed:19476346, PubMed:19650874). Binding requires glycosylation of Asn-573 (PubMed:19476346).1 Publication1 Publication
Miscellaneous
Identified as the brain binding-site for the antiepileptic drug levetiracetam/lev.
Caution
The use of this protein as a coreceptor for C.botulinum type D (BoNT/D, botD) is controversial. In double SV2A/SV2B knockout mice BoNT/D does not degrade its synaptobrevin target; introducing SV2A, SV2B or SV2C restores target cleavage (PubMed:21483489). However another group does not find a convincing interaction with SV2 (PubMed:21632541).2 Publications
GO - Molecular functioni
- protein kinase binding Source: RGD
- transmembrane transporter activity Source: InterPro
GO - Biological processi
- cellular calcium ion homeostasis Source: RGD
- neurotransmitter transport Source: RGD
- regulation of gamma-aminobutyric acid secretion Source: RGD
- synaptic vesicle priming Source: RGD
Keywordsi
Molecular function | Receptor |
Biological process | Neurotransmitter transport, Transport |
Protein family/group databases
TCDBi | 2.A.1.22.1, the major facilitator superfamily (mfs) |
Names & Taxonomyi
Protein namesi | Recommended name: Synaptic vesicle glycoprotein 2AShort name: Synaptic vesicle protein 2 Short name: Synaptic vesicle protein 2A |
Gene namesi | Name:Sv2a Synonyms:Sv2 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 619715, Sv2a |
Subcellular locationi
Other locations
- presynapse By similarity
- synaptic vesicle membrane 3 Publications; Multi-pass membrane protein 3 Publications
Note: Enriched in chromaffin granules, not present in adrenal microsomes. Associated with both insulin granules and synaptic-like microvesicles in insulin-secreting cells of the pancreas. Colocalizes with ATP2B1 at photoreceptor synaptic terminals.By similarity2 Publications
Endoplasmic reticulum
- endoplasmic reticulum Source: Ensembl
Other locations
- cell-cell junction Source: RGD
- dendrite Source: RGD
- GABA-ergic synapse Source: RGD
- glutamatergic synapse Source: RGD
- integral component of membrane Source: RGD
- integral component of synaptic vesicle membrane Source: SynGO
- neuromuscular junction Source: RGD
- neuron projection Source: RGD
- neuronal cell body Source: RGD
- presynaptic active zone Source: UniProtKB
- synapse Source: MGI
- synaptic vesicle Source: SynGO
- synaptic vesicle membrane Source: RGD
- terminal bouton Source: ParkinsonsUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 169 | CytoplasmicSequence analysisAdd BLAST | 169 | |
Transmembranei | 170 – 190 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 191 – 205 | ExtracellularSequence analysis1 PublicationAdd BLAST | 15 | |
Transmembranei | 206 – 226 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 227 – 233 | CytoplasmicSequence analysis | 7 | |
Transmembranei | 234 – 254 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 255 – 262 | ExtracellularSequence analysis | 8 | |
Transmembranei | 263 – 283 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 284 – 294 | CytoplasmicSequence analysisAdd BLAST | 11 | |
Transmembranei | 295 – 315 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 316 – 334 | ExtracellularSequence analysis1 PublicationAdd BLAST | 19 | |
Transmembranei | 335 – 355 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 356 – 447 | CytoplasmicSequence analysisAdd BLAST | 92 | |
Transmembranei | 448 – 468 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 469 – 598 | ExtracellularSequence analysis2 PublicationsAdd BLAST | 130 | |
Transmembranei | 599 – 619 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 620 – 626 | CytoplasmicSequence analysis | 7 | |
Transmembranei | 627 – 647 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 648 – 651 | ExtracellularSequence analysis | 4 | |
Transmembranei | 652 – 672 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 673 – 685 | CytoplasmicSequence analysisAdd BLAST | 13 | |
Transmembranei | 686 – 708 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 709 – 712 | ExtracellularSequence analysis | 4 | |
Transmembranei | 713 – 731 | HelicalSequence analysisAdd BLAST | 19 | |
Topological domaini | 732 – 742 | CytoplasmicSequence analysisAdd BLAST | 11 |
Keywords - Cellular componenti
Cell junction, Cell projection, Cytoplasmic vesicle, Membrane, SynapsePathology & Biotechi
Disruption phenotypei
Short hairpin-mediated RNA knockdown of the protein in PC12 cells leads to increased resistance to C.botulinum neurotoxin type A (BoNT/A, botA) as assayed by reduced SNAP25 cleavage; uptake and degradation are restored by expression of SV2B or SV2C (PubMed:16543415).1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 196 – 200 | Missing : No change in uptake of C.botulinum neurotoxin type D (BoNT/D, botD) or C.botulinum neurotoxin type E (BoNT/E). 1 Publication | 5 | |
Mutagenesisi | 321 – 331 | Missing : No change in uptake of BoNT/D or BoNT/E. 1 PublicationAdd BLAST | 11 | |
Mutagenesisi | 498 | N → Q: No change in uptake of BoNT/E or C.botulinum neurotoxin type A (BoNT/A, botA) by mouse SV2A/SV2B knockout neurons; SV2A apparent molecular weight decreases. No change in uptake of BoNT/E; when associated with Q-548. No change in uptake of BoNT/D. 2 Publications | 1 | |
Mutagenesisi | 548 | N → Q: No change in uptake of BoNT/E or BoNT/A by mouse SV2A/SV2B knockout neurons; SV2A apparent molecular weight decreases. No change in uptake of BoNT/E; when associated with Q-498. No change in uptake of BoNT/D. 2 Publications | 1 | |
Mutagenesisi | 570 – 573 | RLVN → TLVQ: Restores apparent molecular weight to wild-type, does not restore uptake of BoNT/E. 1 Publication | 4 | |
Mutagenesisi | 573 | N → Q: BoNT/E not taken up by mouse SV2A/SV2B knockout neurons, decreased uptake of BoNT/A; SV2A apparent molecular weight decreases. No change in uptake of BoNT/D. 2 Publications | 1 |
Chemistry databases
ChEMBLi | CHEMBL4381 |
DrugCentrali | Q02563 |
GuidetoPHARMACOLOGYi | 2634 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000084882 | 1 – 742 | Synaptic vesicle glycoprotein 2AAdd BLAST | 742 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 80 | PhosphoserineBy similarity | 1 | |
Modified residuei | 81 | PhosphoserineBy similarity | 1 | |
Modified residuei | 84 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 127 | PhosphoserineCombined sources | 1 | |
Modified residuei | 393 | PhosphoserineCombined sources | 1 | |
Modified residuei | 480 | PhosphotyrosineBy similarity | 1 | |
Glycosylationi | 498 | N-linked (GlcNAc...) asparagineSequence analysis1 Publication | 1 | |
Glycosylationi | 548 | N-linked (GlcNAc...) asparagineSequence analysis1 Publication | 1 | |
Glycosylationi | 573 | N-linked (GlcNAc...) asparagine; alternateSequence analysis1 Publication | 1 | |
Glycosylationi | 573 | N-linked (HexNAc...) asparagine; alternateCombined sources | 1 |
Post-translational modificationi
Phosphorylation by CK1 of the N-terminal cytoplasmic domain regulates interaction with SYT1.1 Publication
N-glycosylated, on at least 3 residues.3 Publications1 Publication
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
jPOSTi | Q02563 |
PaxDbi | Q02563 |
PRIDEi | Q02563 |
PTM databases
GlyGeni | Q02563, 3 sites, 5 N-linked glycans (1 site) |
iPTMneti | Q02563 |
PhosphoSitePlusi | Q02563 |
SwissPalmi | Q02563 |
Expressioni
Tissue specificityi
Widely expressed throughout the brain (at protein level). Expressed by neural and endocrine cells of brain and spinal cord.1 Publication
Gene expression databases
Bgeei | ENSRNOG00000021182, Expressed in brain and 21 other tissues |
Genevisiblei | Q02563, RN |
Interactioni
Subunit structurei
Interacts with SYT1/synaptotagmin-1 in a calcium-dependent manner. Binds the adapter protein complex AP-2.
4 Publications(Microbial infection) Copurifies with C.botulinum neurotoxin type B (BoNT/B, botB) and synaptotagmin 1 (SYT1) (PubMed:19476346). Interaction does not require glycosylation of SV2 or SYT1 proteins (PubMed:19476346). Another group finds only copurification with SYT1 and SYT2 (PubMed:19650874).
2 PublicationsBinary interactionsi
Hide detailsQ02563
With | #Exp. | IntAct |
---|---|---|
Syt1 [P21707] | 2 | EBI-466194,EBI-458098 |
APBB1 [O00213] from Homo sapiens. | 3 | EBI-466194,EBI-81694 |
botA [P0DPI0] from Clostridium botulinum. | 2 | EBI-466194,EBI-8178893 |
GO - Molecular functioni
- protein kinase binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 250772, 2 interactors |
IntActi | Q02563, 7 interactors |
MINTi | Q02563 |
STRINGi | 10116.ENSRNOP00000028760 |
Chemistry databases
BindingDBi | Q02563 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 57 | Interaction with SYT1Add BLAST | 57 |
Sequence similaritiesi
Belongs to the major facilitator superfamily.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0255, Eukaryota |
GeneTreei | ENSGT00950000182940 |
HOGENOMi | CLU_001265_46_15_1 |
InParanoidi | Q02563 |
OMAi | LFHQVWN |
OrthoDBi | 724235at2759 |
PhylomeDBi | Q02563 |
TreeFami | TF324824 |
Family and domain databases
InterProi | View protein in InterPro IPR001646, 5peptide_repeat IPR011701, MFS IPR020846, MFS_dom IPR005828, MFS_sugar_transport-like IPR036259, MFS_trans_sf IPR005829, Sugar_transporter_CS IPR022308, SV2 |
Pfami | View protein in Pfam PF07690, MFS_1, 1 hit PF13599, Pentapeptide_4, 1 hit PF00083, Sugar_tr, 1 hit |
SUPFAMi | SSF103473, SSF103473, 2 hits |
TIGRFAMsi | TIGR01299, synapt_SV2, 1 hit |
PROSITEi | View protein in PROSITE PS50850, MFS, 1 hit |
i Sequence
Sequence statusi: Complete.
Q02563-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEEGFRDRAA FIRGAKDIAK EVKKHAAKKV VKGLDRVQDE YSRRSYSRFE
60 70 80 90 100
EEEDDDDFPA PADGYYRGEG AQDEEEGGAS SDATEGHDED DEIYEGEYQG
110 120 130 140 150
IPRAESGGKG ERMADGAPLA GVRGGLSDGE GPPGGRGEAQ RRKDREELAQ
160 170 180 190 200
QYETILRECG HGRFQWTLYF VLGLALMADG VEVFVVGFVL PSAEKDMCLS
210 220 230 240 250
DSNKGMLGLI VYLGMMVGAF LWGGLADRLG RRQCLLISLS VNSVFAFFSS
260 270 280 290 300
FVQGYGTFLF CRLLSGVGIG GSIPIVFSYF SEFLAQEKRG EHLSWLCMFW
310 320 330 340 350
MIGGVYAAAM AWAIIPHYGW SFQMGSAYQF HSWRVFVLVC AFPSVFAIGA
360 370 380 390 400
LTTQPESPRF FLENGKHDEA WMVLKQVHDT NMRAKGHPER VFSVTHIKTI
410 420 430 440 450
HQEDELIEIQ SDTGTWYQRW GVRALSLGGQ VWGNFLSCFS PEYRRITLMM
460 470 480 490 500
MGVWFTMSFS YYGLTVWFPD MIRHLQAVDY AARTKVFPGE RVEHVTFNFT
510 520 530 540 550
LENQIHRGGQ YFNDKFIGLR LKSVSFEDSL FEECYFEDVT SSNTFFRNCT
560 570 580 590 600
FINTVFYNTD LFEYKFVNSR LVNSTFLHNK EGCPLDVTGT GEGAYMVYFV
610 620 630 640 650
SFLGTLAVLP GNIVSALLMD KIGRLRMLAG SSVLSCVSCF FLSFGNSESA
660 670 680 690 700
MIALLCLFGG VSIASWNALD VLTVELYPSD KRTTAFGFLN ALCKLAAVLG
710 720 730 740
ISIFTSFVGI TKAAPILFAS AALALGSSLA LKLPETRGQV LQ
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 340 | C → F in AAA42188 (PubMed:1355409).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L01788 Genomic RNA No translation available. L05435 mRNA Translation: AAA42188.1 BC092132 mRNA Translation: AAH92132.1 |
PIRi | A43344 |
RefSeqi | NP_476558.2, NM_057210.2 XP_006233014.1, XM_006232952.3 |
Genome annotation databases
Ensembli | ENSRNOT00000028760; ENSRNOP00000028760; ENSRNOG00000021182 |
GeneIDi | 117559 |
KEGGi | rno:117559 |
UCSCi | RGD:619715, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L01788 Genomic RNA No translation available. L05435 mRNA Translation: AAA42188.1 BC092132 mRNA Translation: AAH92132.1 |
PIRi | A43344 |
RefSeqi | NP_476558.2, NM_057210.2 XP_006233014.1, XM_006232952.3 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 250772, 2 interactors |
IntActi | Q02563, 7 interactors |
MINTi | Q02563 |
STRINGi | 10116.ENSRNOP00000028760 |
Chemistry databases
BindingDBi | Q02563 |
ChEMBLi | CHEMBL4381 |
DrugCentrali | Q02563 |
GuidetoPHARMACOLOGYi | 2634 |
Protein family/group databases
TCDBi | 2.A.1.22.1, the major facilitator superfamily (mfs) |
PTM databases
GlyGeni | Q02563, 3 sites, 5 N-linked glycans (1 site) |
iPTMneti | Q02563 |
PhosphoSitePlusi | Q02563 |
SwissPalmi | Q02563 |
Proteomic databases
jPOSTi | Q02563 |
PaxDbi | Q02563 |
PRIDEi | Q02563 |
Genome annotation databases
Ensembli | ENSRNOT00000028760; ENSRNOP00000028760; ENSRNOG00000021182 |
GeneIDi | 117559 |
KEGGi | rno:117559 |
UCSCi | RGD:619715, rat |
Organism-specific databases
CTDi | 9900 |
RGDi | 619715, Sv2a |
Phylogenomic databases
eggNOGi | KOG0255, Eukaryota |
GeneTreei | ENSGT00950000182940 |
HOGENOMi | CLU_001265_46_15_1 |
InParanoidi | Q02563 |
OMAi | LFHQVWN |
OrthoDBi | 724235at2759 |
PhylomeDBi | Q02563 |
TreeFami | TF324824 |
Miscellaneous databases
PROi | PR:Q02563 |
Gene expression databases
Bgeei | ENSRNOG00000021182, Expressed in brain and 21 other tissues |
Genevisiblei | Q02563, RN |
Family and domain databases
InterProi | View protein in InterPro IPR001646, 5peptide_repeat IPR011701, MFS IPR020846, MFS_dom IPR005828, MFS_sugar_transport-like IPR036259, MFS_trans_sf IPR005829, Sugar_transporter_CS IPR022308, SV2 |
Pfami | View protein in Pfam PF07690, MFS_1, 1 hit PF13599, Pentapeptide_4, 1 hit PF00083, Sugar_tr, 1 hit |
SUPFAMi | SSF103473, SSF103473, 2 hits |
TIGRFAMsi | TIGR01299, synapt_SV2, 1 hit |
PROSITEi | View protein in PROSITE PS50850, MFS, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SV2A_RAT | |
Accessioni | Q02563Primary (citable) accession number: Q02563 Secondary accession number(s): Q58DZ8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | June 13, 2006 | |
Last modified: | February 10, 2021 | |
This is version 159 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families