SV2C_MOUSE
ID SV2C_MOUSE Reviewed; 727 AA.
AC Q69ZS6;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Synaptic vesicle glycoprotein 2C;
DE Short=Synaptic vesicle protein 2C;
GN Name=Sv2c; Synonyms=Kiaa1054;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [2]
RP INDUCTION.
RX PubMed=11483953; DOI=10.1038/35087000;
RA Xu T., Bajjalieh S.M.;
RT "SV2 modulates the size of the readily releasable pool of secretory
RT vesicles.";
RL Nat. Cell Biol. 3:691-698(2001).
RN [3]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12687700; DOI=10.1002/cne.10636;
RA Wang M.M., Janz R., Belizaire R., Frishman L.J., Sherry D.M.;
RT "Differential distribution and developmental expression of synaptic vesicle
RT protein 2 isoforms in the mouse retina.";
RL J. Comp. Neurol. 460:106-122(2003).
RN [4]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE A RECEPTOR (MICROBIAL INFECTION),
RP AND SUBUNIT (MICROBIAL INFECTION).
RX PubMed=16545378; DOI=10.1016/j.febslet.2006.02.074;
RA Mahrhold S., Rummel A., Bigalke H., Davletov B., Binz T.;
RT "The synaptic vesicle protein 2C mediates the uptake of botulinum
RT neurotoxin A into phrenic nerves.";
RL FEBS Lett. 580:2011-2014(2006).
RN [5]
RP FUNCTION AS BOTULINUM NEUROTOXIN TYPE A RECEPTOR (MICROBIAL INFECTION),
RP SUBUNIT (MICROBIAL INFECTION), TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16543415; DOI=10.1126/science.1123654;
RA Dong M., Yeh F., Tepp W.H., Dean C., Johnson E.A., Janz R., Chapman E.R.;
RT "SV2 is the protein receptor for botulinum neurotoxin A.";
RL Science 312:592-596(2006).
RN [6]
RP NOT A C.BOTULINUM NEUROTOXIN TYPE E RECEPTOR, AND TISSUE SPECIFICITY.
RX PubMed=18815274; DOI=10.1091/mbc.e08-07-0765;
RA Dong M., Liu H., Tepp W.H., Johnson E.A., Janz R., Chapman E.R.;
RT "Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin E
RT into neurons.";
RL Mol. Biol. Cell 19:5226-5237(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP POSSIBLE FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE D RECEPTOR (MICROBIAL
RP INFECTION), SUBUNIT (MICROBIAL INFECTION), AND TISSUE SPECIFICITY.
RX PubMed=21483489; DOI=10.1371/journal.ppat.1002008;
RA Peng L., Tepp W.H., Johnson E.A., Dong M.;
RT "Botulinum neurotoxin D uses synaptic vesicle protein SV2 and gangliosides
RT as receptors.";
RL PLoS Pathog. 7:E1002008-E1002008(2011).
RN [9]
RP NOT RECEPTOR FOR C.BOTULINUM NEUROTOXIN TYPE D (MICROBIAL INFECTION).
RX PubMed=21632541; DOI=10.1074/jbc.m111.254086;
RA Kroken A.R., Karalewitz A.P., Fu Z., Kim J.J., Barbieri J.T.;
RT "Novel ganglioside-mediated entry of botulinum neurotoxin serotype D into
RT neurons.";
RL J. Biol. Chem. 286:26828-26837(2011).
CC -!- FUNCTION: Plays a role in the control of regulated secretion in neural
CC and endocrine cells, enhancing selectively low-frequency
CC neurotransmission. Positively regulates vesicle fusion by maintaining
CC the readily releasable pool of secretory vesicles.
CC {ECO:0000250|UniProtKB:Q9Z2I6}.
CC -!- FUNCTION: (Microbial infection) Receptor for C.botulinum neurotoxin
CC type A (BoNT/A, botA); the toxin binds Sv2c via extracellular loop 4
CC (PubMed:16543415). {ECO:0000269|PubMed:16543415,
CC ECO:0000269|PubMed:16545378}.
CC -!- FUNCTION: (Microbial infection) Possible receptor for C.botulinum
CC neurotoxin type D (BoNT/D, botD) (PubMed:21483489).
CC {ECO:0000269|PubMed:21483489}.
CC -!- SUBUNIT: Interacts with SYT1 in a calcium-dependent manner.
CC {ECO:0000250|UniProtKB:Q9Z2I6}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.botulinum neurotoxin
CC type A (BoNT/A, botA). {ECO:0000269|PubMed:16545378,
CC ECO:0000305|PubMed:16543415}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.botulinum neurotoxin
CC type D (BoNT/D, botD). {ECO:0000269|PubMed:21483489}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250|UniProtKB:Q9Z2I6}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:Q9Z2I6}. Note=Enriched in small synaptic
CC vesicles and adrenal microsomes, not present in chromaffin granules.
CC Associated with both insulin granules and synaptic-like microvesicles
CC in insulin-secreting cells of the pancreas.
CC {ECO:0000250|UniProtKB:Q9Z2I6}.
CC -!- TISSUE SPECIFICITY: Expressed in specific subsets of conventional
CC synapses in the retina (at protein level) (PubMed:12687700). Expressed
CC in diaphragm motor nerve terminals (at protein level)
CC (PubMed:16543415). Expressed in a subset of hippocampus neurons (at
CC protein level) (PubMed:18815274, PubMed:21483489).
CC {ECO:0000269|PubMed:12687700, ECO:0000269|PubMed:16543415,
CC ECO:0000269|PubMed:18815274, ECO:0000269|PubMed:21483489}.
CC -!- DEVELOPMENTAL STAGE: Expressed during synaptogenesis in the retina (at
CC protein level). {ECO:0000269|PubMed:12687700}.
CC -!- INDUCTION: Up-regulated upon Sv2a depletion.
CC {ECO:0000269|PubMed:11483953}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9Z2I6}.
CC -!- DISRUPTION PHENOTYPE: Small interfering RNA knockdown of the protein in
CC Neuro-2a cells (which only express this SV2 protein) prevents uptake of
CC C.botulinum neurotoxin type A (BoNT/A, botA); uptake is restored by
CC expression of rat SV2A or SV2B (PubMed:16543415).
CC {ECO:0000269|PubMed:16543415}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC {ECO:0000305}.
CC -!- CAUTION: The use of this protein as a coreceptor for C.botulinum type D
CC (BoNT/D, botD) is controversial. In double SV2A/SV2B knockout mice
CC BoNT/D does not degrade its synaptobrevin target; introducing SV2A,
CC SV2B or SV2C restores target cleavage (PubMed:21483489). However
CC another group does not find a convincing interaction with SV2
CC (PubMed:21632541). {ECO:0000269|PubMed:21483489,
CC ECO:0000269|PubMed:21632541}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32370.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK173092; BAD32370.1; ALT_INIT; mRNA.
DR CCDS; CCDS49333.1; -.
DR RefSeq; NP_083486.1; NM_029210.1.
DR AlphaFoldDB; Q69ZS6; -.
DR BioGRID; 217304; 1.
DR STRING; 10090.ENSMUSP00000124473; -.
DR GlyConnect; 2747; 1 N-Linked glycan (1 site).
DR GlyGen; Q69ZS6; 5 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q69ZS6; -.
DR PhosphoSitePlus; Q69ZS6; -.
DR MaxQB; Q69ZS6; -.
DR PaxDb; Q69ZS6; -.
DR PRIDE; Q69ZS6; -.
DR ProteomicsDB; 258677; -.
DR Antibodypedia; 24435; 133 antibodies from 25 providers.
DR Ensembl; ENSMUST00000161263; ENSMUSP00000124473; ENSMUSG00000051111.
DR GeneID; 75209; -.
DR KEGG; mmu:75209; -.
DR UCSC; uc007rmt.2; mouse.
DR CTD; 22987; -.
DR MGI; MGI:1922459; Sv2c.
DR VEuPathDB; HostDB:ENSMUSG00000051111; -.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00950000182940; -.
DR InParanoid; Q69ZS6; -.
DR OMA; MENQVHT; -.
DR OrthoDB; 724235at2759; -.
DR PhylomeDB; Q69ZS6; -.
DR TreeFam; TF324824; -.
DR BioGRID-ORCS; 75209; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Sv2c; mouse.
DR PRO; PR:Q69ZS6; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q69ZS6; protein.
DR Bgee; ENSMUSG00000051111; Expressed in superior frontal gyrus and 64 other tissues.
DR ExpressionAtlas; Q69ZS6; baseline and differential.
DR Genevisible; Q69ZS6; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0008021; C:synaptic vesicle; IDA:MGI.
DR GO; GO:0030672; C:synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:MGI.
DR GO; GO:0006836; P:neurotransmitter transport; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR001646; 5peptide_repeat.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR005828; MFS_sugar_transport-like.
DR InterPro; IPR036259; MFS_trans_sf.
DR InterPro; IPR005829; Sugar_transporter_CS.
DR InterPro; IPR022308; SV2.
DR Pfam; PF07690; MFS_1; 1.
DR Pfam; PF13599; Pentapeptide_4; 1.
DR Pfam; PF00083; Sugar_tr; 1.
DR SUPFAM; SSF103473; SSF103473; 2.
DR TIGRFAMs; TIGR01299; synapt_SV2; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cytoplasmic vesicle; Glycoprotein; Membrane; Neurotransmitter transport;
KW Phosphoprotein; Receptor; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..727
FT /note="Synaptic vesicle glycoprotein 2C"
FT /id="PRO_0000239772"
FT TOPO_DOM 1..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 176..191
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 213..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..247
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 249..269
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..280
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 281..301
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 302..320
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 321..341
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 342..437
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..458
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 459..578
FT /note="Extracellular"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:16543415,
FT ECO:0000305|PubMed:16545378"
FT TRANSMEM 579..599
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 600..609
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 610..630
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 631..636
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 637..657
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 658..670
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 671..693
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 694..697
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 698..716
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 717..727
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..57
FT /note="Interaction with SYT1"
FT /evidence="ECO:0000250"
FT REGION 22..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..51
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 73..91
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 113..128
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L0J3"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L0J3"
FT MOD_RES 79
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q7L0J3"
FT MOD_RES 466
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIS5"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 484
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 534
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 559
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 565
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 727 AA; 82291 MW; E1D78203D4E3183A CRC64;
MEDSYKDRTS LMKGAKDIAK EVKKQTVKKV NQAVDRAQDE YTQRSYSRFQ DEEDDDDYYP
PGETYSGEVN DDEGSSEATE GHDEEDEIYE GEYQGIPSTN QGKDSIVSVG QPKGDEYKDR
RELESERRAD EEELAQQYEL IIQECGHGRF QWALFFVLGM ALMADGVEVF VVGFVLPSAE
TDLCIPNSGS GWLGSIVYLG MMVGAFFWGG LADKVGRKQS LLICMSVNGF FAFLSSFVQG
YGFFLVCRLL SGFGIGGAIP TVFSYFAEVL AREKRGEHLS WLCMFWMIGG IYASAMAWAI
IPHYGWSFSM GSAYQFHSWR VFVIVCALPC VSSVVALTFM PESPRFLLEV GKHDEAWMIL
KLIHDTNMRA RGQPEKVFTV NKIKTPKQID ELIEIESDTG TWYRRCFVRI RTELYGIWLT
FMRCFNYPVR ENTIKLTIVW FTLSFGYYGL SVWFPDVIKH LQSDEYALLT RNVQKDKYAN
FSINFTMENQ IHTGMEYENG RFLGVKFKSV TFKDSVFKSC TFDDVTSVNT YFKNCTFIDT
LFDNTDFEPY KFIDSEFQNC SFLHNKTGCQ ITFDDDYSAY WIYFVNFLGT LAVLPGNIVS
ALLMDRIGRL TMLGGSMVLS GISCFFLWFG TSESMMIGML CLYNGLTISA WNSLDVVTVE
LYPTDRRATG FGFLNALCKA AAVLGNLIFG SLVSITKAIP ILLASTVLVC GGLVGLRLPD
TRTQVLM
