SV2C_RAT
ID SV2C_RAT Reviewed; 727 AA.
AC Q9Z2I6;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Synaptic vesicle glycoprotein 2C;
DE Short=Synaptic vesicle protein 2C;
GN Name=Sv2c;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], GLYCOSYLATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9801366; DOI=10.1523/jneurosci.18-22-09269.1998;
RA Janz R., Hofmann K., Suedhof T.C.;
RT "SVOP, an evolutionarily conserved synaptic vesicle protein, suggests novel
RT transport functions of synaptic vesicles.";
RL J. Neurosci. 18:9269-9281(1998).
RN [2]
RP GLYCOSYLATION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=10625067; DOI=10.1016/s0306-4522(99)00370-x;
RA Janz R., Suedhof T.C.;
RT "SV2C is a synaptic vesicle protein with an unusually restricted
RT localization: anatomy of a synaptic vesicle protein family.";
RL Neuroscience 94:1279-1290(1999).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16306227; DOI=10.1242/jcs.02658;
RA Iezzi M., Theander S., Janz R., Loze C., Wollheim C.B.;
RT "SV2A and SV2C are not vesicular Ca2+ transporters but control glucose-
RT evoked granule recruitment.";
RL J. Cell Sci. 118:5647-5660(2005).
RN [4]
RP FUNCTION, AND INTERACTION WITH SYT1.
RX PubMed=15866046; DOI=10.1016/j.mcn.2004.12.011;
RA Schivell A.E., Mochida S., Kensel-Hammes P., Custer K.L., Bajjalieh S.M.;
RT "SV2A and SV2C contain a unique synaptotagmin-binding site.";
RL Mol. Cell. Neurosci. 29:56-64(2005).
RN [5]
RP FUNCTION AS BOTULINUM NEUROTOXIN TYPE A RECEPTOR (MICROBIAL INFECTION),
RP SUBUNIT (MICROBIAL INFECTION), AND DOMAIN.
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.
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 FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE F RECEPTOR (MICROBIAL INFECTION),
RP AND SUBUNIT (MICROBIAL INFECTION).
RX PubMed=19476346; DOI=10.1021/bi9002138;
RA Fu Z., Chen C., Barbieri J.T., Kim J.J., Baldwin M.R.;
RT "Glycosylated SV2 and gangliosides as dual receptors for botulinum
RT neurotoxin serotype F.";
RL Biochemistry 48:5631-5641(2009).
RN [8]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPES A AND F RECEPTOR (MICROBIAL
RP INFECTION), AND SUBUNIT (MICROBIAL INFECTION).
RX PubMed=19650874; DOI=10.1111/j.1471-4159.2009.06298.x;
RA Rummel A., Haefner K., Mahrhold S., Darashchonak N., Holt M., Jahn R.,
RA Beermann S., Karnath T., Bigalke H., Binz T.;
RT "Botulinum neurotoxins C, E and F bind gangliosides via a conserved binding
RT site prior to stimulation-dependent uptake with botulinum neurotoxin F
RT utilising the three isoforms of SV2 as second receptor.";
RL J. Neurochem. 110:1942-1954(2009).
RN [9]
RP POSSIBLE FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE D RECEPTOR (MICROBIAL
RP INFECTION), AND SUBUNIT (MICROBIAL INFECTION).
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 [10]
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).
RN [11] {ECO:0007744|PDB:5JMC}
RP X-RAY CRYSTALLOGRAPHY (2.64 ANGSTROMS) OF 455-577, FUNCTION AS C.BOTULINUM
RP NEUROTOXIN TYPE A RECEPTOR (MICROBIAL INFECTION), SUBUNIT (MICROBIAL
RP INFECTION), MUTAGENESIS OF ASN-559, AND GLYCOSYLATION AT ASN-559.
RX PubMed=27294781; DOI=10.1038/nsmb.3245;
RA Yao G., Zhang S., Mahrhold S., Lam K.H., Stern D., Bagramyan K., Perry K.,
RA Kalkum M., Rummel A., Dong M., Jin R.;
RT "N-linked glycosylation of SV2 is required for binding and uptake of
RT botulinum neurotoxin A.";
RL Nat. Struct. Mol. Biol. 23:656-662(2016).
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:0000269|PubMed:15866046, ECO:0000269|PubMed:16306227}.
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). Restores uptake of BoNT/A in rat cells that are
CC deleted for SV2 receptor (PubMed:16543415, PubMed:18815274).
CC {ECO:0000269|PubMed:16543415, ECO:0000269|PubMed:19650874,
CC ECO:0000269|PubMed:27294781}.
CC -!- FUNCTION: (Microbial infection) Possible receptor for C.botulinum
CC neurotoxin type D (BoNT/D, botD); BoNT/D does not bind to extracellular
CC loop 4 as do BoNT/A and BoNT/E (PubMed:21483489). Another group does
CC not find a convincing interaction with SV2 (PubMed:21632541).
CC {ECO:0000269|PubMed:21483489, ECO:0000269|PubMed:21632541}.
CC -!- FUNCTION: (Microbial infection) Receptor for C.botulinum neurotoxin
CC type F (BoNT/F); binding requires glycosylation of Asn-573
CC (PubMed:19476346, PubMed:19650874). {ECO:0000269|PubMed:19650874,
CC ECO:0000305|PubMed:19476346}.
CC -!- SUBUNIT: Interacts with SYT1 in a calcium-dependent manner.
CC {ECO:0000269|PubMed:15866046}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.botulinum neurotoxin
CC type A (BoNT/A, botA). {ECO:0000269|PubMed:16543415,
CC ECO:0000269|PubMed:19650874, ECO:0000269|PubMed:21483489,
CC ECO:0000269|PubMed:27294781}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.botulinum neurotoxin
CC type F (BoNT/F) (PubMed:19650874). Interaction requires glycosylation
CC of SV2 proteins (PubMed:19476346, PubMed:19650874).
CC {ECO:0000269|PubMed:19650874, ECO:0000305|PubMed:19476346}.
CC -!- INTERACTION:
CC Q9Z2I6; P0DPI0: botA; Xeno; NbExp=12; IntAct=EBI-8178859, EBI-8178893;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000269|PubMed:10625067,
CC ECO:0000269|PubMed:16306227}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:10625067, ECO:0000269|PubMed:16306227}.
CC Note=Enriched in small synaptic vesicles and adrenal microsomes, not
CC present in chromaffin granules. Associated with both insulin granules
CC and synaptic-like microvesicles in insulin-secreting cells of the
CC pancreas.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in very few brain areas
CC including the striatum, midbrain and hindbrain, and in the olfactory
CC bulb. Expressed at lower levels in cerebrum, hippocampus and cerebellum
CC (at protein level). Mainly expressed in brain; also detected in lung,
CC liver, kidney. {ECO:0000269|PubMed:10625067,
CC ECO:0000269|PubMed:9801366}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10625067,
CC ECO:0000269|PubMed:27294781, ECO:0000269|PubMed:9801366}.
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}.
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DR EMBL; AF060174; AAC78628.1; -; mRNA.
DR RefSeq; NP_113781.1; NM_031593.1.
DR RefSeq; XP_017446285.1; XM_017590796.1.
DR PDB; 5JMC; X-ray; 2.64 A; B/D/F/H=455-577.
DR PDBsum; 5JMC; -.
DR AlphaFoldDB; Q9Z2I6; -.
DR SMR; Q9Z2I6; -.
DR IntAct; Q9Z2I6; 1.
DR MINT; Q9Z2I6; -.
DR STRING; 10116.ENSRNOP00000024459; -.
DR GlyGen; Q9Z2I6; 5 sites.
DR iPTMnet; Q9Z2I6; -.
DR PhosphoSitePlus; Q9Z2I6; -.
DR PaxDb; Q9Z2I6; -.
DR PRIDE; Q9Z2I6; -.
DR Ensembl; ENSRNOT00000024459; ENSRNOP00000024459; ENSRNOG00000018094.
DR GeneID; 29643; -.
DR KEGG; rno:29643; -.
DR UCSC; RGD:619718; rat.
DR CTD; 22987; -.
DR RGD; 619718; Sv2c.
DR eggNOG; KOG0255; Eukaryota.
DR GeneTree; ENSGT00950000182940; -.
DR HOGENOM; CLU_001265_46_15_1; -.
DR InParanoid; Q9Z2I6; -.
DR OMA; MENQVHT; -.
DR OrthoDB; 724235at2759; -.
DR PhylomeDB; Q9Z2I6; -.
DR TreeFam; TF324824; -.
DR PRO; PR:Q9Z2I6; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000018094; Expressed in cerebellum and 9 other tissues.
DR Genevisible; Q9Z2I6; RN.
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; IDA:SynGO.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
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; IEA:InterPro.
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 3D-structure; Cytoplasmic vesicle; Glycoprotein; Membrane;
KW Neurotransmitter transport; Phosphoprotein; Receptor; Reference proteome;
KW Synapse; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..727
FT /note="Synaptic vesicle glycoprotein 2C"
FT /id="PRO_0000239773"
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 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:0000269|PubMed:15866046"
FT REGION 22..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..566
FT /note="(Microbial infection) C.botulinum neurotoxin type A-
FT binding"
FT /evidence="ECO:0000269|PubMed:16543415,
FT ECO:0000269|PubMed:27294781"
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 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:0000305|PubMed:27294781"
FT CARBOHYD 565
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 559
FT /note="N->A: Loss of one glycosylation site. No effect on
FT C.botulinum neurotoxin type A (BoNT/A, botA) binding, but
FT reduces the uptake of BoNT/A."
FT /evidence="ECO:0000269|PubMed:27294781"
FT STRAND 478..480
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 488..494
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 496..499
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 501..504
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 506..509
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 511..514
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 516..519
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 521..524
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 526..529
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 531..534
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 536..539
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 541..545
FT /evidence="ECO:0007829|PDB:5JMC"
FT HELIX 549..551
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 552..554
FT /evidence="ECO:0007829|PDB:5JMC"
FT STRAND 556..562
FT /evidence="ECO:0007829|PDB:5JMC"
SQ SEQUENCE 727 AA; 82249 MW; 4C154C69341D8DB7 CRC64;
MEDSYKDRTS LMKGAKDIAK EVKKQTVKKV NQAVDRAQDE YTQRSYSRFQ DEDDDDDYYP
PGETYSGEAN DDEGSSEATE GHDEEDEIYE GEYQGIPSTN QGKDSIVSVG QPKGDEYKDR
RELESERRAD EEELAQQYEL IIQECGHGRF QWALFFVLGM ALMADGVEVF VVGFVLPSAE
TDLCIPNSGS GWLGSIVYLG MMVGAFFWGG LADKVGRKQS LLICMSVNGF FAFLSSFVQG
YGFFLLCRLL SGFGIGGAIP TVFSYFAEVL AREKRGEHLS WLCMFWMIGG IYASAMAWAI
IPHYGWSFSM GSAYQFHSWR VFVIVCALPC VSSVVALTFM PESPRFLLEV GKHDEAWMIL
KLIHDTNMRA RGQPEKVFTV NKIKTPKQID ELIEIESDTG TWYRRCFVRI RTELYGIWLT
FMRCFNYPVR ENTIKLTIVW FTLSFGYYGL SVWFPDVIKH LQSDEYALLT RNVQKDKYAN
FSINFTMENQ VHTGMEYDNG RFLGVKFKSV TFKDSVFKSC TFDDVTSVNT YFKNCTFIDT
LFENTDFEPY KFIDSEFQNC SFLHNKTGCQ ITFDDDYSAY WIYFVNFLGT LAVLPGNIVS
ALLMDRIGRL TMLGGSMVLS GISCFFLWFG TSESMMIGML CLYNGLTISA WNSLDVVTVE
LYPTDRRATG FGFLNALCKA AAVLGNLIFG SLVSITKAIP ILLASTVLVC GGLVGLRLPD
TRTQVLM
