SV2B_RAT
ID SV2B_RAT Reviewed; 683 AA.
AC Q63564;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Synaptic vesicle glycoprotein 2B;
DE Short=Synaptic vesicle protein 2B;
GN Name=Sv2b; Synonyms=Sv2bb;
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], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=7681585; DOI=10.1073/pnas.90.6.2150;
RA Bajjalieh S.M., Peterson K.E., Linial M., Scheller R.H.;
RT "Brain contains two forms of synaptic vesicle protein 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:2150-2154(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RX PubMed=11741278; DOI=10.1006/bbrc.2001.5932;
RA Heese K., Nagai Y., Sawada T.;
RT "Identification of a new synaptic vesicle protein 2B mRNA transcript which
RT is up-regulated in neurons by amyloid beta peptide fragment (1-42).";
RL Biochem. Biophys. Res. Commun. 289:924-928(2001).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=9648885; DOI=10.1046/j.1471-4159.1998.71010356.x;
RA Hayashi M., Yamamoto A., Yatsushiro S., Yamada H., Futai M., Yamaguchi A.,
RA Moriyama Y.;
RT "Synaptic vesicle protein SV2B, but not SV2A, is predominantly expressed
RT and associated with microvesicles in rat pinealocytes.";
RL J. Neurochem. 71:356-365(1998).
RN [4]
RP GLYCOSYLATION.
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 [5]
RP TISSUE SPECIFICITY.
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 [6]
RP PHOSPHORYLATION BY CK1.
RX PubMed=10747945; DOI=10.1074/jbc.m000674200;
RA Pyle R.A., Schivell A.E., Hidaka H., Bajjalieh S.M.;
RT "Phosphorylation of synaptic vesicle protein 2 modulates binding to
RT synaptotagmin.";
RL J. Biol. Chem. 275:17195-17200(2000).
RN [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12754292; DOI=10.1177/002215540305100612;
RA Redecker P., Kreutz M.R., Bockmann J., Gundelfinger E.D., Boeckers T.M.;
RT "Brain synaptic junctional proteins at the acrosome of rat testicular germ
RT cells.";
RL J. Histochem. Cytochem. 51:809-819(2003).
RN [8]
RP 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 [9]
RP 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 [10]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE A RECEPTOR (MICROBIAL INFECTION),
RP AND SUBUNIT (MICROBIAL INFECTION).
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 [11]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPES A AND E RECEPTOR (MICROBIAL
RP INFECTION), AND SUBUNIT (MICROBIAL INFECTION).
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 [12]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE F RECEPTOR (MICROBIAL INFECTION),
RP SUBUNIT (MICROBIAL INFECTION), AND GLYCOSYLATION.
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 [13]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE A; E 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 [14]
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 [15]
RP NOT RECEPTOR FOR C.BOTULINUM NEUROTOXIN TYPE D (MICROBIAL INFECTION), AND
RP SUBUNIT (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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33 AND THR-36, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [17]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE A2 RECEPTOR (MICROBIAL INFECTION),
RP SUBUNIT (MICROBIAL INFECTION), AND GLYCOSYLATION.
RX PubMed=29649119; DOI=10.3390/toxins10040153;
RA Gustafsson R., Zhang S., Masuyer G., Dong M., Stenmark P.;
RT "Crystal structure of botulinum neurotoxin A2 in complex with the human
RT protein receptor SV2C reveals plasticity in receptor binding.";
RL Toxins 10:0-0(2018).
CC -!- FUNCTION: Probably plays a role in the control of regulated secretion
CC in neural and endocrine cells. {ECO:0000250}.
CC -!- FUNCTION: (Microbial infection) Receptor for C.botulinum neurotoxin
CC type A (BoNT/A, botA); the toxin binds via extracellular loop 4
CC (PubMed:16543415). Restores uptake of BoNT/A in mouse and rat cells
CC that are deleted for SV2 receptor (PubMed:16543415, PubMed:18815274).
CC Glycosylation of SV2B is not essential for receptor activity, but
CC enhances the interaction (PubMed:18815274, PubMed:19650874). Also
CC serves as a receptor for the closely related C.botulinum neurotoxin
CC type A2; glycosylation is not essential but enhances the interaction
CC (PubMed:29649119). {ECO:0000269|PubMed:16543415,
CC ECO:0000269|PubMed:18815274, ECO:0000269|PubMed:19650874,
CC ECO:0000269|PubMed:29649119}.
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 E (BoNT/E); the toxin probably binds via extracellular loop 4
CC (PubMed:18815274). Restores uptake of BoNT/E in mouse cells that are
CC deleted for SV2 receptor (PubMed:18815274). Glycosylation of SV2B is
CC not essential for receptor activity, but enhances the interaction
CC (PubMed:19650874). {ECO:0000269|PubMed:18815274,
CC ECO:0000269|PubMed:19650874}.
CC -!- FUNCTION: (Microbial infection) Receptor for C.botulinum neurotoxin
CC type F (BoNT/F); binding requires glycosylation of this protein
CC (PubMed:19476346, PubMed:19650874). {ECO:0000269|PubMed:19650874,
CC ECO:0000305|PubMed:19476346}.
CC -!- SUBUNIT: Interacts with SYT1 in a calcium-independent manner. Forms a
CC complex with SYT1, syntaxin-1 and SNAP25 (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.botulinum neurotoxin
CC type A1 and type A2 (BoNT/A, botA) (PubMed:16543415, PubMed:21632541,
CC PubMed:21483489). Interaction is improved by glycosylation of SV2
CC (PubMed:29649119). {ECO:0000269|PubMed:16543415,
CC ECO:0000269|PubMed:19650874, ECO:0000269|PubMed:21483489,
CC ECO:0000269|PubMed:29649119}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.botulinum neurotoxin
CC type D (BoNT/D, botD). {ECO:0000269|PubMed:21483489}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.botulinum neurotoxin
CC type E (BoNT/E) (PubMed:18815274, PubMed:19476346, PubMed:19650874).
CC Interaction requires glycosylation of SV2 proteins (PubMed:19476346).
CC {ECO:0000269|PubMed:18815274, ECO:0000269|PubMed:19476346,
CC ECO:0000269|PubMed:19650874}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.botulinum neurotoxin
CC type F (BoNT/F) (PubMed:19650874). Interaction requires glycosylation
CC of SV2 proteins (PubMed:19650874). {ECO:0000269|PubMed:19650874}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000269|PubMed:16306227,
CC ECO:0000269|PubMed:7681585}; Multi-pass membrane protein {ECO:0000255}.
CC Cytoplasmic vesicle, secretory vesicle, acrosome
CC {ECO:0000269|PubMed:12754292}. Note=Associated with synaptic-like
CC microvesicles but not with insulin-containing vesicles in insulin-
CC secreting cells of the pancreas (PubMed:16306227). Localizes to
CC microvesicles in the pinealocytes. Localizes to the acrosome in
CC spermatids (PubMed:12754292). {ECO:0000269|PubMed:12754292,
CC ECO:0000269|PubMed:16306227}.
CC -!- TISSUE SPECIFICITY: Widely expressed throughout the brain. Specifically
CC expressed by pinealocytes in the pineal gland. Also detected in testis
CC (at protein level). Specifically expressed in neural tissues. Expressed
CC in the spinal cord and in all brain regions with a stronger expression
CC in hippocampus and cortex. {ECO:0000269|PubMed:10625067,
CC ECO:0000269|PubMed:12754292, ECO:0000269|PubMed:7681585,
CC ECO:0000269|PubMed:9648885}.
CC -!- INDUCTION: By amyloid beta peptide. {ECO:0000269|PubMed:11741278}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9801366,
CC ECO:0000305|PubMed:29649119}.
CC -!- PTM: The N-terminal cytoplasmic domain is phosphorylated by CK1.
CC {ECO:0000269|PubMed:10747945}.
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; L10362; AAA42189.1; -; mRNA.
DR EMBL; AF372834; AAL47714.1; -; mRNA.
DR PIR; S34961; S34961.
DR RefSeq; NP_476555.1; NM_057207.3.
DR AlphaFoldDB; Q63564; -.
DR SMR; Q63564; -.
DR BioGRID; 250769; 2.
DR IntAct; Q63564; 4.
DR MINT; Q63564; -.
DR GlyGen; Q63564; 3 sites.
DR iPTMnet; Q63564; -.
DR PhosphoSitePlus; Q63564; -.
DR PaxDb; Q63564; -.
DR PRIDE; Q63564; -.
DR GeneID; 117556; -.
DR KEGG; rno:117556; -.
DR UCSC; RGD:619716; rat.
DR CTD; 9899; -.
DR RGD; 619716; Sv2b.
DR InParanoid; Q63564; -.
DR OrthoDB; 724235at2759; -.
DR PhylomeDB; Q63564; -.
DR PRO; PR:Q63564; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
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:0016020; C:membrane; IDA:RGD.
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:0043195; C:terminal bouton; HDA:ParkinsonsUK-UCL.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0007268; P:chemical synaptic transmission; IEA:InterPro.
DR GO; GO:0001504; P:neurotransmitter uptake; TAS:RGD.
DR Gene3D; 1.20.1250.20; -; 2.
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; 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..683
FT /note="Synaptic vesicle glycoprotein 2B"
FT /id="PRO_0000239770"
FT TOPO_DOM 1..110
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 132..148
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 170..182
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 183..203
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 204..205
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..277
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..298
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 299..390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 391..411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 412..535
FT /note="Extracellular"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:16543415"
FT TRANSMEM 536..556
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 557..565
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 566..586
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 587..592
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 593..613
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 614..626
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 627..649
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 650..653
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 654..672
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 673..683
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..47
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..65
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 36
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 423
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8BG39"
FT CARBOHYD 441
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 516
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 683 AA; 77502 MW; BF862EFD4B99EA7B CRC64;
MDDYRYRDNY EGYAPNDGYY RGNEQNPEED AQSDVTEGHD EEDEIYEGEY QGIPHPDDVK
SKQTKMAPSR ADGLRGQADL MAERMEDEEQ LAHQYETIID ECGHGRFQWT LFFVLVLALM
ADGVEVFVVS FALPSAEKDM CLSSSKKGML GLIVYLGMMA GAFILGGLAD KLGRKKVLSM
SLAINASFAS LSSFVQGYGA FLFCRLISGI GIGGSLPIVF AYFSEFLSRE KRGEHLSWLG
IFWMTGGIYA SAMAWSIIPH YGWGFSMGTN YHFHSWRVFV IVCALPATVS MVALKFMPES
PRFLLEMGKH DEAWMILKQV HDTNMRAKGT PEKVFTVSHI KTPKQMDEFI EIQSSTGTWY
QRWLVRFMTI FKQVWDNALY CVMGPYRMNT LILAVVWFTM ALSYYGLTVW FPDMIRYFQD
EEYKSKMKVF FGEHVHGATI NFTMENQIHQ HGKLVNDKFI KMYFKHVLFE DTFFDKCYFE
DVTSTDTYFK NCTIESTTFY NTDLYKHKFI DCRFINSTFL EQKEGCHMDF EEDNDFLIYL
VSFLGSLSVL PGNIISALLM DRIGRLKMIG GSMLISAVCC FFLFFGNSES AMIGWQCLFC
GTSIAAWNAL DVITVELYPT NQRATAFGIL NGLCKLGAIL GNTIFASFVG ITKVVPILLA
AASLVGGGLV ALRLPETREQ VLM
