SYT1_RAT
ID SYT1_RAT Reviewed; 421 AA.
AC P21707; Q3S2E6; Q707P5;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 3.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Synaptotagmin-1;
DE AltName: Full=Synaptotagmin I;
DE Short=SytI;
DE AltName: Full=p65;
GN Name=Syt1;
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].
RX PubMed=2333096; DOI=10.1038/345260a0;
RA Perin M.S., Fried V.A., Mignery G.A., Jahn R., Suedhof T.C.;
RT "Phospholipid binding by a synaptic vesicle protein homologous to the
RT regulatory region of protein kinase C.";
RL Nature 345:260-263(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15238157; DOI=10.1186/1471-2164-5-43;
RA Craxton M.A.;
RT "Synaptotagmin gene content of the sequenced genomes.";
RL BMC Genomics 5:43-43(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Wistar;
RA Sunitha S.S., Thekkuveettil A.;
RT "Functional analysis of synaptotagmin.";
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 214-233; 289-297; 355-366 AND 376-388, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP PROTEIN SEQUENCE OF 201-213 AND 333-352, FUNCTION AS C.BOTULINUM NEUROTOXIN
RP TYPE B RECEPTOR (MICROBIAL INFECTION), AND SUBUNIT (MICROBIAL INFECTION).
RX PubMed=8144634; DOI=10.1016/s0021-9258(17)34087-5;
RA Nishiki T., Kamata Y., Nemoto Y., Omori A., Ito T., Takahashi M.,
RA Kozaki S.;
RT "Identification of protein receptor for Clostridium botulinum type B
RT neurotoxin in rat brain synaptosomes.";
RL J. Biol. Chem. 269:10498-10503(1994).
RN [6]
RP INTERACTION WITH SV2A, AND DOMAIN.
RX PubMed=8910372; DOI=10.1074/jbc.271.44.27770;
RA Schivell A.E., Batchelor R.H., Bajjalieh S.M.;
RT "Isoform-specific, calcium-regulated interaction of the synaptic vesicle
RT proteins SV2 and synaptotagmin.";
RL J. Biol. Chem. 271:27770-27775(1996).
RN [7]
RP INTERACTION WITH RIMS1.
RC TISSUE=Brain;
RX PubMed=11438518; DOI=10.1074/jbc.m100929200;
RA Coppola T., Magnin-Luethi S., Perret-Menoud V., Gattesco S., Schiavo G.,
RA Regazzi R.;
RT "Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25,
RT and synaptotagmin.";
RL J. Biol. Chem. 276:32756-32762(2001).
RN [8]
RP INTERACTION WITH DNAJC5.
RX PubMed=11931641; DOI=10.1042/bj20020123;
RA Evans G.J., Morgan A.;
RT "Phosphorylation-dependent interaction of the synaptic vesicle proteins
RT cysteine string protein and synaptotagmin I.";
RL Biochem. J. 364:343-347(2002).
RN [9]
RP COFACTOR, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF ARG-233.
RX PubMed=11823420; DOI=10.1093/emboj/21.3.270;
RA Sugita S., Shin O.H., Han W., Lao Y., Suedhof T.C.;
RT "Synaptotagmins form a hierarchy of exocytotic Ca(2+) sensors with distinct
RT Ca(2+) affinities.";
RL EMBO J. 21:270-280(2002).
RN [10]
RP PALMITOYLATION AT CYS-74; CYS-75; CYS-77; CYS-79 AND CYS-82.
RX PubMed=12782290; DOI=10.1016/s0014-5793(03)00449-6;
RA Heindel U., Schmidt M.F., Veit M.;
RT "Palmitoylation sites and processing of synaptotagmin I, the putative
RT calcium sensor for neurosecretion.";
RL FEBS Lett. 544:57-62(2003).
RN [11]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE B RECEPTOR (MICROBIAL INFECTION),
RP AND SUBUNIT (MICROBIAL INFECTION).
RX PubMed=14504267; DOI=10.1083/jcb.200305098;
RA Dong M., Richards D.A., Goodnough M.C., Tepp W.H., Johnson E.A.,
RA Chapman E.R.;
RT "Synaptotagmins I and II mediate entry of botulinum neurotoxin B into
RT cells.";
RL J. Cell Biol. 162:1293-1303(2003).
RN [12]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE G RECEPTOR (MICROBIAL INFECTION),
RP AND SUBUNIT (MICROBIAL INFECTION).
RX PubMed=15123599; DOI=10.1074/jbc.m403945200;
RA Rummel A., Karnath T., Henke T., Bigalke H., Binz T.;
RT "Synaptotagmins I and II act as nerve cell receptors for botulinum
RT neurotoxin G.";
RL J. Biol. Chem. 279:30865-30870(2004).
RN [13]
RP INTERACTION WITH SV2A; SV2B AND SV2C.
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 [14]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE B RECEPTOR (MICROBIAL INFECTION),
RP SUBUNIT (MICROBIAL INFECTION), AND MUTAGENESIS OF 47-MET--LEU-50; MET-47
RP AND LEU-50.
RX PubMed=17167421; DOI=10.1038/nature05387;
RA Jin R., Rummel A., Binz T., Brunger A.T.;
RT "Botulinum neurotoxin B recognizes its protein receptor with high affinity
RT and specificity.";
RL Nature 444:1092-1095(2006).
RN [15]
RP FUNCTION AS C.BOTULINUM NEUROTOXIN TYPE B RECEPTOR (MICROBIAL INFECTION),
RP SUBUNIT (MICROBIAL INFECTION), AND MUTAGENESIS OF 50-LEU-ASN-51.
RX PubMed=17167418; DOI=10.1038/nature05411;
RA Chai Q., Arndt J.W., Dong M., Tepp W.H., Johnson E.A., Chapman E.R.,
RA Stevens R.C.;
RT "Structural basis of cell surface receptor recognition by botulinum
RT neurotoxin B.";
RL Nature 444:1096-1100(2006).
RN [16]
RP INTERACTION WITH SYT12, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP GLYCOSYLATION.
RX PubMed=17190793; DOI=10.1083/jcb.200607021;
RA Maximov A., Shin O.H., Liu X., Suedhof T.C.;
RT "Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates
RT spontaneous neurotransmitter release.";
RL J. Cell Biol. 176:113-124(2007).
RN [17]
RP SUBUNIT (MICROBIAL INFECTION).
RX PubMed=20219474; DOI=10.1016/j.jmb.2010.02.041;
RA Stenmark P., Dong M., Dupuy J., Chapman E.R., Stevens R.C.;
RT "Crystal structure of the botulinum neurotoxin type G binding domain:
RT insight into cell surface binding.";
RL J. Mol. Biol. 397:1287-1297(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-128; SER-342 AND SER-344, 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 [19]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 132-266.
RX PubMed=7697723; DOI=10.1016/0092-8674(95)90296-1;
RA Sutton R.B., Davletov B.A., Berghuis A.M., Suedhof T.C., Sprang S.R.;
RT "Structure of the first C2 domain of synaptotagmin I: a novel
RT Ca2+/phospholipid-binding fold.";
RL Cell 80:929-938(1995).
RN [20]
RP STRUCTURE BY NMR OF 140-267 IN COMPLEX WITH CALCIUM.
RX PubMed=9819203; DOI=10.1021/bi981789h;
RA Shao X., Fernandez I., Suedhof T.C., Rizo J.;
RT "Solution structures of the Ca2+-free and Ca2+-bound C2A domain of
RT synaptotagmin I: does Ca2+ induce a conformational change?";
RL Biochemistry 37:16106-16115(1998).
RN [21]
RP STRUCTURE BY NMR OF 270-421.
RX PubMed=11754837; DOI=10.1016/s0896-6273(01)00548-7;
RA Fernandez I., Arac D., Ubach J., Gerber S.H., Shin O., Gao Y.,
RA Anderson R.G., Suedhof T.C., Rizo J.;
RT "Three-dimensional structure of the synaptotagmin 1 C2B-domain:
RT synaptotagmin 1 as a phospholipid binding machine.";
RL Neuron 32:1057-1069(2001).
RN [22]
RP MUTAGENESIS OF ILE-367.
RX PubMed=25705886; DOI=10.1172/jci79765;
RA Baker K., Gordon S.L., Grozeva D., van Kogelenberg M., Roberts N.Y.,
RA Pike M., Blair E., Hurles M.E., Chong W.K., Baldeweg T., Kurian M.A.,
RA Boyd S.G., Cousin M.A., Raymond F.L.;
RT "Identification of a human synaptotagmin-1 mutation that perturbs synaptic
RT vesicle cycling.";
RL J. Clin. Invest. 125:1670-1678(2015).
RN [23]
RP INTERACTION WITH RAB3A.
RX PubMed=28057568; DOI=10.1016/j.ijbiomac.2016.12.074;
RA Tang X., Xie C., Wang Y., Wang X.;
RT "Localization of Rab3A-binding site on C2A domain of synaptotagmin I to
RT reveal its regulatory mechanism.";
RL Int. J. Biol. Macromol. 96:736-742(2017).
RN [24]
RP FUNCTION, AND MUTAGENESIS OF MET-302; ASP-303; ASP-365; ILE-367 AND
RP ASN-370.
RX PubMed=30107533; DOI=10.1093/brain/awy209;
RG Broad Center for Mendelian Genomics;
RA Baker K., Gordon S.L., Melland H., Bumbak F., Scott D.J., Jiang T.J.,
RA Owen D., Turner B.J., Boyd S.G., Rossi M., Al-Raqad M., Elpeleg O.,
RA Peck D., Mancini G.M.S., Wilke M., Zollino M., Marangi G., Weigand H.,
RA Borggraefe I., Haack T., Stark Z., Sadedin S., Tan T.Y., Jiang Y.,
RA Gibbs R.A., Ellingwood S., Amaral M., Kelley W., Kurian M.A., Cousin M.A.,
RA Raymond F.L.;
RT "SYT1-associated neurodevelopmental disorder: a case series.";
RL Brain 141:2576-2591(2018).
CC -!- FUNCTION: Calcium sensor that participates in triggering
CC neurotransmitter release at the synapse (PubMed:30107533). May have a
CC regulatory role in the membrane interactions during trafficking of
CC synaptic vesicles at the active zone of the synapse. It binds acidic
CC phospholipids with a specificity that requires the presence of both an
CC acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction
CC between synaptotagmin and putative receptors for activated protein
CC kinase C has also been reported. It can bind to at least three
CC additional proteins in a Ca(2+)-independent manner; these are
CC neurexins, syntaxin and AP2. Plays a role in dendrite formation by
CC melanocytes. {ECO:0000250|UniProtKB:P21579,
CC ECO:0000269|PubMed:30107533}.
CC -!- FUNCTION: (Microbial infection) Receptor for C.botulinum neurotoxin
CC type B (BoNT/B, botB); interaction is improved in the presence of
CC gangliosides (PubMed:8144634, PubMed:14504267, PubMed:17167418). BoNT/B
CC toxin binds to the membrane proximal vesicular domain of Syt1 (residues
CC 32-51) (PubMed:14504267, PubMed:17167421).
CC {ECO:0000269|PubMed:14504267, ECO:0000269|PubMed:17167418,
CC ECO:0000269|PubMed:17167421, ECO:0000269|PubMed:8144634}.
CC -!- FUNCTION: (Microbial infection) Receptor for C.botulinum neurotoxin
CC type G (BoNT/G, botG); unlike the case with BoNT/B, interaction is not
CC improved in the presence of gangliosides (PubMed:15123599,
CC PubMed:20219474). BoNT/G toxin binds to the vesicular domain of Syt1
CC (residues 32-53) (PubMed:15123599, PubMed:20219474).
CC {ECO:0000269|PubMed:15123599, ECO:0000269|PubMed:20219474}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041,
CC ECO:0000269|PubMed:11823420, ECO:0000269|PubMed:9819203};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domains. {ECO:0000269|PubMed:9819203};
CC -!- SUBUNIT: Homotetramer (Probable). Interacts with SCAMP5 (By
CC similarity). Interacts with STON2 (By similarity). Forms a complex with
CC SV2B, syntaxin 1 and SNAP25 (By similarity). Interacts with SV2A, SV2B
CC and SV2C (PubMed:8910372, PubMed:15866046). Interacts with RIMS1
CC (PubMed:11438518). Interacts with PRRT2 (By similarity). Interacts with
CC DNAJC5 in a phosphorylation-dependent manner (PubMed:11931641).
CC Interacts (via N-terminus) with RAB3A (PubMed:28057568). Interacts with
CC SYT12 (PubMed:17190793). Interacts with calmodulin (By similarity).
CC {ECO:0000250|UniProtKB:P21579, ECO:0000250|UniProtKB:P46096,
CC ECO:0000250|UniProtKB:P48018, ECO:0000269|PubMed:11438518,
CC ECO:0000269|PubMed:11931641, ECO:0000269|PubMed:15866046,
CC ECO:0000269|PubMed:17190793, ECO:0000269|PubMed:28057568,
CC ECO:0000269|PubMed:8910372, ECO:0000305}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.botulinum neurotoxin
CC type B (BoNT/B, botB). Has lower affinity for BoNT/B than Syt2;
CC mutating its residues to match those in Syt2 increases its affinity
CC (PubMed:17167421, PubMed:17167418). {ECO:0000269|PubMed:14504267,
CC ECO:0000269|PubMed:17167418, ECO:0000269|PubMed:17167421,
CC ECO:0000269|PubMed:20219474, ECO:0000269|PubMed:8144634}.
CC -!- SUBUNIT: (Microbial infection) Interacts with C.botulinum neurotoxin
CC type G (BoNT/G, botG). {ECO:0000269|PubMed:15123599,
CC ECO:0000269|PubMed:20219474}.
CC -!- INTERACTION:
CC P21707; P18484: Ap2a2; NbExp=5; IntAct=EBI-458098, EBI-539360;
CC P21707; Q02294: Cacna1b; NbExp=2; IntAct=EBI-458098, EBI-540038;
CC P21707; Q00954: Scn1b; NbExp=2; IntAct=EBI-458098, EBI-2619363;
CC P21707; P04775: Scn2a; NbExp=2; IntAct=EBI-458098, EBI-2619448;
CC P21707; P60881: Snap25; NbExp=24; IntAct=EBI-458098, EBI-1027214;
CC P21707; Q02563: Sv2a; NbExp=2; IntAct=EBI-458098, EBI-466194;
CC P21707; P21707: Syt1; NbExp=4; IntAct=EBI-458098, EBI-458098;
CC P21707; P50232: Syt4; NbExp=3; IntAct=EBI-458098, EBI-540118;
CC P21707; P63045: Vamp2; NbExp=7; IntAct=EBI-458098, EBI-520880;
CC P21707; Q8WXE9: STON2; Xeno; NbExp=2; IntAct=EBI-458098, EBI-539742;
CC P21707; O35526: Stx1a; Xeno; NbExp=3; IntAct=EBI-458098, EBI-400878;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000269|PubMed:11823420}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC membrane {ECO:0000269|PubMed:17190793}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, chromaffin
CC granule membrane; Single-pass membrane protein. Cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in the brain (at protein level)
CC (PubMed:17190793). Predominantly expressed in rostral, phylogenetically
CC younger brain regions, and in some endocrine tissues.
CC {ECO:0000269|PubMed:17190793}.
CC -!- DOMAIN: The first C2 domain mediates Ca(2+)-dependent phospholipid
CC binding. {ECO:0000269|PubMed:11823420, ECO:0000269|PubMed:8910372}.
CC -!- DOMAIN: The second C2 domain mediates interaction with SV2A and
CC probably with STN2. {ECO:0000269|PubMed:8910372}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:17190793}.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
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DR EMBL; X52772; CAA36981.1; -; mRNA.
DR EMBL; AJ617615; CAE85101.1; -; mRNA.
DR EMBL; DQ181550; ABA00482.1; -; mRNA.
DR PIR; S09595; S09595.
DR RefSeq; NP_001028852.2; NM_001033680.2.
DR RefSeq; XP_017450168.1; XM_017594679.1.
DR PDB; 1BYN; NMR; -; A=140-267.
DR PDB; 1K5W; NMR; -; A=270-421.
DR PDB; 1RSY; X-ray; 1.90 A; A=132-266.
DR PDB; 1TJM; X-ray; 1.18 A; A=271-421.
DR PDB; 1TJX; X-ray; 1.04 A; A=271-421.
DR PDB; 1UOV; X-ray; 1.65 A; A=271-421.
DR PDB; 1UOW; X-ray; 1.04 A; A=271-421.
DR PDB; 2YOA; X-ray; 1.50 A; A/B=271-421.
DR PDB; 4WEE; X-ray; 0.89 A; A=140-266.
DR PDB; 5CCG; X-ray; 3.50 A; E/F/K=141-421.
DR PDB; 5CCH; X-ray; 3.60 A; E/F=141-421.
DR PDB; 5CCI; X-ray; 4.10 A; E/F=141-421.
DR PDB; 5CCJ; X-ray; 1.65 A; A/B/C/D=271-421.
DR PDB; 5KJ7; X-ray; 3.50 A; E/F/K=141-419.
DR PDB; 5KJ8; X-ray; 4.10 A; E/F/K=141-419.
DR PDB; 5W5C; X-ray; 1.85 A; F=140-421.
DR PDB; 5W5D; X-ray; 2.50 A; F=270-421.
DR PDB; 6CXW; X-ray; 1.83 A; A=140-182, A=201-265.
DR PDB; 6MTI; EM; 10.40 A; 1/6=141-267, 2/3/4/5=141-421.
DR PDBsum; 1BYN; -.
DR PDBsum; 1K5W; -.
DR PDBsum; 1RSY; -.
DR PDBsum; 1TJM; -.
DR PDBsum; 1TJX; -.
DR PDBsum; 1UOV; -.
DR PDBsum; 1UOW; -.
DR PDBsum; 2YOA; -.
DR PDBsum; 4WEE; -.
DR PDBsum; 5CCG; -.
DR PDBsum; 5CCH; -.
DR PDBsum; 5CCI; -.
DR PDBsum; 5CCJ; -.
DR PDBsum; 5KJ7; -.
DR PDBsum; 5KJ8; -.
DR PDBsum; 5W5C; -.
DR PDBsum; 5W5D; -.
DR PDBsum; 6CXW; -.
DR PDBsum; 6MTI; -.
DR AlphaFoldDB; P21707; -.
DR SMR; P21707; -.
DR BioGRID; 247745; 7.
DR CORUM; P21707; -.
DR DIP; DIP-29064N; -.
DR IntAct; P21707; 25.
DR MINT; P21707; -.
DR STRING; 10116.ENSRNOP00000049624; -.
DR GlyGen; P21707; 1 site.
DR iPTMnet; P21707; -.
DR PhosphoSitePlus; P21707; -.
DR SwissPalm; P21707; -.
DR jPOST; P21707; -.
DR PaxDb; P21707; -.
DR PRIDE; P21707; -.
DR Ensembl; ENSRNOT00000048880; ENSRNOP00000049624; ENSRNOG00000006426.
DR GeneID; 25716; -.
DR KEGG; rno:25716; -.
DR UCSC; RGD:3803; rat.
DR CTD; 6857; -.
DR RGD; 3803; Syt1.
DR eggNOG; KOG1028; Eukaryota.
DR GeneTree; ENSGT00940000155394; -.
DR InParanoid; P21707; -.
DR OMA; TELRHWM; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; P21707; -.
DR TreeFam; TF315600; -.
DR Reactome; R-RNO-181429; Serotonin Neurotransmitter Release Cycle.
DR Reactome; R-RNO-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-RNO-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-RNO-212676; Dopamine Neurotransmitter Release Cycle.
DR Reactome; R-RNO-264642; Acetylcholine Neurotransmitter Release Cycle.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-RNO-888590; GABA synthesis, release, reuptake and degradation.
DR EvolutionaryTrace; P21707; -.
DR PRO; PR:P21707; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000006426; Expressed in frontal cortex and 15 other tissues.
DR Genevisible; P21707; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0042584; C:chromaffin granule membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0031045; C:dense core granule; IDA:RGD.
DR GO; GO:0060076; C:excitatory synapse; IDA:BHF-UCL.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IDA:SynGO.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0043229; C:intracellular organelle; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; ISO:RGD.
DR GO; GO:0044306; C:neuron projection terminus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0042734; C:presynaptic membrane; ISO:RGD.
DR GO; GO:0030141; C:secretory granule; IDA:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:SynGO.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:CAFA.
DR GO; GO:0043195; C:terminal bouton; HDA:ParkinsonsUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; IDA:RGD.
DR GO; GO:0061891; F:calcium ion sensor activity; ISO:RGD.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:BHF-UCL.
DR GO; GO:0048306; F:calcium-dependent protein binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005516; F:calmodulin binding; IDA:RGD.
DR GO; GO:0030276; F:clathrin binding; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISO:RGD.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005543; F:phospholipid binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:0000149; F:SNARE binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0019905; F:syntaxin binding; IDA:BHF-UCL.
DR GO; GO:0017075; F:syntaxin-1 binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030348; F:syntaxin-3 binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; ISO:RGD.
DR GO; GO:0099502; P:calcium-dependent activation of synaptic vesicle fusion; ISO:RGD.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0071277; P:cellular response to calcium ion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0005513; P:detection of calcium ion; IDA:RGD.
DR GO; GO:0098746; P:fast, calcium ion-dependent exocytosis of neurotransmitter; ISS:ParkinsonsUK-UCL.
DR GO; GO:0007269; P:neurotransmitter secretion; ISO:RGD.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; IDA:RGD.
DR GO; GO:1903235; P:positive regulation of calcium ion-dependent exocytosis of neurotransmitter; ISS:UniProtKB.
DR GO; GO:1903861; P:positive regulation of dendrite extension; ISO:RGD.
DR GO; GO:0033603; P:positive regulation of dopamine secretion; IMP:CACAO.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISS:ParkinsonsUK-UCL.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051291; P:protein heterooligomerization; IPI:ARUK-UCL.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0014059; P:regulation of dopamine secretion; ISO:RGD.
DR GO; GO:1903305; P:regulation of regulated secretory pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISS:ParkinsonsUK-UCL.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IDA:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; IDA:RGD.
DR GO; GO:0061669; P:spontaneous neurotransmitter secretion; ISO:RGD.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IBA:GO_Central.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0071911; P:synchronous neurotransmitter secretion; ISO:RGD.
DR GO; GO:0048278; P:vesicle docking; IDA:RGD.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 2.60.40.150; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR001565; Synaptotagmin.
DR InterPro; IPR015428; Synaptotagmin1.
DR PANTHER; PTHR10024:SF239; PTHR10024:SF239; 1.
DR Pfam; PF00168; C2; 2.
DR PRINTS; PR00360; C2DOMAIN.
DR PRINTS; PR00399; SYNAPTOTAGMN.
DR SMART; SM00239; C2; 2.
DR SUPFAM; SSF49562; SSF49562; 2.
DR PROSITE; PS50004; C2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cytoplasm; Cytoplasmic vesicle; Differentiation;
KW Direct protein sequencing; Glycoprotein; Lipoprotein; Membrane;
KW Metal-binding; Palmitate; Phosphoprotein; Reference proteome; Repeat;
KW Synapse; Transmembrane; Transmembrane helix.
FT CHAIN 1..421
FT /note="Synaptotagmin-1"
FT /id="PRO_0000183940"
FT TOPO_DOM 1..57
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 58..79
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 80..421
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 141..260
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 272..405
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 112..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 135..381
FT /note="Phospholipid binding"
FT /evidence="ECO:0000305"
FT BINDING 171
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 178
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 235
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 236
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 238
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 238
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 303
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 303
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 309
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 363
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 363
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 365
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 365
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 371
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 128
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 229
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P46096"
FT MOD_RES 264
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46096"
FT MOD_RES 342
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT LIPID 74
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:12782290"
FT LIPID 75
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:12782290"
FT LIPID 77
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:12782290"
FT LIPID 79
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:12782290"
FT LIPID 82
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:12782290"
FT CARBOHYD 24
FT /note="N-linked (GlcNAc...) asparagine"
FT MUTAGEN 47..50
FT /note="MNEL->FNEI: Greatly increased binding of fragment 1-
FT 53 to C.botulinum type B (BoNT/B, botB) heavy chain;
FT increases its resemblance to Syt2."
FT /evidence="ECO:0000269|PubMed:17167421"
FT MUTAGEN 47
FT /note="M->F: Slightly increased binding of fragment 1-53 to
FT BoNT/B heavy chain."
FT /evidence="ECO:0000269|PubMed:17167421"
FT MUTAGEN 50..51
FT /note="LH->IN: Binds to BoNT/B in the absence of
FT gangliosides."
FT /evidence="ECO:0000269|PubMed:17167418"
FT MUTAGEN 50
FT /note="L->I: Increased binding of fragment 1-53 to BoNT/B
FT heavy chain."
FT /evidence="ECO:0000269|PubMed:17167421"
FT MUTAGEN 233
FT /note="R->Q: Impaired Ca(2+)-affinity."
FT /evidence="ECO:0000269|PubMed:11823420"
FT MUTAGEN 302
FT /note="M->K: Fails to localize at nerve terminals."
FT /evidence="ECO:0000269|PubMed:30107533"
FT MUTAGEN 303
FT /note="D->G: Fails to relocalize to nerve terminals after
FT stimulation of neurotransmitter release."
FT /evidence="ECO:0000269|PubMed:30107533"
FT MUTAGEN 365
FT /note="D->E: Fails to relocalize to nerve terminals after
FT stimulation of neurotransmitter release."
FT /evidence="ECO:0000269|PubMed:30107533"
FT MUTAGEN 367
FT /note="I->T: Slows synaptic vesicle fusion kinetics and
FT exocytosis. Impairs the kinetics of synaptic vesicle
FT endocytosis."
FT /evidence="ECO:0000269|PubMed:25705886,
FT ECO:0000269|PubMed:30107533"
FT MUTAGEN 370
FT /note="N->K: Slows synaptic vesicle fusion kinetics and
FT exocytosis."
FT /evidence="ECO:0000269|PubMed:30107533"
FT CONFLICT 188
FT /note="D -> E (in Ref. 1; CAA36981)"
FT /evidence="ECO:0000305"
FT CONFLICT 374
FT /note="G -> D (in Ref. 1; CAA36981)"
FT /evidence="ECO:0000305"
FT CONFLICT 393
FT /note="M -> I (in Ref. 1; CAA36981)"
FT /evidence="ECO:0000305"
FT STRAND 144..152
FT /evidence="ECO:0007829|PDB:4WEE"
FT TURN 153..156
FT /evidence="ECO:0007829|PDB:4WEE"
FT STRAND 157..166
FT /evidence="ECO:0007829|PDB:4WEE"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:4WEE"
FT STRAND 179..187
FT /evidence="ECO:0007829|PDB:4WEE"
FT STRAND 205..212
FT /evidence="ECO:0007829|PDB:4WEE"
FT HELIX 216..219
FT /evidence="ECO:0007829|PDB:4WEE"
FT STRAND 223..230
FT /evidence="ECO:0007829|PDB:4WEE"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:4WEE"
FT STRAND 238..246
FT /evidence="ECO:0007829|PDB:4WEE"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:4WEE"
FT STRAND 256..261
FT /evidence="ECO:0007829|PDB:4WEE"
FT STRAND 275..283
FT /evidence="ECO:0007829|PDB:1TJX"
FT TURN 284..287
FT /evidence="ECO:0007829|PDB:1TJX"
FT STRAND 288..298
FT /evidence="ECO:0007829|PDB:1TJX"
FT STRAND 302..306
FT /evidence="ECO:0007829|PDB:5W5D"
FT STRAND 310..318
FT /evidence="ECO:0007829|PDB:1TJX"
FT STRAND 321..327
FT /evidence="ECO:0007829|PDB:1TJX"
FT STRAND 338..346
FT /evidence="ECO:0007829|PDB:1TJX"
FT HELIX 349..354
FT /evidence="ECO:0007829|PDB:1TJX"
FT STRAND 356..363
FT /evidence="ECO:0007829|PDB:1TJX"
FT STRAND 366..368
FT /evidence="ECO:0007829|PDB:1TJX"
FT STRAND 371..379
FT /evidence="ECO:0007829|PDB:1TJX"
FT HELIX 384..395
FT /evidence="ECO:0007829|PDB:1TJX"
FT STRAND 396..399
FT /evidence="ECO:0007829|PDB:1K5W"
FT STRAND 401..406
FT /evidence="ECO:0007829|PDB:1TJX"
FT HELIX 410..417
FT /evidence="ECO:0007829|PDB:1TJX"
SQ SEQUENCE 421 AA; 47399 MW; 06CE28F04C97A722 CRC64;
MVSASHPEAL AAPVTTVATL VPHNATEPAS PGEGKEDAFS KLKQKFMNEL HKIPLPPWAL
IAIAIVAVLL VVTCCFCVCK KCLFKKKNKK KGKEKGGKNA INMKDVKDLG KTMKDQALKD
DDAETGLTDG EEKEEPKEEE KLGKLQYSLD YDFQNNQLLV GIIQAAELPA LDMGGTSDPY
VKVFLLPDKK KKFETKVHRK TLNPVFNEQF TFKVPYSELG GKTLVMAVYD FDRFSKHDII
GEFKVPMNTV DFGHVTEEWR DLQSAEKEEQ EKLGDICFSL RYVPTAGKLT VVILEAKNLK
KMDVGGLSDP YVKIHLMQNG KRLKKKKTTI KKNTLNPYYN ESFSFEVPFE QIQKVQVVVT
VLDYDKIGKN DAIGKVFVGY NSTGAELRHW SDMLANPRRP IAQWHTLQVE EEVDAMLAVK
K
