SYT7_MOUSE
ID SYT7_MOUSE Reviewed; 403 AA.
AC Q9R0N7; A4QPF1; E9PZA8; Q0D2K7; Q8CF95; Q8CF96;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Synaptotagmin-7 {ECO:0000305};
DE AltName: Full=Synaptotagmin VII {ECO:0000303|PubMed:10531343};
DE Short=SytVII {ECO:0000303|PubMed:10531343};
GN Name=Syt7 {ECO:0000312|MGI:MGI:1859545};
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 [MRNA] (ISOFORM 1).
RC STRAIN=ICR; TISSUE=Cerebellum;
RX PubMed=10531343; DOI=10.1074/jbc.274.44.31421;
RA Fukuda M., Kanno E., Mikoshiba K.;
RT "Conserved N-terminal cysteine motif is essential for homo- and heterodimer
RT formation of synaptotagmins III, V, VI, and X.";
RL J. Biol. Chem. 274:31421-31427(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=12071850; DOI=10.1042/bj20011877;
RA Fukuda M., Ogata Y., Saegusa C., Kanno E., Mikoshiba K.;
RT "Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and
RT human.";
RL Biochem. J. 365:173-180(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP SUBUNIT.
RX PubMed=10871604; DOI=10.1074/jbc.m001376200;
RA Fukuda M., Mikoshiba K.;
RT "Distinct self-oligomerization activities of synaptotagmin family. Unique
RT calcium-dependent oligomerization properties of synaptotagmin VII.";
RL J. Biol. Chem. 275:28180-28185(2000).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=11395007; DOI=10.1016/s0896-6273(01)00290-2;
RA Sugita S., Han W., Butz S., Liu X., Fernandez-Chacon R., Lao Y.,
RA Sudhof T.C.;
RT "Synaptotagmin VII as a plasma membrane Ca(2+) sensor in exocytosis.";
RL Neuron 30:459-473(2001).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=12925704; DOI=10.1083/jcb.200305131;
RA Chakrabarti S., Kobayashi K.S., Flavell R.A., Marks C.B., Miyake K.,
RA Liston D.R., Fowler K.T., Gorelick F.S., Andrews N.W.;
RT "Impaired membrane resealing and autoimmune myositis in synaptotagmin VII-
RT deficient mice.";
RL J. Cell Biol. 162:543-549(2003).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 225-ASP--ASP-227 AND
RP 357-ASP--ASP-359.
RX PubMed=16982801; DOI=10.1083/jcb.200605004;
RA Czibener C., Sherer N.M., Becker S.M., Pypaert M., Hui E., Chapman E.R.,
RA Mothes W., Andrews N.W.;
RT "Ca2+ and synaptotagmin VII-dependent delivery of lysosomal membrane to
RT nascent phagosomes.";
RL J. Cell Biol. 174:997-1007(2006).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=17720139; DOI=10.1016/j.bbrc.2007.08.023;
RA Li Y., Wang P., Xu J., Gorelick F., Yamazaki H., Andrews N., Desir G.V.;
RT "Regulation of insulin secretion and GLUT4 trafficking by the calcium
RT sensor synaptotagmin VII.";
RL Biochem. Biophys. Res. Commun. 362:658-664(2007).
RN [10]
RP FUNCTION.
RX PubMed=18539119; DOI=10.1016/j.devcel.2008.03.022;
RA Zhao H., Ito Y., Chappel J., Andrews N.W., Teitelbaum S.L., Ross F.P.;
RT "Synaptotagmin VII regulates bone remodeling by modulating osteoclast and
RT osteoblast secretion.";
RL Dev. Cell 14:914-925(2008).
RN [11]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=18308938; DOI=10.1073/pnas.0711700105;
RA Gustavsson N., Lao Y., Maximov A., Chuang J.C., Kostromina E., Repa J.J.,
RA Li C., Radda G.K., Suedhof T.C., Han W.;
RT "Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null
RT mutant mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3992-3997(2008).
RN [12]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=19171650; DOI=10.1113/jphysiol.2008.168005;
RA Gustavsson N., Wei S.H., Hoang D.N., Lao Y., Zhang Q., Radda G.K.,
RA Rorsman P., Suedhof T.C., Han W.;
RT "Synaptotagmin-7 is a principal Ca2+ sensor for Ca2+ -induced glucagon
RT exocytosis in pancreas.";
RL J. Physiol. (Lond.) 587:1169-1178(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52; THR-58; SER-61 AND
RP SER-122, AND 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 [14]
RP FUNCTION, PALMITOYLATION, SUBCELLULAR LOCATION, INTERACTION WITH CD63, AND
RP MUTAGENESIS OF 35-CYS--CYS-43.
RX PubMed=21041449; DOI=10.1083/jcb.201003021;
RA Flannery A.R., Czibener C., Andrews N.W.;
RT "Palmitoylation-dependent association with CD63 targets the Ca2+ sensor
RT synaptotagmin VII to lysosomes.";
RL J. Cell Biol. 191:599-613(2010).
RN [15]
RP FUNCTION.
RX PubMed=20956309; DOI=10.1073/pnas.1014070107;
RA Segovia M., Ales E., Montes M.A., Bonifas I., Jemal I., Lindau M.,
RA Maximov A., Suedhof T.C., Alvarez de Toledo G.;
RT "Push-and-pull regulation of the fusion pore by synaptotagmin-7.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:19032-19037(2010).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, INTERACTION WITH
RP CALMODULIN, AND MUTAGENESIS OF 225-ASP--ASP-227 AND 357-ASP--ASP-359.
RX PubMed=24569478; DOI=10.7554/elife.01524;
RA Liu H., Bai H., Hui E., Yang L., Evans C.S., Wang Z., Kwon S.E.,
RA Chapman E.R.;
RT "Synaptotagmin 7 functions as a Ca2+-sensor for synaptic vesicle
RT replenishment.";
RL Elife 3:E01524-E01524(2014).
RN [17]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-169 AND ARG-171 (ISOFORM 4), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [18]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25860611; DOI=10.1016/j.cell.2015.02.019;
RA Chu B.B., Liao Y.C., Qi W., Xie C., Du X., Wang J., Yang H., Miao H.H.,
RA Li B.L., Song B.L.;
RT "Cholesterol transport through lysosome-peroxisome membrane contacts.";
RL Cell 161:291-306(2015).
RN [19]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 225-ASP--ASP-232.
RX PubMed=26738595; DOI=10.1038/nature16507;
RA Jackman S.L., Turecek J., Belinsky J.E., Regehr W.G.;
RT "The calcium sensor synaptotagmin 7 is required for synaptic
RT facilitation.";
RL Nature 529:88-91(2016).
RN [20]
RP INTERACTION WITH APP.
RX PubMed=30429473; DOI=10.1038/s41467-018-06813-x;
RA Barthet G., Jorda-Siquier T., Rumi-Masante J., Bernadou F., Mueller U.,
RA Mulle C.;
RT "Presenilin-mediated cleavage of APP regulates synaptotagmin-7 and
RT presynaptic plasticity.";
RL Nat. Commun. 9:4780-4780(2018).
RN [21] {ECO:0007744|PDB:3N5A}
RP X-RAY CRYSTALLOGRAPHY (1.44 ANGSTROMS) OF 266-403 IN COMPLEX WITH CALCIUM,
RP AND COFACTOR.
RX PubMed=20824061; DOI=10.1371/journal.pone.0012544;
RA Xue M., Craig T.K., Shin O.H., Li L., Brautigam C.A., Tomchick D.R.,
RA Sudhof T.C., Rosenmund C., Rizo J.;
RT "Structural and mutational analysis of functional differentiation between
RT synaptotagmins-1 and -7.";
RL PLoS ONE 5:E12544-E12544(2010).
CC -!- FUNCTION: Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of
CC secretory and synaptic vesicles through Ca(2+) and phospholipid binding
CC to the C2 domain. Ca(2+) induces binding of the C2-domains to
CC phospholipid membranes and to assembled SNARE-complexes; both actions
CC contribute to triggering exocytosis. SYT7 binds Ca(2+) with high
CC affinity and slow kinetics compared to other synaptotagmins
CC (PubMed:26738595). Involved in Ca(2+)-triggered lysosomal exocytosis, a
CC major component of the plasma membrane repair (By similarity). Ca(2+)-
CC regulated delivery of lysosomal membranes to the cell surface is also
CC involved in the phagocytic uptake of particles by macrophages
CC (PubMed:16982801, PubMed:21041449). Ca(2+)-triggered lysosomal
CC exocytosis also plays a role in bone remodeling by regulating secretory
CC pathways in osteoclasts and osteoblasts (PubMed:18539119). Involved in
CC cholesterol transport from lysosome to peroxisome by promoting membrane
CC contacts between lysosomes and peroxisomes: probably acts by promoting
CC vesicle fusion by binding phosphatidylinositol-4,5-bisphosphate on
CC peroxisomal membranes (PubMed:25860611). Acts as a key mediator of
CC synaptic facilitation, a process also named short-term synaptic
CC potentiation: synaptic facilitation takes place at synapses with a low
CC initial release probability and is caused by influx of Ca(2+) into the
CC axon terminal after spike generation, increasing the release
CC probability of neurotransmitters (PubMed:24569478, PubMed:26738595).
CC Probably mediates synaptic facilitation by directly increasing the
CC probability of release (PubMed:26738595). May also contribute to
CC synaptic facilitation by regulating synaptic vesicle replenishment, a
CC process required to ensure that synaptic vesicles are ready for the
CC arrival of the next action potential: SYT7 is required for synaptic
CC vesicle replenishment by acting as a sensor for Ca(2+) and by forming a
CC complex with calmodulin (PubMed:24569478). Also acts as a regulator of
CC Ca(2+)-dependent insulin and glucagon secretion in beta-cells
CC (PubMed:18308938, PubMed:19171650). Triggers exocytosis by promoting
CC fusion pore opening and fusion pore expansion in chromaffin cells
CC (PubMed:20956309). Also regulates the secretion of some non-synaptic
CC secretory granules of specialized cells (By similarity).
CC {ECO:0000250|UniProtKB:Q62747, ECO:0000269|PubMed:16982801,
CC ECO:0000269|PubMed:18308938, ECO:0000269|PubMed:18539119,
CC ECO:0000269|PubMed:19171650, ECO:0000269|PubMed:20956309,
CC ECO:0000269|PubMed:21041449, ECO:0000269|PubMed:24569478,
CC ECO:0000269|PubMed:25860611, ECO:0000269|PubMed:26738595}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041,
CC ECO:0000269|PubMed:20824061};
CC Note=Binds 3 Ca(2+) ions per C2 domain. {ECO:0000255|PROSITE-
CC ProRule:PRU00041, ECO:0000269|PubMed:20824061};
CC -!- SUBUNIT: Homodimer (PubMed:10871604). Can also form heterodimers with
CC SYT6, SYT9 and SYT10 (PubMed:10871604). Interacts with calmodulin
CC (CALM1, CALM2 or CALM3) (PubMed:24569478). Interacts with CD63;
CC required for localization to lysosomes (PubMed:21041449). Interacts
CC with APP (PubMed:30429473). {ECO:0000269|PubMed:10871604,
CC ECO:0000269|PubMed:21041449, ECO:0000269|PubMed:24569478,
CC ECO:0000269|PubMed:30429473}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q62747};
CC Single-pass membrane protein {ECO:0000255}. Presynaptic cell membrane
CC {ECO:0000269|PubMed:11395007}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC membrane {ECO:0000269|PubMed:24569478}; Single-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:21041449,
CC ECO:0000269|PubMed:25860611}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000269|PubMed:16982801}; Single-pass membrane protein
CC {ECO:0000255}. Peroxisome membrane {ECO:0000269|PubMed:25860611};
CC Single-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle,
CC secretory vesicle membrane {ECO:0000250|UniProtKB:Q62747}; Single-pass
CC membrane protein {ECO:0000255}. Note=Localization to lysosomes is
CC dependent on N-terminal palmitoylation and interaction with CD63.
CC {ECO:0000269|PubMed:21041449}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Synaptotagmin VIIalpha {ECO:0000303|PubMed:12071850},
CC Syt7alpha {ECO:0000305};
CC IsoId=Q9R0N7-1; Sequence=Displayed;
CC Name=2; Synonyms=Synaptotagmin VIIgamma {ECO:0000303|PubMed:12071850},
CC Syt7gamma {ECO:0000305};
CC IsoId=Q9R0N7-2; Sequence=VSP_058236;
CC Name=3; Synonyms=Synaptotagmin VIIbeta {ECO:0000303|PubMed:12071850},
CC Syt7beta {ECO:0000305};
CC IsoId=Q9R0N7-3; Sequence=VSP_058235;
CC Name=4;
CC IsoId=Q9R0N7-4; Sequence=VSP_058237;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in insulin-secreting
CC cells (PubMed:18308938). Present in glucagon-secreting cells (at
CC protein level) (PubMed:19171650). {ECO:0000269|PubMed:18308938,
CC ECO:0000269|PubMed:19171650}.
CC -!- DOMAIN: The C2 domains bind Ca(2+) and membranes. Binding to membranes
CC involves Ca(2+)-dependent phospholipid binding. Compared to other
CC members of the family, the C2 domains of SYT7 dock and insert into
CC cellular membranes in response to intracellular Ca(2+) concentrations
CC that are lower than those required for other synaptotagmins. The two C2
CC domains bind independently to planar membranes, without interdomain
CC cooperativity. Moreover, SYT7 C2 domains insert more deeply into
CC membranes compared to other synaptotagmins.
CC {ECO:0000250|UniProtKB:O43581}.
CC -!- PTM: Palmitoylated at its vesicular N-terminus; palmitoylation is
CC required for localization to lysosome and phagocytosis in macrophages.
CC {ECO:0000269|PubMed:21041449}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice were born at the
CC expected Mendelian ratio and do not show gross abnormalities and/or
CC obvious neurological defects. Mice have a normal life span and are
CC fertile, although reproductive capacity is declining faster with age
CC (PubMed:12925704). Embryonic fibroblasts from Syt7 deficient mice are
CC less susceptible to Trypanosoma cruzi invasion, and display impaired
CC lysosomal exocytosis and resealing after wounding (PubMed:12925704).
CC Mutant mice display impaired insulin secretion: they exhibit normal
CC insulin sensitivity and normal metabolic and Ca(2+) responses but
CC impaired insulin release, due to Ca(2+)-sensing defects
CC (PubMed:18308938). Impaired glucagon secretion (PubMed:19171650).
CC Neurons show enhanced synaptic depression: spontaneous synaptic vesicle
CC release is unaffected, while replenishment is impaired
CC (PubMed:24569478). Abolished synaptic facilitation at all synapses
CC except for mossy fiber synapses, where the remaining enhancement is
CC consistent with use-dependent spike broadening that occurs at this
CC synapse (PubMed:26738595). The loss of facilitation is not due to
CC slowed recovery from depression. The initial probability of release and
CC the presynaptic residual Ca(2+) signals are not affected
CC (PubMed:26738595). {ECO:0000269|PubMed:12925704,
CC ECO:0000269|PubMed:18308938, ECO:0000269|PubMed:19171650,
CC ECO:0000269|PubMed:24569478, ECO:0000269|PubMed:26738595}.
CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform.
CC {ECO:0000269|PubMed:12071850}.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
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DR EMBL; AB026804; BAA85776.1; -; mRNA.
DR EMBL; AB075900; BAC44832.1; -; mRNA.
DR EMBL; AB075901; BAC44833.1; -; mRNA.
DR EMBL; AC124169; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC105660; AAI05661.1; -; mRNA.
DR EMBL; BC139806; AAI39807.1; -; mRNA.
DR CCDS; CCDS29575.1; -. [Q9R0N7-1]
DR CCDS; CCDS29576.1; -. [Q9R0N7-3]
DR CCDS; CCDS50388.1; -. [Q9R0N7-4]
DR RefSeq; NP_061271.1; NM_018801.3. [Q9R0N7-1]
DR RefSeq; NP_775090.1; NM_173067.3. [Q9R0N7-3]
DR RefSeq; NP_775091.2; NM_173068.2. [Q9R0N7-4]
DR PDB; 3N5A; X-ray; 1.44 A; A=266-403.
DR PDB; 6LCY; X-ray; 2.30 A; A=263-403.
DR PDBsum; 3N5A; -.
DR PDBsum; 6LCY; -.
DR AlphaFoldDB; Q9R0N7; -.
DR SMR; Q9R0N7; -.
DR BioGRID; 207673; 4.
DR iPTMnet; Q9R0N7; -.
DR PhosphoSitePlus; Q9R0N7; -.
DR SwissPalm; Q9R0N7; -.
DR MaxQB; Q9R0N7; -.
DR PaxDb; Q9R0N7; -.
DR PRIDE; Q9R0N7; -.
DR ProteomicsDB; 254620; -. [Q9R0N7-1]
DR ProteomicsDB; 254621; -. [Q9R0N7-2]
DR ProteomicsDB; 254622; -. [Q9R0N7-3]
DR ProteomicsDB; 254623; -. [Q9R0N7-4]
DR ABCD; Q9R0N7; 1 sequenced antibody.
DR Antibodypedia; 2220; 272 antibodies from 33 providers.
DR Ensembl; ENSMUST00000073899; ENSMUSP00000073560; ENSMUSG00000024743. [Q9R0N7-1]
DR Ensembl; ENSMUST00000223586; ENSMUSP00000153482; ENSMUSG00000024743. [Q9R0N7-3]
DR Ensembl; ENSMUST00000224135; ENSMUSP00000153132; ENSMUSG00000024743. [Q9R0N7-4]
DR GeneID; 54525; -.
DR KEGG; mmu:54525; -.
DR UCSC; uc008gpp.2; mouse.
DR UCSC; uc008gpq.2; mouse. [Q9R0N7-1]
DR UCSC; uc012bin.1; mouse.
DR CTD; 9066; -.
DR MGI; MGI:1859545; Syt7.
DR VEuPathDB; HostDB:ENSMUSG00000024743; -.
DR eggNOG; KOG1028; Eukaryota.
DR GeneTree; ENSGT00940000157180; -.
DR HOGENOM; CLU_023008_11_3_1; -.
DR InParanoid; Q9R0N7; -.
DR OMA; QNHEANS; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; Q9R0N7; -.
DR TreeFam; TF315600; -.
DR BioGRID-ORCS; 54525; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Syt7; mouse.
DR PRO; PR:Q9R0N7; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9R0N7; protein.
DR Bgee; ENSMUSG00000024743; Expressed in medial dorsal nucleus of thalamus and 185 other tissues.
DR ExpressionAtlas; Q9R0N7; baseline and differential.
DR Genevisible; Q9R0N7; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043679; C:axon terminus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0030425; C:dendrite; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031045; C:dense core granule; ISO:MGI.
DR GO; GO:0032009; C:early phagosome; IDA:UniProtKB.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0042734; C:presynaptic membrane; IDA:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; IMP:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; ISO:MGI.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0030276; F:clathrin binding; ISO:MGI.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0000149; F:SNARE binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0019905; F:syntaxin binding; ISO:MGI.
DR GO; GO:1990927; P:calcium ion regulated lysosome exocytosis; IMP:UniProtKB.
DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; IMP:UniProtKB.
DR GO; GO:0099502; P:calcium-dependent activation of synaptic vesicle fusion; IDA:SynGO.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; ISO:MGI.
DR GO; GO:0071277; P:cellular response to calcium ion; IBA:GO_Central.
DR GO; GO:0006909; P:phagocytosis; IMP:UniProtKB.
DR GO; GO:0090385; P:phagosome-lysosome fusion; IMP:UniProtKB.
DR GO; GO:0001778; P:plasma membrane repair; IDA:MGI.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; ISO:MGI.
DR GO; GO:0046850; P:regulation of bone remodeling; IMP:UniProtKB.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0014059; P:regulation of dopamine secretion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0070092; P:regulation of glucagon secretion; IMP:UniProtKB.
DR GO; GO:0050796; P:regulation of insulin secretion; IMP:UniProtKB.
DR GO; GO:0050764; P:regulation of phagocytosis; IMP:UniProtKB.
DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; IDA:SynGO.
DR GO; GO:1990926; P:short-term synaptic potentiation; IDA:UniProtKB.
DR GO; GO:0036465; P:synaptic vesicle recycling; IMP:UniProtKB.
DR GO; GO:0090119; P:vesicle-mediated cholesterol transport; IDA:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR CDD; cd08386; C2A_Synaptotagmin-7; 1.
DR CDD; cd08405; C2B_Synaptotagmin-7; 1.
DR Gene3D; 2.60.40.150; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037732; C2A_Synaptotagmin-7.
DR InterPro; IPR037741; C2B_Synaptotagmin-7.
DR InterPro; IPR001565; Synaptotagmin.
DR InterPro; IPR015427; Synaptotagmin7.
DR PANTHER; PTHR10024:SF358; PTHR10024:SF358; 2.
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; Alternative splicing; Calcium; Calmodulin-binding;
KW Cell membrane; Cell projection; Cytoplasmic vesicle; Exocytosis;
KW Lipoprotein; Lysosome; Membrane; Metal-binding; Methylation; Palmitate;
KW Peroxisome; Phosphoprotein; Reference proteome; Repeat; Synapse;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..403
FT /note="Synaptotagmin-7"
FT /id="PRO_0000183958"
FT TOPO_DOM 1..16
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..403
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 135..255
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 266..399
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 53..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 166
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 166
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 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000305|PubMed:26738595"
FT BINDING 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000305|PubMed:26738595"
FT BINDING 227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000305|PubMed:26738595"
FT BINDING 227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000305|PubMed:26738595"
FT BINDING 227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000305|PubMed:26738595"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000305|PubMed:26738595"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000305|PubMed:26738595"
FT BINDING 297
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000269|PubMed:20824061, ECO:0007744|PDB:3N5A"
FT BINDING 297
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000269|PubMed:20824061, ECO:0007744|PDB:3N5A"
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 ECO:0000269|PubMed:20824061, ECO:0007744|PDB:3N5A"
FT BINDING 357
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000269|PubMed:20824061, ECO:0007744|PDB:3N5A"
FT BINDING 357
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000269|PubMed:20824061, ECO:0007744|PDB:3N5A"
FT BINDING 359
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000269|PubMed:20824061, ECO:0007744|PDB:3N5A"
FT BINDING 359
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000269|PubMed:20824061, ECO:0007744|PDB:3N5A"
FT BINDING 359
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000269|PubMed:20824061, ECO:0007744|PDB:3N5A"
FT BINDING 362
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000269|PubMed:20824061, ECO:0007744|PDB:3N5A"
FT BINDING 365
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000269|PubMed:20824061,
FT ECO:0007744|PDB:3N5A"
FT BINDING 365
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041,
FT ECO:0000269|PubMed:20824061, ECO:0007744|PDB:3N5A"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 58
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62747"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 71
FT /note="I -> INDLDRDFWNNNESTVQQKWSSYPPKEFILNISPYAPYGDPRLSL
FT (in isoform 3)"
FT /id="VSP_058235"
FT VAR_SEQ 72
FT /note="K -> NFEDSTLSTATTLESIPSSAGEPKCQRPRTLMRQQSLQQPLSQNQRG
FT RQPSQPTTSWDHVVGQIRNRGLDMKSFLEGRMVVLSLVLGLSEQDDFANIPDLQNPGTQ
FT QNQNAQGDKR (in isoform 2)"
FT /id="VSP_058236"
FT VAR_SEQ 72
FT /note="K -> NFEDSTLSTATTLESIPSSAGEPKCQRPRTLMRQQSLQQPLSQNQQG
FT RQPSQPTTSQSLGQLQAHAASAPGSNPRAYGRGQARQGTSAGSKYRAAGGRSRSNPGSW
FT DHVVGQIRNRGLDMKSFLEGRMVVLSLVLGLSEQDDFANIPDLQNPGTQQNQNAQGDKR
FT (in isoform 4)"
FT /id="VSP_058237"
FT MUTAGEN 35..41
FT /note="CGLCHWC->SGLSHWS: Abolishes palmitoylation. Impaired
FT phagocytosis and localization to lysosomes."
FT /evidence="ECO:0000269|PubMed:21041449"
FT MUTAGEN 225..233
FT /note="DYDRFSRND->AYARFSRNA: In C2A*; loss of function due
FT to abolished Ca(2+)-binding to the first C2 domain.
FT Impaired ability to mediate synaptic facilitation."
FT /evidence="ECO:0000269|PubMed:26738595"
FT MUTAGEN 225..227
FT /note="DYD->NYN: Loss of Ca(2+)-binding in the first C2
FT domain. Impaired delivery of lysosomal membrane to nascent
FT phagosomes; when associated with 357-N--N-359. Impaired
FT synaptic vesicle replenishment; when associated with 357-
FT N--N-359."
FT /evidence="ECO:0000269|PubMed:16982801,
FT ECO:0000269|PubMed:24569478"
FT MUTAGEN 357..359
FT /note="DKD->NKN: Loss of Ca(2+)-binding in the second C2
FT domain. Impaired delivery of lysosomal membrane to nascent
FT phagosomes; when associated with 225-N--N-227. Impaired
FT synaptic vesicle replenishment; when associated with 225-
FT N--N-227."
FT /evidence="ECO:0000269|PubMed:16982801,
FT ECO:0000269|PubMed:24569478"
FT STRAND 269..277
FT /evidence="ECO:0007829|PDB:3N5A"
FT TURN 278..281
FT /evidence="ECO:0007829|PDB:3N5A"
FT STRAND 282..292
FT /evidence="ECO:0007829|PDB:3N5A"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:3N5A"
FT STRAND 304..312
FT /evidence="ECO:0007829|PDB:3N5A"
FT STRAND 315..321
FT /evidence="ECO:0007829|PDB:3N5A"
FT STRAND 332..340
FT /evidence="ECO:0007829|PDB:3N5A"
FT HELIX 343..348
FT /evidence="ECO:0007829|PDB:3N5A"
FT STRAND 349..357
FT /evidence="ECO:0007829|PDB:3N5A"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:3N5A"
FT STRAND 365..376
FT /evidence="ECO:0007829|PDB:3N5A"
FT HELIX 378..389
FT /evidence="ECO:0007829|PDB:3N5A"
FT STRAND 395..400
FT /evidence="ECO:0007829|PDB:3N5A"
FT MOD_RES Q9R0N7-4:169
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES Q9R0N7-4:171
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
SQ SEQUENCE 403 AA; 45472 MW; 4E63C5779C2ED43E CRC64;
MYRDPEAASP GAPTRDVLLV SAIITVSLSV TIVLCGLCHW CQRKLGKRYK NSLETVGTPD
SGRGRGEKKA IKLPAGGKAV NTAPVPGQTP HDESDRRTET RSSVSDLVNS LTSEMLMLSP
GSEEDEAHEG CSRENLGRIQ FSVGYNFQES TLTVKVMKAQ ELPAKDFSGT SDPFVKIYLL
PDKKHKLETK VKRKNLNPHW NETFLFEGFP YEKVVQRVLY LQVLDYDRFS RNDPIGEVSI
PLNKVDLTQM QTFWKDLKPC SDGSGSRGEL LLSLCYNPSA NSIIVNIIKA RNLKAMDIGG
TSDPYVKVWL MYKDKRVEKK KTVTKKRNLN PIFNESFAFD IPTEKLRETT IIITVMDKDK
LSRNDVIGKI YLSWKSGPGE VKHWKDMIAR PRQPVAQWHQ LKA
