SYT3_MOUSE
ID SYT3_MOUSE Reviewed; 587 AA.
AC O35681; P97791; Q80WV1;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Synaptotagmin-3;
DE AltName: Full=Synaptotagmin III;
DE Short=SytIII;
GN Name=Syt3;
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].
RC STRAIN=BALB/cJ; TISSUE=Brain;
RA Kataoka M.;
RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CYSTEINE MOTIF, SUBUNIT, DISULFIDE BOND, AND
RP MUTAGENESIS OF CYS-10; CYS-21 AND CYS-33.
RC STRAIN=ICR;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4]
RP SUBUNIT.
RC STRAIN=ICR; TISSUE=Cerebellum;
RX PubMed=10531344; DOI=10.1074/jbc.274.44.31428;
RA Fukuda M., Mikoshiba K.;
RT "A novel alternatively spliced variant of synaptotagmin VI lacking a
RT transmembrane domain. Implications for distinct functions of the two
RT isoforms.";
RL J. Biol. Chem. 274:31428-31434(1999).
RN [5]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-286, AND IDENTIFICATION BY MASS
RP 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).
CC -!- FUNCTION: Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of
CC secretory vesicles through Ca(2+) and phospholipid binding to the C2
CC domain. Ca(2+) induces binding of the C2-domains to phospholipid
CC membranes and to assembled SNARE-complexes; both actions contribute to
CC triggering exocytosis. Plays a role in dendrite formation by
CC melanocytes. {ECO:0000250|UniProtKB:P40748,
CC ECO:0000250|UniProtKB:Q9BQG1}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domains. {ECO:0000250|UniProtKB:P40748};
CC -!- SUBUNIT: Homodimer; disulfide-linked via the cysteine motif
CC (PubMed:10531343). Can also form heterodimers with SYT6, SYT9 and SYT10
CC (PubMed:10531343, PubMed:10531344). {ECO:0000269|PubMed:10531343,
CC ECO:0000269|PubMed:10531344}.
CC -!- INTERACTION:
CC O35681; Q9R0N4: Syt10; NbExp=2; IntAct=EBI-457995, EBI-5239459;
CC O35681; O35681: Syt3; NbExp=4; IntAct=EBI-457995, EBI-457995;
CC O35681; Q9R0N8: Syt6; NbExp=2; IntAct=EBI-457995, EBI-5239378;
CC O35681; Q9R0N9: Syt9; NbExp=2; IntAct=EBI-457995, EBI-458006;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P40748};
CC Single-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle,
CC secretory vesicle membrane {ECO:0000305}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- DOMAIN: The cysteine motif mediates homo- or heterodimer formation via
CC formation of disulfide bonds. {ECO:0000269|PubMed:10531343}.
CC -!- DOMAIN: The first C2 domain mediates Ca(2+)-dependent phospholipid
CC binding. {ECO:0000250|UniProtKB:P40748}.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
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DR EMBL; D45858; BAA08292.1; -; mRNA.
DR EMBL; AB000893; BAA19204.1; -; mRNA.
DR EMBL; BC051969; AAH51969.1; -; mRNA.
DR CCDS; CCDS21205.1; -.
DR RefSeq; NP_001107588.1; NM_001114116.1.
DR RefSeq; NP_057872.3; NM_016663.3.
DR AlphaFoldDB; O35681; -.
DR SMR; O35681; -.
DR BioGRID; 203613; 6.
DR IntAct; O35681; 7.
DR MINT; O35681; -.
DR STRING; 10090.ENSMUSP00000112432; -.
DR iPTMnet; O35681; -.
DR PhosphoSitePlus; O35681; -.
DR SwissPalm; O35681; -.
DR MaxQB; O35681; -.
DR PaxDb; O35681; -.
DR PeptideAtlas; O35681; -.
DR PRIDE; O35681; -.
DR ProteomicsDB; 254798; -.
DR ABCD; O35681; 1 sequenced antibody.
DR DNASU; 20981; -.
DR GeneID; 20981; -.
DR KEGG; mmu:20981; -.
DR CTD; 84258; -.
DR MGI; MGI:99665; Syt3.
DR eggNOG; KOG1028; Eukaryota.
DR InParanoid; O35681; -.
DR PhylomeDB; O35681; -.
DR BioGRID-ORCS; 20981; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Syt3; mouse.
DR PRO; PR:O35681; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O35681; protein.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0099699; C:integral component of synaptic membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030276; F:clathrin binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISO:MGI.
DR GO; GO:0001786; F:phosphatidylserine binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0000149; F:SNARE binding; ISO:MGI.
DR GO; GO:0019905; F:syntaxin binding; ISO:MGI.
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; IBA:GO_Central.
DR GO; GO:1903861; P:positive regulation of dendrite extension; ISO:MGI.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; ISO:MGI.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; ISO:MGI.
DR GO; GO:0014059; P:regulation of dopamine secretion; IBA:GO_Central.
DR GO; GO:0051592; P:response to calcium ion; ISO:MGI.
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; IPR028682; SYT3.
DR PANTHER; PTHR10024:SF176; PTHR10024:SF176; 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 Calcium; Cell membrane; Cytoplasmic vesicle; Differentiation;
KW Disulfide bond; Exocytosis; Membrane; Metal-binding; Methylation;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..587
FT /note="Synaptotagmin-3"
FT /id="PRO_0000183946"
FT TOPO_DOM 1..54
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 55..75
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 76..587
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 296..417
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 428..562
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 10..34
FT /note="Cysteine motif"
FT /evidence="ECO:0000269|PubMed:10531343"
FT REGION 183..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 210..248
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 327
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 327
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 333
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 385
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 385
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 386
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 387
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 387
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 387
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 393
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 393
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 459
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 465
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 519
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 521
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 286
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MUTAGEN 10
FT /note="C->A: Abolishes disulfide-dependent
FT homodimerization. Abolishes disulfide-dependent
FT homodimerization; when associated with A-21."
FT /evidence="ECO:0000269|PubMed:10531343"
FT MUTAGEN 21
FT /note="C->A: Abolishes disulfide-dependent
FT homodimerization; when associated with A-10. Does not
FT affect disulfide-dependent homodimerization; when
FT associated with A-33."
FT /evidence="ECO:0000269|PubMed:10531343"
FT MUTAGEN 33
FT /note="C->A: Does not affect disulfide-dependent
FT homodimerization; when associated with A-21."
FT /evidence="ECO:0000269|PubMed:10531343"
FT CONFLICT 111
FT /note="V -> L (in Ref. 1; BAA08292)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="P -> A (in Ref. 1; BAA08292)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="H -> Q (in Ref. 1; BAA08292/BAA19204)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 587 AA; 63254 MW; 87EAEAADF22D5A4C CRC64;
MSGDYEDDLC RRALILVSDL CARVRDADTN DRCQEFNELR IRGYPRGPDA DISVSLLSVI
VTFCGIVLLG VSLFVSWKLC WVPWRDKGGS AVGGGPLRKD LAPGVGLAGL VGGGGHHLGA
SLGGHPLLGG PHHHGHTAHH PPFAELLEPG GLGGSEPPEP SYLDMDSYPE AAVASVVAAG
VKPSQTSPEL PSEGGTGSGL LLLPPSGGGL PSAQSHQQVT SLAPTTRYPA LPRPLTQQTL
TTQADPSTEE RPPALPLPLP GGEEKAKLIG QIKPELYQGT GPGGRRGGGS GEAGAPCGRI
SFALRYLYGS DHLVVRILQA LDLPAKDSNG FSDPYVKIYL LPDRKKKFQT KVHRKTLNPI
FNETFQFSVP LAELAQRKLH FSVYDFDRFS RHDLIGQVVL DNLLELAEQP PDRPLWRDIL
EGGSEKADLG ELNFSLCYLP TAGRLTVTII KASNLKAMDL TGFSDPYVKA SLISEGRRLK
KRKTSIKKNT LNPTYNEALV FDVAPESVEN VGLSIAVVDY DCIGHNEVIG VCRVGPEAAD
PHGREHWAEM LANPRKPVEH WHQLVEEKTL SSFTKGGKGL SEKENSE
