SYT3_RAT
ID SYT3_RAT Reviewed; 588 AA.
AC P40748; Q925B7;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Synaptotagmin-3;
DE AltName: Full=Synaptotagmin III;
DE Short=SytIII;
GN Name=Syt3;
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], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=8163462; DOI=10.1016/s0021-9258(17)32622-4;
RA Mizuta M., Inagaki N., Nemoto Y., Matsukura S., Takahashi M., Seino S.;
RT "Synaptotagmin III is a novel isoform of rat synaptotagmin expressed in
RT endocrine and neuronal cells.";
RL J. Biol. Chem. 269:11675-11678(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shin O.-H., Li C., Ullrich B., Zhang J.Z., Anderson R.G.W., Brose N.,
RA Suedhof T.C.;
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SUBCELLULAR LOCATION, FUNCTION, COFACTOR, DOMAIN, AND MUTAGENESIS OF
RP ASP-334.
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 [4]
RP FUNCTION.
RX PubMed=18508778; DOI=10.1074/jbc.m709628200;
RA Bhalla A., Chicka M.C., Chapman E.R.;
RT "Analysis of the synaptotagmin family during reconstituted membrane fusion.
RT Uncovering a class of inhibitory isoforms.";
RL J. Biol. Chem. 283:21799-21807(2008).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 293-588.
RX PubMed=10545502; DOI=10.1083/jcb.147.3.589;
RA Sutton R.B., Ernst J.A., Brunger A.T.;
RT "Crystal structure of the cytosolic C2A-C2B domains of synaptotagmin III.
RT Implications for Ca(2+)-independent SNARE complex interaction.";
RL J. Cell Biol. 147:589-598(1999).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 292-587 IN COMPLEX WITH CALCIUM,
RP AND COFACTOR.
RX PubMed=20173762; DOI=10.1038/nsmb.1764;
RA Vrljic M., Strop P., Ernst J.A., Sutton R.B., Chu S., Brunger A.T.;
RT "Molecular mechanism of the synaptotagmin-SNARE interaction in Ca2+-
RT triggered vesicle fusion.";
RL Nat. Struct. Mol. Biol. 17:325-331(2010).
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 (PubMed:11823420, PubMed:18508778). Plays a role
CC in dendrite formation by melanocytes (By similarity).
CC {ECO:0000250|UniProtKB:Q9BQG1, ECO:0000269|PubMed:11823420,
CC ECO:0000269|PubMed:18508778}.
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:20173762};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domains. {ECO:0000269|PubMed:20173762};
CC -!- SUBUNIT: Homodimer; disulfide-linked via the cysteine motif. Can also
CC form heterodimers with SYT6, SYT9 and SYT10.
CC {ECO:0000250|UniProtKB:O35681}.
CC -!- INTERACTION:
CC P40748; P19491: Gria2; NbExp=3; IntAct=EBI-458106, EBI-77718;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11823420};
CC Single-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle,
CC secretory vesicle membrane {ECO:0000305}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Brain, various endocrine tissues and hormone-
CC secreting clonal cells. {ECO:0000269|PubMed:8163462}.
CC -!- DOMAIN: The first C2 domain mediates Ca(2+)-dependent phospholipid
CC binding. {ECO:0000269|PubMed:11823420}.
CC -!- DOMAIN: The cysteine motif mediates homo- or heterodimer formation via
CC formation of disulfide bonds. {ECO:0000250|UniProtKB:O35681}.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
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DR EMBL; D28512; BAA05870.1; -; mRNA.
DR EMBL; AF375464; AAK56959.1; -; mRNA.
DR PIR; A53563; A53563.
DR RefSeq; NP_061995.1; NM_019122.1.
DR RefSeq; XP_006229040.1; XM_006228978.3.
DR RefSeq; XP_006229041.1; XM_006228979.3.
DR RefSeq; XP_008757547.1; XM_008759325.2.
DR RefSeq; XP_017444322.1; XM_017588833.1.
DR PDB; 1DQV; X-ray; 3.20 A; A=293-588.
DR PDB; 3HN8; X-ray; 3.50 A; A/B/C=292-587.
DR PDBsum; 1DQV; -.
DR PDBsum; 3HN8; -.
DR AlphaFoldDB; P40748; -.
DR SMR; P40748; -.
DR BioGRID; 247760; 1.
DR IntAct; P40748; 5.
DR STRING; 10116.ENSRNOP00000026251; -.
DR iPTMnet; P40748; -.
DR PhosphoSitePlus; P40748; -.
DR PaxDb; P40748; -.
DR PRIDE; P40748; -.
DR ABCD; P40748; 1 sequenced antibody.
DR GeneID; 25731; -.
DR KEGG; rno:25731; -.
DR UCSC; RGD:3805; rat.
DR CTD; 84258; -.
DR RGD; 3805; Syt3.
DR eggNOG; KOG1028; Eukaryota.
DR InParanoid; P40748; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; P40748; -.
DR TreeFam; TF315600; -.
DR EvolutionaryTrace; P40748; -.
DR PRO; PR:P40748; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0099699; C:integral component of synaptic membrane; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0045202; C:synapse; NAS:RGD.
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:RGD.
DR GO; GO:0030276; F:clathrin binding; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein 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:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0000149; F:SNARE binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0019905; F:syntaxin binding; IDA: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; IBA:GO_Central.
DR GO; GO:1903861; P:positive regulation of dendrite extension; ISO:RGD.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; IDA:RGD.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0014059; P:regulation of dopamine secretion; IBA:GO_Central.
DR GO; GO:0051592; P:response to calcium ion; IDA:RGD.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; TAS: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; 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 3D-structure; Calcium; Cell membrane; Cytoplasmic vesicle; Differentiation;
KW Disulfide bond; Membrane; Metal-binding; Methylation; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix.
FT CHAIN 1..588
FT /note="Synaptotagmin-3"
FT /id="PRO_0000183947"
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..588
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 297..418
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 429..563
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 10..34
FT /note="Cysteine motif"
FT /evidence="ECO:0000250|UniProtKB:O35681"
FT REGION 129..161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 183..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 238..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 328
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 328
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 334
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
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 386
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="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 388
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 388
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 388
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 391
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 394
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 394
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 460
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 466
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 520
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 522
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:0000250|UniProtKB:O35681"
FT MUTAGEN 334
FT /note="D->N: Abolishes Ca(2+)-dependent phospholipid-
FT binding."
FT /evidence="ECO:0000269|PubMed:11823420"
FT CONFLICT 287
FT /note="T -> S (in Ref. 2; AAK56959)"
FT /evidence="ECO:0000305"
FT CONFLICT 445
FT /note="L -> R (in Ref. 2; AAK56959)"
FT /evidence="ECO:0000305"
FT STRAND 300..306
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 313..322
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 335..340
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 344..350
FT /evidence="ECO:0007829|PDB:3HN8"
FT STRAND 361..369
FT /evidence="ECO:0007829|PDB:1DQV"
FT HELIX 372..375
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 381..386
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 389..391
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 395..400
FT /evidence="ECO:0007829|PDB:1DQV"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 412..414
FT /evidence="ECO:0007829|PDB:3HN8"
FT STRAND 416..419
FT /evidence="ECO:0007829|PDB:3HN8"
FT STRAND 432..440
FT /evidence="ECO:0007829|PDB:1DQV"
FT TURN 441..444
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 445..455
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 460..463
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 467..471
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 478..484
FT /evidence="ECO:0007829|PDB:3HN8"
FT STRAND 490..493
FT /evidence="ECO:0007829|PDB:3HN8"
FT STRAND 495..498
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 501..503
FT /evidence="ECO:0007829|PDB:3HN8"
FT HELIX 507..510
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 517..520
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 523..525
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 528..532
FT /evidence="ECO:0007829|PDB:1DQV"
FT HELIX 542..549
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 551..557
FT /evidence="ECO:0007829|PDB:1DQV"
FT STRAND 561..564
FT /evidence="ECO:0007829|PDB:3HN8"
FT HELIX 568..570
FT /evidence="ECO:0007829|PDB:3HN8"
SQ SEQUENCE 588 AA; 63313 MW; 9D9D33CF5BAD8331 CRC64;
MSGDYEDDLC RRALILVSDL CARIRDADTN DRCQEFNELR IRGYPRGPDA DISVSLLSVI
VTFCGIVLLG VSLFVSWKLC WVPWRDKGGS AVGGGPLRKD LAPGVGLAGL VGGGGHHLGA
SLGGHPLLGG PHHHAHPAHH PPFAELLEPG GLGGSEPPEP SYLDMDSYPE AAVASVVAAG
VKPSQTSPEL PSEGGTGSGL LLLPPSGGGL PSAQSHQQVT SLAPTTRYPA LPRPLTQQTL
TTQADPSSEE RPPALPLPLP GGEEKAKLIG QIKPELYQGT GPGGRRTGGG SGEAGAPCGR
ISFALRYLYG SDQLVVRILQ ALDLPAKDSN GFSDPYVKIY LLPDRKKKFQ TKVHRKTLNP
IFNETFQFSV PLAELAQRKL HFSVYDFDRF SRHDLIGQVV LDNLLELAEQ PPDRPLWRDI
LEGGSEKADL GELNFSLCYL PTAGLLTVTI IKASNLKAMD LTGFSDPYVK ASLISEGRRL
KKRKTSIKKN TLNPTYNEAL VFDVAPESVE NVGLSIAVVD YDCIGHNEVI GVCRVGPEAA
DPHGREHWAE MLANPRKPVE HWHQLVEEKT LSSFTKGGKG LSEKENSE
