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 04-NOV-2026, entry version 191. 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. 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 IN COMPLEX WITH CALCIUM, 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; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00041, ECO:0000269|PubMed:11823420, CC 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_006229041.1; XM_006228979.5. 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 AlphaFoldDB; P40748; -. DR SMR; P40748; -. DR BioGRID; 247760; 1. DR FunCoup; P40748; 690. DR IntAct; P40748; 5. DR STRING; 10116.ENSRNOP00000026251; -. DR iPTMnet; P40748; -. DR PhosphoSitePlus; P40748; -. DR PaxDb; 10116-ENSRNOP00000026251; -. DR ABCD; P40748; 1 sequenced antibody. DR GeneID; 25731; -. DR KEGG; rno:25731; -. DR UCSC; RGD:3805; rat. DR AGR; RGD:3805; -. DR CTD; 84258; -. DR RGD; 3805; Syt3. DR eggNOG; KOG1028; Eukaryota. DR InParanoid; P40748; -. DR OMA; ADTNDRC; -. DR OrthoDB; 67700at2759; -. DR PhylomeDB; P40748; -. DR EvolutionaryTrace; P40748; -. DR PRO; PR:P40748; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005768; C:endosome; ISO:RGD. DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; EXP:UniProtKB. DR GO; GO:0098794; C:postsynapse; ISO:RGD. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:0097060; C:synaptic membrane; IDA:SynGO. DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005509; F:calcium ion binding; TAS:RGD. DR GO; GO:0061891; F:calcium ion sensor activity; 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:0017156; P:calcium-ion regulated exocytosis; TAS:RGD. DR GO; GO:0007268; P:chemical synaptic transmission; 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:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; ISO:RGD. 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 CDD; cd08385; C2A_Synaptotagmin-1-5-6-9-10; 1. DR CDD; cd08403; C2B_Synaptotagmin-3-5-6-9-10; 1. DR FunFam; 2.60.40.150:FF:000005; Synaptotagmin 6; 1. DR FunFam; 2.60.40.150:FF:000011; Synaptotagmin 6; 1. DR Gene3D; 2.60.40.150; C2 domain; 2. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR001565; Synaptotagmin. DR PANTHER; PTHR10024; SYNAPTOTAGMIN; 1. DR PANTHER; PTHR10024:SF176; SYNAPTOTAGMIN-3; 1. DR Pfam; PF00168; C2; 2. DR PRINTS; PR00360; C2DOMAIN. DR PRINTS; PR00399; SYNAPTOTAGMN. DR SMART; SM00239; C2; 2. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 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 COMPBIAS 183..205 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 213..222 FT /note="Polar residues" 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 FT phospholipid-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 //