ID   SYT3_HUMAN              Reviewed;         590 AA.
AC   Q9BQG1; Q8N5Z1; Q8N640;
DT   18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   24-JAN-2024, entry version 185.
DE   RecName: Full=Synaptotagmin-3;
DE   AltName: Full=Synaptotagmin III;
DE            Short=SytIII;
GN   Name=SYT3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Amygdala;
RX   PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA   Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA   Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA   Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA   Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA   Klein M., Poustka A.;
RT   "Towards a catalog of human genes and proteins: sequencing and analysis of
RT   500 novel complete protein coding human cDNAs.";
RL   Genome Res. 11:422-435(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   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   [3]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=23999003; DOI=10.1016/j.jdermsci.2013.07.010;
RA   Yoo J.C., Lim T.Y., Park J.S., Hah Y.S., Park N., Hong S.G., Park J.Y.,
RA   Yoon T.J.;
RT   "SYT14L, especially its C2 domain, is involved in regulating melanocyte
RT   differentiation.";
RL   J. Dermatol. Sci. 72:246-251(2013).
RN   [4]
RP   VARIANT [LARGE SCALE ANALYSIS] PHE-474.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
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 (By similarity). Plays a role in dendrite
CC       formation by melanocytes (PubMed:23999003).
CC       {ECO:0000250|UniProtKB:P40748, ECO:0000269|PubMed:23999003}.
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE-
CC         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. Can also
CC       form heterodimers with SYT6, SYT9 and SYT10.
CC       {ECO:0000250|UniProtKB:O35681}.
CC   -!- INTERACTION:
CC       Q9BQG1; P07339: CTSD; NbExp=3; IntAct=EBI-17284568, EBI-2115097;
CC       Q9BQG1; P42858: HTT; NbExp=12; IntAct=EBI-17284568, EBI-466029;
CC       Q9BQG1; P48051: KCNJ6; NbExp=3; IntAct=EBI-17284568, EBI-12017638;
CC       Q9BQG1; Q6IN84: MRM1; NbExp=3; IntAct=EBI-17284568, EBI-5454865;
CC       Q9BQG1; P07196: NEFL; NbExp=3; IntAct=EBI-17284568, EBI-475646;
CC       Q9BQG1; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-17284568, EBI-396669;
CC       Q9BQG1; O76024: WFS1; NbExp=3; IntAct=EBI-17284568, EBI-720609;
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   -!- TISSUE SPECIFICITY: Expressed in melanocytes (PubMed:23999003).
CC       {ECO:0000269|PubMed:23999003}.
CC   -!- DOMAIN: The cysteine motif mediates homo- or heterodimer formation via
CC       formation of disulfide bonds. {ECO:0000250|UniProtKB:O35681}.
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; AL136594; CAB66529.1; -; mRNA.
DR   EMBL; BC028379; AAH28379.1; -; mRNA.
DR   EMBL; BC031067; AAH31067.1; -; mRNA.
DR   CCDS; CCDS12798.1; -.
DR   RefSeq; NP_001153800.1; NM_001160328.1.
DR   RefSeq; NP_001153801.1; NM_001160329.1.
DR   RefSeq; NP_115674.1; NM_032298.2.
DR   RefSeq; XP_011525692.1; XM_011527390.2.
DR   RefSeq; XP_011525693.1; XM_011527391.2.
DR   AlphaFoldDB; Q9BQG1; -.
DR   SMR; Q9BQG1; -.
DR   BioGRID; 123985; 18.
DR   ELM; Q9BQG1; -.
DR   IntAct; Q9BQG1; 15.
DR   STRING; 9606.ENSP00000340914; -.
DR   iPTMnet; Q9BQG1; -.
DR   PhosphoSitePlus; Q9BQG1; -.
DR   BioMuta; SYT3; -.
DR   DMDM; 18202733; -.
DR   EPD; Q9BQG1; -.
DR   MassIVE; Q9BQG1; -.
DR   MaxQB; Q9BQG1; -.
DR   PaxDb; 9606-ENSP00000340914; -.
DR   PeptideAtlas; Q9BQG1; -.
DR   ProteomicsDB; 78676; -.
DR   ABCD; Q9BQG1; 1 sequenced antibody.
DR   Antibodypedia; 32348; 235 antibodies from 27 providers.
DR   DNASU; 84258; -.
DR   Ensembl; ENST00000338916.8; ENSP00000340914.3; ENSG00000213023.11.
DR   Ensembl; ENST00000593901.5; ENSP00000468982.1; ENSG00000213023.11.
DR   Ensembl; ENST00000600079.6; ENSP00000469398.1; ENSG00000213023.11.
DR   GeneID; 84258; -.
DR   KEGG; hsa:84258; -.
DR   MANE-Select; ENST00000600079.6; ENSP00000469398.1; NM_001160329.2; NP_001153801.1.
DR   UCSC; uc002pst.3; human.
DR   AGR; HGNC:11511; -.
DR   CTD; 84258; -.
DR   DisGeNET; 84258; -.
DR   GeneCards; SYT3; -.
DR   HGNC; HGNC:11511; SYT3.
DR   HPA; ENSG00000213023; Tissue enriched (brain).
DR   MIM; 600327; gene.
DR   neXtProt; NX_Q9BQG1; -.
DR   OpenTargets; ENSG00000213023; -.
DR   PharmGKB; PA36292; -.
DR   VEuPathDB; HostDB:ENSG00000213023; -.
DR   eggNOG; KOG1028; Eukaryota.
DR   GeneTree; ENSGT00940000161770; -.
DR   HOGENOM; CLU_023008_8_3_1; -.
DR   InParanoid; Q9BQG1; -.
DR   OMA; SHNERCD; -.
DR   OrthoDB; 590187at2759; -.
DR   PhylomeDB; Q9BQG1; -.
DR   TreeFam; TF315600; -.
DR   PathwayCommons; Q9BQG1; -.
DR   SignaLink; Q9BQG1; -.
DR   BioGRID-ORCS; 84258; 20 hits in 1149 CRISPR screens.
DR   GeneWiki; SYT3; -.
DR   GenomeRNAi; 84258; -.
DR   Pharos; Q9BQG1; Tbio.
DR   PRO; PR:Q9BQG1; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q9BQG1; Protein.
DR   Bgee; ENSG00000213023; Expressed in primary visual cortex and 84 other cell types or tissues.
DR   ExpressionAtlas; Q9BQG1; baseline and differential.
DR   GO; GO:0005768; C:endosome; IDA:LIFEdb.
DR   GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
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; IBA:GO_Central.
DR   GO; GO:0030276; F:clathrin binding; IBA:GO_Central.
DR   GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR   GO; GO:0000149; F:SNARE binding; IBA:GO_Central.
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; IDA:UniProtKB.
DR   GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IBA:GO_Central.
DR   GO; GO:0014059; P:regulation of dopamine secretion; 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   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.
DR   Genevisible; Q9BQG1; HS.
PE   1: Evidence at protein level;
KW   Calcium; Cell membrane; Cytoplasmic vesicle; Differentiation;
KW   Disulfide bond; Membrane; Metal-binding; Methylation; Reference proteome;
KW   Repeat; Transmembrane; Transmembrane helix.
FT   CHAIN           1..590
FT                   /note="Synaptotagmin-3"
FT                   /id="PRO_0000183945"
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..590
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          299..420
FT                   /note="C2 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          431..565
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          143..220
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          234..260
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          273..295
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         330
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         330
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         336
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         389
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         390
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         390
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
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="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         396
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         396
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         462
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   BINDING         468
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   BINDING         524
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   MOD_RES         284
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:O35681"
FT   VARIANT         474
FT                   /note="S -> F (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036389"
FT   CONFLICT        82
FT                   /note="P -> H (in Ref. 2; AAH31067)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        324
FT                   /note="L -> M (in Ref. 2; AAH28379)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   590 AA;  63304 MW;  1E6B9F2CF44E7935 CRC64;
     MSGDYEDDLC RRALILVSDL CARVRDADTN DRCQEFNDRI RGYPRGPDAD ISVSLLSVIV
     TFCGIVLLGV SLFVSWKLCW VPWRDKGGSA VGGGPLRKDL GPGVGLAGLV GGGGHHLAAG
     LGGHPLLGGP HHHAHAAHHP PFAELLEPGS LGGSDTPEPS YLDMDSYPEA AAAAVAAGVK
     PSQTSPELPS EGGAGSGLLL LPPSGGGLPS AQSHQQVTSL APTTRYPALP RPLTQQTLTS
     QPDPSSEERP PALPLPLPGG EEKAKLIGQI KPELYQGTGP GGRRSGGGPG SGEAGTGAPC
     GRISFALRYL YGSDQLVVRI LQALDLPAKD SNGFSDPYVK IYLLPDRKKK FQTKVHRKTL
     NPVFNETFQF SVPLAELAQR KLHFSVYDFD RFSRHDLIGQ VVLDNLLELA EQPPDRPLWR
     DIVEGGSEKA DLGELNFSLC YLPTAGRLTV TIIKASNLKA MDLTGFSDPY VKASLISEGR
     RLKKRKTSIK KNTLNPTYNE ALVFDVAPES VENVGLSIAV VDYDCIGHNE VIGVCRVGPD
     AADPHGREHW AEMLANPRKP VEHWHQLVEE KTVTSFTKGS KGLSEKENSE
//