SYT3_HUMAN
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 03-AUG-2022, entry version 177.
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;
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. 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; 17.
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; Q9BQG1; -.
DR PeptideAtlas; Q9BQG1; -.
DR PRIDE; Q9BQG1; -.
DR ProteomicsDB; 78676; -.
DR ABCD; Q9BQG1; 1 sequenced antibody.
DR Antibodypedia; 32348; 212 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 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; PWRDKGA; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; Q9BQG1; -.
DR TreeFam; TF315600; -.
DR PathwayCommons; Q9BQG1; -.
DR SignaLink; Q9BQG1; -.
DR BioGRID-ORCS; 84258; 20 hits in 1073 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 83 other tissues.
DR ExpressionAtlas; Q9BQG1; baseline and differential.
DR Genevisible; Q9BQG1; HS.
DR GO; GO:0005768; C:endosome; IDA:LIFEdb.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0019905; F:syntaxin 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 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; 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
