SYT6_MOUSE
ID SYT6_MOUSE Reviewed; 511 AA.
AC Q9R0N8; E9QJV2; Q9QUK7;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Synaptotagmin-6;
DE AltName: Full=Synaptotagmin VI;
DE Short=SytVI;
GN Name=Syt6;
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] (ISOFORM 1), SUBUNIT, AND DISULFIDE BOND.
RC STRAIN=ICR; TISSUE=Cerebellum;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY (ISOFORMS 1 AND
RP 2), SUBUNIT, SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), AND ALTERNATIVE
RP SPLICING.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP SUBUNIT.
RX PubMed=10871604; DOI=10.1074/jbc.m001376200;
RA Fukuda M., Mikoshiba K.;
RT "Distinct self-oligomerization activities of synaptotagmin family. Unique
RT calcium-dependent oligomerization properties of synaptotagmin VII.";
RL J. Biol. Chem. 275:28180-28185(2000).
RN [5]
RP FUNCTION, AND INTERACTION WITH STX1A; STX1B AND STX2.
RX PubMed=15774481; DOI=10.1074/jbc.m412920200;
RA Hutt D.M., Baltz J.M., Ngsee J.K.;
RT "Synaptotagmin VI and VIII and syntaxin 2 are essential for the mouse sperm
RT acrosome reaction.";
RL J. Biol. Chem. 280:20197-20203(2005).
CC -!- FUNCTION: May be involved in Ca(2+)-dependent exocytosis of secretory
CC vesicles through Ca(2+) and phospholipid binding to the C2 domain or
CC may serve as Ca(2+) sensors in the process of vesicular trafficking and
CC exocytosis (By similarity). May mediate Ca(2+)-regulation of exocytosis
CC in acrosomal reaction in sperm (PubMed:15774481). {ECO:0000250,
CC ECO:0000269|PubMed:15774481}.
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: Isoform 1: Homodimer; disulfide-linked via the cysteine motif
CC (PubMed:10531343, PubMed:10531344). Isoform 1: Can also form
CC heterodimers with SYT3, SYT7, SYT9 and SYT10 (PubMed:10531343,
CC PubMed:10531344, PubMed:10871604). Isoform 1: Interacts with STX1A,
CC STX1B and STX2; the interaction is Ca(2+)-dependent (PubMed:15774481).
CC Isoform 2: Is not able to form homodimer and heterodimers
CC (PubMed:10531344). {ECO:0000269|PubMed:10531343,
CC ECO:0000269|PubMed:10531344, ECO:0000269|PubMed:10871604,
CC ECO:0000269|PubMed:15774481}.
CC -!- INTERACTION:
CC Q9R0N8; Q9R0N4: Syt10; NbExp=2; IntAct=EBI-5239378, EBI-5239459;
CC Q9R0N8; O35681: Syt3; NbExp=2; IntAct=EBI-5239378, EBI-457995;
CC Q9R0N8; Q9R0N8: Syt6; NbExp=2; IntAct=EBI-5239378, EBI-5239378;
CC Q9R0N8; Q9R0N9: Syt9; NbExp=2; IntAct=EBI-5239378, EBI-458006;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000269|PubMed:10531344}; Single-pass membrane
CC protein {ECO:0000269|PubMed:10531344}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Membrane; Single-pass membrane
CC protein. Note=Localized predominantly to endoplasmic reticulum (ER)
CC and/or Golgi-like perinuclear compartment (PubMed:10531344).
CC {ECO:0000269|PubMed:10531344}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm, cytosol
CC {ECO:0000269|PubMed:10531344}. Cell membrane
CC {ECO:0000269|PubMed:10531344}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10531344}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=SytVI;
CC IsoId=Q9R0N8-1; Sequence=Displayed;
CC Name=2; Synonyms=SytVIdeltaTM1;
CC IsoId=Q9R0N8-2; Sequence=VSP_041729;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in the olfactory bulb.
CC Isoform 2 is expressed in the brain (at protein level).
CC {ECO:0000269|PubMed:10531344}.
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; AB026803; BAA85775.1; -; mRNA.
DR EMBL; AB026809; BAA85781.1; -; mRNA.
DR EMBL; AB026810; BAA85782.1; -; mRNA.
DR EMBL; AC123057; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS38575.1; -. [Q9R0N8-1]
DR CCDS; CCDS71296.1; -. [Q9R0N8-2]
DR RefSeq; NP_061270.2; NM_018800.4. [Q9R0N8-1]
DR AlphaFoldDB; Q9R0N8; -.
DR SMR; Q9R0N8; -.
DR BioGRID; 207672; 4.
DR IntAct; Q9R0N8; 4.
DR MINT; Q9R0N8; -.
DR STRING; 10090.ENSMUSP00000088196; -.
DR iPTMnet; Q9R0N8; -.
DR PhosphoSitePlus; Q9R0N8; -.
DR MaxQB; Q9R0N8; -.
DR PaxDb; Q9R0N8; -.
DR PRIDE; Q9R0N8; -.
DR ProteomicsDB; 254618; -. [Q9R0N8-1]
DR ProteomicsDB; 254619; -. [Q9R0N8-2]
DR Antibodypedia; 53758; 332 antibodies from 28 providers.
DR Ensembl; ENSMUST00000090697; ENSMUSP00000088196; ENSMUSG00000027849. [Q9R0N8-1]
DR Ensembl; ENSMUST00000117221; ENSMUSP00000113373; ENSMUSG00000027849. [Q9R0N8-2]
DR Ensembl; ENSMUST00000121834; ENSMUSP00000112997; ENSMUSG00000027849. [Q9R0N8-1]
DR GeneID; 54524; -.
DR KEGG; mmu:54524; -.
DR UCSC; uc008qsy.2; mouse. [Q9R0N8-1]
DR CTD; 148281; -.
DR MGI; MGI:1859544; Syt6.
DR VEuPathDB; HostDB:ENSMUSG00000027849; -.
DR eggNOG; KOG1028; Eukaryota.
DR GeneTree; ENSGT00940000157665; -.
DR HOGENOM; CLU_023008_8_1_1; -.
DR InParanoid; Q9R0N8; -.
DR OMA; VMRVGCN; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; Q9R0N8; -.
DR TreeFam; TF315600; -.
DR BioGRID-ORCS; 54524; 3 hits in 72 CRISPR screens.
DR PRO; PR:Q9R0N8; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9R0N8; protein.
DR Bgee; ENSMUSG00000027849; Expressed in cortical layer VI and 54 other tissues.
DR ExpressionAtlas; Q9R0N8; baseline and differential.
DR Genevisible; Q9R0N8; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IDA:BHF-UCL.
DR GO; GO:0099699; C:integral component of synaptic membrane; ISO:MGI.
DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030672; C:synaptic 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:0048306; F:calcium-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0030276; F:clathrin binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:ParkinsonsUK-UCL.
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; IBA:GO_Central.
DR GO; GO:0019905; F:syntaxin binding; ISO:MGI.
DR GO; GO:0060478; P:acrosomal vesicle exocytosis; ISO:MGI.
DR GO; GO:0007340; P:acrosome reaction; IDA:HGNC-UCL.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IBA:GO_Central.
DR GO; GO:0071277; P:cellular response to calcium ion; IBA:GO_Central.
DR GO; GO:0099525; P:presynaptic dense core vesicle exocytosis; ISO:MGI.
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; IPR028701; SYT6.
DR PANTHER; PTHR10024:SF45; PTHR10024:SF45; 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 Alternative splicing; Calcium; Cell membrane; Cytoplasm;
KW Cytoplasmic vesicle; Disulfide bond; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Synapse; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..511
FT /note="Synaptotagmin-6"
FT /id="PRO_0000183955"
FT TOPO_DOM 1..59
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..511
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 230..351
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 362..495
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 12..38
FT /note="Cysteine motif"
FT /evidence="ECO:0000250|UniProtKB:O35681"
FT REGION 92..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 157..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 483..511
FT /note="Necessary for cell membrane association (isoform 2)"
FT /evidence="ECO:0000269|PubMed:10531344"
FT COMPBIAS 93..114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 261
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 261
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 267
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 319
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 319
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 320
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 321
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 321
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 321
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 324
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
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 327
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="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 399
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 453
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 455
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T7P8"
FT VAR_SEQ 1..85
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10531344"
FT /id="VSP_041729"
FT CONFLICT 428
FT /note="I -> V (in Ref. 1; BAA85775 and 2; BAA85781/
FT BAA85782)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 511 AA; 57204 MW; C37C9305E3D05572 CRC64;
MSGVWGAGGP RCQAALAVLA SLCRARPPPL GLDVETCRSF ELQSPEQSPS AADSGTSVSL
LAVVVIVCGV ALVAVFLFLF WKLCWMPWRK KEASSPSSAN PASETLQSPS SRGNMADKLK
DPSALGFLEA AVKISHTSPD IPAEVQMSVK EHIMRHTKLQ RQTTEPASST RHTSFKRHLP
RQMHVSSVDY GNELPPAAAE QPTSIGRIKP ELYKQKSVDG DDAKSEAAKS CGKINFSLRY
DYESETLIVR ILKAFDLPAK DFCGSSDPYV KIYLLPDRKC KLQTRVHRKT LNPTFDENFH
FPVPYEELAD RKLHLSVFDF DRFSRHDMIG EVILDNLFEA SDLSRETSIW KDIQYATSES
VDLGEIMFSL CYLPTAGRLT LTVIKCRNLK AMDITGYSDP YVKVSLLCDG RRLKKKKTTI
KKNTLNPIYN EAIIFDIPPE NMDQVSLLIS VMDYDRVGHN EIIGVCRVGI NAEGLGRDHW
NEMLAYPRKP IAHWHSLVEV KKSFKEGTPR L
