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 24-JAN-2024, entry version 174. 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; 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: 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}. 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; 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; 10090-ENSMUSP00000088196; -. DR ProteomicsDB; 254618; -. [Q9R0N8-1] DR ProteomicsDB; 254619; -. [Q9R0N8-2] DR Antibodypedia; 53758; 362 antibodies from 28 providers. DR Ensembl; ENSMUST00000090697.11; ENSMUSP00000088196.5; ENSMUSG00000027849.20. [Q9R0N8-1] DR Ensembl; ENSMUST00000117221.9; ENSMUSP00000113373.2; ENSMUSG00000027849.20. [Q9R0N8-2] DR Ensembl; ENSMUST00000121834.8; ENSMUSP00000112997.2; ENSMUSG00000027849.20. [Q9R0N8-1] DR GeneID; 54524; -. DR KEGG; mmu:54524; -. DR UCSC; uc008qsy.2; mouse. [Q9R0N8-1] DR AGR; MGI:1859544; -. 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; 590187at2759; -. DR PhylomeDB; Q9R0N8; -. DR TreeFam; TF315600; -. DR BioGRID-ORCS; 54524; 3 hits in 77 CRISPR screens. DR PRO; PR:Q9R0N8; -. DR Proteomes; UP000000589; Chromosome 3. DR RNAct; Q9R0N8; Protein. DR Bgee; ENSMUSG00000027849; Expressed in cortical layer VI and 55 other cell types or tissues. DR ExpressionAtlas; Q9R0N8; baseline and differential. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central. DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0098794; C:postsynapse; IEA:GOC. DR GO; GO:0097060; C:synaptic membrane; ISO:MGI. 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: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:0150038; P:postsynaptic 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 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:SF45; SYNAPTOTAGMIN-6; 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; Q9R0N8; MM. 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; FT BAA85781/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 //