SYT8_MOUSE
ID SYT8_MOUSE Reviewed; 395 AA.
AC Q9R0N6; A9JAL0; Q64366; Q8C6E7;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Synaptotagmin-8;
DE AltName: Full=Synaptotagmin VIII;
DE Short=SytVIII;
GN Name=Syt8;
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).
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Stomach;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 41-395 (ISOFORM 1), FUNCTION,
RP AND INTERACTION WITH AP2.
RC STRAIN=129/Sv; TISSUE=Embryo;
RX PubMed=7791877; DOI=10.1038/375594a0;
RA Li C., Ullrich B., Zhang J.Z., Anderson R.G.W., Brose N., Suedhof T.C.;
RT "Ca(2+)-dependent and -independent activities of neural and non-neural
RT synaptotagmins.";
RL Nature 375:594-599(1995).
RN [5]
RP INTERACTION WITH INOSITOL 1,3,4,5-TETRAKISPHOSPHATE.
RX PubMed=9575177; DOI=10.1074/jbc.273.20.12267;
RA Ibata K., Fukuda M., Mikoshiba K.;
RT "Inositol 1,3,4,5-tetrakisphosphate binding activities of neuronal and non-
RT neuronal synaptotagmins. Identification of conserved amino acid
RT substitutions that abolish inositol 1,3,4,5-tetrakisphosphate binding to
RT synaptotagmins III, V, and X.";
RL J. Biol. Chem. 273:12267-12273(1998).
RN [6]
RP MEMBRANE TOPOLOGY, AND OLIGOMERIZATION.
RX PubMed=11011146; DOI=10.1093/oxfordjournals.jbchem.a022796;
RA Fukuda M., Mikoshiba K.;
RT "Calcium-dependent and -independent hetero-oligomerization in the
RT synaptotagmin family.";
RL J. Biochem. 128:637-645(2000).
RN [7]
RP INTERACTION WITH SYNCRIP.
RX PubMed=10734137; DOI=10.1074/jbc.275.13.9823;
RA Mizutani A., Fukuda M., Ibata K., Shiraishi Y., Mikoshiba K.;
RT "SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear
RT ribonucleoprotein R, interacts with ubiquitous synaptotagmin isoforms.";
RL J. Biol. Chem. 275:9823-9831(2000).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11751263; DOI=10.1095/biolreprod66.1.50;
RA Hutt D.M., Cardullo R.A., Baltz J.M., Ngsee J.K.;
RT "Synaptotagmin VIII is localized to the mouse sperm head and may function
RT in acrosomal exocytosis.";
RL Biol. Reprod. 66:50-56(2002).
RN [9]
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).
RN [10]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16386321; DOI=10.1016/j.bbamcr.2005.11.008;
RA Monterrat C., Boal F., Grise F., Hemar A., Lang J.;
RT "Synaptotagmin 8 is expressed both as a calcium-insensitive soluble and
RT membrane protein in neurons, neuroendocrine and endocrine cells.";
RL Biochim. Biophys. Acta 1763:73-81(2006).
CC -!- FUNCTION: Involved in the trafficking and exocytosis of secretory
CC vesicles in non-neuronal tissues. Mediates Ca(2+)-regulation of
CC exocytosis acrosomal reaction in sperm. May mediate Ca(2+)-regulation
CC of exocytosis in insulin secreted cells. {ECO:0000269|PubMed:11751263,
CC ECO:0000269|PubMed:15774481, ECO:0000269|PubMed:7791877}.
CC -!- SUBUNIT: Homodimer or homooligomer. Homodimerization and
CC homooligomerization do not depend on Ca(2+). Interacts with SYNCRIP
CC isoform 2 C-terminus. Binds inositol 1,3,4,5-tetrakisphosphate (IP4).
CC Binds to AP2 in a Ca(2+)-independent manner. Interacts with STX1A,
CC STX1B and STX2; the interaction is Ca(2+)-dependent.
CC {ECO:0000269|PubMed:10734137, ECO:0000269|PubMed:15774481,
CC ECO:0000269|PubMed:7791877, ECO:0000269|PubMed:9575177}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Single-pass type III
CC membrane protein. Cytoplasmic vesicle, secretory vesicle, acrosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9R0N6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9R0N6-2; Sequence=VSP_009028, VSP_009029;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Detected in testis and brain. Expressed
CC in primary neurons, neuroendocrine and endocrine cells.
CC {ECO:0000269|PubMed:11751263, ECO:0000269|PubMed:16386321}.
CC -!- DOMAIN: The first C2 domain/C2A does not mediate Ca(2+)-dependent
CC phospholipid binding.
CC -!- DOMAIN: The second C2 domain/C2B is responsible for SYNCRIP and
CC inositol 1,3,4,5-tetrakisphosphate (IP4)-binding.
CC -!- MISCELLANEOUS: [Isoform 2]: May be due to competing donor and acceptor
CC splice sites. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
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DR EMBL; AB026805; BAA85777.1; -; mRNA.
DR EMBL; AK075832; BAC35993.1; -; mRNA.
DR EMBL; AL603651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U20107; AAA87723.1; -; mRNA.
DR EMBL; U20109; AAA87727.1; -; Genomic_DNA.
DR CCDS; CCDS22030.1; -. [Q9R0N6-2]
DR CCDS; CCDS72070.1; -. [Q9R0N6-1]
DR PIR; S58401; S58401.
DR RefSeq; NP_001272786.1; NM_001285857.1.
DR RefSeq; NP_001272787.1; NM_001285858.1.
DR RefSeq; NP_001272790.1; NM_001285861.1. [Q9R0N6-1]
DR RefSeq; NP_061272.2; NM_018802.5. [Q9R0N6-2]
DR RefSeq; XP_011240318.1; XM_011242016.2. [Q9R0N6-1]
DR AlphaFoldDB; Q9R0N6; -.
DR SMR; Q9R0N6; -.
DR STRING; 10090.ENSMUSP00000113545; -.
DR PhosphoSitePlus; Q9R0N6; -.
DR PaxDb; Q9R0N6; -.
DR PRIDE; Q9R0N6; -.
DR ProteomicsDB; 253446; -. [Q9R0N6-1]
DR ProteomicsDB; 253447; -. [Q9R0N6-2]
DR Antibodypedia; 55775; 92 antibodies from 22 providers.
DR DNASU; 55925; -.
DR Ensembl; ENSMUST00000118276; ENSMUSP00000113545; ENSMUSG00000031098. [Q9R0N6-2]
DR Ensembl; ENSMUST00000122393; ENSMUSP00000112689; ENSMUSG00000031098. [Q9R0N6-1]
DR GeneID; 55925; -.
DR KEGG; mmu:55925; -.
DR UCSC; uc009kmw.2; mouse. [Q9R0N6-2]
DR UCSC; uc009kmx.2; mouse. [Q9R0N6-1]
DR CTD; 90019; -.
DR MGI; MGI:1859867; Syt8.
DR VEuPathDB; HostDB:ENSMUSG00000031098; -.
DR eggNOG; KOG1028; Eukaryota.
DR GeneTree; ENSGT00940000160892; -.
DR InParanoid; Q9R0N6; -.
DR OMA; CPMFEET; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; Q9R0N6; -.
DR TreeFam; TF315600; -.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR BioGRID-ORCS; 55925; 3 hits in 73 CRISPR screens.
DR PRO; PR:Q9R0N6; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9R0N6; protein.
DR Bgee; ENSMUSG00000031098; Expressed in urinary bladder urothelium and 47 other tissues.
DR ExpressionAtlas; Q9R0N6; baseline and differential.
DR Genevisible; Q9R0N6; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031045; C:dense core granule; IBA:GO_Central.
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:0030672; C:synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
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:0048306; F:calcium-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0030276; F:clathrin binding; ISO:MGI.
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:0007340; P:acrosome reaction; IDA:HGNC-UCL.
DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; IBA:GO_Central.
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: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:0048488; P:synaptic vesicle endocytosis; 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; IPR030540; SYT8.
DR PANTHER; PTHR10024:SF249; PTHR10024:SF249; 1.
DR Pfam; PF00168; C2; 2.
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; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Membrane; Reference proteome; Repeat; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..395
FT /note="Synaptotagmin-8"
FT /id="PRO_0000183960"
FT TOPO_DOM 1..44
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..65
FT /note="Helical; Signal-anchor for type III membrane
FT protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 66..395
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 113..229
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 241..370
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT VAR_SEQ 1..6
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_009028"
FT VAR_SEQ 40
FT /note="W -> SCAPGLG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_009029"
SQ SEQUENCE 395 AA; 44093 MW; 10E833FA8C454A3B CRC64;
MQADRSMKMG HALNPFSTSA PLDATAGPSL IPDLITRIPW PRWTLFIAIL AAGVLLVSCL
LCVICCYCHR HRHRKQPKDK ETVGLGSARN STTTHLVQPD VDCLEPCSGG DQQWGRLLLS
LEYDFGSQEI RVGLRQAGNL KAEGTADPYA WVSVSTQSGR RHETKVHRGT LSPMFEETCC
FLVPPAELPK ATLKVQLWDF KRFSEHEPLG ELQLPLGTVD LQHVLESWYQ LGPPGTTEPE
QMGELCFSLR YVPSSGSLTV VVLEARGLNP GLAEAYVKIQ LMLNQRKWKK SKTSSKKGTT
TPYFNEAFVF LVPVSQLQSV DLVLAVWARG LQLRTEPVGK VLLGSRASGQ PLQHWADMLA
HARRPIAQWH HLRSPREVDR VLALQPRLPL LRPRS
