SYT1_HUMAN
ID SYT1_HUMAN Reviewed; 422 AA.
AC P21579; Q6AI31;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Synaptotagmin-1;
DE AltName: Full=Synaptotagmin I;
DE Short=SytI;
DE AltName: Full=p65;
GN Name=SYT1; Synonyms=SVP65, SYT;
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 [MRNA].
RX PubMed=1840599; DOI=10.1016/s0021-9258(18)52479-0;
RA Perin M.S., Johnston P.A., Oezcelik T., Jahn R., Francke U., Suedhof T.C.;
RT "Structural and functional conservation of synaptotagmin (p65) in
RT Drosophila and humans.";
RL J. Biol. Chem. 266:615-622(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala, and Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS;
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 [6]
RP INTERACTION WITH STON2.
RX PubMed=11381094; DOI=10.1083/jcb.153.5.1111;
RA Martina J.A., Bonangelino C.J., Aguilar R.C., Bonifacino J.S.;
RT "Stonin 2: an adaptor-like protein that interacts with components of the
RT endocytic machinery.";
RL J. Cell Biol. 153:1111-1120(2001).
RN [7]
RP INTERACTION WITH SCAMP5.
RX PubMed=19234194; DOI=10.4049/jimmunol.0802002;
RA Han C., Chen T., Yang M., Li N., Liu H., Cao X.;
RT "Human SCAMP5, a novel secretory carrier membrane protein, facilitates
RT calcium-triggered cytokine secretion by interaction with SNARE machinery.";
RL J. Immunol. 182:2986-2996(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-129, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [9]
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 [10]
RP VARIANT BAGOS LYS-303.
RX PubMed=25712080; DOI=10.1038/ejhg.2015.19;
RA Cafiero C., Marangi G., Orteschi D., Ali M., Asaro A., Ponzi E.,
RA Moncada A., Ricciardi S., Murdolo M., Mancano G., Contaldo I., Leuzzi V.,
RA Battaglia D., Mercuri E., Slavotinek A.M., Zollino M.;
RT "Novel de novo heterozygous loss-of-function variants in MED13L and further
RT delineation of the MED13L haploinsufficiency syndrome.";
RL Eur. J. Hum. Genet. 23:1499-1504(2015).
RN [11]
RP INVOLVEMENT IN BAGOS, AND VARIANT BAGOS THR-368.
RX PubMed=25705886; DOI=10.1172/jci79765;
RA Baker K., Gordon S.L., Grozeva D., van Kogelenberg M., Roberts N.Y.,
RA Pike M., Blair E., Hurles M.E., Chong W.K., Baldeweg T., Kurian M.A.,
RA Boyd S.G., Cousin M.A., Raymond F.L.;
RT "Identification of a human synaptotagmin-1 mutation that perturbs synaptic
RT vesicle cycling.";
RL J. Clin. Invest. 125:1670-1678(2015).
RN [12]
RP INVOLVEMENT IN BAGOS, VARIANTS BAGOS LYS-303; GLY-304; GLU-366; THR-368 AND
RP LYS-371, AND CHARACTERIZATION OF VARIANTS BAGOS LYS-303; GLY-304; GLU-366;
RP THR-368 AND LYS-371.
RX PubMed=30107533; DOI=10.1093/brain/awy209;
RG Broad Center for Mendelian Genomics;
RA Baker K., Gordon S.L., Melland H., Bumbak F., Scott D.J., Jiang T.J.,
RA Owen D., Turner B.J., Boyd S.G., Rossi M., Al-Raqad M., Elpeleg O.,
RA Peck D., Mancini G.M.S., Wilke M., Zollino M., Marangi G., Weigand H.,
RA Borggraefe I., Haack T., Stark Z., Sadedin S., Tan T.Y., Jiang Y.,
RA Gibbs R.A., Ellingwood S., Amaral M., Kelley W., Kurian M.A., Cousin M.A.,
RA Raymond F.L.;
RT "SYT1-associated neurodevelopmental disorder: a case series.";
RL Brain 141:2576-2591(2018).
CC -!- FUNCTION: Calcium sensor that participates in triggering
CC neurotransmitter release at the synapse (By similarity). May have a
CC regulatory role in the membrane interactions during trafficking of
CC synaptic vesicles at the active zone of the synapse (By similarity). It
CC binds acidic phospholipids with a specificity that requires the
CC presence of both an acidic head group and a diacyl backbone. A Ca(2+)-
CC dependent interaction between synaptotagmin and putative receptors for
CC activated protein kinase C has also been reported. It can bind to at
CC least three additional proteins in a Ca(2+)-independent manner; these
CC are neurexins, syntaxin and AP2. Plays a role in dendrite formation by
CC melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:P46096,
CC 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:P21707};
CC -!- SUBUNIT: Homotetramer (Probable). Interacts with SCAMP5
CC (PubMed:19234194). Interacts with STON2 (PubMed:11381094). Forms a
CC complex with SV2B, syntaxin 1 and SNAP25 (By similarity). Interacts
CC with SV2A, SV2B and SV2C (By similarity). Interacts with RIMS1 (By
CC similarity). Interacts with PRRT2 (By similarity). Interacts with
CC DNAJC5 in a phosphorylation-dependent manner (By similarity). Interacts
CC (via N-terminus) with RAB3A (By similarity). Interacts with SYT12 (By
CC similarity). Interacts with calmodulin (By similarity).
CC {ECO:0000250|UniProtKB:P21707, ECO:0000250|UniProtKB:P46096,
CC ECO:0000250|UniProtKB:P48018, ECO:0000269|PubMed:11381094,
CC ECO:0000269|PubMed:19234194, ECO:0000305}.
CC -!- INTERACTION:
CC P21579; Q12982: BNIP2; NbExp=3; IntAct=EBI-524909, EBI-752094;
CC P21579; Q8WVV5: BTN2A2; NbExp=3; IntAct=EBI-524909, EBI-8648738;
CC P21579; O00305-2: CACNB4; NbExp=2; IntAct=EBI-524909, EBI-714855;
CC P21579; Q8N6G5: CSGALNACT2; NbExp=3; IntAct=EBI-524909, EBI-10267100;
CC P21579; O43169: CYB5B; NbExp=3; IntAct=EBI-524909, EBI-1058710;
CC P21579; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-524909, EBI-6166686;
CC P21579; P30519: HMOX2; NbExp=3; IntAct=EBI-524909, EBI-712096;
CC P21579; Q9Y6K9: IKBKG; NbExp=3; IntAct=EBI-524909, EBI-81279;
CC P21579; P30301: MIP; NbExp=3; IntAct=EBI-524909, EBI-8449636;
CC P21579; Q9H115: NAPB; NbExp=3; IntAct=EBI-524909, EBI-3921185;
CC P21579; Q9P0S9: TMEM14C; NbExp=3; IntAct=EBI-524909, EBI-2339195;
CC P21579; Q8TBM7: TMEM254; NbExp=3; IntAct=EBI-524909, EBI-11956809;
CC P21579; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-524909, EBI-2852148;
CC P21579; P16473: TSHR; NbExp=2; IntAct=EBI-524909, EBI-13939599;
CC P21579; Q9Y5Z9: UBIAD1; NbExp=3; IntAct=EBI-524909, EBI-2819725;
CC P21579; O95159: ZFPL1; NbExp=3; IntAct=EBI-524909, EBI-718439;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000250|UniProtKB:P21707}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC membrane {ECO:0000250|UniProtKB:P21707}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:P21707}. Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule membrane {ECO:0000250|UniProtKB:P21707}; Single-pass
CC membrane protein {ECO:0000250|UniProtKB:P21707}. Cytoplasm
CC {ECO:0000250|UniProtKB:P21707}.
CC -!- TISSUE SPECIFICITY: Expressed in melanocytes (PubMed:23999003).
CC {ECO:0000269|PubMed:23999003}.
CC -!- DOMAIN: The first C2 domain mediates Ca(2+)-dependent phospholipid
CC binding. {ECO:0000250|UniProtKB:P21707}.
CC -!- DOMAIN: The second C2 domain mediates interaction with SV2A and
CC probably with STN2. {ECO:0000250|UniProtKB:P21707}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P21707}.
CC -!- DISEASE: Baker-Gordon syndrome (BAGOS) [MIM:618218]: An autosomal
CC dominant neurodevelopmental disorder characterized by infantile
CC hypotonia, congenital ophthalmic abnormalities, involuntary and
CC hyperkinetic movements, stereotypic behavior, poor or absent speech,
CC EEG abnormalities, and global developmental delay varying in severity
CC from moderate to profound. Behavioral characteristics include sleep
CC disturbance and episodic agitation. {ECO:0000269|PubMed:25705886,
CC ECO:0000269|PubMed:25712080, ECO:0000269|PubMed:30107533}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
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DR EMBL; M55047; AAA60609.1; -; mRNA.
DR EMBL; AK094616; BAG52897.1; -; mRNA.
DR EMBL; AK126908; BAG54392.1; -; mRNA.
DR EMBL; CR627387; CAH10483.1; -; mRNA.
DR EMBL; CH471054; EAW97343.1; -; Genomic_DNA.
DR EMBL; BC058917; AAH58917.1; -; mRNA.
DR CCDS; CCDS9017.1; -.
DR PIR; A39052; BMHU1Y.
DR RefSeq; NP_001129277.1; NM_001135805.1.
DR RefSeq; NP_001129278.1; NM_001135806.1.
DR RefSeq; NP_005630.1; NM_005639.2.
DR RefSeq; XP_011537012.1; XM_011538710.1.
DR RefSeq; XP_016875398.1; XM_017019909.1.
DR PDB; 2K45; NMR; -; A=141-268.
DR PDB; 2K4A; NMR; -; A=141-268.
DR PDB; 2K8M; NMR; -; A/D=141-268.
DR PDB; 2KI6; NMR; -; A/F=141-268.
DR PDB; 2LHA; NMR; -; A=271-422.
DR PDB; 2N1T; NMR; -; E=272-419.
DR PDB; 2R83; X-ray; 2.70 A; A/B=141-422.
DR PDB; 3F00; X-ray; 1.36 A; A=141-266.
DR PDB; 3F01; X-ray; 1.70 A; A=141-266.
DR PDB; 3F04; X-ray; 1.35 A; A=141-266.
DR PDB; 3F05; X-ray; 1.40 A; A=141-266.
DR PDB; 4ISQ; X-ray; 2.65 A; D/E/F=33-53.
DR PDB; 4V11; X-ray; 1.95 A; A=273-422.
DR PDB; 6G5F; X-ray; 2.50 A; P=33-53.
DR PDB; 6G5K; X-ray; 2.00 A; C/D=33-53.
DR PDB; 6QNS; X-ray; 2.40 A; S=33-53.
DR PDB; 6TZ3; X-ray; 1.17 A; A=272-422.
DR PDB; 6U41; X-ray; 1.70 A; A=272-422.
DR PDB; 6U4U; X-ray; 1.30 A; A=272-422.
DR PDB; 6U4W; X-ray; 1.40 A; A=272-422.
DR PDB; 6ZVN; X-ray; 2.50 A; BBB=33-53.
DR PDBsum; 2K45; -.
DR PDBsum; 2K4A; -.
DR PDBsum; 2K8M; -.
DR PDBsum; 2KI6; -.
DR PDBsum; 2LHA; -.
DR PDBsum; 2N1T; -.
DR PDBsum; 2R83; -.
DR PDBsum; 3F00; -.
DR PDBsum; 3F01; -.
DR PDBsum; 3F04; -.
DR PDBsum; 3F05; -.
DR PDBsum; 4ISQ; -.
DR PDBsum; 4V11; -.
DR PDBsum; 6G5F; -.
DR PDBsum; 6G5K; -.
DR PDBsum; 6QNS; -.
DR PDBsum; 6TZ3; -.
DR PDBsum; 6U41; -.
DR PDBsum; 6U4U; -.
DR PDBsum; 6U4W; -.
DR PDBsum; 6ZVN; -.
DR AlphaFoldDB; P21579; -.
DR SMR; P21579; -.
DR BioGRID; 112723; 75.
DR DIP; DIP-34042N; -.
DR ELM; P21579; -.
DR IntAct; P21579; 56.
DR MINT; P21579; -.
DR STRING; 9606.ENSP00000261205; -.
DR TCDB; 1.F.1.1.1; the synaptosomal vesicle fusion pore (svf-pore) family.
DR GlyGen; P21579; 1 site.
DR iPTMnet; P21579; -.
DR PhosphoSitePlus; P21579; -.
DR SwissPalm; P21579; -.
DR BioMuta; SYT1; -.
DR DMDM; 135086; -.
DR EPD; P21579; -.
DR jPOST; P21579; -.
DR MassIVE; P21579; -.
DR PaxDb; P21579; -.
DR PeptideAtlas; P21579; -.
DR PRIDE; P21579; -.
DR ProteomicsDB; 53878; -.
DR Antibodypedia; 1609; 850 antibodies from 44 providers.
DR DNASU; 6857; -.
DR Ensembl; ENST00000261205.9; ENSP00000261205.4; ENSG00000067715.14.
DR Ensembl; ENST00000393240.7; ENSP00000376932.3; ENSG00000067715.14.
DR Ensembl; ENST00000552744.5; ENSP00000447575.1; ENSG00000067715.14.
DR GeneID; 6857; -.
DR KEGG; hsa:6857; -.
DR MANE-Select; ENST00000261205.9; ENSP00000261205.4; NM_005639.3; NP_005630.1.
DR UCSC; uc001sys.4; human.
DR CTD; 6857; -.
DR DisGeNET; 6857; -.
DR GeneCards; SYT1; -.
DR HGNC; HGNC:11509; SYT1.
DR HPA; ENSG00000067715; Group enriched (brain, retina).
DR MalaCards; SYT1; -.
DR MIM; 185605; gene.
DR MIM; 618218; phenotype.
DR neXtProt; NX_P21579; -.
DR OpenTargets; ENSG00000067715; -.
DR Orphanet; 522077; Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome.
DR PharmGKB; PA36290; -.
DR VEuPathDB; HostDB:ENSG00000067715; -.
DR eggNOG; KOG1028; Eukaryota.
DR GeneTree; ENSGT00940000155394; -.
DR InParanoid; P21579; -.
DR OMA; FTENTXQ; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; P21579; -.
DR TreeFam; TF315600; -.
DR PathwayCommons; P21579; -.
DR Reactome; R-HSA-181429; Serotonin Neurotransmitter Release Cycle.
DR Reactome; R-HSA-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-HSA-212676; Dopamine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-264642; Acetylcholine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-5250958; Toxicity of botulinum toxin type B (botB).
DR Reactome; R-HSA-5250989; Toxicity of botulinum toxin type G (botG).
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-888590; GABA synthesis, release, reuptake and degradation.
DR SignaLink; P21579; -.
DR SIGNOR; P21579; -.
DR BioGRID-ORCS; 6857; 159 hits in 1071 CRISPR screens.
DR ChiTaRS; SYT1; human.
DR EvolutionaryTrace; P21579; -.
DR GeneWiki; SYT1; -.
DR GenomeRNAi; 6857; -.
DR Pharos; P21579; Tbio.
DR PRO; PR:P21579; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P21579; protein.
DR Bgee; ENSG00000067715; Expressed in middle temporal gyrus and 151 other tissues.
DR ExpressionAtlas; P21579; baseline and differential.
DR Genevisible; P21579; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0042584; C:chromaffin granule membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0060201; C:clathrin-sculpted acetylcholine transport vesicle membrane; TAS:Reactome.
DR GO; GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome.
DR GO; GO:0060203; C:clathrin-sculpted glutamate transport vesicle membrane; TAS:Reactome.
DR GO; GO:0070083; C:clathrin-sculpted monoamine transport vesicle membrane; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0031045; C:dense core granule; IBA:GO_Central.
DR GO; GO:0060076; C:excitatory synapse; IEA:Ensembl.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; ISS:ParkinsonsUK-UCL.
DR GO; GO:0044306; C:neuron projection terminus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0042734; C:presynaptic membrane; IEA:Ensembl.
DR GO; GO:0008021; C:synaptic vesicle; TAS:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0061891; F:calcium ion sensor activity; IEA:Ensembl.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0048306; F:calcium-dependent protein binding; IEA:Ensembl.
DR GO; GO:0005516; F:calmodulin binding; IEA:Ensembl.
DR GO; GO:0030276; F:clathrin binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IDA:MGI.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IEA:Ensembl.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0000149; F:SNARE binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0019905; F:syntaxin binding; IBA:GO_Central.
DR GO; GO:0017075; F:syntaxin-1 binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030348; F:syntaxin-3 binding; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; IBA:GO_Central.
DR GO; GO:0099502; P:calcium-dependent activation of synaptic vesicle fusion; IEA:Ensembl.
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; ISS:ParkinsonsUK-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0005513; P:detection of calcium ion; TAS:UniProtKB.
DR GO; GO:0098746; P:fast, calcium ion-dependent exocytosis of neurotransmitter; ISS:ParkinsonsUK-UCL.
DR GO; GO:0007269; P:neurotransmitter secretion; TAS:UniProtKB.
DR GO; GO:1903235; P:positive regulation of calcium ion-dependent exocytosis of neurotransmitter; ISS:UniProtKB.
DR GO; GO:1903861; P:positive regulation of dendrite extension; IDA:UniProtKB.
DR GO; GO:0033603; P:positive regulation of dopamine secretion; IEA:Ensembl.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; ISS:ParkinsonsUK-UCL.
DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl.
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:0017157; P:regulation of exocytosis; TAS:UniProtKB.
DR GO; GO:1903305; P:regulation of regulated secretory pathway; ISS:ParkinsonsUK-UCL.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISS:ParkinsonsUK-UCL.
DR GO; GO:0061669; P:spontaneous neurotransmitter secretion; IEA:Ensembl.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IBA:GO_Central.
DR GO; GO:0071911; P:synchronous neurotransmitter secretion; IEA:Ensembl.
DR GO; GO:0048278; P:vesicle docking; IEA:Ensembl.
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; IPR015428; Synaptotagmin1.
DR PANTHER; PTHR10024:SF239; PTHR10024:SF239; 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 3D-structure; Calcium; Cytoplasm; Cytoplasmic vesicle; Differentiation;
KW Disease variant; Glycoprotein; Lipoprotein; Membrane; Metal-binding;
KW Palmitate; Phosphoprotein; Reference proteome; Repeat; Synapse;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..422
FT /note="Synaptotagmin-1"
FT /id="PRO_0000183936"
FT TOPO_DOM 1..57
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 58..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..422
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 142..261
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 273..406
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 113..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..382
FT /note="Phospholipid binding"
FT /evidence="ECO:0000305"
FT BINDING 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 231
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 236
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 237
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 239
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 239
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 304
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 304
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 310
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 364
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 364
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 366
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 366
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 372
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 129
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 230
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P46096"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P46096"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P21707"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P21707"
FT LIPID 75
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P21707"
FT LIPID 76
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P21707"
FT LIPID 78
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P21707"
FT LIPID 80
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P21707"
FT LIPID 83
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P21707"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 303
FT /note="M -> K (in BAGOS)"
FT /evidence="ECO:0000269|PubMed:25712080,
FT ECO:0000269|PubMed:30107533"
FT /id="VAR_081536"
FT VARIANT 304
FT /note="D -> G (in BAGOS)"
FT /evidence="ECO:0000269|PubMed:30107533"
FT /id="VAR_081537"
FT VARIANT 366
FT /note="D -> E (in BAGOS)"
FT /evidence="ECO:0000269|PubMed:30107533"
FT /id="VAR_081538"
FT VARIANT 368
FT /note="I -> T (in BAGOS; dbSNP:rs1135402761)"
FT /evidence="ECO:0000269|PubMed:25705886,
FT ECO:0000269|PubMed:30107533"
FT /id="VAR_072911"
FT VARIANT 371
FT /note="N -> K (in BAGOS)"
FT /evidence="ECO:0000269|PubMed:30107533"
FT /id="VAR_081539"
FT HELIX 39..51
FT /evidence="ECO:0007829|PDB:6G5K"
FT STRAND 145..153
FT /evidence="ECO:0007829|PDB:3F04"
FT TURN 154..157
FT /evidence="ECO:0007829|PDB:3F04"
FT STRAND 158..167
FT /evidence="ECO:0007829|PDB:3F04"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:3F04"
FT STRAND 180..188
FT /evidence="ECO:0007829|PDB:3F04"
FT STRAND 206..213
FT /evidence="ECO:0007829|PDB:3F04"
FT HELIX 217..220
FT /evidence="ECO:0007829|PDB:3F04"
FT STRAND 224..231
FT /evidence="ECO:0007829|PDB:3F04"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:3F04"
FT STRAND 239..247
FT /evidence="ECO:0007829|PDB:3F04"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:3F04"
FT STRAND 257..262
FT /evidence="ECO:0007829|PDB:3F04"
FT STRAND 276..284
FT /evidence="ECO:0007829|PDB:6TZ3"
FT TURN 285..288
FT /evidence="ECO:0007829|PDB:6TZ3"
FT STRAND 289..299
FT /evidence="ECO:0007829|PDB:6TZ3"
FT STRAND 304..307
FT /evidence="ECO:0007829|PDB:6U41"
FT STRAND 311..319
FT /evidence="ECO:0007829|PDB:6TZ3"
FT STRAND 322..328
FT /evidence="ECO:0007829|PDB:6TZ3"
FT STRAND 333..337
FT /evidence="ECO:0007829|PDB:2LHA"
FT STRAND 339..347
FT /evidence="ECO:0007829|PDB:6TZ3"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:6TZ3"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:6TZ3"
FT STRAND 357..364
FT /evidence="ECO:0007829|PDB:6TZ3"
FT STRAND 367..369
FT /evidence="ECO:0007829|PDB:6TZ3"
FT STRAND 372..380
FT /evidence="ECO:0007829|PDB:6TZ3"
FT HELIX 385..396
FT /evidence="ECO:0007829|PDB:6TZ3"
FT STRAND 402..407
FT /evidence="ECO:0007829|PDB:6TZ3"
FT HELIX 411..418
FT /evidence="ECO:0007829|PDB:6TZ3"
SQ SEQUENCE 422 AA; 47573 MW; 467F7C58E411AFA9 CRC64;
MVSESHHEAL AAPPVTTVAT VLPSNATEPA SPGEGKEDAF SKLKEKFMNE LHKIPLPPWA
LIAIAIVAVL LVLTCCFCIC KKCLFKKKNK KKGKEKGGKN AINMKDVKDL GKTMKDQALK
DDDAETGLTD GEEKEEPKEE EKLGKLQYSL DYDFQNNQLL VGIIQAAELP ALDMGGTSDP
YVKVFLLPDK KKKFETKVHR KTLNPVFNEQ FTFKVPYSEL GGKTLVMAVY DFDRFSKHDI
IGEFKVPMNT VDFGHVTEEW RDLQSAEKEE QEKLGDICFS LRYVPTAGKL TVVILEAKNL
KKMDVGGLSD PYVKIHLMQN GKRLKKKKTT IKKNTLNPYY NESFSFEVPF EQIQKVQVVV
TVLDYDKIGK NDAIGKVFVG YNSTGAELRH WSDMLANPRR PIAQWHTLQV EEEVDAMLAV
KK
