SY65_APLCA
ID SY65_APLCA Reviewed; 428 AA.
AC P41823; Q6EI08;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Synaptotagmin-1;
DE AltName: Full=Synaptotagmin I;
DE AltName: Full=p65;
GN Name=SYT1;
OS Aplysia californica (California sea hare).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Heterobranchia; Euthyneura; Tectipleura; Aplysiida; Aplysioidea;
OC Aplysiidae; Aplysia.
OX NCBI_TaxID=6500;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Ganglion;
RX PubMed=7479985; DOI=10.1073/pnas.92.24.11307;
RA Martin K.C., Hu Y., Armitage B.A., Siegelbaum S.A., Kandel E.R.,
RA Kaang B.-K.;
RT "Evidence for synaptotagmin as an inhibitory clamp on synaptic vesicle
RT release in Aplysia neurons.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11307-11311(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION AT SER-123, AND MUTAGENESIS OF SER-123.
RX PubMed=12867508; DOI=10.1523/jneurosci.23-15-06238.2003;
RA Nakhost A., Houeland G., Castellucci V.F., Sossin W.S.;
RT "Differential regulation of transmitter release by alternatively spliced
RT forms of synaptotagmin I.";
RL J. Neurosci. 23:6238-6244(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH SNAP25, AND MUTAGENESIS OF ASN-347 AND GLY-358.
RX PubMed=15056279; DOI=10.1111/j.1471-4159.2004.02325.x;
RA Nakhost A., Houeland G., Blandford V.E., Castellucci V.F., Sossin W.S.;
RT "Identification and characterization of a novel C2B splice variant of
RT synaptotagmin I.";
RL J. Neurochem. 89:354-363(2004).
CC -!- FUNCTION: Acts as inhibitor of neurotransmitter release. Overexpression
CC leads to a decrease in the amplitude of the excitatory postsynaptic
CC potential in dissected cholinergic and glutaminergic neurons while
CC depletion with antisense oligonucleotides leads to an increase.
CC Overexpression of isoform 1 blocks the reversal of synaptic depression
CC by serotonin in sensory neurons. {ECO:0000269|PubMed:12867508,
CC ECO:0000269|PubMed:15056279, ECO:0000269|PubMed:7479985}.
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};
CC -!- SUBUNIT: Binds SNAP25. Isoform 3 binds SNAP25 with higher affinity.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane; Single-pass membrane protein. Synapse. Note=And
CC vesicle-like structures.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Syt1VQ;
CC IsoId=P41823-1; Sequence=Displayed;
CC Name=2; Synonyms=Syt1, Syt1 C2B alpha;
CC IsoId=P41823-2; Sequence=VSP_013344;
CC Name=3; Synonyms=Syt1 C2B beta;
CC IsoId=P41823-3; Sequence=VSP_013345;
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
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DR EMBL; U03125; AAA03567.1; -; mRNA.
DR EMBL; AY325502; AAQ91785.1; -; mRNA.
DR RefSeq; NP_001191553.1; NM_001204624.1.
DR RefSeq; NP_001191565.1; NM_001204636.1. [P41823-2]
DR AlphaFoldDB; P41823; -.
DR SMR; P41823; -.
DR iPTMnet; P41823; -.
DR PRIDE; P41823; -.
DR GeneID; 100533340; -.
DR OrthoDB; 925064at2759; -.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IEA:InterPro.
DR GO; GO:0000149; F:SNARE binding; IDA:UniProtKB.
DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; IDA:UniProtKB.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IDA:UniProtKB.
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 Alternative splicing; Calcium; Cytoplasmic vesicle; Membrane;
KW Metal-binding; Phosphoprotein; Repeat; Synapse; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..428
FT /note="Synaptotagmin-1"
FT /id="PRO_0000183987"
FT TOPO_DOM 1..67
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 93..428
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 153..272
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 286..419
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 16..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 147..395
FT /note="Phospholipid binding"
FT /evidence="ECO:0000305"
FT BINDING 184
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 184
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 190
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 242
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 242
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 243
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 244
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 244
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 244
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 247
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 250
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 250
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 317
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 323
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 377
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 379
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 123
FT /note="Phosphoserine; by PRKC2"
FT /evidence="ECO:0000269|PubMed:12867508"
FT VAR_SEQ 128..129
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7479985"
FT /id="VSP_013344"
FT VAR_SEQ 329..358
FT /note="ALLQGTKRLKKKKTTIKKNTLNPYFNESFG -> SLMLNGKRVKKKKTTIKK
FT CTLNPYYNESFT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15056279"
FT /id="VSP_013345"
FT MUTAGEN 123
FT /note="S->A: Loss of phosphorylation by PRKC2."
FT /evidence="ECO:0000269|PubMed:12867508"
FT MUTAGEN 347
FT /note="N->C: Confers higher proteolytic instability."
FT /evidence="ECO:0000269|PubMed:15056279"
FT MUTAGEN 358
FT /note="G->T: Confers higher proteolytic stability
FT characteristic for isoform 3 to isoform 1."
FT /evidence="ECO:0000269|PubMed:15056279"
FT CONFLICT 95
FT /note="S -> C (in Ref. 3; AAQ91785)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 428 AA; 47687 MW; EC58D0F2B08AF559 CRC64;
MDSLLARVKR AADADALNPA QEGVTGGPDA AGLPDVSTSS PGGGGAGDKL KEKMDEYKDK
LINEIENLPI WAIVLIIAGS LLFLVCCVYC VCRRSCRKRK KKEGKKGLKG AVDLKSVQLL
GNSYKEKVQP DLDELPVNME DNEDAESTKS EVKLGKLQFS LDYDFQKGEL SVNVIQAADL
PGMDMSGTSD PYVKVYLLPD KKKKYETKVH RKTLNPVFNE SFTFKVPYAE VGSKILTFAV
YDFDRFSKHD QIGQVQVPLN SIDLGRVVED WKDLQSPDTE SEKENKLGDI CFSLRYVPTA
GKLTVVILEA KNLKKMDVGG LSDPYVKIAL LQGTKRLKKK KTTIKKNTLN PYFNESFGFE
VPFEQIQKVT LIITVVDYDR IGTSEPIGRC VLGCNSSGTE LRHWSDMLAN PRRPIAQWHT
LQEVPEKN
