SYT1

Synaptotagmin I
PDB rendering based on 1byn.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2K45​, 2K4A​, 2K8M​, 2KI6​, 2LHA​, 2N1T​, 2R83​, 3F00​, 3F01​, 3F04​, 3F05​, 4ISQ​, 4V11​
Identifiers
Symbols	SYT1 ; P65; SVP65; SYT
External IDs	OMIM: 185605 MGI: 99667 HomoloGene: 4122 ChEMBL: 1953 GeneCards: SYT1 Gene
Gene ontology Molecular function • SNARE binding • calcium ion binding • protein binding • calcium-dependent phospholipid binding • 1-phosphatidylinositol binding • phosphatidylinositol-4,5-bisphosphate binding • syntaxin-1 binding • clathrin binding • calcium-dependent protein binding • low-density lipoprotein particle receptor binding Cellular component • plasma membrane • synaptic vesicle • integral component of membrane • cell junction • synaptic vesicle membrane • chromaffin granule membrane • presynaptic membrane • neuron projection • clathrin-sculpted acetylcholine transport vesicle membrane • clathrin-sculpted glutamate transport vesicle membrane • clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane • clathrin-sculpted monoamine transport vesicle membrane Biological process • detection of calcium ion • synaptic transmission • neurotransmitter secretion • glutamate secretion • synaptic vesicle exocytosis • regulation of exocytosis • regulation of calcium ion-dependent exocytosis • synaptic vesicle endocytosis • calcium ion-dependent exocytosis of neurotransmitter • positive regulation of synaptic transmission • protein homooligomerization • regulation of synaptic transmission, glutamatergic • fast, calcium ion-dependent exocytosis of neurotransmitter • regulation of regulated secretory pathway • positive regulation of dendrite extension Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6857	20979
Ensembl	ENSG00000067715	ENSMUSG00000035864
UniProt	P21579	P46096
RefSeq (mRNA)	NM_001135805	NM_001252341
RefSeq (protein)	NP_001129277	NP_001239270
Location (UCSC)	Chr 12: 78.86 – 79.45 Mb	Chr 10: 108.5 – 109.01 Mb
PubMed search

Synaptotagmin-1 is a protein that in humans is encoded by the SYT1 gene.^[1]

Function

The synaptotagmins are integral membrane proteins of synaptic vesicles thought to serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. Calcium binding to synaptotagmin I participates in triggering neurotransmitter release at the synapse (Fernandez-Chacon et al., 2001).[supplied by OMIM]^[2]

SYT1 is the master switch responsible for allowing the human brain to release neurotransmitters. SYT1 senses calcium concentrations as low as 10 ppm and subsequently signals the SNARE complex to open fusion pores.^[3]

Interactions

SYT1 has been shown to interact with SNAP-25,^[4][5] STX1A^[6][7] and S100A13.^[8][9]

References

1. Perin MS, Johnston PA, Ozcelik T, Jahn R, Francke U, Südhof TC (Jan 1991). "Structural and functional conservation of synaptotagmin (p65) in Drosophila and humans". The Journal of Biological Chemistry 266 (1): 615–22. PMID 1840599.
2. "Entrez Gene: SYT1 synaptotagmin I".
3. Lee HK, Yang Y, Su Z, Hyeon C, Lee TS, Lee HW, Kweon DH, Shin YK, Yoon TY (May 2010). "Dynamic Ca2+-dependent stimulation of vesicle fusion by membrane-anchored synaptotagmin 1". Science 328 (5979): 760–3. doi:10.1126/science.1187722. PMC 2994549. PMID 20448186. Lay summary – sciencedaily.com.
4. Gerona RR, Larsen EC, Kowalchyk JA, Martin TF (Mar 2000). "The C terminus of SNAP25 is essential for Ca(2+)-dependent binding of synaptotagmin to SNARE complexes". The Journal of Biological Chemistry 275 (9): 6328–36. doi:10.1074/jbc.275.9.6328. PMID 10692432.
5. Zhang X, Kim-Miller MJ, Fukuda M, Kowalchyk JA, Martin TF (May 2002). "Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis". Neuron 34 (4): 599–611. doi:10.1016/S0896-6273(02)00671-2. PMID 12062043.
6. Shao X, Li C, Fernandez I, Zhang X, Südhof TC, Rizo J (Jan 1997). "Synaptotagmin-syntaxin interaction: the C2 domain as a Ca2+-dependent electrostatic switch". Neuron 18 (1): 133–42. doi:10.1016/S0896-6273(01)80052-0. PMID 9010211.
7. Thomas DM, Ferguson GD, Herschman HR, Elferink LA (Jul 1999). "Functional and biochemical analysis of the C2 domains of synaptotagmin IV". Molecular Biology of the Cell 10 (7): 2285–95. doi:10.1091/mbc.10.7.2285. PMC 25443. PMID 10397765.
8. Mouta Carreira C, LaVallee TM, Tarantini F, Jackson A, Lathrop JT, Hampton B, Burgess WH, Maciag T (Aug 1998). "S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro". The Journal of Biological Chemistry 273 (35): 22224–31. doi:10.1074/jbc.273.35.22224. PMID 9712836.
9. Landriscina M, Bagalá C, Mandinova A, Soldi R, Micucci I, Bellum S, Prudovsky I, Maciag T (Jul 2001). "Copper induces the assembly of a multiprotein aggregate implicated in the release of fibroblast growth factor 1 in response to stress". The Journal of Biological Chemistry 276 (27): 25549–57. doi:10.1074/jbc.M102925200. PMID 11432880.

Further reading

• Mochly-Rosen D, Miller KG, Scheller RH, Khaner H, Lopez J, Smith BL (Sep 1992). "p65 fragments, homologous to the C2 region of protein kinase C, bind to the intracellular receptors for protein kinase C". Biochemistry 31 (35): 8120–4. doi:10.1021/bi00150a003. PMID 1326322.
• McMahon HT, Missler M, Li C, Südhof TC (Oct 1995). "Complexins: cytosolic proteins that regulate SNAP receptor function". Cell 83 (1): 111–9. doi:10.1016/0092-8674(95)90239-2. PMID 7553862.
• O'Regan S, Diebler MF, Meunier FM, Vyas S (Jan 1995). "A Ewing's sarcoma cell line showing some, but not all, of the traits of a cholinergic neuron". Journal of Neurochemistry 64 (1): 69–76. doi:10.1046/j.1471-4159.1995.64010069.x. PMID 7798952.
• Zhang JZ, Davletov BA, Südhof TC, Anderson RG (Sep 1994). "Synaptotagmin I is a high affinity receptor for clathrin AP-2: implications for membrane recycling". Cell 78 (5): 751–60. doi:10.1016/S0092-8674(94)90442-1. PMID 8087843.
• Chapman ER, Blasi J, An S, Brose N, Johnston PA, Südhof TC, Jahn R (Aug 1996). "Fatty acylation of synaptotagmin in PC12 cells and synaptosomes". Biochemical and Biophysical Research Communications 225 (1): 326–32. doi:10.1006/bbrc.1996.1174. PMID 8769138.
• Perin MS (Oct 1996). "Mirror image motifs mediate the interaction of the COOH terminus of multiple synaptotagmins with the neurexins and calmodulin". Biochemistry 35 (43): 13808–16. doi:10.1021/bi960853x. PMID 8901523.
• Betz A, Okamoto M, Benseler F, Brose N (Jan 1997). "Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin". The Journal of Biological Chemistry 272 (4): 2520–6. doi:10.1074/jbc.272.4.2520. PMID 8999968.
• Shao X, Li C, Fernandez I, Zhang X, Südhof TC, Rizo J (Jan 1997). "Synaptotagmin-syntaxin interaction: the C2 domain as a Ca2+-dependent electrostatic switch". Neuron 18 (1): 133–42. doi:10.1016/S0896-6273(01)80052-0. PMID 9010211.
• Charvin N, L'evêque C, Walker D, Berton F, Raymond C, Kataoka M, Shoji-Kasai Y, Takahashi M, De Waard M, Seagar MJ (Aug 1997). "Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel". The EMBO Journal 16 (15): 4591–6. doi:10.1093/emboj/16.15.4591. PMC 1170085. PMID 9303303.
• Mouta Carreira C, LaVallee TM, Tarantini F, Jackson A, Lathrop JT, Hampton B, Burgess WH, Maciag T (Aug 1998). "S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro". The Journal of Biological Chemistry 273 (35): 22224–31. doi:10.1074/jbc.273.35.22224. PMID 9712836.
• Thomas DM, Ferguson GD, Herschman HR, Elferink LA (Jul 1999). "Functional and biochemical analysis of the C2 domains of synaptotagmin IV". Molecular Biology of the Cell 10 (7): 2285–95. doi:10.1091/mbc.10.7.2285. PMC 25443. PMID 10397765.
• Gerona RR, Larsen EC, Kowalchyk JA, Martin TF (Mar 2000). "The C terminus of SNAP25 is essential for Ca(2+)-dependent binding of synaptotagmin to SNARE complexes". The Journal of Biological Chemistry 275 (9): 6328–36. doi:10.1074/jbc.275.9.6328. PMID 10692432.
• Mizutani A, Fukuda M, Ibata K, Shiraishi Y, Mikoshiba K (Mar 2000). "SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear ribonucleoprotein R, interacts with ubiquitous synaptotagmin isoforms". The Journal of Biological Chemistry 275 (13): 9823–31. doi:10.1074/jbc.275.13.9823. PMID 10734137.
• Kimura N, Shiraishi S, Mizunashi K, Ohtsu H, Kimura I (Mar 2001). "Synaptotagmin I expression in mast cells of normal human tissues, systemic mast cell disease, and a human mast cell leukemia cell line". The Journal of Histochemistry and Cytochemistry 49 (3): 341–6. doi:10.1177/002215540104900308. PMID 11181737.
• Fernández-Chacón R, Königstorfer A, Gerber SH, García J, Matos MF, Stevens CF, Brose N, Rizo J, Rosenmund C, Südhof TC (Mar 2001). "Synaptotagmin I functions as a calcium regulator of release probability". Nature 410 (6824): 41–9. doi:10.1038/35065004. PMID 11242035.
• Fukuda M, Mikoshiba K (Mar 2001). "Synaptotagmin-like protein 1-3: a novel family of C-terminal-type tandem C2 proteins". Biochemical and Biophysical Research Communications 281 (5): 1226–33. doi:10.1006/bbrc.2001.4512. PMID 11243866.
• Martina JA, Bonangelino CJ, Aguilar RC, Bonifacino JS (May 2001). "Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery". The Journal of Cell Biology 153 (5): 1111–20. doi:10.1083/jcb.153.5.1111. PMC 2174325. PMID 11381094.
• Landriscina M, Bagalá C, Mandinova A, Soldi R, Micucci I, Bellum S, Prudovsky I, Maciag T (Jul 2001). "Copper induces the assembly of a multiprotein aggregate implicated in the release of fibroblast growth factor 1 in response to stress". The Journal of Biological Chemistry 276 (27): 25549–57. doi:10.1074/jbc.M102925200. PMID 11432880.
• Coppola T, Magnin-Luthi S, Perret-Menoud V, Gattesco S, Schiavo G, Regazzi R (Aug 2001). "Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin". The Journal of Biological Chemistry 276 (35): 32756–62. doi:10.1074/jbc.M100929200. PMID 11438518.