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Gene Review

SYT1  -  synaptotagmin I

Homo sapiens

Synonyms: P65, SVP65, SYT, Synaptotagmin I, Synaptotagmin-1, ...
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Disease relevance of SYT1


Psychiatry related information on SYT1


High impact information on SYT1


Chemical compound and disease context of SYT1


Biological context of SYT1


Anatomical context of SYT1


Associations of SYT1 with chemical compounds

  • Synaptotagmin I (STG I) is a Ca(2+) sensor and one of the synaptic vesicle proteins that mediate exocytosis [3].
  • Using a combination of competition and direct binding assays, we demonstrate that synaptotagmin I, an intrinsic membrane protein of synaptic vesicles, has all of the properties of the AP-2 receptor and that AP-2 binds to the second C2 domain in the molecule [21].
  • To test the effect of synaptotagmin I on membrane fusion, we incorporated it into a SNARE-mediated liposome fusion assay [22].
  • Utilization of antisense technology showed that p65 but not p50 or c-Rel mediated IL-1beta-stimulated PGE2 formation [23].
  • Notably, the binding activity to phosphatidylserine is inhibited by a physiological range of the Ca(2+) concentration attained after secretagogue stimulation, which presents a striking contrast to the Ca(2+)-stimulatory activity of the C2A domain of synaptotagmin I [24].

Physical interactions of SYT1

  • In synaptic vesicles, synaptotagmin-12 forms a complex with synaptotagmin-1 that prevents synaptotagmin-1 from interacting with SNARE complexes [25].
  • Interestingly, stimulated IL-8 production was not inhibited by the classical NFkappaB decoy but was reduced by treatment with antisense to both p65 and c-Rel supporting preferential binding of c-Rel-p65 to the "alternative" IL-8 kappaB motif [23].
  • Dvl inhibited the binding of Syt I to the complex consisting of syntaxin-1A and SNAP-25 [26].
  • We also demonstrate that it does not participate directly in Cav2.1 Ca2+ channel gating but serves as a binding site in protein-protein interactions with synaptotagmin I and the LC2 domain of microtubule-associated protein 1A [27].
  • Models of the two zinc-binding modules of PKC alpha are based on nuclear magnetic resonance and crystal structures of such modules in other PKC isoforms while the calcium phospholipid binding module (C2) is based on the crystal structure of a repeating unit in synaptotagmin I [28].

Regulatory relationships of SYT1


Other interactions of SYT1

  • It is well established that syntaxin 1A, synaptosomal-associated protein of 25 kDa (SNAP-25) and synaptotagmin either alone or in combination, modulate the kinetic properties of voltage-gated Ca(2+) channels Ca(v)1.2 (Lc-channel) Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) [19].
  • Co-expression of Ca(v)2.3 with syntaxin 1A, SNAP-25 and synaptotagmin together, produced a channel with distinctive kinetic properties analogous to excitosome multiprotein complex generated by Ca(v)1.2 and Ca(v)2 [19].
  • Thus, synaptotagmin-2 is an essential synaptotagmin isoform that functions in concert with other synaptotagmins in the Ca2+ triggering of neurotransmitter release [29].
  • S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro [32].
  • The p52/p65 heterodimer formed in the nucleus, bound specifically to the promoter of the tumor suppressor protein p53, effecting a 25 to 30-fold increase in the level of this protein [33].

Analytical, diagnostic and therapeutic context of SYT1


  1. Structural and functional conservation of synaptotagmin (p65) in Drosophila and humans. Perin, M.S., Johnston, P.A., Ozcelik, T., Jahn, R., Francke, U., Südhof, T.C. J. Biol. Chem. (1991) [Pubmed]
  2. Botulinum neurotoxin A activity is dependent upon the presence of specific gangliosides in neuroblastoma cells expressing synaptotagmin I. Yowler, B.C., Kensinger, R.D., Schengrund, C.L. J. Biol. Chem. (2002) [Pubmed]
  3. Synaptotagmin I expression in mast cells of normal human tissues, systemic mast cell disease, and a human mast cell leukemia cell line. Kimura, N., Shiraishi , S., Mizunashi, K., Ohtsu, H., Kimura, I. J. Histochem. Cytochem. (2001) [Pubmed]
  4. Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Schüpbach, J., Popovic, M., Gilden, R.V., Gonda, M.A., Sarngadharan, M.G., Gallo, R.C. Science (1984) [Pubmed]
  5. Chronic hypoxia stress-induced differential modulation of heat-shock protein 70 and presynaptic proteins. Fei, G., Guo, C., Sun, H.S., Feng, Z.P. J. Neurochem. (2007) [Pubmed]
  6. Synaptosomal proteins, beta-soluble N-ethylmaleimide-sensitive factor attachment protein (beta-SNAP), gamma-SNAP and synaptotagmin I in brain of patients with Down syndrome and Alzheimer's disease. Yoo, B.C., Cairns, N., Fountoulakis, M., Lubec, G. Dementia and geriatric cognitive disorders. (2001) [Pubmed]
  7. Role of nigral NFkappaB p50 and p65 subunit expression in haloperidol-induced neurotoxicity and stereotyped behavior in rats. Saldaña, M., Bonastre, M., Aguilar, E., Marin, C. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. (2006) [Pubmed]
  8. Moderate alcohol intake in humans attenuates monocyte inflammatory responses: inhibition of nuclear regulatory factor kappa B and induction of interleukin 10. Mandrekar, P., Catalano, D., White, B., Szabo, G. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  9. Long-term behavioral effects of repetitive pain in neonatal rat pups. Anand, K.J., Coskun, V., Thrivikraman, K.V., Nemeroff, C.B., Plotsky, P.M. Physiol. Behav. (1999) [Pubmed]
  10. A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Tang, J., Maximov, A., Shin, O.H., Dai, H., Rizo, J., Südhof, T.C. Cell (2006) [Pubmed]
  11. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. Kawai, A., Woodruff, J., Healey, J.H., Brennan, M.F., Antonescu, C.R., Ladanyi, M. N. Engl. J. Med. (1998) [Pubmed]
  12. Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Neurath, M.F., Pettersson, S., Meyer zum Büschenfelde, K.H., Strober, W. Nat. Med. (1996) [Pubmed]
  13. A family of serine proteases expressed exclusively in myelo-monocytic cells specifically processes the nuclear factor-kappa B subunit p65 in vitro and may impair human immunodeficiency virus replication in these cells. Franzoso, G., Biswas, P., Poli, G., Carlson, L.M., Brown, K.D., Tomita-Yamaguchi, M., Fauci, A.S., Siebenlist, U.K. J. Exp. Med. (1994) [Pubmed]
  14. MDM2 induces NF-kappaB/p65 expression transcriptionally through Sp1-binding sites: a novel, p53-independent role of MDM2 in doxorubicin resistance in acute lymphoblastic leukemia. Gu, L., Findley, H.W., Zhou, M. Blood (2002) [Pubmed]
  15. Sp1 increases expression of cyclooxygenase-2 in hypoxic vascular endothelium. Implications for the mechanisms of aortic aneurysm and heart failure. Xu, Q., Ji, Y.S., Schmedtje, J.F. J. Biol. Chem. (2000) [Pubmed]
  16. Overexpression of p65/RelA potentiates curcumin-induced apoptosis in HCT116 human colon cancer cells. Collett, G.P., Campbell, F.C. Carcinogenesis (2006) [Pubmed]
  17. Differences between the radiation hybrid and genetic linkage maps of bovine chromosome 5 resolved with a quasi-phylogenetic method of analysis. Barendse, W., Armitage, S.M., Aleyasin, A., Womack, J.E. Mamm. Genome (2000) [Pubmed]
  18. SV2B regulates synaptotagmin 1 by direct interaction. Lazzell, D.R., Belizaire, R., Thakur, P., Sherry, D.M., Janz, R. J. Biol. Chem. (2004) [Pubmed]
  19. R-type voltage-gated Ca(2+) channel interacts with synaptic proteins and recruits synaptotagmin to the plasma membrane of Xenopus oocytes. Cohen, R., Atlas, D. Neuroscience (2004) [Pubmed]
  20. Fatty acylation of synaptotagmin in PC12 cells and synaptosomes. Chapman, E.R., Blasi, J., An, S., Brose, N., Johnston, P.A., Südhof, T.C., Jahn, R. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  21. Synaptotagmin I is a high affinity receptor for clathrin AP-2: implications for membrane recycling. Zhang, J.Z., Davletov, B.A., Südhof, T.C., Anderson, R.G. Cell (1994) [Pubmed]
  22. Calcium-independent stimulation of membrane fusion and SNAREpin formation by synaptotagmin I. Mahal, L.K., Sequeira, S.M., Gureasko, J.M., Söllner, T.H. J. Cell Biol. (2002) [Pubmed]
  23. Manipulation of distinct NFkappaB proteins alters interleukin-1beta-induced human rheumatoid synovial fibroblast prostaglandin E2 formation. Roshak, A.K., Jackson, J.R., McGough, K., Chabot-Fletcher, M., Mochan, E., Marshall, L.A. J. Biol. Chem. (1996) [Pubmed]
  24. Exophilin4/Slp2-a Targets Glucagon Granules to the Plasma Membrane through Unique Ca2+-inhibitory Phospholipid-binding Activity of the C2A Domain. Yu, M., Kasai, K., Nagashima, K., Torii, S., Yokota-Hashimoto, H., Okamoto, K., Takeuchi, T., Gomi, H., Izumi, T. Mol. Biol. Cell (2007) [Pubmed]
  25. Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous neurotransmitter release. Maximov, A., Shin, O.H., Liu, X., S??dhof, T.C. J. Cell Biol. (2007) [Pubmed]
  26. Dvl regulates endo- and exocytotic processes through binding to synaptotagmin. Kishida, S., Hamao, K., Inoue, M., Hasegawa, M., Matsuura, Y., Mikoshiba, K., Fukuda, M., Kikuchi, A. Genes Cells (2007) [Pubmed]
  27. Alternative splicing of the voltage-gated Ca2+ channel beta4 subunit creates a uniquely folded N-terminal protein binding domain with cell-specific expression in the cerebellar cortex. Vendel, A.C., Terry, M.D., Striegel, A.R., Iverson, N.M., Leuranguer, V., Rithner, C.D., Lyons, B.A., Pickard, G.E., Tobet, S.A., Horne, W.A. J. Neurosci. (2006) [Pubmed]
  28. Structural aspects of the functional modules in human protein kinase-C alpha deduced from comparative analyses. Srinivasan, N., Bax, B., Blundell, T.L., Parker, P.J. Proteins (1996) [Pubmed]
  29. Synaptotagmin-2 is essential for survival and contributes to Ca2+ triggering of neurotransmitter release in central and neuromuscular synapses. Pang, Z.P., Melicoff, E., Padgett, D., Liu, Y., Teich, A.F., Dickey, B.F., Lin, W., Adachi, R., S??dhof, T.C. J. Neurosci. (2006) [Pubmed]
  30. WNK1: analysis of protein kinase structure, downstream targets, and potential roles in hypertension. Xu, B.E., Lee, B.H., Min, X., Lenertz, L., Heise, C.J., Stippec, S., Goldsmith, E.J., Cobb, M.H. Cell Res. (2005) [Pubmed]
  31. Effects of synaptotagmin reveal two distinct mechanisms of agonist-stimulated internalization of the M4 muscarinic acetylcholine receptor. Madziva, M.T., Bai, J., Bhalla, A., Chapman, E.R., Edwardson, J.M. Br. J. Pharmacol. (2005) [Pubmed]
  32. S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro. Mouta Carreira, C., LaVallee, T.M., Tarantini, F., Jackson, A., Lathrop, J.T., Hampton, B., Burgess, W.H., Maciag, T. J. Biol. Chem. (1998) [Pubmed]
  33. NF-kappaB (p65/RelA) as a regulator of TNFalpha-mediated ML-1 cell differentiation. Mudipalli, A., Li, Z., Hromchak, R., Bloch, A. Leukemia (2001) [Pubmed]
  34. The first C2 domain of synaptotagmin is required for exocytosis of insulin from pancreatic beta-cells: action of synaptotagmin at low micromolar calcium. Lang, J., Fukuda, M., Zhang, H., Mikoshiba, K., Wollheim, C.B. EMBO J. (1997) [Pubmed]
  35. Identification of synaptic vesicle, pre- and postsynaptic proteins in human cerebrospinal fluid using liquid-phase isoelectric focusing. Davidsson, P., Puchades, M., Blennow, K. Electrophoresis (1999) [Pubmed]
  36. Expression of synaptotagmin and syntaxin associated with N-type calcium channels in small cell lung cancer. David, P., el Far, O., Martin-Mouto, N., Poupon, M.F., Takahashi, M., Seagar, M.J. FEBS Lett. (1993) [Pubmed]
  37. Variations of synaptotagmin I, synaptotagmin IV, and synaptophysin mRNA levels in rat hippocampus during the estrous cycle. Crispino, M., Stone, D.J., Wei, M., Anderson, C.P., Tocco, G., Finch, C.E., Baudry, M. Exp. Neurol. (1999) [Pubmed]
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