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Gene Review

Stxbp1  -  syntaxin binding protein 1

Rattus norvegicus

Synonyms: ANC18HA, Munc18-1, N-Sec1, NSEC1A, Protein unc-18 homolog 1, ...
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Disease relevance of Stxbp1

  • To investigate whether p67 is essential for the survival of mammalian cells, the basal level of p67 was lowered from rat tumor hepatoma cells using antisense approach [1].
  • We show that a soluble Escherichia coli recombinant version of p67 (p67(635)), in which a prokaryotic signal peptide replaces the eukaryotic one, confers protection comparable to that induced by the full-length molecule, but is unstable [2].
  • Recombinant p67 is, therefore, a candidate antigen for development of an anti-sporozoite vaccine for East Coast fever in cattle [3].

High impact information on Stxbp1

  • Three-dimensional structure of the neuronal-Sec1-syntaxin 1a complex [4].
  • Our data suggest that Munc-18 is a previously unidentified essential component of the synaptic vesicle fusion protein complex [5].
  • Control of fusion pore dynamics during exocytosis by Munc18 [6].
  • Here, in adrenal chromaffin cells, we expressed a Munc18 mutant with reduced affinity for syntaxin, which specifically modified the kinetics of single-granule exocytotic release events, consistent with an acceleration of fusion pore expansion [6].
  • All vesicle transport steps also have an essential requirement for a member of the Sec1 protein family, including the neuronal Munc18-1 (also known as nSec1) in regulated exocytosis [6].

Biological context of Stxbp1


Anatomical context of Stxbp1


Associations of Stxbp1 with chemical compounds


Physical interactions of Stxbp1


Regulatory relationships of Stxbp1

  • Exogenously expressed p67 stimulated Cdk5 kinase activity in vitro in a dose-dependent manner and when presented as an affinity matrix, selectively adsorbed Cdk5 from a cleared rat brain homogenate [10].

Other interactions of Stxbp1

  • When recombinant taxilin was incubated with the extract from the rat brain crude membrane fraction, recombinant taxilin bound to syntaxin-1s free of at least VAMP2, SNAP-25, and Munc18 [19].
  • In contrast, deletion of the transmembrane domain potentiates SNAP-25 and rbSec1A/nsec-1/munc18 binding [20].
  • Our data indicate that the production of PI(4,5)P(2) is necessary for proper control of beta-cell secretion and suggest that at least part of the effect of PI on insulin exocytosis could be exerted through the activation of phospholipase D1, Ca(2+)-dependent activator protein for secretion 1, and Munc18-interacting protein 1 [21].
  • Furthermore, Munc18, synaptophysin, and high amounts of the isoforms I and II of synaptotagmin were also found in DRM [22].
  • Studies of signaling pathways involved in synaptic potentiation revealed that this blockade was due to a reduction of the phosphorylation by protein kinase C (PKC) of proteins that regulate SV recycling, such as myristoylated alanine-rich C kinase substrate (MARCKS) and Munc18-1/nSec1 [23].

Analytical, diagnostic and therapeutic context of Stxbp1


  1. Induction of apoptosis due to lowering the level of eukaryotic initiation factor 2-associated protein, p67, from mammalian cells by antisense approach. Datta, B., Datta, R. Exp. Cell Res. (1999) [Pubmed]
  2. Immunity to East Coast fever in cattle induced by a polypeptide fragment of the major surface coat protein of Theileria parva sporozoites. Bishop, R., Nene, V., Staeyert, J., Rowlands, J., Nyanjui, J., Osaso, J., Morzaria, S., Musoke, A. Vaccine (2003) [Pubmed]
  3. Characterisation of the gene encoding a candidate vaccine antigen of Theileria parva sporozoites. Nene, V., Iams, K.P., Gobright, E., Musoke, A.J. Mol. Biochem. Parasitol. (1992) [Pubmed]
  4. Three-dimensional structure of the neuronal-Sec1-syntaxin 1a complex. Misura, K.M., Scheller, R.H., Weis, W.I. Nature (2000) [Pubmed]
  5. Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin. Hata, Y., Slaughter, C.A., Südhof, T.C. Nature (1993) [Pubmed]
  6. Control of fusion pore dynamics during exocytosis by Munc18. Fisher, R.J., Pevsner, J., Burgoyne, R.D. Science (2001) [Pubmed]
  7. nSec1 binds a closed conformation of syntaxin1A. Yang, B., Steegmaier, M., Gonzalez, L.C., Scheller, R.H. J. Cell Biol. (2000) [Pubmed]
  8. Pancreatic beta-cell protein granuphilin binds Rab3 and Munc-18 and controls exocytosis. Coppola, T., Frantz, C., Perret-Menoud, V., Gattesco, S., Hirling, H., Regazzi, R. Mol. Biol. Cell (2002) [Pubmed]
  9. A novel ubiquitous form of Munc-18 interacts with multiple syntaxins. Use of the yeast two-hybrid system to study interactions between proteins involved in membrane traffic. Hata, Y., Südhof, T.C. J. Biol. Chem. (1995) [Pubmed]
  10. Molecular characterization of a neuronal-specific protein that stimulates the activity of Cdk5. Shetty, K.T., Kaech, S., Link, W.T., Jaffe, H., Flores, C.M., Wray, S., Pant, H.C., Beushausen, S. J. Neurochem. (1995) [Pubmed]
  11. Nuclear localization of Munc18-1 (p67) in the adult rat brain and PC12 cells. Sharma, V.M., Shareef, M.M., Bhaskar, K., Kalidas, S., Shetty, P.A., Christopher, R., Ramamohan, Y., Pant, H.C., Shetty, T.K. Neurochem. Int. (2005) [Pubmed]
  12. In chromaffin cells, the mammalian Sec1p homologue is a syntaxin 1A-binding protein associated with chromaffin granules. Hodel, A., Schäfer, T., Gerosa, D., Burger, M.M. J. Biol. Chem. (1994) [Pubmed]
  13. n-Sec1: a neural-specific syntaxin-binding protein. Pevsner, J., Hsu, S.C., Scheller, R.H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  14. Arachidonic acid allows SNARE complex formation in the presence of Munc18. Rickman, C., Davletov, B. Chem. Biol. (2005) [Pubmed]
  15. Peroxynitrite affects exocytosis and SNARE complex formation and induces tyrosine nitration of synaptic proteins. Di Stasi, A.M., Mallozzi, C., Macchia, G., Maura, G., Petrucci, T.C., Minetti, M. J. Neurochem. (2002) [Pubmed]
  16. Ethanol induced changes in cyclin-dependent kinase-5 activity and its activators, P35, P67 (Munc-18) in rat brain. Rajgopal, Y., Vemuri, M.C. Neurosci. Lett. (2001) [Pubmed]
  17. Rat p67 GBP is induced by interferon-gamma and isoprenoid-modified in macrophages. Vestal, D.J., Buss, J.E., Kelner, G.S., Maciejewski, D., Asundi, V.K., Maki, R.A. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  18. Evidence for SNARE zippering during Ca2+-triggered exocytosis in PC12 cells. Matos, M.F., Mukherjee, K., Chen, X., Rizo, J., Südhof, T.C. Neuropharmacology (2003) [Pubmed]
  19. Interaction of taxilin with syntaxin which does not form the SNARE complex. Nogami, S., Satoh, S., Nakano, M., Terano, A., Shirataki, H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  20. The transmembrane domain of syntaxin 1A is critical for cytoplasmic domain protein-protein interactions. Lewis, J.L., Dong, M., Earles, C.A., Chapman, E.R. J. Biol. Chem. (2001) [Pubmed]
  21. Role of phosphoinositide signaling in the control of insulin exocytosis. Waselle, L., Gerona, R.R., Vitale, N., Martin, T.F., Bader, M.F., Regazzi, R. Mol. Endocrinol. (2005) [Pubmed]
  22. Synaptic proteins and SNARE complexes are localized in lipid rafts from rat brain synaptosomes. Gil, C., Soler-Jover, A., Blasi, J., Aguilera, J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  23. Borna disease virus blocks potentiation of presynaptic activity through inhibition of protein kinase C signaling. Volmer, R., Monnet, C., Gonzalez-Dunia, D. PLoS Pathog. (2006) [Pubmed]
  24. A rat brain Sec1 homologue related to Rop and UNC18 interacts with syntaxin. Garcia, E.P., Gatti, E., Butler, M., Burton, J., De Camilli, P. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  25. Munc-18 associates with syntaxin and serves as a negative regulator of exocytosis in the pancreatic beta -cell. Zhang, W., Efanov, A., Yang, S.N., Fried, G., Kolare, S., Brown, H., Zaitsev, S., Berggren, P.O., Meister, B. J. Biol. Chem. (2000) [Pubmed]
  26. A glycosylation site, 60SGTS63, of p67 is required for its ability to regulate the phosphorylation and activity of eukaryotic initiation factor 2alpha. Datta, R., Choudhury, P., Ghosh, A., Datta, B. Biochemistry (2003) [Pubmed]
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