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Gene Review

STXBP1  -  syntaxin binding protein 1

Homo sapiens

Synonyms: MUNC18-1, N-Sec1, NSEC1, P67, Protein unc-18 homolog 1, ...
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Disease relevance of STXBP1


Psychiatry related information on STXBP1


High impact information on STXBP1


Biological context of STXBP1


Anatomical context of STXBP1


Associations of STXBP1 with chemical compounds


Physical interactions of STXBP1

  • Mint 1 and 2 are proteins that bind to munc18-1, an essential component of the synaptic vesicle fusion machinery, and are detectably expressed only in neurons [Okamoto and Südhof, J. Biol. Chem. 272, 31459-31464 (1997)] [22].
  • We conclude that Munc18-1 allows for the formation of a complex between syntaxin and SNAP-25 that serves as an acceptor for vesicle-bound synaptobrevin and that thus represents an intermediate in the pathway towards exocytosis [23].

Other interactions of STXBP1

  • Syntaxin 1A is delivered to the apical and basolateral domains of epithelial cells: the role of munc-18 proteins [24].
  • Furthermore, overexpression of the ubiquitous isoform of munc-18, munc-18-2, is also capable of rescuing the transport of the t-SNARE [24].
  • We conclude that like other Sec1/Munc18 proteins, VPS33B is involved in intracellular vesicle trafficking, being essential for the development of platelet alpha-granules but not for granule secretion [3].
  • Thrombin ligation of protease-activated receptor-1 activated the phosphorylation of syntaxin 4 and Munc18c, which, in turn, disrupted the interaction between syntaxin 4 and Munc18 [25].
  • We then applied this method to find plausible binding partners for proteins with uncharacterized binding specificities in the syntaxin/Unc-18 protein and TGF-beta/TGF-beta receptor families [26].

Analytical, diagnostic and therapeutic context of STXBP1

  • Findings from immunofluorescence studies in PC12 cells have shown co-localization of Munc18-1 and Cdk5 with neurofilaments and microtubules [27].
  • Using site-directed mutagenesis, we find that disruption of the closed conformation abolishes the ability of syntaxin to bind to munc18-1 and to inhibit secretion in PC12 cells [28].
  • The induction of 53 genes was confirmed by using microarray analysis and quantitative real-time PCR: among these genes was MetAP2/p67, which encodes an activator of translational initiation and represents a validated target for inhibition of neovascularization [29].
  • By contrast, p67-positive subclones stably expressed the antigen, and in situ hybridization to metaphase spreads demonstrated that amplified human DNA sequences were integrated into a specific marker chromosome [30].
  • Using these enzyme forms, we have identified for the first time a direct role of residues within the N-terminal domain in modulating topoisomerase I catalysis, as revealed by significant differences between p67 and p91 in DNA binding, cleavage, strand rotation, and ligation [31].


  1. Autoimmunity to munc-18 in Rasmussen's encephalitis. Yang, R., Puranam, R.S., Butler, L.S., Qian, W.H., He, X.P., Moyer, M.B., Blackburn, K., Andrews, P.I., McNamara, J.O. Neuron (2000) [Pubmed]
  2. Identification and characterization of a nuclear localization sequence-binding protein in yeast. Lee, W.C., Mélèse, T. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  3. Requirement of VPS33B, a member of the Sec1/Munc18 protein family, in megakaryocyte and platelet alpha-granule biogenesis. Lo, B., Li, L., Gissen, P., Christensen, H., McKiernan, P.J., Ye, C., Abdelhaleem, M., Hayes, J.A., Williams, M.D., Chitayat, D., Kahr, W.H. Blood (2005) [Pubmed]
  4. Increased phosphorylation of eukaryotic initiation factor 2alpha at the G2/M boundary in human osteosarcoma cells correlates with deglycosylation of p67 and a decreased rate of protein synthesis. Datta, B., Datta, R., Mukherjee, S., Zhang, Z. Exp. Cell Res. (1999) [Pubmed]
  5. MAPs and POEP of the roads from prokaryotic to eukaryotic kingdoms. Datta, B. Biochimie (2000) [Pubmed]
  6. Cdk5 and munc-18/p67 co-localization in early stage neurofibrillary tangles-bearing neurons in Alzheimer type dementia brains. Takahashi, M., Iseki, E., Kosaka, K. J. Neurol. Sci. (2000) [Pubmed]
  7. Selective Activation of Cognate SNAREpins by Sec1/Munc18 Proteins. Shen, J., Tareste, D.C., Paumet, F., Rothman, J.E., Melia, T.J. Cell (2007) [Pubmed]
  8. Regulation of CFTR chloride channels by syntaxin and Munc18 isoforms. Naren, A.P., Nelson, D.J., Xie, W., Jovov, B., Pevsner, J., Bennett, M.K., Benos, D.J., Quick, M.W., Kirk, K.L. Nature (1997) [Pubmed]
  9. The riddle of the Sec1/Munc-18 proteins - new twists added to their interactions with SNAREs. Gallwitz, D., Jahn, R. Trends Biochem. Sci. (2003) [Pubmed]
  10. Sec1/Munc18 proteins: mediators of membrane fusion moving to center stage. Jahn, R. Neuron (2000) [Pubmed]
  11. Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C: its implication in regulating the interaction of Munc-18/n-Sec1/rbSec1 with syntaxin. Fujita, Y., Sasaki, T., Fukui, K., Kotani, H., Kimura, T., Hata, Y., Südhof, T.C., Scheller, R.H., Takai, Y. J. Biol. Chem. (1996) [Pubmed]
  12. Mints, Munc18-interacting proteins in synaptic vesicle exocytosis. Okamoto, M., Südhof, T.C. J. Biol. Chem. (1997) [Pubmed]
  13. Fluorescence resonance energy transfer reports properties of syntaxin1a interaction with Munc18-1 in vivo. Liu, J., Ernst, S.A., Gladycheva, S.E., Lee, Y.Y., Lentz, S.I., Ho, C.S., Li, Q., Stuenkel, E.L. J. Biol. Chem. (2004) [Pubmed]
  14. Specific SNARE complex binding mode of the Sec1/Munc-18 protein, Sec1p. Togneri, J., Cheng, Y.S., Munson, M., Hughson, F.M., Carr, C.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  15. Phosphorylation of Munc18 by protein kinase C regulates the kinetics of exocytosis. Barclay, J.W., Craig, T.J., Fisher, R.J., Ciufo, L.F., Evans, G.J., Morgan, A., Burgoyne, R.D. J. Biol. Chem. (2003) [Pubmed]
  16. Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings. Shuang, R., Zhang, L., Fletcher, A., Groblewski, G.E., Pevsner, J., Stuenkel, E.L. J. Biol. Chem. (1998) [Pubmed]
  17. DOC2 proteins in rat brain: complementary distribution and proposed function as vesicular adapter proteins in early stages of secretion. Verhage, M., de Vries, K.J., Røshol, H., Burbach, J.P., Gispen, W.H., Südhof, T.C. Neuron (1997) [Pubmed]
  18. A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants. Gengyo-Ando, K., Kitayama, H., Mukaida, M., Ikawa, Y. J. Neurosci. (1996) [Pubmed]
  19. The molecular machinery of synaptic vesicle exocytosis. Li, L., Chin, L.S. Cell. Mol. Life Sci. (2003) [Pubmed]
  20. Dissecting docking and tethering of secretory vesicles at the target membrane. Toonen, R.F., Kochubey, O., de Wit, H., Gulyas-Kovacs, A., Konijnenburg, B., Sørensen, J.B., Klingauf, J., Verhage, M. EMBO J. (2006) [Pubmed]
  21. Mechanism of arachidonic acid action on syntaxin-Munc18. Connell, E., Darios, F., Broersen, K., Gatsby, N., Peak-Chew, S.Y., Rickman, C., Davletov, B. EMBO Rep. (2007) [Pubmed]
  22. Mint 3: a ubiquitous mint isoform that does not bind to munc18-1 or -2. Okamoto, M., Südhof, T.C. Eur. J. Cell Biol. (1998) [Pubmed]
  23. Munc18-Bound Syntaxin Readily Forms SNARE Complexes with Synaptobrevin in Native Plasma Membranes. Zilly, F.E., S??rensen, J.B., Jahn, R., Lang, T. PLoS Biol. (2006) [Pubmed]
  24. Syntaxin 1A is delivered to the apical and basolateral domains of epithelial cells: the role of munc-18 proteins. Rowe, J., Calegari, F., Taverna, E., Longhi, R., Rosa, P. J. Cell. Sci. (2001) [Pubmed]
  25. Protease-activated receptor-1 activation of endothelial cells induces protein kinase Calpha-dependent phosphorylation of syntaxin 4 and Munc18c: role in signaling p-selectin expression. Fu, J., Naren, A.P., Gao, X., Ahmmed, G.U., Malik, A.B. J. Biol. Chem. (2005) [Pubmed]
  26. Co-evolutionary analysis reveals insights into protein-protein interactions. Goh, C.S., Cohen, F.E. J. Mol. Biol. (2002) [Pubmed]
  27. Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins. Bhaskar, K., Shareef, M.M., Sharma, V.M., Shetty, A.P., Ramamohan, Y., Pant, H.C., Raju, T.R., Shetty, K.T. Neurochem. Int. (2004) [Pubmed]
  28. A conformational switch in syntaxin during exocytosis: role of munc18. Dulubova, I., Sugita, S., Hill, S., Hosaka, M., Fernandez, I., Südhof, T.C., Rizo, J. EMBO J. (1999) [Pubmed]
  29. Characterization of the c-MYC-regulated transcriptome by SAGE: identification and analysis of c-MYC target genes. Menssen, A., Hermeking, H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  30. Amplification of genes encoding human myeloid membrane antigens after DNA-mediated gene transfer. Look, A.T., Peiper, S.C., Douglass, E.C., Trent, J.M., Sherr, C.J. Blood (1986) [Pubmed]
  31. Residues within the N-terminal domain of human topoisomerase I play a direct role in relaxation. Lisby, M., Olesen, J.R., Skouboe, C., Krogh, B.O., Straub, T., Boege, F., Velmurugan, S., Martensen, P.M., Andersen, A.H., Jayaram, M., Westergaard, O., Knudsen, B.R. J. Biol. Chem. (2001) [Pubmed]
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