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Gene Review

STX1A  -  syntaxin 1A (brain)

Homo sapiens

Synonyms: HPC-1, Neuron-specific antigen HPC-1, P35-1, STX1, SYN1A, ...
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Disease relevance of STX1A


Psychiatry related information on STX1A


High impact information on STX1A


Chemical compound and disease context of STX1A


Biological context of STX1A


Anatomical context of STX1A


Associations of STX1A with chemical compounds

  • Syntaxin 1A directly binds to the neuronal GABA transporter GAT-1 and inhibits its reuptake function [22].
  • Specific proteasome inhibitors such as lactacystin greatly stabilize p35 in vivo [18].
  • Although present, p35, the regulatory protein of cdk5, showed no significant changes in protein expression with the introduction of ciglitazone [3].
  • Syntaxin 1A and receptor for activated C kinase interact with the N-terminal region of human dopamine transporter [23].
  • When two helix-breaking proline residues are introduced into the juxtamembrane region of VAMP, there is little or no effect on fusion, and the same change in syntaxin 1A only reduced the extent and rate of fusion by half [24].

Physical interactions of STX1A


Enzymatic interactions of STX1A


Regulatory relationships of STX1A

  • This phenotype was not rescued when syntaxin 1A was co-expressed with SNAP-25 [32].
  • Basal ENaC currents were inhibited by syntaxin 1A and stimulated by syntaxin 3 [33].
  • Syntaxin 1A inhibits GABA uptake of an endogenous GABA transporter in neuronal cultures from rat hippocampus and in reconstitution systems expressing the cloned rat brain GABA transporter GAT1 [34].
  • Apoptosis induced by Stx1 (200 ng/ml) and apoptosis induced by Stx2 (200 ng/ml) were maximal following incubation with cells for 24 h (94.3% +/- 1.8% and 81.7% +/- 5.2% of the cells, respectively) [35].
  • This tonic inhibition was dramatically attenuated following incubation with botulinum toxin C, indicating that syntaxin 1A expression was indeed responsible for the enhanced G protein modulation [36].

Other interactions of STX1A

  • Here we show that CFTR channels are coordinately regulated by two cognate t-SNAREs, SNAP-23 (synaptosome-associated protein of 23 kDa) and syntaxin 1A [25].
  • SNARE motif sequences fall into four classes, homologous to the neuronal proteins syntaxin 1a, VAMP 2, and the N- and C-terminal SNARE motifs of SNAP-25 (S25N and S25C), and it is thought that one member from each class interacts to form a SNARE complex [21].
  • LIMK1 and STX1A are good candidates for cognitive or behavioral aspects of WS [37].
  • A fourth mutant protein, S48D, shows abolishment of syntaxin 3 interaction but binds syntaxin 2 at normal and syntaxin 1A at mildly reduced efficiency [38].
  • Furthermore, expression of a cytosolic mutant syntaxin 1A did not interfere with SNAP-25 membrane interactions or palmitoylation in the neuronal cell line NG108-15 [32].

Analytical, diagnostic and therapeutic context of STX1A


  1. Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes. Botta, A., Novelli, G., Mari, A., Novelli, A., Sabani, M., Korenberg, J., Osborne, L.R., Digilio, M.C., Giannotti, A., Dallapiccola, B. J. Med. Genet. (1999) [Pubmed]
  2. Expression of syntaxin 1C, an alternative splice variant of HPC-1/syntaxin 1A, is enhanced by phorbol-ester stimulation in astroglioma: participation of the PKC signaling pathway. Nakayama, T., Mikoshiba, K., Yamamori, T., Akagawa, K. FEBS Lett. (2003) [Pubmed]
  3. CDK5 is a novel regulatory protein in PPARgamma ligand-induced antiproliferation. Kim, E., Chen, F., Wang, C.C., Harrison, L.E. Int. J. Oncol. (2006) [Pubmed]
  4. Altered immunoreactivity of HPC-1/syntaxin 1A in proliferated nerve fibers in the human aganglionic colon of Hirschsprung's disease. Nirasawa, Y., Ito, Y., Fujiwara, T., Seki, N., Tanaka, H., Akagawa, K. J. Mol. Neurosci. (2001) [Pubmed]
  5. Octaplex PCR and fluorescence-based capillary electrophoresis for identification of human diarrheagenic Escherichia coli and Shigella spp. Brandal, L.T., Lindstedt, B.A., Aas, L., Stavnes, T.L., Lassen, J., Kapperud, G. J. Microbiol. Methods (2007) [Pubmed]
  6. Inhibition of cyclin-dependent kinases, GSK-3beta and CK1 by hymenialdisine, a marine sponge constituent. Meijer, L., Thunnissen, A.M., White, A.W., Garnier, M., Nikolic, M., Tsai, L.H., Walter, J., Cleverley, K.E., Salinas, P.C., Wu, Y.Z., Biernat, J., Mandelkow, E.M., Kim, S.H., Pettit, G.R. Chem. Biol. (2000) [Pubmed]
  7. Downregulation of neuronal cdk5/p35 in opioid addicts and opiate-treated rats: relation to neurofilament phosphorylation. Ferrer-Alcón, M., La Harpe, R., Guimón, J., García-Sevilla, J.A. Neuropsychopharmacology (2003) [Pubmed]
  8. Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Patrick, G.N., Zukerberg, L., Nikolic, M., de la Monte, S., Dikkes, P., Tsai, L.H. Nature (1999) [Pubmed]
  9. The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity. Nikolic, M., Chou, M.M., Lu, W., Mayer, B.J., Tsai, L.H. Nature (1998) [Pubmed]
  10. Evidence that syntaxin 1A is involved in storage in the secretory pathway. Bittner, M.A., Bennett, M.K., Holz, R.W. J. Biol. Chem. (1996) [Pubmed]
  11. Emerging Shiga Toxin-Producing Escherichia coli Serotypes in Europe: O100:H- and O127:H40. Orth, D., Grif, K., Fisher, I., Fruth, A., Tsch??pe, H., Scheutz, F., Dierich, M.P., W??rzner, R. Curr. Microbiol. (2006) [Pubmed]
  12. Involvement of Cdk5/p25 in digoxin-triggered prostate cancer cell apoptosis. Lin, H., Juang, J.L., Wang, P.S. J. Biol. Chem. (2004) [Pubmed]
  13. Glucose-induced expression of the cyclin-dependent protein kinase 5 activator p35 involved in Alzheimer's disease regulates insulin gene transcription in pancreatic beta-cells. Ubeda, M., Kemp, D.M., Habener, J.F. Endocrinology (2004) [Pubmed]
  14. Activation of a CrmA-insensitive, p35-sensitive pathway in ionizing radiation-induced apoptosis. Datta, R., Kojima, H., Banach, D., Bump, N.J., Talanian, R.V., Alnemri, E.S., Weichselbaum, R.R., Wong, W.W., Kufe, D.W. J. Biol. Chem. (1997) [Pubmed]
  15. Mapping of the human HPC-1/syntaxin 1A gene (STX1A) to chromosome 7 band q11.2. Nakayama, T., Fujiwara, T., Miyazawa, A., Asakawa, S., Shimizu, N., Shimizu, Y., Mikoshiba, K., Akagawa, K. Genomics (1997) [Pubmed]
  16. 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]
  17. Syntaxin 1A inhibits CFTR chloride channels by means of domain-specific protein-protein interactions. Naren, A.P., Quick, M.W., Collawn, J.F., Nelson, D.J., Kirk, K.L. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  18. p35, the neuronal-specific activator of cyclin-dependent kinase 5 (Cdk5) is degraded by the ubiquitin-proteasome pathway. Patrick, G.N., Zhou, P., Kwon, Y.T., Howley, P.M., Tsai, L.H. J. Biol. Chem. (1998) [Pubmed]
  19. Supernumerary ring chromosome 7 mosaicism: case report, investigation of the gene content, and delineation of the phenotype. Lichtenbelt, K.D., Hochstenbach, R., van Dam, W.M., Eleveld, M.J., Poot, M., Beemer, F.A. Am. J. Med. Genet. A (2005) [Pubmed]
  20. Syntaxin 1A is expressed in airway epithelial cells, where it modulates CFTR Cl(-) currents. Naren, A.P., Di, A., Cormet-Boyaka, E., Boyaka, P.N., McGhee, J.R., Zhou, W., Akagawa, K., Fujiwara, T., Thome, U., Engelhardt, J.F., Nelson, D.J., Kirk, K.L. J. Clin. Invest. (2000) [Pubmed]
  21. Three-dimensional structure of the amino-terminal domain of syntaxin 6, a SNAP-25 C homolog. Misura, K.M., Bock, J.B., Gonzalez, L.C., Scheller, R.H., Weis, W.I. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  22. SNAP-25/Syntaxin 1A Complex Functionally Modulates Neurotransmitter {gamma}-Aminobutyric Acid Reuptake. Fan, H.P., Fan, F.J., Bao, L., Pei, G. J. Biol. Chem. (2006) [Pubmed]
  23. Syntaxin 1A and receptor for activated C kinase interact with the N-terminal region of human dopamine transporter. Lee, K.H., Kim, M.Y., Kim, D.H., Lee, Y.S. Neurochem. Res. (2004) [Pubmed]
  24. The length of the flexible SNAREpin juxtamembrane region is a critical determinant of SNARE-dependent fusion. McNew, J.A., Weber, T., Engelman, D.M., Söllner, T.H., Rothman, J.E. Mol. Cell (1999) [Pubmed]
  25. CFTR chloride channels are regulated by a SNAP-23/syntaxin 1A complex. Cormet-Boyaka, E., Di, A., Chang, S.Y., Naren, A.P., Tousson, A., Nelson, D.J., Kirk, K.L. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  26. Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs. Fasshauer, D., Sutton, R.B., Brunger, A.T., Jahn, R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  27. Membrane localization and biological activity of SNAP-25 cysteine mutants in insulin-secreting cells. Gonelle-Gispert, C., Molinete, M., Halban, P.A., Sadoul, K. J. Cell. Sci. (2000) [Pubmed]
  28. Identification of syntaxin 1A as a novel binding protein for presenilin-1. Smith, S.K., Anderson, H.A., Yu, G., Robertson, A.G., Allen, S.J., Tyler, S.J., Naylor, R.L., Mason, G., Wilcock, G.W., Roche, P.A., Fraser, P.E., Dawbarn, D. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  29. Increase of cdk5 is related to neurofibrillary pathology in progressive supranuclear palsy. Borghi, R., Giliberto, L., Assini, A., Delacourte, A., Perry, G., Smith, M.A., Strocchi, P., Zaccheo, D., Tabaton, M. Neurology (2002) [Pubmed]
  30. Cyclin-dependent kinase-5/p35 phosphorylates Presenilin 1 to regulate carboxy-terminal fragment stability. Lau, K.F., Howlett, D.R., Kesavapany, S., Standen, C.L., Dingwall, C., McLoughlin, D.M., Miller, C.C. Mol. Cell. Neurosci. (2002) [Pubmed]
  31. Interaction of Shiga toxin from Escherichia coli with human intestinal epithelial cell lines and explants: Stx2 induces epithelial damage in organ culture. Schüller, S., Frankel, G., Phillips, A.D. Cell. Microbiol. (2004) [Pubmed]
  32. SNAP-25 traffics to the plasma membrane by a syntaxin-independent mechanism. Loranger, S.S., Linder, M.E. J. Biol. Chem. (2002) [Pubmed]
  33. Interaction of syntaxins with the amiloride-sensitive epithelial sodium channel. Saxena, S., Quick, M.W., Tousson, A., Oh, Y., Warnock, D.G. J. Biol. Chem. (1999) [Pubmed]
  34. Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A. Beckman, M.L., Bernstein, E.M., Quick, M.W. J. Neurosci. (1998) [Pubmed]
  35. Escherichia coli shiga-like toxins induce apoptosis and cleavage of poly(ADP-ribose) polymerase via in vitro activation of caspases. Ching, J.C., Jones, N.L., Ceponis, P.J., Karmali, M.A., Sherman, P.M. Infect. Immun. (2002) [Pubmed]
  36. G protein modulation of N-type calcium channels is facilitated by physical interactions between syntaxin 1A and Gbetagamma. Jarvis, S.E., Magga, J.M., Beedle, A.M., Braun, J.E., Zamponi, G.W. J. Biol. Chem. (2000) [Pubmed]
  37. Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes. Tassabehji, M., Metcalfe, K., Karmiloff-Smith, A., Carette, M.J., Grant, J., Dennis, N., Reardon, W., Splitt, M., Read, A.P., Donnai, D. Am. J. Hum. Genet. (1999) [Pubmed]
  38. Analysis of the Munc18b-syntaxin binding interface. Use of a mutant Munc18b to dissect the functions of syntaxins 2 and 3. Kauppi, M., Wohlfahrt, G., Olkkonen, V.M. J. Biol. Chem. (2002) [Pubmed]
  39. Regulation of the amiloride-sensitive epithelial sodium channel by syntaxin 1A. Qi, J., Peters, K.W., Liu, C., Wang, J.M., Edinger, R.S., Johnson, J.P., Watkins, S.C., Frizzell, R.A. J. Biol. Chem. (1999) [Pubmed]
  40. Cloning and sequence analysis of a cDNA encoding human syntaxin 1A, a polypeptide essential for exocytosis. Zhang, R., Maksymowych, A.B., Simpson, L.L. Gene (1995) [Pubmed]
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