Syntaxin-1A is a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins possess a single C-terminal transmembrane domain, a SNARE [Soluble NSF (N-ethylmaleimide-sensitive fusion protein)-Attachment protein REceptor] domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. Syntaxin-1A is a key protein in ion channel regulation and synaptic exocytosis.[2]
Clinical significance
Syntaxins serve as a substrate for botulinum neurotoxin type C, a metalloprotease that blocks exocytosis and has high affinity for a molecular complex that includes the alpha-latrotoxin receptor which produces explosive exocytosis.[3]
The expression level of STX1A is directly correlated with intelligence in Williams syndrome.[4]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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↑Bennett MK, Calakos N, Scheller RH (July 1992). "Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones". Science. 257 (5067): 255–9. doi:10.1126/science.1321498. PMID1321498.
↑Zhang R, Maksymowych AB, Simpson LL (July 1995). "Cloning and sequence analysis of a cDNA encoding human syntaxin 1A, a polypeptide essential for exocytosis". Gene. 159 (2): 293–4. doi:10.1016/0378-1119(95)00152-V. PMID7622072.
↑Hanson PI, Otto H, Barton N, Jahn R (July 1995). "The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin". The Journal of Biological Chemistry. 270 (28): 16955–61. doi:10.1074/jbc.270.28.16955. PMID7622514.
↑Chin LS, Vavalle JP, Li L (September 2002). "Staring, a novel E3 ubiquitin-protein ligase that targets syntaxin 1 for degradation". The Journal of Biological Chemistry. 277 (38): 35071–9. doi:10.1074/jbc.M203300200. PMID12121982.
↑Berdiev BK, Jovov B, Tucker WC, Naren AP, Fuller CM, Chapman ER, Benos DJ (June 2004). "ENaC subunit-subunit interactions and inhibition by syntaxin 1A". American Journal of Physiology. Renal Physiology. 286 (6): F1100–6. doi:10.1152/ajprenal.00344.2003. PMID14996668.
↑Beckman ML, Bernstein EM, Quick MW (August 1998). "Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A". The Journal of Neuroscience. 18 (16): 6103–12. PMID9698305.
↑Deken SL, Beckman ML, Boos L, Quick MW (October 2000). "Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A". Nature Neuroscience. 3 (10): 998–1003. doi:10.1038/79939. PMID11017172.
↑Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID16169070.
↑ 18.018.1Hata Y, Südhof TC (June 1995). "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". The Journal of Biological Chemistry. 270 (22): 13022–8. doi:10.1074/jbc.270.22.13022. PMID7768895.
↑Gonelle-Gispert C, Molinete M, Halban PA, Sadoul K (September 2000). "Membrane localization and biological activity of SNAP-25 cysteine mutants in insulin-secreting cells". Journal of Cell Science. 113 ( Pt 18) (18): 3197–205. PMID10954418.
↑Ilardi JM, Mochida S, Sheng ZH (February 1999). "Snapin: a SNARE-associated protein implicated in synaptic transmission". Nature Neuroscience. 2 (2): 119–24. doi:10.1038/5673. PMID10195194.
↑Li Y, Chin LS, Weigel C, Li L (November 2001). "Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis". The Journal of Biological Chemistry. 276 (44): 40824–33. doi:10.1074/jbc.M106141200. PMID11524423.
↑ 22.022.1Ravichandran V, Chawla A, Roche PA (June 1996). "Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues". The Journal of Biological Chemistry. 271 (23): 13300–3. doi:10.1074/jbc.271.23.13300. PMID8663154.
↑Chapman ER, An S, Barton N, Jahn R (November 1994). "SNAP-25, a t-SNARE which binds to both syntaxin and synaptobrevin via domains that may form coiled coils". The Journal of Biological Chemistry. 269 (44): 27427–32. PMID7961655.
↑ 24.024.1Steegmaier M, Yang B, Yoo JS, Huang B, Shen M, Yu S, Luo Y, Scheller RH (December 1998). "Three novel proteins of the syntaxin/SNAP-25 family". The Journal of Biological Chemistry. 273 (51): 34171–9. doi:10.1074/jbc.273.51.34171. PMID9852078.
↑Imai A, Nashida T, Yoshie S, Shimomura H (August 2003). "Intracellular localisation of SNARE proteins in rat parotid acinar cells: SNARE complexes on the apical plasma membrane". Archives of Oral Biology. 48 (8): 597–604. doi:10.1016/S0003-9969(03)00116-X. PMID12828989.
↑Li G, Alexander EA, Schwartz JH (May 2003). "Syntaxin isoform specificity in the regulation of renal H+-ATPase exocytosis". The Journal of Biological Chemistry. 278 (22): 19791–7. doi:10.1074/jbc.M212250200. PMID12651853.
↑Araki S, Tamori Y, Kawanishi M, Shinoda H, Masugi J, Mori H, Niki T, Okazawa H, Kubota T, Kasuga M (May 1997). "Inhibition of the binding of SNAP-23 to syntaxin 4 by Munc18c". Biochemical and Biophysical Research Communications. 234 (1): 257–62. doi:10.1006/bbrc.1997.6560. PMID9168999.
↑Bhaskar K, Shareef MM, Sharma VM, Shetty AP, Ramamohan Y, Pant HC, Raju TR, Shetty KT (January 2004). "Co-purification and localization of Munc18-1 (p67) and Cdk5 with neuronal cytoskeletal proteins". Neurochemistry International. 44 (1): 35–44. doi:10.1016/S0197-0186(03)00099-8. PMID12963086.
↑ 29.029.1Pérez-Brangulí F, Muhaisen A, Blasi J (June 2002). "Munc 18a binding to syntaxin 1A and 1B isoforms defines its localization at the plasma membrane and blocks SNARE assembly in a three-hybrid system assay". Molecular and Cellular Neurosciences. 20 (2): 169–80. doi:10.1006/mcne.2002.1122. PMID12093152.
↑Widberg CH, Bryant NJ, Girotti M, Rea S, James DE (September 2003). "Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation". The Journal of Biological Chemistry. 278 (37): 35093–101. doi:10.1074/jbc.M304261200. PMID12832401.
↑Fujita Y, Shirataki H, Sakisaka T, Asakura T, Ohya T, Kotani H, Yokoyama S, Nishioka H, Matsuura Y, Mizoguchi A, Scheller RH, Takai Y (May 1998). "Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process". Neuron. 20 (5): 905–15. doi:10.1016/S0896-6273(00)80472-9. PMID9620695.
↑Shao X, Li C, Fernandez I, Zhang X, Südhof TC, Rizo J (January 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. PMID9010211.
↑Betz A, Okamoto M, Benseler F, Brose N (January 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. PMID8999968.
↑Margittai M, Otto H, Jahn R (March 1999). "A stable interaction between syntaxin 1a and synaptobrevin 2 mediated by their transmembrane domains". FEBS Letters. 446 (1): 40–4. doi:10.1016/S0014-5793(99)00028-9. PMID10100611.
↑Hao JC, Salem N, Peng XR, Kelly RB, Bennett MK (March 1997). "Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes". The Journal of Neuroscience. 17 (5): 1596–603. PMID9030619.
↑Nagamatsu S, Nakamichi Y, Watanabe T, Matsushima S, Yamaguchi S, Ni J, Itagaki E, Ishida H (January 2001). "Localization of cellubrevin-related peptide, endobrevin, in the early endosome in pancreatic beta cells and its physiological function in exo-endocytosis of secretory granules". Journal of Cell Science. 114 (Pt 1): 219–227. PMID11112705.
Further reading
Peters KW, Qi J, Johnson JP, Watkins SC, Frizzell RA (2002). "Role of snare proteins in CFTR and ENaC trafficking". Pflügers Archiv. 443 Suppl 1: S65–9. doi:10.1007/s004240100647. PMID11845306.
McMahon HT, Missler M, Li C, Südhof TC (October 1995). "Complexins: cytosolic proteins that regulate SNAP receptor function". Cell. 83 (1): 111–9. doi:10.1016/0092-8674(95)90239-2. PMID7553862.
Zhang R, Maksymowych AB, Simpson LL (July 1995). "Cloning and sequence analysis of a cDNA encoding human syntaxin 1A, a polypeptide essential for exocytosis". Gene. 159 (2): 293–4. doi:10.1016/0378-1119(95)00152-V. PMID7622072.
Hanson PI, Otto H, Barton N, Jahn R (July 1995). "The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin". The Journal of Biological Chemistry. 270 (28): 16955–61. doi:10.1074/jbc.270.28.16955. PMID7622514.
Hata Y, Südhof TC (June 1995). "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". The Journal of Biological Chemistry. 270 (22): 13022–8. doi:10.1074/jbc.270.22.13022. PMID7768895.
Li C, Ullrich B, Zhang JZ, Anderson RG, Brose N, Südhof TC (June 1995). "Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins". Nature. 375 (6532): 594–9. doi:10.1038/375594a0. PMID7791877.
Betz A, Okamoto M, Benseler F, Brose N (January 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. PMID8999968.
Shao X, Li C, Fernandez I, Zhang X, Südhof TC, Rizo J (January 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. PMID9010211.
Hao JC, Salem N, Peng XR, Kelly RB, Bennett MK (March 1997). "Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes". The Journal of Neuroscience. 17 (5): 1596–603. PMID9030619.
Tellam JT, Macaulay SL, McIntosh S, Hewish DR, Ward CW, James DE (March 1997). "Characterization of Munc-18c and syntaxin-4 in 3T3-L1 adipocytes. Putative role in insulin-dependent movement of GLUT-4". The Journal of Biological Chemistry. 272 (10): 6179–86. doi:10.1074/jbc.272.10.6179. PMID9045631.
Coffield JA, Bakry N, Zhang RD, Carlson J, Gomella LG, Simpson LL (March 1997). "In vitro characterization of botulinum toxin types A, C and D action on human tissues: combined electrophysiologic, pharmacologic and molecular biologic approaches". The Journal of Pharmacology and Experimental Therapeutics. 280 (3): 1489–98. PMID9067339.
Nakayama T, Fujiwara T, Miyazawa A, Asakawa S, Shimizu N, Shimizu Y, Mikoshiba K, Akagawa K (May 1997). "Mapping of the human HPC-1/syntaxin 1A gene (STX1A) to chromosome 7 band q11.2". Genomics. 42 (1): 173–6. doi:10.1006/geno.1997.4650. PMID9177791.
Naren AP, Nelson DJ, Xie W, Jovov B, Pevsner J, Bennett MK, Benos DJ, Quick MW, Kirk KL (November 1997). "Regulation of CFTR chloride channels by syntaxin and Munc18 isoforms". Nature. 390 (6657): 302–5. doi:10.1038/36882. PMID9384384.
Okamoto M, Südhof TC (December 1997). "Mints, Munc18-interacting proteins in synaptic vesicle exocytosis". The Journal of Biological Chemistry. 272 (50): 31459–64. doi:10.1074/jbc.272.50.31459. PMID9395480.
Shuang R, Zhang L, Fletcher A, Groblewski GE, Pevsner J, Stuenkel EL (February 1998). "Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings". The Journal of Biological Chemistry. 273 (9): 4957–66. doi:10.1074/jbc.273.9.4957. PMID9478941.
Vinogradova TI (January 1977). "[Destructive tuberculosis of the lung in adolescents]". Problemy Tuberkuleza (in Russian) (1): 19–22. PMID834751.CS1 maint: Unrecognized language (link)
