STX1A

Syntaxin 1A (brain)
PDB rendering based on 1br0.
Available structures PDB 1br0, 1dn1, 1ez3, 1hvv, 1jth, 1kil, 1n7s, 1sfc, 1urq
Identifiers
Symbols	STX1A; HPC-1; P35-1; STX1; SYN1A
External IDs	OMIM: 186590 MGI: 109355 HomoloGene: 37941 GeneCards: STX1A Gene
Gene Ontology Molecular function • SNARE binding • glycoprotein binding • SNAP receptor activity • protein binding • myosin binding • calcium channel inhibitor activity • protein domain specific binding • protein binding, bridging • myosin head/neck binding • ATP-dependent protein binding • protein heterodimerization activity • protein N-terminus binding • calcium-dependent protein binding Cellular component • extracellular region • plasma membrane • plasma membrane • integral to membrane • synaptosome • cell junction • stored secretory granule • synaptic vesicle membrane • cytoplasmic vesicle • actomyosin • neuron projection • protein complex • synapse • synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex • synaptobrevin 2-SNAP-25-syntaxin-1a complex Biological process • positive regulation of neurotransmitter secretion • energy reserve metabolic process • intracellular protein transport • synaptic transmission • neurotransmitter secretion • response to gravity • glutamate secretion • synaptic vesicle docking involved in exocytosis • calcium ion-dependent exocytosis • positive regulation of exocytosis • regulation of insulin secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6804	20907
Ensembl	ENSG00000106089	ENSMUSG00000007207
UniProt	Q16623	Q497P1
RefSeq (mRNA)	NM_001165903.1	NM_016801.3
RefSeq (protein)	NP_001159375.1	NP_058081.2
Location (UCSC)	Chr 7: 73.11 – 73.13 Mb	Chr 5: 135.5 – 135.53 Mb
PubMed search	[1]	[2]

Syntaxin-1A is a protein that in humans is encoded by the STX1A gene.^[1]

Function

Synaptic vesicles store neurotransmitters that are released during calcium-regulated exocytosis. The specificity of neurotransmitter release requires the localization of both synaptic vesicles and calcium channels to the presynaptic active zone. Syntaxins function in this vesicle fusion process.

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 levels of the 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. ^[5]

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Nicotine Activity on Dopaminergic Neurons edit

Interactions

STX1A has been shown to interact with:

• CPLX1,^[6][7][8]
• CFTR,^[9][10]
• NAPA,^[11][12]
• RNF40,^[13]
• SCNN1G,^[14]
• SLC6A1,^[15][16][17]
• SNAP-25,^{[6][7][11][18][19][20][21][22][23][24][25]}
• SNAP23,^{[23][25][26][27][28]}
• STXBP1,^{[6][11][19][29][30]}
• STXBP5,^[31][32]
• SYT1^[33][34]
• UNC13B,^[35]
• VAMP2,^{[6][7][11][30][36][37]} and
• VAMP8.^[38]

See also

• Syntaxin

References

1. ^ Bennett MK, Calakos N, Scheller RH (Aug 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. PMID 1321498. 
2. ^ "Entrez Gene: STX1A syntaxin 1A (brain)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6804. 
3. ^ 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. PMID 7622072. 
4. ^ Gao MC, Bellugi U, Dai L, Mills DL, Sobel EM, Lange K, Korenberg JR (2010). "Intelligence in Williams Syndrome is related to STX1A, which encodes a component of the presynaptic SNARE complex". PLoS ONE 5 (4): e10292. doi:10.1371/journal.pone.0010292. PMC 2858212. PMID 20422020. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2858212. Lay summary – The Salt Lake Tribune. 
5. ^ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602". http://www.wikipathways.org/index.php/Pathway:WP1602. 
6. ^ ^{a b c d} Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J (August 1999). "A conformational switch in syntaxin during exocytosis: role of munc18". EMBO J. 18 (16): 4372–82. doi:10.1093/emboj/18.16.4372. PMC 1171512. PMID 10449403. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171512. 
7. ^ ^{a b c} Chen X, Tomchick DR, Kovrigin E, Araç D, Machius M, Südhof TC, Rizo J (January 2002). "Three-dimensional structure of the complexin/SNARE complex". Neuron 33 (3): 397–409. doi:10.1016/S0896-6273(02)00583-4. PMID 11832227. 
8. ^ Hu K, Carroll J, Rickman C, Davletov B (November 2002). "Action of complexin on SNARE complex". J. Biol. Chem. 277 (44): 41652–6. doi:10.1074/jbc.M205044200. PMID 12200427. 
9. ^ 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. PMID 9384384. 
10. ^ Cormet-Boyaka E, Di A, Chang SY, Naren AP, Tousson A, Nelson DJ, Kirk KL (September 2002). "CFTR chloride channels are regulated by a SNAP-23/syntaxin 1A complex". Proc. Natl. Acad. Sci. U.S.A. 99 (19): 12477–82. doi:10.1073/pnas.192203899. PMC 129470. PMID 12209004. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=129470. 
11. ^ ^{a b c d} 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. PMID 7553862. 
12. ^ 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". J. Biol. Chem. 270 (28): 16955–61. doi:10.1074/jbc.270.28.16955. PMID 7622514. 
13. ^ Chin LS, Vavalle JP, Li L (September 2002). "Staring, a novel E3 ubiquitin-protein ligase that targets syntaxin 1 for degradation". J. Biol. Chem. 277 (38): 35071–9. doi:10.1074/jbc.M203300200. PMID 12121982. 
14. ^ 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". Am. J. Physiol. Renal Physiol. 286 (6): F1100–6. doi:10.1152/ajprenal.00344.2003. PMID 14996668. 
15. ^ Beckman ML, Bernstein EM, Quick MW (August 1998). "Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A". J. Neurosci. 18 (16): 6103–12. PMID 9698305. 
16. ^ Quick MW (April 2002). "Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5686–91. doi:10.1073/pnas.082712899. PMC 122832. PMID 11960023. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122832. 
17. ^ Deken SL, Beckman ML, Boos L, Quick MW (October 2000). "Transport rates of GABA transporters: regulation by the N-terminal domain and syntaxin 1A". Nat. Neurosci. 3 (10): 998–1003. doi:10.1038/79939. PMID 11017172. 
18. ^ 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. PMID 16169070. 
19. ^ ^{a b} 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". J. Biol. Chem. 270 (22): 13022–8. doi:10.1074/jbc.270.22.13022. PMID 7768895. 
20. ^ 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". J. Cell. Sci. 113 ( Pt 18): 3197–205. PMID 10954418. 
21. ^ Ilardi JM, Mochida S, Sheng ZH (February 1999). "Snapin: a SNARE-associated protein implicated in synaptic transmission". Nat. Neurosci. 2 (2): 119–24. doi:10.1038/5673. PMID 10195194. 
22. ^ Li Y, Chin LS, Weigel C, Li L (November 2001). "Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis". J. Biol. Chem. 276 (44): 40824–33. doi:10.1074/jbc.M106141200. PMID 11524423. 
23. ^ ^{a b} Ravichandran V, Chawla A, Roche PA (June 1996). "Identification of a novel syntaxin- and synaptobrevin/VAMP-binding protein, SNAP-23, expressed in non-neuronal tissues". J. Biol. Chem. 271 (23): 13300–3. doi:10.1074/jbc.271.23.13300. PMID 8663154. 
24. ^ 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". J. Biol. Chem. 269 (44): 27427–32. PMID 7961655. 
25. ^ ^{a b} Steegmaier 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". J. Biol. Chem. 273 (51): 34171–9. doi:10.1074/jbc.273.51.34171. PMID 9852078. 
26. ^ 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". Arch. Oral Biol. 48 (8): 597–604. doi:10.1016/S0003-9969(03)00116-X. PMID 12828989. 
27. ^ Li G, Alexander EA, Schwartz JH (May 2003). "Syntaxin isoform specificity in the regulation of renal H+-ATPase exocytosis". J. Biol. Chem. 278 (22): 19791–7. doi:10.1074/jbc.M212250200. PMID 12651853. 
28. ^ 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". Biochem. Biophys. Res. Commun. 234 (1): 257–62. doi:10.1006/bbrc.1997.6560. PMID 9168999. 
29. ^ 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". Neurochem. Int. 44 (1): 35–44. doi:10.1016/S0197-0186(03)00099-8. PMID 12963086. 
30. ^ ^{a b} Pérez-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". Mol. Cell. Neurosci. 20 (2): 169–80. doi:10.1006/mcne.2002.1122. PMID 12093152. 
31. ^ 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". J. Biol. Chem. 278 (37): 35093–101. doi:10.1074/jbc.M304261200. PMID 12832401. 
32. ^ 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. PMID 9620695. 
33. ^ 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. PMID 9010211. 
34. ^ Thomas DM, Ferguson GD, Herschman HR, Elferink LA (July 1999). "Functional and biochemical analysis of the C2 domains of synaptotagmin IV". Mol. Biol. Cell 10 (7): 2285–95. PMC 25443. PMID 10397765. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=25443. 
35. ^ 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". J. Biol. Chem. 272 (4): 2520–6. doi:10.1074/jbc.272.4.2520. PMID 8999968. 
36. ^ Margittai M, Otto H, Jahn R (March 1999). "A stable interaction between syntaxin 1a and synaptobrevin 2 mediated by their transmembrane domains". FEBS Lett. 446 (1): 40–4. doi:10.1016/S0014-5793(99)00028-9. PMID 10100611. 
37. ^ 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". J. Neurosci. 17 (5): 1596–603. PMID 9030619. 
38. ^ 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". J. Cell. Sci. 114 (Pt 1): 219–227. PMID 11112705. 

Further reading

• Peters KW, Qi J, Johnson JP, et al. (2002). "Role of snare proteins in CFTR and ENaC trafficking.". Pflugers Arch. 443 Suppl 1: S65–9. doi:10.1007/s004240100647. PMID 11845306. 
• Wilson DW, Whiteheart SW, Wiedmann M, et al. (1992). "A multisubunit particle implicated in membrane fusion.". J. Cell Biol. 117 (3): 531–8. doi:10.1083/jcb.117.3.531. PMC 2289450. PMID 1315316. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2289450. 
• McMahon HT, Missler M, Li C, Südhof TC (1995). "Complexins: cytosolic proteins that regulate SNAP receptor function.". Cell 83 (1): 111–9. doi:10.1016/0092-8674(95)90239-2. PMID 7553862. 
• Zhang R, Maksymowych AB, Simpson LL (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. PMID 7622072. 
• Hanson PI, Otto H, Barton N, Jahn R (1995). "The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin.". J. Biol. Chem. 270 (28): 16955–61. doi:10.1074/jbc.270.28.16955. PMID 7622514. 
• Hata Y, Südhof TC (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.". J. Biol. Chem. 270 (22): 13022–8. doi:10.1074/jbc.270.22.13022. PMID 7768895. 
• Li C, Ullrich B, Zhang JZ, et al. (1995). "Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins.". Nature 375 (6532): 594–9. doi:10.1038/375594a0. PMID 7791877. 
• Pevsner J, Hsu SC, Scheller RH (1994). "n-Sec1: a neural-specific syntaxin-binding protein.". Proc. Natl. Acad. Sci. U.S.A. 91 (4): 1445–9. doi:10.1073/pnas.91.4.1445. PMC 43176. PMID 8108429. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43176. 
• Betz A, Okamoto M, Benseler F, Brose N (1997). "Direct interaction of the rat unc-13 homologue Munc13-1 with the N terminus of syntaxin.". J. Biol. Chem. 272 (4): 2520–6. doi:10.1074/jbc.272.4.2520. PMID 8999968. 
• Jagadish MN, Tellam JT, Macaulay SL, et al. (1997). "Novel isoform of syntaxin 1 is expressed in mammalian cells.". Biochem. J. 321 ( Pt 1): 151–6. PMC 1218049. PMID 9003414. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1218049. 
• Shao X, Li C, Fernandez I, et al. (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. PMID 9010211. 
• Hao JC, Salem N, Peng XR, et al. (1997). "Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes.". J. Neurosci. 17 (5): 1596–603. PMID 9030619. 
• Tellam JT, Macaulay SL, McIntosh S, et al. (1997). "Characterization of Munc-18c and syntaxin-4 in 3T3-L1 adipocytes. Putative role in insulin-dependent movement of GLUT-4.". J. Biol. Chem. 272 (10): 6179–86. doi:10.1074/jbc.272.10.6179. PMID 9045631. 
• Coffield JA, Bakry N, Zhang RD, et al. (1997). "In vitro characterization of botulinum toxin types A, C and D action on human tissues: combined electrophysiologic, pharmacologic and molecular biologic approaches.". J. Pharmacol. Exp. Ther. 280 (3): 1489–98. PMID 9067339. 
• Nakayama T, Fujiwara T, Miyazawa A, et al. (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. PMID 9177791. 
• Osborne LR, Soder S, Shi XM, et al. (1997). "Hemizygous deletion of the syntaxin 1A gene in individuals with Williams syndrome.". Am. J. Hum. Genet. 61 (2): 449–52. doi:10.1086/514850. PMC 1715888. PMID 9311751. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1715888. 
• Naren AP, Nelson DJ, Xie W, et al. (1997). "Regulation of CFTR chloride channels by syntaxin and Munc18 isoforms.". Nature 390 (6657): 302–5. doi:10.1038/36882. PMID 9384384. 
• Okamoto M, Südhof TC (1998). "Mints, Munc18-interacting proteins in synaptic vesicle exocytosis.". J. Biol. Chem. 272 (50): 31459–64. doi:10.1074/jbc.272.50.31459. PMID 9395480. 
• Shuang R, Zhang L, Fletcher A, et al. (1998). "Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings.". J. Biol. Chem. 273 (9): 4957–66. doi:10.1074/jbc.273.9.4957. PMID 9478941. 
• Vinogradova TI (January 1977). "[Destructive tuberculosis of the lung in adolescents]" (in Russian). Probl Tuberk (1): 19–22. PMID 834751. 
• Burgess RW, Deitcher DL, Schwarz TL (August 1997). "The synaptic protein syntaxin1 is required for cellularization of Drosophila embryos". J. Cell Biol. 138 (4): 861–75. doi:10.1083/jcb.138.4.861. PMC 2138053. PMID 9265652. http://www.jcb.org/cgi/pmidlookup?view=long&pmid=9265652. 
• Littleton JT, Chapman ER, Kreber R, Garment MB, Carlson SD, Ganetzky B (August 1998). "Temperature-sensitive paralytic mutations demonstrate that synaptic exocytosis requires SNARE complex assembly and disassembly". Neuron 21 (2): 401–13. doi:10.1016/S0896-6273(00)80549-8. PMID 9728921. http://linkinghub.elsevier.com/retrieve/pii/S0896-6273(00)80549-8. 
• Lagow RD, Bao H, Cohen EN, et al. (April 2007). "Modification of a hydrophobic layer by a point mutation in syntaxin 1A regulates the rate of synaptic vesicle fusion". PLoS Biol. 5 (4): e72. doi:10.1371/journal.pbio.0050072. PMC 1808484. PMID 17341138. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1808484. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.