From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
Syntaxin-1A is a
protein that in humans is encoded by the STX1A
gene .
[5]
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.
[6]
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.
[7]
The expression level of STX1A is directly correlated with intelligence in
Williams syndrome .
[8]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
[§ 1]
[[File:
|alt=Nicotine Activity on Dopaminergic Neurons
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Nicotine Activity on Dopaminergic Neurons
Interactions
STX1A has been shown to
interact with:
CPLX1 ,
[9]
[10]
[11]
CFTR ,
[12]
[13]
NAPA ,
[14]
[15]
RNF40 ,
[16]
SCNN1G ,
[17]
SLC6A1 ,
[18]
[19]
[20]
SNAP-25 ,
[9]
[10]
[14]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
SNAP23 ,
[26]
[28]
[29]
[30]
[31]
STXBP1 ,
[9]
[14]
[22]
[32]
[33]
STXBP5 ,
[34]
[35]
SYT1
[36]
[37]
UNC13B ,
[38]
VAMP2 ,
[9]
[10]
[14]
[33]
[39]
[40] and
VAMP8 .
[41]
See also
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000106089 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000007207 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
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1992Sci...257..255B .
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10.1126/science.1321498 .
PMID
1321498 .
^
"Entrez Gene: STX1A syntaxin 1A (brain)" .
^ 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 .
^ Gao MC, Bellugi U, Dai L, Mills DL, Sobel EM, Lange K, Korenberg JR (2010). Toland AE (ed.).
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^
a
b
c
d Dulubova I, Sugita S, Hill S, Hosaka M, Fernandez I, Südhof TC, Rizo J (August 1999).
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^
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b
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^ Hu K, Carroll J, Rickman C, Davletov B (November 2002).
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^ 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.
Bibcode :
1997Natur.390..302N .
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PMID
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^ 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" . Proceedings of the National Academy of Sciences of the United States of America . 99 (19): 12477–82.
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^
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 .
S2CID
675343 .
^ 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 .
PMID
7622514 .
^ 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.
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PMID
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^ 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.
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10.1152/ajprenal.00344.2003 .
PMID
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S2CID
18384316 .
^ 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.
doi :
10.1523/JNEUROSCI.18-16-06103.1998 .
PMC
6793212 .
PMID
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^ Quick MW (April 2002).
"Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner" . Proceedings of the National Academy of Sciences of the United States of America . 99 (8): 5686–91.
Bibcode :
2002PNAS...99.5686Q .
doi :
10.1073/pnas.082712899 .
PMC
122832 .
PMID
11960023 .
^ 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 .
PMID
11017172 .
S2CID
11312913 .
^ 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 .
hdl :
11858/00-001M-0000-0010-8592-0 .
PMID
16169070 .
S2CID
8235923 .
^
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" . The Journal of Biological Chemistry . 270 (22): 13022–8.
doi :
10.1074/jbc.270.22.13022 .
PMID
7768895 .
^ 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.
doi :
10.1242/jcs.113.18.3197 .
PMID
10954418 .
^ Ilardi JM, Mochida S, Sheng ZH (February 1999). "Snapin: a SNARE-associated protein implicated in synaptic transmission". Nature Neuroscience . 2 (2): 119–24.
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10.1038/5673 .
PMID
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S2CID
25524692 .
^ 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 :
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PMID
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^
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" . The Journal of Biological Chemistry . 271 (23): 13300–3.
doi :
10.1074/jbc.271.23.13300 .
PMID
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^ 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.
doi :
10.1016/S0021-9258(18)47003-2 .
PMID
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^
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" . The Journal of Biological Chemistry . 273 (51): 34171–9.
doi :
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PMID
9852078 .
^ 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 .
PMID
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^ 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 .
PMID
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^ 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.
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hdl :
20.500.14094/D2002245 .
PMID
9168999 .
^ 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 :
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PMID
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S2CID
23783141 .
^
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". Molecular and Cellular Neurosciences . 20 (2): 169–80.
doi :
10.1006/mcne.2002.1122 .
PMID
12093152 .
S2CID
23927545 .
^ 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.
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PMID
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^ 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 .
S2CID
12597505 .
^ 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 :
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PMID
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^ Thomas DM, Ferguson GD, Herschman HR, Elferink LA (July 1999).
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^ 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.
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PMID
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^ 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.
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^ 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.
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^ 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.
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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 .
PMID
11845306 .
S2CID
21790638 .
Wilson DW, Whiteheart SW, Wiedmann M, Brunner M, Rothman JE (May 1992).
"A multisubunit particle implicated in membrane fusion" . The Journal of Cell Biology . 117 (3): 531–8.
doi :
10.1083/jcb.117.3.531 .
PMC
2289450 .
PMID
1315316 .
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 .
S2CID
675343 .
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 .
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 .
PMID
7622514 .
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 .
PMID
7768895 .
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.
Bibcode :
1995Natur.375..594L .
doi :
10.1038/375594a0 .
PMID
7791877 .
S2CID
4265549 .
Pevsner J, Hsu SC, Scheller RH (February 1994).
"n-Sec1: a neural-specific syntaxin-binding protein" . Proceedings of the National Academy of Sciences of the United States of America . 91 (4): 1445–9.
Bibcode :
1994PNAS...91.1445P .
doi :
10.1073/pnas.91.4.1445 .
PMC
43176 .
PMID
8108429 .
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 .
PMID
8999968 .
Jagadish MN, Tellam JT, Macaulay SL, Gough KH, James DE, Ward CW (January 1997).
"Novel isoform of syntaxin 1 is expressed in mammalian cells" . The Biochemical Journal . 321 ( Pt 1) (Pt 1): 151–6.
doi :
10.1042/bj3210151 .
PMC
1218049 .
PMID
9003414 .
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 .
S2CID
17947552 .
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.
doi :
10.1523/JNEUROSCI.17-05-01596.1997 .
PMC
6573372 .
PMID
9030619 .
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 .
PMID
9045631 .
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.
PMID
9067339 .
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 .
PMID
9177791 .
Osborne LR, Soder S, Shi XM, Pober B, Costa T, Scherer SW, Tsui LC (August 1997).
"Hemizygous deletion of the syntaxin 1A gene in individuals with Williams syndrome" . American Journal of Human Genetics . 61 (2): 449–52.
doi :
10.1086/514850 .
PMC
1715888 .
PMID
9311751 .
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.
Bibcode :
1997Natur.390..302N .
doi :
10.1038/36882 .
PMID
9384384 .
S2CID
4395005 .
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 .
PMID
9395480 .
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 .
PMID
9478941 .
Vinogradova TI (January 1977). "[Destructive tuberculosis of the lung in adolescents]". Problemy Tuberkuleza (in Russian) (1): 19–22.
PMID
834751 .
Burgess RW, Deitcher DL, Schwarz TL (August 1997).
"The synaptic protein syntaxin1 is required for cellularization of Drosophila embryos" . The Journal of Cell Biology . 138 (4): 861–75.
doi :
10.1083/jcb.138.4.861 .
PMC
2138053 .
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 .
S2CID
15119362 .
Lagow RD, Bao H, Cohen EN, Daniels RW, Zuzek A, Williams WH, Macleod GT, Sutton RB, Zhang B (April 2007).
"Modification of a hydrophobic layer by a point mutation in syntaxin 1A regulates the rate of synaptic vesicle fusion" . PLOS Biology . 5 (4): e72.
doi :
10.1371/journal.pbio.0050072 .
PMC
1808484 .
PMID
17341138 .
External links
Overview of all the structural information available in the
PDB for
UniProt :
P32851 (Rat Syntaxin-1A) at the
PDBe-KB .
PDB gallery
1br0 : THREE DIMENSIONAL STRUCTURE OF THE N-TERMINAL DOMAIN OF SYNTAXIN 1A
1dn1 :
1ez3 : CRYSTAL STRUCTURE OF THE NEURONAL T-SNARE SYNTAXIN-1A
1hvv : SELF-ASSOCIATION OF THE H3 REGION OF SYNTAXIN 1A: IMPLICATIONS FOR SNARE COMPLEX ASSEMBLY
1jth : Crystal structure and biophysical properties of a complex between the N-terminal region of SNAP25 and the SNARE region of syntaxin 1a
1kil : Three-dimensional structure of the complexin/SNARE complex
1n7s : High Resolution Structure of a Truncated Neuronal SNARE Complex
1sfc : NEURONAL SYNAPTIC FUSION COMPLEX
1urq : CRYSTAL STRUCTURE OF NEURONAL Q-SNARES IN COMPLEX WITH R-SNARE MOTIF OF TOMOSYN
This article incorporates text from the
United States National Library of Medicine , which is in the
public domain .