STX1A

Syntaxin-1A is a protein that in humans is encoded by the STX1A gene.[5]

STX1A
Identifiers
AliasesSTX1A, HPC-1, P35-1, STX1, SYN1A, syntaxin 1A
External IDsOMIM: 186590 MGI: 109355 HomoloGene: 37941 GeneCards: STX1A
Orthologs
SpeciesHumanMouse
Entrez

6804

20907

Ensembl

ENSG00000106089

ENSMUSG00000007207

UniProt

Q16623
Q75ME0

O35526

RefSeq (mRNA)

NM_001165903
NM_004603

NM_016801
NM_001359179

RefSeq (protein)

NP_001159375
NP_004594
NP_004594.1

NP_058081
NP_001346108

Location (UCSC)Chr 7: 73.7 – 73.72 MbChr 5: 135.05 – 135.08 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

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NicotineDopaminergic_WP1602
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Nicotine Activity on Dopaminergic Neurons edit
  1. The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602".

Interactions

STX1A has been shown to interact with:

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000106089 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000007207 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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. Bibcode:1992Sci...257..255B. doi:10.1126/science.1321498. PMID 1321498.
  6. "Entrez Gene: STX1A syntaxin 1A (brain)".
  7. 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.
  8. Gao MC, Bellugi U, Dai L, Mills DL, Sobel EM, Lange K, Korenberg JR (2010). Toland AE (ed.). "Intelligence in Williams Syndrome is related to STX1A, which encodes a component of the presynaptic SNARE complex". PLOS ONE. 5 (4): e10292. Bibcode:2010PLoSO...510292G. doi:10.1371/journal.pone.0010292. PMC 2858212. PMID 20422020.
  9. 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". The EMBO Journal. 18 (16): 4372–82. doi:10.1093/emboj/18.16.4372. PMC 1171512. PMID 10449403.
  10. 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. S2CID 17878965.
  11. Hu K, Carroll J, Rickman C, Davletov B (November 2002). "Action of complexin on SNARE complex". The Journal of Biological Chemistry. 277 (44): 41652–6. doi:10.1074/jbc.M205044200. PMID 12200427.
  12. 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.
  13. 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. Bibcode:2002PNAS...9912477C. doi:10.1073/pnas.192203899. PMC 129470. PMID 12209004.
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  15. 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.
  16. 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. PMID 12121982.
  17. 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. PMID 14996668. S2CID 18384316.
  18. 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 9698305.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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. PMID 10195194. S2CID 25524692.
  25. 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. PMID 11524423.
  26. 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 8663154.
  27. 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 7961655.
  28. 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:10.1074/jbc.273.51.34171. PMID 9852078.
  29. 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 12828989.
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  31. 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. PMID 9168999.
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Further reading
  • Overview of all the structural information available in the PDB for UniProt: P32851 (Rat Syntaxin-1A) at the PDBe-KB.

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