TCDB is operated by the Saier Lab Bioinformatics Group

8.A.91 The Syntaxin (Syntaxin) Family

Syntaxins, Syxs, play roles in hormone and neurotransmitter exocytosis and are potentially involved in docking of synaptic vesicles at presynaptic active zones. During exocytosis, vesicle-associated v-SNARE (synaptobrevin) and target cell-associated t-SNAREs (syntaxin and SNAP-25) assemble into a core trans-SNARE complex. This complex plays a versatile role at various stages of exocytosis ranging from the priming to fusion pore formation and expansion, finally resulting in the release or exchange of the vesicle content (Han et al. 2017). Syntaxins may also mediate Ca2+-regulation of exocytosis in the acrosomal reaction in sperm (Hutt et al. 2005). SNARE proteins (synaptobrevin, SNAP25 and syntaxin), synaptophysin, Ca2+/calmodulin, and members of the synaptotagmin protein family (Syt1, Syt4, Syt7 and Syt11) are involved in the balance and tight coupling of exo-endocytosis in neurons (Xie et al. 2017). Syntaxins regulate many channels and carriers including those listed in TCDB under TC#s 1.A.1.11.3, 1.A.1.11.4, 1.A.1.11.8, 1.A.1.2.13, 1.A.6.1.1 and 2.A.22.1.4 (see these entries) (Saxena et al. 2006). Some syntaxins are listed under family 1.F.1 (see 1.F.1.1.3 and 1.F.1.1.4). Syntaxin 5 (Stx5) in mammals and its ortholog Sed5p in Saccharomyces cerevisiae mediate anterograde and retrograde endoplasmic reticulum (ER)-Golgi trafficking. The TMSs of syntaxin line the fusion pore of Ca2+-triggered exocytosis, and the fusion pore is formed at least in part by a circular arrangement of 5 to 8 Syx TMSs in the plasma membrane (Han et al. 2004).

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Syntaxin5, human Stx5 (TC# 8.A.91.1.9) and yeast Sed5p (TC# 8.A.91.1.10), are structurally conserved and are both regulated by interactions with other ER-Golgi SNARE proteins, the Sec1/Munc18-like protein Scfd1/Sly1p and the membrane tethering complexes COG, p115, and GM130. Despite these similarities, yeast Sed5p and mammalian Stx5 are differently recruited to COPII-coated vesicles, and Stx5 interacts with the microtubular cytoskeleton, whereas Sed5p does not. Possibly these different Stx5 interactions contribute to structural differences in ER-Golgi transport between mammalian and yeast cells (Linders et al. 2019).

References associated with 8.A.91 family:

Ampah, K.K., J. Greaves, A.S. Shun-Shion, A.W. Asnawi, J.A. Lidster, L.H. Chamberlain, M.O. Collins, and A.A. Peden. (2018). S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19. J Cell Sci 131:. 30254024
Borisovska, M. (2018). Syntaxins on granules promote docking of granules via interactions with munc18. Sci Rep 8: 193. 29317735
Cheng, X., X. Ma, X. Ding, L. Li, X. Jiang, Z. Shen, S. Chen, W. Liu, W. Gong, and Q. Sun. (2017). Pacer Mediates the Function of Class III PI3K and HOPS Complexes in Autophagosome Maturation by Engaging Stx17. Mol. Cell 65: 1029-1043.e5. 28306502
Ghaemmaghami, S., W.K. Huh, K. Bower, R.W. Howson, A. Belle, N. Dephoure, E.K. O'Shea, and J.S. Weissman. (2003). Global analysis of protein expression in yeast. Nature 425: 737-741. 14562106
Giovannone, A.J., C. Winterstein, P. Bhattaram, E. Reales, S.H. Low, J.E. Baggs, M. Xu, M.A. Lalli, J.B. Hogenesch, and T. Weimbs. (2018). Soluble syntaxin 3 functions as a transcriptional regulator. J. Biol. Chem. 293: 5478-5491. 29475951
Han, J., K. Pluhackova, and R.A. Böckmann. (2017). The Multifaceted Role of SNARE Proteins in Membrane Fusion. Front Physiol 8: 5. 28163686
Han, X., C.T. Wang, J. Bai, E.R. Chapman, and M.B. Jackson. (2004). Transmembrane segments of syntaxin line the fusion pore of Ca2+-triggered exocytosis. Science 304: 289-292. 15016962
Hutt, D.M., J.M. Baltz, and J.K. Ngsee. (2005). Synaptotagmin VI and VIII and syntaxin 2 are essential for the mouse sperm acrosome reaction. J. Biol. Chem. 280: 20197-20203. 15774481
Julia, J., V. Shui, N. Mittal, J. Heim-Hall, and C.L. Blanco. (2019). Microvillus inclusion disease, a diagnosis to consider when abnormal stools and neurological impairments run together due to a rare syntaxin 3 gene mutation. J Neonatal Perinatal Med 12: 313-319. 30909251
Kuge, H., I. Miyamoto, K.I. Yagyu, and K. Honke. (2020). PLRP2 selectively localizes synaptic membrane proteins via acyl-chain remodeling of phospholipids. J Lipid Res. [Epub: Ahead of Print] 32963038
Li, B., Y. Li, F. Liu, X. Tan, Q. Rui, Y. Tong, L. Qiao, R. Gao, G. Li, R. Shi, Y. Li, and Y. Bao. (2019). Overexpressed Tomosyn Binds Syntaxins and Blocks Secretion during Pollen Development. Plant Physiol. 181: 1114-1126. 31530628
Li, G., Q. Yang, E.A. Alexander, and J.H. Schwartz. (2005). Syntaxin 1A has a specific binding site in the H3 domain that is critical for targeting of H+-ATPase to apical membrane of renal epithelial cells. Am. J. Physiol. Cell Physiol. 289: C665-672. 15872013
Linders, P.T., C.V. Horst, M.T. Beest, and G. van den Bogaart. (2019). Stx5-Mediated ER-Golgi Transport in Mammals and Yeast. Cells 8:. 31357511
Liu, L., C. Li, Z.W.N. Teo, B. Zhang, and H. Yu. (2019). The MCTP-SNARE Complex Regulates Florigen Transport in Arabidopsis. Plant Cell. [Epub: Ahead of Print] 31439803
Okamoto, M. and T.C. Südhof. (1997). Mints, Munc18-interacting proteins in synaptic vesicle exocytosis. J. Biol. Chem. 272: 31459-31464. 9395480
Padmanabhan, P., A.T. Bademosi, R. Kasula, E. Lauwers, P. Verstreken, and F.A. Meunier. (2019). Need for speed: Super-resolving the dynamic nanoclustering of syntaxin-1 at exocytic fusion sites. Neuropharmacology 107554. [Epub: Ahead of Print] 30826343
Sajman, J., M. Trus, D. Atlas, and E. Sherman. (2017). The L-type Voltage-Gated Calcium Channel co-localizes with Syntaxin 1A in nano-clusters at the plasma membrane. Sci Rep 7: 11350. 28900128
Saxena, S.K., M. Singh, S. Kaur, and C. George. (2006). Distinct domain-dependent effect of syntaxin1A on amiloride-sensitive sodium channel (ENaC) currents in HT-29 colonic epithelial cells. Int J Biol Sci 3: 47-56. 17200691
Suga, K., T. Tomiyama, H. Mori, and K. Akagawa. (2004). Syntaxin 5 interacts with presenilin holoproteins, but not with their N- or C-terminal fragments, and affects β-amyloid peptide production. Biochem. J. 381: 619-628. 15109302
Szule, J.A. and J.R. Coorssen. (2004). Comment on "Transmembrane segments of syntaxin line the fusion pore of Ca2+-triggered exocytosis". Science 306: 813; author reply 813. 15514140
Teh, O.K., Y. Shimono, M. Shirakawa, Y. Fukao, K. Tamura, T. Shimada, and I. Hara-Nishimura. (2013). The AP-1 μ adaptin is required for KNOLLE localization at the cell plate to mediate cytokinesis in Arabidopsis. Plant Cell Physiol. 54: 838-847. 23543752
Viret, C. and M. Faure. (2019). Regulation of Syntaxin 17 during Autophagosome Maturation. Trends Cell Biol. 29: 1-3. 30415939
Xie, Z., J. Long, J. Liu, Z. Chai, X. Kang, and C. Wang. (2017). Molecular Mechanisms for the Coupling of Endocytosis to Exocytosis in Neuron.s. Front Mol Neurosci 10: 47. 28348516
Zhang, Y. and Y.K. Shin. (2006). Transmembrane organization of yeast syntaxin-analogue Sso1p. Biochemistry 45: 4173-4181. 16566591