8.A.91 The Syntaxin (Syntaxin) Family

Syntaxins 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).

This family belongs to the .



Borisovska, M. (2018). Syntaxins on granules promote docking of granules via interactions with munc18. Sci Rep 8: 193.

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.

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.

Han, J., K. Pluhackova, and R.A. Böckmann. (2017). The Multifaceted Role of SNARE Proteins in Membrane Fusion. Front Physiol 8: 5.

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.

Okamoto, M. and T.C. Südhof. (1997). Mints, Munc18-interacting proteins in synaptic vesicle exocytosis. J. Biol. Chem. 272: 31459-31464.

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.

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.

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.

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.

Zhang, Y. and Y.K. Shin. (2006). Transmembrane organization of yeast syntaxin-analogue Sso1p. Biochemistry 45: 4173-4181.


TC#NameOrganismal TypeExample

Syntaxin-related protein, Knolle, of 310 aas and 1 C-terminal TMS.  Acts as a cell plate-specific syntaxin, required for the fusion of vesicles at the plane of cell division. It is abundant in flowers and developing siliques but is present in low amounts in the seedlings, roots, and leaves. Localizes to the cell plate to mediate cytokinesis (Teh et al. 2013).

Knolle of Arabidopsis thaliana (Mouse-ear cress)


Syntaxin, Stx1b2-prov, of 290 aas and 1 C-terminal TMS.


Stx1b2 of Xenopus laevis (African clawed frog)


Syntaxin 7L, Stx7, of 259 aas and 1 C-terminal TMS.

Stx7 of Xenopus laevis (African clawed frog)


Syntaxin-1A (Stx1; Stx1A; Sx1) of 288 aas.  Co-localizes with L-type Ca2+-channels (Cav1.2) in nano clusters at the plasma membrane (Sajman et al. 2017). Munc18 bridges the few syntaxin molecules residing on granules to the syntaxin cluster on the plasma membrane, suggesting that the number of syntaxins on vesicles determines docking and possibly fusion probability  (Borisovska 2018). Munc18-1 (P61764; see 1.F.1.1.3)), a neuronal protein that interacts with syntaxin 1 and is required for synaptic vesicle exocytosis, depends on two Munc18-1-interacting proteins called Mint1 or APBA1 (TC# 8.A.24.2.2) and Mint2 or SAPBA2 (TC# 8.A.24.2.3) (Okamoto and Südhof 1997).

Syntaxin 1A of Homo sapiens


Syntaxin homologue, Sso1 of 290 aas and 1 C-terminal TMS (Ghaemmaghami et al. 2003). Membrane fusion transits through hemifusion, a condition in which the outer leaflets of the bilayers are mixed, but the inner leaflets are not. Hemifusion then proceeds to the fusion pore that connects the two internal contents. The TMSs of the fusion proteins play an essential role in the transition from hemifusion to the fusion pore. Sso1p, a target membrane t-SNARE involved in the trafficking from Golgi to plasma membrane. The TMS of Sso1p is a well-defined membrane spanning α-helix. There is an equilibrium between the monomers and the oligomers, and oligomerization is mainly mediated through the interaction at the N-terminal half of the TMS, whereas the C-terminal half is free of the tertiary interaction (Zhang and Shin 2006).

Sso1 of Saccharomyces cerevisiae (Baker's yeast)


Syntaxin 3 (Stx3) of 289 aas with a C-terminal transmembrane anchor domain, is a  SNARE protein that is required for its membrane fusion activity.  Stx3 also functions as a nuclear regulator of gene expression. Alternative splicing creates a soluble isoform (Stx3S), lacking the transmembrane anchor which binds to the nuclear import factor RanBP5 (RAN-binding protein 5), targets to the nucleus, and interacts physically and functionally with several transcription factors (Giovannone et al. 2018).

Stx3 of Homo sapiens