STX2 explained

Syntaxin-2, also known as epimorphin, is a protein that in humans is encoded by the STX2 gene.^{[1] [2] [3]}

The product of this gene belongs to the syntaxin/epimorphin family of proteins. The syntaxins are a large protein family implicated in the targeting and fusion of intracellular transport vesicles. The product of this gene regulates epithelial-mesenchymal interactions and epithelial cell morphogenesis and activation. Alternatively spliced transcript variants encoding different isoforms have been identified.^[3] When the N terminus is on the cytosolic face it acts as a t-SNARE involved in intracellular vesicle docking and is called Syntaxin-2. When flipped inside out, i.e. N terminus hangs out on the extracellular surface (by some nonclassical secretion pathway) it acts as a versatile morphogen and is called epimorphin. This membrane protein enjoys the double choice of another form of topological alternatives of being targeted to either apical or basolateral surface of an epithelial cell in a regulated way depending on various contexts. When expressed by mesenchymal cells it can instruct epithelial morphogenesis at epithelial mesenchymal interfaces.

Interactions

STX2 has been shown to interact with SNAP-25,^{[4] [5]} SNAP23,^{[5] [6] [7] [8]} STXBP1^{[4] [9]} and Syntaxin binding protein 3.^[9]

Further reading

• Hirai Y, Takebe K, Takashina M, Kobayashi S, Takeichi M . Epimorphin: a mesenchymal protein essential for epithelial morphogenesis . Cell . 69 . 3 . 471–81 . May 1992 . 1581962 . 10.1016/0092-8674(92)90448-L . 32814241 .
• Hata Y, Südhof TC . 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 . Jun 1995 . 7768895 . 10.1074/jbc.270.22.13022 . free .
• Li C, Ullrich B, Zhang JZ, Anderson RG, Brose N, Südhof TC . Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins . Nature . 375 . 6532 . 594–9 . Jun 1995 . 7791877 . 10.1038/375594a0 . 1995Natur.375..594L . 4265549 .
• Hirai Y . Molecular cloning of human epimorphin: identification of isoforms and their unique properties . Biochemical and Biophysical Research Communications . 191 . 3 . 1332–7 . Mar 1993 . 8466509 . 10.1006/bbrc.1993.1363 .
• Oka Y, Hirai Y . Inductive influences of epimorphin on endothelial cells in vitro . Experimental Cell Research . 222 . 1 . 189–98 . Jan 1996 . 8549663 . 10.1006/excr.1996.0024 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . Apr 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Betz A, Okamoto M, Benseler F, Brose N . 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 . Jan 1997 . 8999968 . 10.1074/jbc.272.4.2520 . free .
• Tellam JT, Macaulay SL, McIntosh S, Hewish DR, Ward CW, James DE . 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 . Mar 1997 . 9045631 . 10.1074/jbc.272.10.6179 . free.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . Apr 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Koshida S, Hirai Y . Identification of cellular recognition sequence of epimorphin and critical role of cell/epimorphin interaction in lung branching morphogenesis . Biochemical and Biophysical Research Communications . 234 . 2 . 522–5 . May 1997 . 9177305 . 10.1006/bbrc.1997.6673 .
• Hirai Y, Lochter A, Galosy S, Koshida S, Niwa S, Bissell MJ . Epimorphin functions as a key morphoregulator for mammary epithelial cells . The Journal of Cell Biology . 140 . 1 . 159–69 . Jan 1998 . 9425164 . 2132590 . 10.1083/jcb.140.1.159 .
• Thomas DM, Ferguson GD, Herschman HR, Elferink LA . Functional and biochemical analysis of the C2 domains of synaptotagmin IV . Molecular Biology of the Cell . 10 . 7 . 2285–95 . Jul 1999 . 10397765 . 25443 . 10.1091/mbc.10.7.2285 .
• Pabst S, Hazzard JW, Antonin W, Südhof TC, Jahn R, Rizo J, Fasshauer D . Selective interaction of complexin with the neuronal SNARE complex. Determination of the binding regions . The Journal of Biological Chemistry . 275 . 26 . 19808–18 . Jun 2000 . 10777504 . 10.1074/jbc.M002571200 . free .
• Kauppi M, Wohlfahrt G, Olkkonen VM . Analysis of the Munc18b-syntaxin binding interface. Use of a mutant Munc18b to dissect the functions of syntaxins 2 and 3 . The Journal of Biological Chemistry . 277 . 46 . 43973–9 . Nov 2002 . 12198139 . 10.1074/jbc.M208315200 . free .
• Terasaki Y, Fukuda Y, Suga M, Ikeguchi N, Takeya M . Epimorphin expression in interstitial pneumonia . Respiratory Research . 6 . 1 . 6 . 2006 . 15651999 . 548284 . 10.1186/1465-9921-6-6 . free .
• Low SH, Vasanji A, Nanduri J, He M, Sharma N, Koo M, Drazba J, Weimbs T . Syntaxins 3 and 4 are concentrated in separate clusters on the plasma membrane before the establishment of cell polarity . Molecular Biology of the Cell . 17 . 2 . 977–89 . Feb 2006 . 16339081 . 1356605 . 10.1091/mbc.E05-05-0462 .

Notes and References

1. Zha H, Remmers EF, Szpirer C, Szpirer J, Zhang H, Kozak CA, Wilder RL . The epimorphin gene is highly conserved among humans, mice, and rats and maps to human chromosome 7, mouse chromosome 5, and rat chromosome 12 . Genomics . 37 . 3 . 386–9 . Nov 1996 . 8938452 . 10.1006/geno.1996.0574 .
2. Band AM, Kuismanen E . Localization of plasma membrane t-SNAREs syntaxin 2 and 3 in intracellular compartments . BMC Cell Biology . 6 . 1 . 26 . Jun 2005 . 15943887 . 1156879 . 10.1186/1471-2121-6-26 . free .
3. Web site: Entrez Gene: STX2 syntaxin 2.
4. Hata Y, Südhof TC . 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 . Jun 1995 . 7768895 . 10.1074/jbc.270.22.13022 . free .
5. Ravichandran V, Chawla A, Roche PA . 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 . Jun 1996 . 8663154 . 10.1074/jbc.271.23.13300 . free .
6. Imai A, Nashida T, Yoshie S, Shimomura H . 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 . Aug 2003 . 12828989 . 10.1016/S0003-9969(03)00116-X .
7. Li G, Alexander EA, Schwartz JH . Syntaxin isoform specificity in the regulation of renal H+-ATPase exocytosis . The Journal of Biological Chemistry . 278 . 22 . 19791–7 . May 2003 . 12651853 . 10.1074/jbc.M212250200 . free .
8. Araki S, Tamori Y, Kawanishi M, Shinoda H, Masugi J, Mori H, Niki T, Okazawa H, Kubota T, Kasuga M . Inhibition of the binding of SNAP-23 to syntaxin 4 by Munc18c . Biochemical and Biophysical Research Communications . 234 . 1 . 257–62 . May 1997 . 9168999 . 10.1006/bbrc.1997.6560 . 20.500.14094/D2002245 . free .
9. Schraw TD, Lemons PP, Dean WL, Whiteheart SW . A role for Sec1/Munc18 proteins in platelet exocytosis . The Biochemical Journal . 374 . Pt 1 . 207–17 . Aug 2003 . 12773094 . 1223584 . 10.1042/BJ20030610 .