| Structural highlights
Function
[ALDOA_RABIT] Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein.[1] [SNX9_HUMAN] May be involved in several stages of intracellular trafficking. Plays a role in endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Promotes internalization of TNFR. Promotes degradation of EGFR after EGF signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1 oligomerization. Promotes activation of the Arp2/3 complex by WASL, and thereby plays a role in the reorganization of the F-actin cytoskeleton. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Has lower affinity for membranes enriched in phosphatidylinositol 3-phosphate.[2] [3] [4] [5] [6] [7] [8] [9]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Sorting nexin 9 (SNX9) functions in a complex with the GTPase dynamin-2 at clathrin-coated pits, where it provokes fission of vesicles to complete endocytosis. Here the SNX9.dynamin-2 complex binds to clathrin and adapter protein complex 2 (AP-2) that line these pits, and this occurs through interactions of the low complexity domain (LC4) of SNX9 with AP-2. Intriguingly, localization of the SNX9.dynamin-2 complex to clathrin-coated pits is blocked by interactions with the abundant glycolytic enzyme aldolase, which also binds to the LC4 domain of SNX9. The crystal structure of the LC4 motif of human SNX9 in complex with aldolase explains the biochemistry and biology of this interaction, where SNX9 binds near the active site of aldolase via residues 165-171 that are also required for the interactions of SNX9 with AP-2. Accordingly, SNX9 binding to aldolase is structurally precluded by the binding of substrate to the active site. Interactions of SNX9 with aldolase are far more extensive and differ from those of the actin-nucleating factor WASP with aldolase, indicating considerable plasticity in mechanisms that direct the functions of the aldolase as a scaffold protein.
Mechanism of aldolase control of sorting nexin 9 function in endocytosis.,Rangarajan ES, Park H, Fortin E, Sygusch J, Izard T J Biol Chem. 2010 Apr 16;285(16):11983-90. Epub 2010 Feb 2. PMID:20129922[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ St-Jean M, Izard T, Sygusch J. A hydrophobic pocket in the active site of glycolytic aldolase mediates interactions with Wiskott-Aldrich syndrome protein. J Biol Chem. 2007 May 11;282(19):14309-15. Epub 2007 Feb 27. PMID:17329259 doi:10.1074/jbc.M611505200
- ↑ Lin Q, Lo CG, Cerione RA, Yang W. The Cdc42 target ACK2 interacts with sorting nexin 9 (SH3PX1) to regulate epidermal growth factor receptor degradation. J Biol Chem. 2002 Mar 22;277(12):10134-8. Epub 2002 Jan 17. PMID:11799118 doi:http://dx.doi.org/10.1074/jbc.M110329200
- ↑ Lundmark R, Carlsson SR. Sorting nexin 9 participates in clathrin-mediated endocytosis through interactions with the core components. J Biol Chem. 2003 Nov 21;278(47):46772-81. Epub 2003 Sep 2. PMID:12952949 doi:http://dx.doi.org/10.1074/jbc.M307334200
- ↑ Soulet F, Yarar D, Leonard M, Schmid SL. SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis. Mol Biol Cell. 2005 Apr;16(4):2058-67. Epub 2005 Feb 9. PMID:15703209 doi:http://dx.doi.org/10.1091/mbc.E04-11-1016
- ↑ Yarar D, Waterman-Storer CM, Schmid SL. SNX9 couples actin assembly to phosphoinositide signals and is required for membrane remodeling during endocytosis. Dev Cell. 2007 Jul;13(1):43-56. PMID:17609109 doi:http://dx.doi.org/10.1016/j.devcel.2007.04.014
- ↑ Shin N, Ahn N, Chang-Ileto B, Park J, Takei K, Ahn SG, Kim SA, Di Paolo G, Chang S. SNX9 regulates tubular invagination of the plasma membrane through interaction with actin cytoskeleton and dynamin 2. J Cell Sci. 2008 Apr 15;121(Pt 8):1252-63. doi: 10.1242/jcs.016709. PMID:18388313 doi:http://dx.doi.org/10.1242/jcs.016709
- ↑ Park J, Kim Y, Lee S, Park JJ, Park ZY, Sun W, Kim H, Chang S. SNX18 shares a redundant role with SNX9 and modulates endocytic trafficking at the plasma membrane. J Cell Sci. 2010 May 15;123(Pt 10):1742-50. doi: 10.1242/jcs.064170. Epub 2010, Apr 27. PMID:20427313 doi:http://dx.doi.org/10.1242/jcs.064170
- ↑ Wang JT, Kerr MC, Karunaratne S, Jeanes A, Yap AS, Teasdale RD. The SNX-PX-BAR family in macropinocytosis: the regulation of macropinosome formation by SNX-PX-BAR proteins. PLoS One. 2010 Oct 29;5(10):e13763. doi: 10.1371/journal.pone.0013763. PMID:21048941 doi:10.1371/journal.pone.0013763
- ↑ Pylypenko O, Lundmark R, Rasmuson E, Carlsson SR, Rak A. The PX-BAR membrane-remodeling unit of sorting nexin 9. EMBO J. 2007 Nov 14;26(22):4788-800. Epub 2007 Oct 18. PMID:17948057
- ↑ Rangarajan ES, Park H, Fortin E, Sygusch J, Izard T. Mechanism of aldolase control of sorting nexin 9 function in endocytosis. J Biol Chem. 2010 Apr 16;285(16):11983-90. Epub 2010 Feb 2. PMID:20129922 doi:10.1074/jbc.M109.092049
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