8,A,194.  The Sorting Nexin (SNX) Family 

SNX1 and other sorting nexins are involved in several stages of intracellular trafficking. It interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (Cozier et al. 2002). It acts as a component of the retromer membrane-deforming SNX-BAR subcomplex (TC families 9.A.3 and 9.A 63). The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) and can sense membrane curvature; it has in vitro vesicle-to-membrane remodeling activity (Bhatia et al. 2009, van Weering et al. 2012). It is also involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptors (IGF2R, M6PR and SORT1) and Shiginella dysenteria toxin, StxB. It plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi (Cozier et al. 2002, Kim et al. 2010). SNX1 interacts  with SNX27 and regulates the heavy metal transporter Irt1 (TC# 2.A.5.1.2) (Chandra et al. 2022). Sorting nexins are also found in TC families 9.A.3 and 9.A.63.

 

 

 

 

 


 

References:

Bhatia, V.K., K.L. Madsen, P.Y. Bolinger, A. Kunding, P. HedegÄrd, U. Gether, and D. Stamou. (2009). Amphipathic motifs in BAR domains are essential for membrane curvature sensing. EMBO. J. 28: 3303-3314.

Chandra, M., B.M. Collins, and L.P. Jackson. (2022). Biochemical basis for an interaction between SNX27 and the flexible SNX1 N-terminus. Adv Biol Regul 83: 100842.

Cozier, G.E., J. Carlton, A.H. McGregor, P.A. Gleeson, R.D. Teasdale, H. Mellor, and P.J. Cullen. (2002). The phox homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation. J. Biol. Chem. 277: 48730-48736.

Ivanov, R., T. Brumbarova, A. Blum, A.M. Jantke, C. Fink-Straube, and P. Bauer. (2014). SORTING NEXIN1 is required for modulating the trafficking and stability of the Arabidopsis IRON-REGULATED TRANSPORTER1. Plant Cell 26: 1294-1307.

Kim, E., Y. Lee, H.J. Lee, J.S. Kim, B.S. Song, J.W. Huh, S.R. Lee, S.U. Kim, S.H. Kim, Y. Hong, I. Shim, and K.T. Chang. (2010). Implication of mouse Vps26b-Vps29-Vps35 retromer complex in sortilin trafficking. Biochem. Biophys. Res. Commun. 403: 167-171.

van Weering, J.R., R.B. Sessions, C.J. Traer, D.P. Kloer, V.K. Bhatia, D. Stamou, S.R. Carlsson, J.H. Hurley, and P.J. Cullen. (2012). Molecular basis for SNX-BAR-mediated assembly of distinct endosomal sorting tubules. EMBO. J. 31: 4466-4480.

Examples:

TC#NameOrganismal TypeExample
8.A.194.1.1

Sorting nextin 1 of 522 aas and possibly one TMS at residue 400. It targets Irt1 (TC# 2.A.5.1.2) to the plasma membrane (Ivanov et al. 2014).

SNX1 of Homo sapiens

 
8.A.194.1.2

Sorting nexin-7-like protein, SNX7, of 477 aas and possibly 1 TMS.

SNX7 of Acromyrmex echinatior

 
8.A.194.1.3

Sorting nexin-11 isoform X2, SNX11X2, of 624 aas and 3 N-terminal TMSs.

SNX11X2 of Xiphophorus hellerii

 
8.A.194.1.4

Uncharacterized nexin protein of 698 aas and possibly 2 TMSs, one N-terminal and one at about residue 470.

UP of Suillus hirtellus

 
8.A.194.1.5

Uncharacterized nexin homologue of 456 aas and 0 TMSs.

UP of Brachypodium distachyon (stiff brome)

 
8.A.194.1.6

Uncharacterized protein of 634 aas and 0 TMSs.

UP of Tuber indicum

 
8.A.194.1.7

Sorting nexin-8 isoform X1, SNX8X1, of 521 aas and possibly 2 TMSs, one near the N- terminus and one at the C-terminus.

SNX8X1 of Sphaeramia orbicularis

 
8.A.194.1.8

Uncharacterized protein of 840 aas and 0 TMSs.

UP of Edaphochlamys debaryana