Sorting nexin-1 (SNX1) belongs to the sorting nexin family, which contains a conserved PX (phox homology) domain that is responsible for binding to specific phosphoinositides []. SNX1 and SNX2 are orthologues of yeast Vps5, which is a component of retromer complex that is essential in endosome-to-Golgi retrograde transport []. The mammalian retromer complex is composed of the SNX1/SNX2 alternative heterodimer or homodimer and the Vps26-Vps29-Vps35 obligate heterotrimer []. Like SNX2, SNX1 also has an additional C-terminal BAR domain. SNX1 and SNX2 play interchangeable but essential roles in retromer structure and function [].SNX1 may have a role in sensing membrane curvature and inducing the formation of tubules [, ].
Sorting nexin-2 (SNX2) belongs to the sorting nexin family, which contains a conserved PX (phox homology) domain that is responsible for binding to specific phosphoinositides []. SNX1 and SNX2 are orthologues of yeast Vps5, which is a component of retromercomplex that is essential in endosome-to-Golgi retrograde transport []. The mammalian retromer complex is composed of the SNX1/2 alternative heterodimer or homodimer and the a Vps26-Vps29-Vps35 obligate heterotrimer []. Like SNX1, SNX2 also has an additional C-terminal BAR domain. SNX1 and SNX2 play interchangeable but essential roles in retromer structure and function [].
Sorting nexin-2 (SNX2) belongs to the sorting nexin family, which contains a conserved PX (phox homology) domain that is responsible for binding to specific phosphoinositides []. SNX1 and SNX2 are orthologues of yeast Vps5, which is a component of retromer complex that is essential in endosome-to-Golgi retrograde transport []. The mammalian retromer complex is composed of the SNX1/2 alternative heterodimer or homodimer and the a Vps26-Vps29-Vps35 obligate heterotrimer []. Like SNX1, SNX2 also has an additional C-terminal BAR domain. SNX1 and SNX2 play interchangeable but essential roles in retromer structure and function [].This entry represents the PX domain of SNX2.
The Phox Homology (PX) domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds phosphoinositides (PIs) and targets the protein to PI-enriched membranes [, ]. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway [, , ].SNX1 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1 []. SNX1 is components of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi []. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex [].This entry represents the SNX1 PX domain.
Sorting nexins (SNXs) are Phox homology (PX) domain-containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains []. The PX-BAR structural unit determines the specific membrane targeting of SNXs [].Vsp5 is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10, as well as other later-Golgi proteins [, , ].
Sorting nexins (SNXs) are hydrophilic molecules that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domains () or through protein-protein interactions with membrane-associated protein complexes []. Indeed, several of the SNXs require several targeting motifs for their appropriate cellular localization. In almost every case studied, mammalian SNXs can be shown to have a role in protein sorting, with the most commonly used experimental model being plasma-membrane receptor endocytosis and sorting through the endosomal pathway. However, it is equally probable that SNXs sort vesicles that are not derived from the plasma membrane, and have a function in the accurate targeting of these vesicles and their cargo. The N-terminal domain appears to be specific to sorting nexins 1 and 2. SNX1 and SNX2 are members of the retromer complex involved in protein sorting within the endocytic pathway []. SNX1 is both membrane-associated and cytosolic, where it probably exists as a tetramer in large protein complexes and may hetero-oligomerize with SNX2.
The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system [, ]. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway [, , ].Vsp5 is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5 binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5 contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1 [].
