High impact information on SNX2

• We screened a human kidney library and identified a sorting nexin, SNX2, as a protein interaction partner of FBP17 [1].
• The association of Vps26-Vps29-Vps35 with endosomes requires the presence of either SNX1 or SNX2, whereas SNX1/2 can be recruited to endosomes independently of Vps26-Vps29-Vps35 [2].
• Interchangeable but essential functions of SNX1 and SNX2 in the association of retromer with endosomes and the trafficking of mannose 6-phosphate receptors [2].
• We also found that the presence of either SNX1 or SNX2 is essential for the retrieval of the cation-independent mannose 6-phosphate receptor to the TGN [2].
• We have obtained full-length cDNAs and deduced the amino acid sequences of three novel homologous proteins, which were denoted human sorting nexins (SNX2, SNX3, and SNX4) [3].

Biological context of SNX2

• These studies are the first to demonstrate a function for SNX2 in protein trafficking [4].
• Searches of human expressed sequence tag databases with SNX1 revealed eleven related human cDNA sequences, termed SNX2 to SNX12, eight of them novel [5].
• However, suppression of sorting nexin-2 results in a subtle alteration in the kinetics of cation-independent mannose 6-phosphate receptor retrieval [6].

Anatomical context of SNX2

• We show that SNX2 resides primarily in early endosomes, whereas SNX1 is found partially in early endosomes and in tubulovesicular-like structures distributed throughout the cytoplasm [4].
• Toward understanding the function of SNX2, we first examined the distribution of endogenous protein in HeLa cells [4].
• These observations indicate that the mammalian retromer complex assembles by sequential association of SNX1/2 and Vps26-Vps29-Vps35 subcomplexes on endosomal membranes and that SNX1 and SNX2 play interchangeable but essential roles in retromer structure and function [2].
• Sorting Nexin-2 (SNX2) is involved in protein sorting in the trans-Golgi network, endosome, and/or lysosome compartments, with loss of function leading to defect in protein sorting and stress on organelles [7].

Associations of SNX2 with chemical compounds

• Here we show that, like sorting nexin-1, sorting nexin-2 binds phosphatidylinositol 3-monophosphate and phosphatidylinositol 3,5-bisphosphate, and possesses a Bin/Amphiphysin/Rvs domain that can sense membrane curvature [6].

Regulatory relationships of SNX2

• Mutant SNX2 markedly inhibited agonist-induced EGFR degradation, whereas internalization remained intact [4].

Other interactions of SNX2

• To assess SNX2 function, we examined the effect of a PX domain-mutated SNX2 that is defective in vesicle localization on EGFR trafficking [4].

References