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Phosphoinositide-binding protein required for multivesicular body formation. Specifically binds phosphatidylinositol 3-phosphate (PtdIns(P3)). Also can bind phosphatidylinositol 4-phosphate (PtdIns(P4)), phosphatidylinositol 5-phosphate (PtdIns(P5)) and phosphatidylinositol 3,5-biphosphate (PtdIns(3,5)P2). Plays a role in protein transport between cellular compartments. Together with RAB7A facilitates endosome membrane association of the retromer cargo-selective subcomplex (CSC/VPS). May in part act as component of the SNX3-retromer complex which mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. Promotes stability and cell surface expression of epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G. Not involved in EGFR degradation. Involved in the regulation of phagocytosis in dendritic cells possibly by regulating EEA1 recruitment to the nascent phagosomes. Involved in iron homeostasis through regulation of endocytic recycling of the transferrin receptor TFRC presumably by delivering the transferrin:transferrin receptor complex to recycling endosomes; the function may involve the CSC retromer subcomplex. In the case of Salmonella enterica infection plays arole in maturation of the Salmonella-containing vacuole (SCV) and promotes recruitment of LAMP1 to SCVs.
基因功能參考文獻(xiàn):
SNX3-retromer complex regulates the surface expression and function of PC1 and PC2 PMID: 28620080
X-ray crystallographic analysis of a 4-component complex comprising the VPS26 & VPS35 subunits of retromer, sorting nexin SNX3, & recycling signal from the divalent cation transporter DMT1-II; analysis identifies a binding site for canonical recycling signals at the interface between VPS26 & SNX3; shows cooperative interactions among the VPS subunits, SNX3 & cargo that couple signal-recognition to membrane recruitment. PMID: 27889239
Data show that over-expression of sorting nexin 3 (hSNX3) alters the morphology of colon cancer SW620 cells, but hardly affects cell migration. PMID: 26271979
SNX3 negatively regulates phagocytosis in DC possibly by modulating recruitment of essential PI3P lipid-binding proteins of the phagocytic pathways, such as EEA1, to phagosomal membranes. PMID: 23237080
This study found that four significant SNX3 SNPs in the discovery sample were replicated in a community-based sample of Israeli-Arabs PMID: 22673115
SNX3 and SNX5 play essential roles in the aspirin-mediated accumulation of endocytosed-TfnR at the early/sorting endosome PMID: 22159558
SNX3 plays a significant role in regulating the maturation of Salmonella containing vacuoles. PMID: 20482551
Sorting nexin 3 (SNX3) is disrupted in a patient with a translocation t(6;13)(q21;q12) and microcephaly, microphthalmia, ectrodactyly, prognathism (MMEP) phenotype PMID: 12471201
we cannot exclude the possibility that deletions at SNX3 may underlie MMEP, given that sequencing is unable to distinguish between homozygosity across loci versus large deletions PMID: 17655765
Data show that Hrs is essential for lysosomal targeting but not multivesicular body biogenesis and transport to late endosomes, while SNX3 is required for multivesicular body formation, but not for EGF receptor degradation. PMID: 18767904