SNX3
Domain
The PX domain mediates specific binding to phosphatidylinositol 3-phosphate (PtdIns(P3)).
Function
Phosphoinositide-binding protein required for multivesicular body formation. Specifically binds phosphatidylinositol 3-phosphate (PtdIns(P3)). Can also bind phosphatidylinositol 4-phosphate (PtdIns(P4)), phosphatidylinositol 5-phosphate (PtdIns(P5)) and phosphatidylinositol 3,5-biphosphate (PtdIns(3,5)P2) (By similarity). 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 (PubMed:21725319, PubMed:24344282, PubMed:30213940). Promotes stability and cell surface expression of epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G (By similarity). Not involved in EGFR degradation. Involved in the regulation of phagocytosis in dendritic cells possibly by regulating EEA1 recruitment to the nascent phagosomes (PubMed:23237080). 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 (By similarity). In the case of Salmonella enterica infection plays arole in maturation of the Salmonella-containing vacuole (SCV) and promotes recruitment of LAMP1 to SCVs (PubMed:20482551).
Involvement in disease
A chromosomal aberration involving SNX3 has been found in patients with syndromic microphthalmia. Translocation t(6;13)(q21;q12).
Post-translational modifications
Ubiquitinated, leading to its proteasomal degradation. Deubiquitinated by USP10 (By similarity).
Sequence Similarities
Belongs to the sorting nexin family.
Cellular localization
- Early endosome
- Cytoplasmic vesicle
- Phagosome
- Colocalizes to clathrin-coated endosomal vesicles morphologically distinct from retromer-decorated non-branched endosomal tubule structures (PubMed:21725319) Colocalizes with EEA1 on nascent phagosomes in dendritic cells but competes with EEA1 for binding to phagosomal membrane (PubMed:23237080). In the case of Salmonella enterica infection localizes to Salmonella-containing vacuoles (SCVs) from which SNX3-containing tubules form 30-60 minutes after infection (PubMed:20482551).
Alternative names
Sorting nexin-3, Protein SDP3, SNX3