Sorting nexin-5
Domain
The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate.
The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of an amphipathic helix (AH) in the membrane (Probable).
Function
Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) (PubMed:15561769). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. 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) (Probable). Does not have in vitro vesicle-to-membrane remodeling activity (PubMed:23085988). Involved in retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:17148574, PubMed:18596235). May function as link between endosomal transport vesicles and dynactin (Probable). Plays a role in the internalization of EGFR after EGF stimulation (Probable). Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C isoform 3 and is retromer-independent (PubMed:23602387). Together with PIP5K1C isoform 3 facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation (Probable). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation (PubMed:24610942). Plays a role in macropinocytosis (PubMed:18854019, PubMed:21048941).
Sequence Similarities
Belongs to the sorting nexin family.
Cellular localization
- Endosome
- Early endosome
- Early endosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cytoplasmic vesicle membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cytoplasm
- Cell projection
- Phagocytic cup
- Cell projection
- Ruffle
- Recruited to the plasma membrane after EGF stimulation, which leads to increased levels of phosphatidylinositol 3,4-bisphosphate (PdtIns(3,4)P2) (PubMed:15561769). Detected on macropinosomes (PubMed:16968745, PubMed:21048941). Targeted to membrane ruffles in response to EGFR stimulation.
Alternative names
Sorting nexin-5, SNX5