SNX5

This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein functions in endosomal sorting, the phosphoinositide-signaling pathway, and macropinocytosis. This gene may play a role in the tumorigenesis of papillary thyroid carcinoma. Alternative splicing results in multiple transcript variants encoding different isoforms.

Full Name

Sorting Nexin 5

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).

Biological Process

Biological Process intracellular protein transportIEA:InterPro
Biological Process pinocytosisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of DNA-templated transcriptionManual Assertion Based On ExperimentIMP:CACAO
Biological Process positive regulation of insulin receptor signaling pathwayManual Assertion Based On ExperimentIMP:CACAO
Biological Process regulation of macroautophagy1 PublicationNAS:ParkinsonsUK-UCL
Biological Process retrograde transport, endosome to GolgiManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Endosome
Early endosome
Early endosome membrane
Cell membrane
Cytoplasmic vesicle membrane
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