SNX3

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 does not contain a coiled coil region, like most family members. This protein interacts with phosphatidylinositol-3-phosphate, and is involved in protein trafficking. [provided by RefSeq]

Full Name

sorting nexin 3

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).

Biological Process

Biological Process endocytic recyclingManual Assertion Based On ExperimentIBA:GO_Central
Biological Process intralumenal vesicle formationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process late endosome to Golgi transportManual Assertion Based On ExperimentIBA:GO_Central
Biological Process membrane invaginationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of early endosome to late endosome transportManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of phagocytosisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of protein transportManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of viral entry into host cellManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of neuron projection developmentISS:UniProtKB
Biological Process protein to membrane dockingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein transportIEA:UniProtKB-KW
Biological Process regulation of Wnt signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process response to bacteriumManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

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 min after infection (PubMed:20482551).

Involvement in disease

A chromosomal aberration involving SNX3 has been found in patients with syndromic microphthalmia. Translocation t(6;13)(q21;q12).

PTM

Ubiquitinated, leading to its proteasomal degradation. Deubiquitinated by USP10 (By similarity).