MGP Database

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MGP003663

UniProt Annotations

Entry Information
Gene Namesorting nexin 3
Protein Entry
UniProt ID
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; IsoId=O60493-1; Sequence=Displayed; Name=2; Synonyms=SNX 3A; IsoId=O60493-2; Sequence=VSP_006190; Name=3; IsoId=O60493-3; Sequence=VSP_012928; Note=No experimental confirmation available.; Name=4; IsoId=O60493-4; Sequence=VSP_014694; Note=No experimental confirmation available.;
DiseaseMicrophthalmia, syndromic, 8 (MCOPS8) [MIM:601349]: A very rare congenital syndrome characterized by microcephaly, microphthalmia, ectrodactyly of the lower limbs and prognathism. Intellectual deficit has been reported. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. {ECO:0000269|PubMed:12471201}. Note=The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving SNX3 has been found in patients with syndromic microphthalmia. Translocation t(6;13)(q21;q12).
DomainThe PX domain mediates specific binding to phosphatidylinositol 3-phosphate (PtdIns(P3)). {ECO:0000269|PubMed:11433298}.
FunctionPhosphoinositide-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) (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). 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 tranferrin: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). {ECO:0000250|UniProtKB:O70492, ECO:0000269|PubMed:11433298, ECO:0000269|PubMed:18767904, ECO:0000269|PubMed:21725319, ECO:0000269|PubMed:23237080, ECO:0000269|PubMed:24344282, ECO:0000305|PubMed:21725319}.
InteractionP46108:CRK; NbExp=2; IntAct=EBI-727209, EBI-886;
PtmUbiquitinated, leading to its proteasomal degradation. Deubiquitinated by USP10 (By similarity). {ECO:0000250|UniProtKB:O70492}.
SimilarityBelongs to the sorting nexin family. {ECO:0000305}.
SimilarityContains 1 PX (phox homology) domain. {ECO:0000255|PROSITE-ProRule:PRU00147}.
Subcellular LocationEarly endosome {ECO:0000269|PubMed:11433298, ECO:0000269|PubMed:21725319}. Cytoplasmic vesicle, phagosome {ECO:0000269|PubMed:23237080}. Note=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). {ECO:0000269|PubMed:20482551, ECO:0000269|PubMed:21725319, ECO:0000269|PubMed:23237080}.
SubunitInteracts with VPS26A, VPS29 and VPS35; the interaction with VPS35 is direct. The association with the retromer CSC subcomplex subunits is proposed to represent a functional distinct retromer variant described as SNX3-retromer complex (PubMed:21725319, PubMed:24344282). Interacts with USP10 and SCNN1A (By similarity). Interacts with TRFC (By similarity). Interacts with SNX8; 2 molecules of SNX8 seems to associate with one molecule of SNX3 (PubMed:24866125). Interacts with PTPRU (PubMed:17622474). {ECO:0000250|UniProtKB:O70492, ECO:0000269|PubMed:17622474, ECO:0000269|PubMed:21725319, ECO:0000269|PubMed:24344282, ECO:0000269|PubMed:24866125, ECO:0000305|PubMed:21725319}.
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