SNX1

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 endosomal protein regulates the cell-surface expression of epidermal growth factor receptor. This protein also has a role in sorting protease-activated receptor-1 from early endosomes to lysosomes. This protein may form oligomeric complexes with family members. This gene results in three transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

Full Name

Sorting Nexin 1

Function

Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:12198132).
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). Can sense membrane curvature and has in vitro vesicle-to-membrane remodeling activity (PubMed:19816406, PubMed:23085988).
Involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptors (IGF2R, M6PR and SORT1) and Shiginella dysenteria toxin stxB. Plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi (PubMed:12198132, PubMed:15498486, PubMed:17550970, PubMed:17101778, PubMed:18088323, PubMed:21040701).
Involvement in retromer-independent endocytic trafficking of P2RY1 and lysosomal degradation of protease-activated receptor-1/F2R (PubMed:16407403, PubMed:20070609).
Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN (PubMed:20604901).
Required for endocytosis of DRD5 upon agonist stimulation but not for basal receptor trafficking (PubMed:23152498).

Biological Process

Biological Process early endosome to Golgi transportManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process intracellular protein transportManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process lamellipodium morphogenesisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of protein catabolic processIEA:Ensembl
Biological Process receptor internalizationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process retrograde transport, endosome to GolgiManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Endosome membrane
Golgi apparatus, trans-Golgi network membrane
Early endosome membrane
Cell projection, lamellipodium
Enriched on tubular elements of the early endosome membrane. Binds preferentially to highly curved membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:15498486).
Colocalized with SORT1 to tubular endosomal membrane structures called endosome-to-TGN transport carriers (ETCs) which are budding from early endosome vacuoles just before maturing into late endosome vacuoles (PubMed:18088323).
Colocalizes with DNAJC13 and Shiginella dysenteria toxin stxB on early endosomes (PubMed:19874558).
Colocalized with F-actin at the leading edge of lamellipodia in a KALRN-dependent manner (PubMed:20604901).