Protein: Sorting nexin-1 (Q13596)
Organism: Homo sapiens (Human)
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). 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. 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. Involvement in retromer-independent endocytic trafficking of P2RY1 and lysosomal degradation of protease-activated receptor-1/F2R. Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN. Required for endocytosis of DRD5 upon agonist stimulation but not for basal receptor trafficking.
Subcellular location: Endosome membrane {ECO:0000269|PubMed:15498486, ECO:0000269|PubMed:18088323, ECO:0000269|PubMed:22431521}; Peripheral membrane protein; Cytoplasmic side. Golgi apparatus, trans-Golgi network membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection, lamellipodium {ECO:0000269|PubMed:20604901}. Note=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). {ECO:0000269|PubMed:15498486, ECO:0000269|PubMed:18088323, ECO:0000269|PubMed:20604901}.
Interaction partners:
- Vacuolar protein sorting-associated protein 29
- Sorting nexin-6
- Sorting nexin-2
- Vacuolar protein sorting-associated protein 26A
- Sorting nexin-5
- Vacuolar protein sorting-associated protein 35
- Vacuolar protein sorting-associated protein 26B
- Sorting nexin-32
- Sorting nexin-27
- Sorting nexin-4
Sequence:
MASGGGGCSASERLPPPFPGLEPESEGAAGGSEPEAGDSDTEGEDIFTGAAVVSKHQSPKITTSLLPINNGSKENGIHEEQDQEPQDLFADATVELSLDSTQNNQKKVLAKTLISLPPQEATNSSKPQPTYEELEEEEQEDQFDLTVGITDPEKIGDGMNAYVAYKVTTQTSLPLFRSKQFAVKRRFSDFLGLYEKLSEKHSQNGFIVPPPPEKSLIGMTKVKVGKEDSSSAEFLEKRRAALERYLQRIVNHPTMLQDPDVREFLEKEELPRAVGTQTLSGAGLLKMFNKATDAVSKMTIKMNESDIWFEEKLQEVECEEQRLRKLHAVVETLVNHRKELALNTAQFAKSLAMLGSSEDNTALSRALSQLAEVEEKIEQLHQEQANNDFFLLAELLSDYIRLLAIVRAAFDQRMKTWQRWQDAQATLQKKREAEARLLWANKPDKLQQAKDEILEWESRVTQYERDFERISTVVRKEVIRFEKEKSKDFKNHVIKYLETLLYSQQQLAKYWEAFLPEAKAIS