FEATURES

FAMILY

DESCRIPTION

Also known as VP26A_BOVIN, VPS26A. Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3.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 SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC complex seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5. Required for retrograde transport of lysosomal enzyme receptor IGF2R. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Required for the endosomal localization of WASHC2 (indicative for the WASH complex). Required for the endosomal localization of TBC1D5. Mediates retromer cargo recognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP. Involved in retromer-independent lysosomal sorting of F2R. Involved in recycling of ADRB2. Acts redundantly with VSP26B in SNX-27 mediated endocytic recycling of SLC2A1/GLUT1. Enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins (By similarity). Component of the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35. The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform. The CSC is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants. The originally described retromer complex (also called SNX-BAR retromer) is a pentamer containing the CSC and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. The CSC associates with SNX3 to form a SNX3-retromer complex. The CSC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to form the SNX27-retromer complex. Interacts with VPS29, VPS35, SNX27, SNX1, SNX2, SNX5, SNX6, SNX3, RAB7A, ECPAS, EHD1, WASHC5, SORL1 (By similarity).

VPS26A

Structural Ligandability

Domains Chains

Distribution