VPS26A
Description
The VPS26A (VPS26 retromer complex component A) is a protein-coding gene located on chromosome 10.
Vacuolar protein sorting-associated protein 26A (VPS26A) is a protein encoded by the VPS26A gene in humans. It belongs to a group of vacuolar protein sorting (VPS) genes. VPS26A is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network (TGN). The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that VPS26A interacts directly with VPS35, which serves as the core of the retromer complex. Alternative splicing results in multiple transcript variants encoding different isoforms. VPS26A is a 38-kDa subunit with a two-lobed structure with a polar core that resembles the arrestin family of trafficking adaptor. This fold consists of two related β-sandwich subdomains with a fibronectin type III domain topology. The two domains are joined together by a flexible linker and are closely associated by an unusual polar core. Arrestins are regulatory proteins known for connecting G-protein coupled receptors (GPCRs) to clathrin during endocytosis.
VPS26A is a component of the retromer cargo-selective complex (CSC). The CSC prevents the mis-sorting of 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 involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC acts as a recruitment hub for other proteins, such as the WASH complex and TBC1D5. VPS26A is required for retrograde transport of lysosomal enzyme receptor IGF2R, regulation of transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA), endosomal localization of WASHC2A and TBC1D5. It mediates retromer cargo recognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP. It is involved in retromer-independent lysosomal sorting of F2R and in recycling of ADRB2. VPS26A enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins.
VPS26A is also known as HB58, Hbeta58, PEP8A, VPS26.
