VPS26A

This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein 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. 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 this protein interacts directly with VPS35, which serves as the core of the retromer complex. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq]

Full Name

vacuolar protein sorting 26 homolog A (S. pombe)

Function

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 (Probable). The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:15078902, PubMed:15078903).
Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15247922).
Required for the endosomal localization of WASHC2A (indicative for the WASH complex) (PubMed:22070227).
Required for the endosomal localization of TBC1D5 (PubMed:20923837).
Mediates retromer cargo recognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP (PubMed:22279231).
Involved in retromer-independent lysosomal sorting of F2R (PubMed:16407403).
Involved in recycling of ADRB2 (PubMed:21602791).
Enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins (By similarity).

Biological Process

Biological Process endocytic recycling Source:UniProtKB1 Publication
Biological Process intracellular protein transport Source:GO_Central1 Publication
Biological Process regulation of macroautophagy Source:ParkinsonsUK-UCL1 Publication
Biological Process retrograde transport, endosome to Golgi Source:UniProtKB1 Publication

Cellular Location

Cytoplasm
Endosome membrane
Early endosome
Localizes to tubular profiles adjacent to endosomes (PubMed:15078903).
Predominantly found in early not late endosomes (By similarity).