VPS26A Human

VPS26A is a component of the retromer complex, a large multimeric complex involved in the retrograde transport of proteins from endosomes to the trans-Golgi network . The retromer complex plays a vital role in preventing the missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway . The recruitment of the retromer complex to the endosomal membrane involves interactions with other proteins such as RAB7A and SNX3 .

Structurally, VPS26A is a 38-kDa subunit that has a two-lobed structure with a polar core resembling the arrestin family of trafficking adaptors . 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 .

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 of the VPS26A gene results in multiple transcript variants encoding different isoforms .

The human recombinant form of VPS26A is produced in E. coli and is a single, non-glycosylated polypeptide chain containing 350 amino acids (1-327 a.a) with a molecular mass of 40.6 kDa . This recombinant protein is fused to a 23 amino acid His-tag at the N-terminus and is purified using proprietary chromatographic techniques .

VPS26A is associated with several diseases, including Parkinson Disease 19A (juvenile-onset) and Charcot-Marie-Tooth Disease Type 1F . It is also involved in important cellular pathways such as the Wnt signaling pathway .