Species Human Entrez 55737 | Human Mouse Ensembl ENSG00000069329 | |
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Aliases VPS35, MEM3, PARK17, VPS35 retromer complex component External IDs MGI: 1890467 HomoloGene: 6221 GeneCards: VPS35 | ||
Vacuolar protein sorting-associated protein 35 is a protein that in humans is encoded by the VPS35 gene.
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.
Structure
Vps35 is the largest subunit of retromer with the molecular weight of 92-kDa and functions as the central platform for the assembly of Vps26 and Vps29. Vps35 resembles many other helical solenoid proteins including AP adaptor protein complexes that are characterized with repeated structural units in a continuous superhelix arrangement involved in coated vesicle trafficking. The curved surface of the 6 even-numbered helices within solenoid structure with series of ridges separating hydrophobic grooves function as potential cargo binding sites. The C-terminal of Vps35 contains an α-solenoid fold that fits into the metal binding pocket of Vps29.
A conserved PRLYL motif at the N-terminus of Vps35 is involved in the binding of Vps26. The structural binding motifs enable this subunit to act as a linker between the SNX dimers and Vps trimer complex, and the binding sites targeting to the N-terminal region of SNX subunits are located at the both ends of the trimer. A study has shown that the knockdown of Vps35 in human HEp-2 epithelial cells had defect on the endosomal recycling of transferrin by DMT1 due to the mis-sorting of DMT1-II to the lysosomal membrane associated protein (LAMP2) structures.