page_title: VPS26A
section_title: Vps26B paralogue
hierarchical_section_title: VPS26A / Vps26B paralogue
caption_attribution_description: English: (A) The overlay of human Vps26A (blue) to mouse Vps26B (Red) (Shi et al, 2006). (B) The Ribbon and surface views of Vps26B with residues that are not conserved in Vps26A shown in gold. Majority of the non-conserved residues are found in the surface patch within the N-terminal subdomain and also at the apex of the intersection of the N-terminal and C-terminal domains. The non-conserved C-terminal tail is reflected by the gold dashed line. Figure taken from journal article by Collins et al, 2008
context_page_description: Vacuolar protein sorting-associated protein 26A is a protein that in humans is encoded by the VPS26A gene.
  This gene belongs to a group of vacuolar protein sorting 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.
context_section_description: In yeast, there is only one Vps26 species, whereas there are two Vps26 paralogues (Vps26A and Vps26B) in mammals.
  X-ray crystallography revealed that the structures of both Vps26A and Vps26B share a similar bilobal β-sandwich structure and possess 70% sequence homology. However, these two paralogues distinctly differ on the surface patch within the N-terminal domain, the apex region where the N-terminal and C-terminal domains meet and the disordered C-terminal tail. Vps26B contains several putative serine phosphorylation residues within this disordered tail, which may represent a potential mechanism to modulate the difference between Vps26A and Vps26B. A recent study conducted by Bugarcic et al. pinpointed that this disordered tail on C-terminal region of Vps26B is one of the underlying factors that contributes to the failure for Vps26B-containing Retromer to associate with CI-M6PR, ultimately leading to CI-M6PR degradation, accompanied with increased cathepsin D secretion.
caption: Structural differences between Vps26A and Vps26B
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