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Available structures
PDB Ortholog search: PDBe RCSB
Aliases VPS35, MEM3, PARK17, VPS35 retromer complex component, retromer complex component
External IDs MGI: 1890467 HomoloGene: 6221 GeneCards: VPS35
RNA expression pattern
PBB GE VPS35 217727 x at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 16: 46.66 – 46.69 Mb Chr 8: 85.26 – 85.3 Mb
PubMed search [1] [2]
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Vacuolar protein sorting-associated protein 35 is a protein that in humans is encoded by the VPS35 gene.[3][4]

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.[4]


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.[5] 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.[6] The C-terminal of Vps35 contains an α-solenoid fold that fits into the metal binding pocket of Vps29.[7]

A conserved PRLYL motif at the N-terminus of Vps35 is involved in the binding of Vps26.[8][9] 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.[10]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Zhang P, Yu L, Gao J, Fu Q, Dai F, Zhao Y, Zheng L, Zhao S (Jan 2001). "Cloning and characterization of human VPS35 and mouse Vps35 and mapping of VPS35 to human chromosome 16q13-q21". Genomics. 70 (2): 253–7. doi:10.1006/geno.2000.6380. PMID 11112353. 
  4. ^ a b "Entrez Gene: VPS35 vacuolar protein sorting 35 homolog (S. cerevisiae)". 
  5. ^ Hierro A, Rojas AL, Rojas R, Murthy N, Effantin G, Kajava AV, Steven AC, Bonifacino JS, Hurley JH (October 2007). "Functional architecture of the retromer cargo-recognition complex". Nature. 449 (7165): 1063–7. doi:10.1038/nature06216. PMC 2377034Freely accessible. PMID 17891154. 
  6. ^ Nothwehr SF, Bruinsma P, Strawn LA (April 1999). "Distinct domains within Vps35p mediate the retrieval of two different cargo proteins from the yeast prevacuolar/endosomal compartment". Mol. Biol. Cell. 10 (4): 875–90. doi:10.1091/mbc.10.4.875. PMC 25208Freely accessible. PMID 10198044. 
  7. ^ Collins BM, Skinner CF, Watson PJ, Seaman MN, Owen DJ (July 2005). "Vps29 has a phosphoesterase fold that acts as a protein interaction scaffold for retromer assembly". Nat. Struct. Mol. Biol. 12 (7): 594–602. doi:10.1038/nsmb954. PMID 15965486. 
  8. ^ Reddy JV, Seaman MN (October 2001). "Vps26p, a component of retromer, directs the interactions of Vps35p in endosome-to-Golgi retrieval". Mol. Biol. Cell. 12 (10): 3242–56. doi:10.1091/mbc.12.10.3242. PMC 60170Freely accessible. PMID 11598206. 
  9. ^ Zhao X, Nothwehr S, Lara-Lemus R, Zhang BY, Peter H, Arvan P (December 2007). "Dominant-negative behavior of mammalian Vps35 in yeast requires a conserved PRLYL motif involved in retromer assembly". Traffic. 8 (12): 1829–40. doi:10.1111/j.1600-0854.2007.00658.x. PMC 2532708Freely accessible. PMID 17916227. 
  10. ^ Tabuchi M, Yanatori I, Kawai Y, Kishi F (March 2010). "Retromer-mediated direct sorting is required for proper endosomal recycling of the mammalian iron transporter DMT1". J. Cell. Sci. 123 (Pt 5): 756–66. doi:10.1242/jcs.060574. PMID 20164305. 

Further reading[edit]