VPS35

VPS35
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2R17
Identifiers
Aliases	VPS35, MEM3, PARK17, VPS35 retromer complex component, retromer complex component
External IDs	OMIM: 601501; MGI: 1890467; HomoloGene: 6221; GeneCards: VPS35; OMA:VPS35 - orthologs
Gene location (Human) Chr. Chromosome 16 (human) Band 16q11.2 Start 46,656,132 bp End 46,689,518 bp
Gene location (Mouse) Chr. Chromosome 8 (mouse) Band 8 C3|8 41.61 cM Start 85,987,021 bp End 86,026,431 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone corpus callosum ganglionic eminence superior frontal gyrus duodenum Achilles tendon islet of Langerhans endometrium monocyte epithelium of colon Top expressed in medial ganglionic eminence calvaria parotid gland pyloric antrum dorsomedial hypothalamic nucleus human fetus olfactory epithelium habenula stroma of bone marrow paraventricular nucleus of hypothalamus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding D1 dopamine receptor binding Cellular component cytoplasm endosome membrane tubular endosome retromer complex lysosomal membrane early endosome extracellular exosome mitochondrion lysosome endosome membrane postsynaptic density retromer, cargo-selective complex mitochondrion-derived vesicle neuron projection neuronal cell body perinuclear region of cytoplasm late endosome cytosol plasma membrane presynapse postsynapse glutamatergic synapse Biological process regulation of protein stability positive regulation of canonical Wnt signaling pathway positive regulation of Wnt protein secretion transcytosis negative regulation of late endosome to lysosome transport retrograde transport, endosome to Golgi protein transport regulation of macroautophagy Wnt signaling pathway regulation of mitochondrion organization mitochondrial fragmentation involved in apoptotic process positive regulation of dopamine receptor signaling pathway positive regulation of mitochondrial fission mitochondrion to lysosome transport neurotransmitter receptor transport, endosome to plasma membrane regulation of dendritic spine maintenance regulation of terminal button organization lysosome organization positive regulation of gene expression negative regulation of gene expression protein destabilization negative regulation of protein homooligomerization protein localization to organelle voluntary musculoskeletal movement positive regulation of locomotion involved in locomotory behavior positive regulation of dopamine biosynthetic process negative regulation of protein localization negative regulation of lysosomal protein catabolic process transport regulation of cellular protein metabolic process negative regulation of inflammatory response negative regulation of cell death negative regulation of neuron death regulation of presynapse assembly intracellular protein transport synapse assembly viral process neurotransmitter receptor transport, endosome to postsynaptic membrane vesicle-mediated transport in synapse protein localization to endosome Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55737 65114 Ensembl ENSG00000069329 ENSMUSG00000031696 UniProt Q96QK1 Q9EQH3 RefSeq (mRNA) NM_018206 NM_022997 RefSeq (protein) NP_060676 NP_075373 Location (UCSC) Chr 16: 46.66 – 46.69 Mb Chr 8: 85.99 – 86.03 Mb PubMed search
Wikidata
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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.

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (1997). "Large-Scale Concatenation cDNA Sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Edgar AJ, Polak JM (2000). "Human homologues of yeast vacuolar protein sorting 29 and 35". Biochem. Biophys. Res. Commun. 277 (3): 622–30. doi:10.1006/bbrc.2000.3727. PMID 11062004.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Haft CR, de la Luz Sierra M, Bafford R, Lesniak MA, Barr VA, Taylor SI (2001). "Human Orthologs of Yeast Vacuolar Protein Sorting Proteins Vps26, 29, and 35: Assembly into Multimeric Complexes". Mol. Biol. Cell. 11 (12): 4105–16. doi:10.1091/mbc.11.12.4105. PMC 15060. PMID 11102511.
• Vergés M, Luton F, Gruber C, Tiemann F, Reinders LG, Huang L, Burlingame AL, Haft CR, Mostov KE (2004). "The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor". Nat. Cell Biol. 6 (8): 763–9. doi:10.1038/ncb1153. PMID 15247922.
• Mingot JM, Bohnsack MT, Jäkle U, Görlich D (2005). "Exportin 7 defines a novel general nuclear export pathway". EMBO J. 23 (16): 3227–36. doi:10.1038/sj.emboj.7600338. PMC 514512. PMID 15282546.