VPS35 information

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)
End	46,689,518 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	86,026,431 bp
RNA expression pattern
	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
	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
	55737
	65114
	ENSG00000069329
	ENSMUSG00000031696
	Q96QK1
	Q9EQH3
	NM_018206
	NM_022997
	NP_060676
	NP_075373
	Wikidata
View/Edit Human	View/Edit Mouse

Vacuolar protein sorting ortholog 35 (VPS35) is a protein involved in autophagy and is implicated in neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD).^[1]^[2]^[3]^[4]^[5] VPS35 is part of a complex called the retromer, which is responsible for transporting select cargo proteins between vesicular structures (e.g., endosomes, lysosomes, vacuoles) and the Golgi apparatus.^[1]^[6]^[7]^[8]^[9] Mutations in the VPS35 gene (VPS35) cause aberrant autophagy, where cargo proteins fail to be transported and dysfunctional or unnecessary proteins fail to be degraded.^[5]^[7] There are numerous pathways affected by altered VPS35 levels and activity, which have clinical significance in neurodegeneration.^[1]^[2]^[3]^[4]^[5] There is therapeutic relevance for VPS35, as interventions aimed at correcting VPS35 function are in speculation.^[5]^[10]^[11]

^ ^a ^b ^c Reitz C (April 2015). "The role of the retromer complex in aging-related neurodegeneration: a molecular and genomic review". Molecular Genetics and Genomics. 290 (2): 413–27. doi:10.1007/s00438-014-0939-9. PMC 4363161. PMID 25332075.
^ ^a ^b Reitz C (May 2018). "Retromer Dysfunction and Neurodegenerative Disease". Current Genomics. 19 (4): 279–288. doi:10.2174/1389202919666171024122809. PMC 5930449. PMID 29755290.
^ ^a ^b Brodin L, Shupliakov O (2018). "Retromer in Synaptic Function and Pathology". Frontiers in Synaptic Neuroscience. 10: 37. doi:10.3389/fnsyn.2018.00037. PMC 6207580. PMID 30405388.
^ ^a ^b Follett J, Bugarcic A, Collins BM, Teasdale RD (2017-07-01). "Retromer's Role in Endosomal Trafficking and Impaired Function in Neurodegenerative Diseases". Current Protein & Peptide Science. 18 (7): 687–701. doi:10.2174/1389203717666160311121246. PMID 26965691.
^ ^a ^b ^c ^d Trousdale C, Kim K (November 2015). "Retromer: Structure, function, and roles in mammalian disease". European Journal of Cell Biology. 94 (11): 513–21. doi:10.1016/j.ejcb.2015.07.002. PMID 26220253.
^ Vagnozzi AN, Li JG, Chiu J, Razmpour R, Warfield R, Ramirez SH, Praticò D (July 2019). "VPS35 regulates tau phosphorylation and neuropathology in tauopathy". Molecular Psychiatry. 26 (11): 6992–7005. doi:10.1038/s41380-019-0453-x. PMC 6949432. PMID 31289348.
^ ^a ^b Rahman AA, Morrison BE (March 2019). "Contributions of VPS35 Mutations to Parkinson's Disease". Neuroscience. 401: 1–10. doi:10.1016/j.neuroscience.2019.01.006. PMC 6422337. PMID 30660673.
^ Vilariño-Güell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, et al. (July 2011). "VPS35 mutations in Parkinson disease". American Journal of Human Genetics. 89 (1): 162–7. doi:10.1016/j.ajhg.2011.06.001. PMC 3135796. PMID 21763482.
^ Williams ET, Chen X, Moore DJ (2017-01-01). "VPS35, the Retromer Complex and Parkinson's Disease". Journal of Parkinson's Disease. 7 (2): 219–233. doi:10.3233/JPD-161020. PMC 5438477. PMID 28222538.
^ Cutillo G, Simon DK, Eleuteri S (November 2020). "VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiology". Neurobiology of Disease. 145: 105056. doi:10.1016/j.nbd.2020.105056. PMID 32853677. S2CID 221277514.
^ Eleuteri S, Albanese A (2019-12-17). "VPS35-Based Approach: A Potential Innovative Treatment in Parkinson's Disease". Frontiers in Neurology. 10: 1272. doi:10.3389/fneur.2019.01272. PMC 6928206. PMID 31920908.
^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000069329 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031696 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Reitz_2015-1] Reitz C (April 2015). "The role of the retromer complex in aging-related neurodegeneration: a molecular and genomic review". Molecular Genetics and Genomics. 290 (2): 413–27. doi:10.1007/s00438-014-0939-9. PMC 4363161. PMID 25332075.

[Reitz_2018-2] Reitz C (May 2018). "Retromer Dysfunction and Neurodegenerative Disease". Current Genomics. 19 (4): 279–288. doi:10.2174/1389202919666171024122809. PMC 5930449. PMID 29755290.

[Brodin_2018-3] Brodin L, Shupliakov O (2018). "Retromer in Synaptic Function and Pathology". Frontiers in Synaptic Neuroscience. 10: 37. doi:10.3389/fnsyn.2018.00037. PMC 6207580. PMID 30405388.

[Follett_2017-4] Follett J, Bugarcic A, Collins BM, Teasdale RD (2017-07-01). "Retromer's Role in Endosomal Trafficking and Impaired Function in Neurodegenerative Diseases". Current Protein & Peptide Science. 18 (7): 687–701. doi:10.2174/1389203717666160311121246. PMID 26965691.

[Trousdale_2015-5] Trousdale C, Kim K (November 2015). "Retromer: Structure, function, and roles in mammalian disease". European Journal of Cell Biology. 94 (11): 513–21. doi:10.1016/j.ejcb.2015.07.002. PMID 26220253.

[Vagnozzi_2019-6] Vagnozzi AN, Li JG, Chiu J, Razmpour R, Warfield R, Ramirez SH, Praticò D (July 2019). "VPS35 regulates tau phosphorylation and neuropathology in tauopathy". Molecular Psychiatry. 26 (11): 6992–7005. doi:10.1038/s41380-019-0453-x. PMC 6949432. PMID 31289348.

[Rahman_2019-7] Rahman AA, Morrison BE (March 2019). "Contributions of VPS35 Mutations to Parkinson's Disease". Neuroscience. 401: 1–10. doi:10.1016/j.neuroscience.2019.01.006. PMC 6422337. PMID 30660673.

[Vilariño-Güell_2011-8] Vilariño-Güell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, et al. (July 2011). "VPS35 mutations in Parkinson disease". American Journal of Human Genetics. 89 (1): 162–7. doi:10.1016/j.ajhg.2011.06.001. PMC 3135796. PMID 21763482.

[Williams_2017-9] Williams ET, Chen X, Moore DJ (2017-01-01). "VPS35, the Retromer Complex and Parkinson's Disease". Journal of Parkinson's Disease. 7 (2): 219–233. doi:10.3233/JPD-161020. PMC 5438477. PMID 28222538.

[Cutillo_2020-10] Cutillo G, Simon DK, Eleuteri S (November 2020). "VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiology". Neurobiology of Disease. 145: 105056. doi:10.1016/j.nbd.2020.105056. PMID 32853677. S2CID 221277514.

[Eleuteri_2019-11] Eleuteri S, Albanese A (2019-12-17). "VPS35-Based Approach: A Potential Innovative Treatment in Parkinson's Disease". Frontiers in Neurology. 10: 1272. doi:10.3389/fneur.2019.01272. PMC 6928206. PMID 31920908.

[refGRCh38Ensembl-12] GRCh38: Ensembl release 89: ENSG00000069329 – Ensembl, May 2017

[refGRCm38Ensembl-13] GRCm38: Ensembl release 89: ENSMUSG00000031696 – Ensembl, May 2017

[14] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[15] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

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