VPS35

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.

VPS35 retromer complex component

Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway (PubMed:30213940).
The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15078903, PubMed:15247922, PubMed:20164305).
Required for endosomal localization of WASHC2C (PubMed:22070227, PubMed:28892079).
Mediates the association of the CSC with the WASH complex via WASHC2 (PubMed:22070227, PubMed:24980502, PubMed:24819384).
Required for the endosomal localization of TBC1D5 (PubMed:20923837).10 Publications4 Publications
(Microbial infection) The heterotrimeric retromer cargo-selective complex (CSC) mediates the exit of human papillomavirus from the early endosome and the delivery to the Golgi apparatus.

Biological Process endocytic recycling Source:UniProtKB2 Publications
Biological Process intracellular protein transport Source:GO_Central1 Publication
Biological Process lysosome organization Source:Ensembl
Biological Process mitochondrial fragmentation involved in apoptotic process Source:ParkinsonsUK-UCL1 Publication
Biological Process mitochondrion to lysosome transport Source:ParkinsonsUK-UCL1 Publication
Biological Process modulation of chemical synaptic transmission Source:Ensembl
Biological Process negative regulation of cell death Source:ParkinsonsUK-UCL1 Publication
Biological Process negative regulation of gene expression Source:Ensembl
Biological Process negative regulation of inflammatory response Source:ParkinsonsUK-UCL1 Publication
Biological Process negative regulation of late endosome to lysosome transport Source:UniProtKB1 Publication
Biological Process negative regulation of lysosomal protein catabolic process Source:Ensembl
Biological Process negative regulation of neuron death Source:ParkinsonsUK-UCL1 Publication
Biological Process negative regulation of protein homooligomerization Source:Ensembl
Biological Process negative regulation of protein localization Source:Ensembl
Biological Process neurotransmitter receptor transport, endosome to plasma membrane Source:ParkinsonsUK-UCL1 Publication
Biological Process neurotransmitter receptor transport, endosome to postsynaptic membrane Source:Ensembl
Biological Process positive regulation of canonical Wnt signaling pathway Source:Ensembl
Biological Process positive regulation of dopamine biosynthetic process Source:Ensembl
Biological Process positive regulation of dopamine receptor signaling pathway Source:ParkinsonsUK-UCL1 Publication
Biological Process positive regulation of gene expression Source:ParkinsonsUK-UCL1 Publication
Biological Process positive regulation of locomotion involved in locomotory behavior Source:Ensembl
Biological Process positive regulation of mitochondrial fission Source:ParkinsonsUK-UCL1 Publication
Biological Process positive regulation of protein catabolic process Source:ParkinsonsUK-UCL1 Publication
Biological Process positive regulation of Wnt protein secretion Source:Ensembl
Biological Process protein destabilization Source:Ensembl
Biological Process protein localization to endosome Source:UniProtKB1 Publication
Biological Process regulation of cellular protein metabolic process Source:ParkinsonsUK-UCL1 Publication
Biological Process regulation of dendritic spine maintenance Source:ParkinsonsUK-UCL1 Publication
Biological Process regulation of macroautophagy Source:ParkinsonsUK-UCL1 Publication
Biological Process regulation of mitochondrion organization Source:ParkinsonsUK-UCL1 Publication
Biological Process regulation of postsynapse assembly Source:Ensembl
Biological Process regulation of presynapse assembly Source:ParkinsonsUK-UCLBy Similarity
Biological Process regulation of protein stability Source:ParkinsonsUK-UCL1 Publication
Biological Process regulation of synapse maturation Source:Ensembl
Biological Process regulation of terminal button organization Source:ParkinsonsUK-UCL1 Publication
Biological Process retrograde transport, endosome to Golgi Source:UniProtKB1 Publication
Biological Process transcytosis Source:UniProtKB1 Publication
Biological Process vesicle-mediated transport in synapse Source:Ensembl
Biological Process voluntary musculoskeletal movement Source:Ensembl
Biological Process Wnt signaling pathway Source:ParkinsonsUK-UCL1 Publication

Cytoplasm
Membrane
Endosome
Early endosome
Late endosome
Localizes to tubular profiles adjacent to endosomes.

Parkinson disease 17 (PARK17):
An autosomal dominant, adult-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.