VPS35

Acts as a 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:24819384, PubMed:24980502). Required for the endosomal localization of TBC1D5 (PubMed:20923837).

(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.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Belongs to the VPS35 family.

Ubiquitous. Highly expressed in heart, brain, placenta, skeletal muscle, spleen, thymus, testis, ovary, small intestine, kidney and colon.

• Cytoplasm
• Membrane
• Peripheral membrane protein
• Endosome
• Early endosome
• Late endosome
• Localizes to tubular profiles adjacent to endosomes.

MEM3, TCCCTA00141, VPS35, Vacuolar protein sorting-associated protein 35, hVPS35, Maternal-embryonic 3, Vesicle protein sorting 35

• entrezGene:55737
• entrezGene:100133770
• omim:601501
• swissprot:Q96QK1

Proteins

Neuroscience

91707Da