FEATURES

FAMILY

DESCRIPTION

Also known as VPS35_HUMAN, VPS35, MEM3. 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)., (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. Component of the heterotrimeric retromer cargo-selective complex (CSC), also decribed as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35 (PubMed:11102511, PubMed:28892079). The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform (By similarity). The CSC is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants. The originally described retromer complex (also called SNX-BAR retromer) is a pentamer containing the CSC and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. The CSC associates with SNX3 to form a SNX3-retromer complex. The CSC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to form the SNX27-retromer complex (Probable). Interacts with VPS26A, VPS26B, VPS29, SNX1, SNX2, IGF2R, SNX3, GOLPH3, LRRK2, SLC11A2, WASHC2A, WASHC2C, FKBP15, WASHC1, RAB7A, SNX27, WASHC5, EHD1 (PubMed:11102511, PubMed:15078903, PubMed:17868075PubMed:22070227, PubMed:19553991, PubMed:21725319, PubMed:22070227, PubMed:22513087, PubMed:23331060, PubMed:23563491, PubMed:23395371, PubMed:24344282, PubMed:24980502, PubMed:17891154, PubMed:19531583, PubMed:30213940). Interacts with MAGEL2; leading to recruitment of the TRIM27:MAGEL2 E3 ubiquitin ligase complex retromer-containing endosomes (PubMed:23452853). Interacts with SORCS2 (By similarity).

EXTERNAL LINKS

VPS35

Mutations

Mutation(s) distribution

Mutations table