8syn

Structural highlights

Disease

VP35L_HUMAN The disease may be caused by variants affecting the gene represented in this entry.

Function

VP35L_HUMAN Acts as component of the retriever complex. The retriever complex is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1) (PubMed:28892079). The recruitment of the retriever complex to the endosomal membrane involves CCC and WASH complexes (PubMed:28892079). In the endosomes, drives the retrieval and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of numerous cell surface proteins associated with processes that include cell migration, cell adhesion, nutrient supply and cell signaling (PubMed:28892079). Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association with the CCC complex and cooperation with the WASH complex on early endosomes. Seems not to be required for CCC complex stability (PubMed:25355947).^{[1] [2]} (Microbial infection) The heterotrimeric retriever complex, in collaboration with the CCC complex, mediates the exit of human papillomavirus to the cell surface.^[3]

References

1. ↑ Phillips-Krawczak CA, Singla A, Starokadomskyy P, Deng Z, Osborne DG, Li H, Dick CJ, Gomez TS, Koenecke M, Zhang JS, Dai H, Sifuentes-Dominguez LF, Geng LN, Kaufmann SH, Hein MY, Wallis M, McGaughran J, Gecz J, Sluis Bv, Billadeau DD, Burstein E. COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A. Mol Biol Cell. 2015 Jan 1;26(1):91-103. PMID:25355947 doi:10.1091/mbc.E14-06-1073
2. ↑ McNally KE, Faulkner R, Steinberg F, Gallon M, Ghai R, Pim D, Langton P, Pearson N, Danson CM, Nägele H, Morris LL, Singla A, Overlee BL, Heesom KJ, Sessions R, Banks L, Collins BM, Berger I, Billadeau DD, Burstein E, Cullen PJ. Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling. Nat Cell Biol. 2017 Oct;19(10):1214-1225. PMID:28892079 doi:10.1038/ncb3610
3. ↑ McNally KE, Faulkner R, Steinberg F, Gallon M, Ghai R, Pim D, Langton P, Pearson N, Danson CM, Nägele H, Morris LL, Singla A, Overlee BL, Heesom KJ, Sessions R, Banks L, Collins BM, Berger I, Billadeau DD, Burstein E, Cullen PJ. Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling. Nat Cell Biol. 2017 Oct;19(10):1214-1225. PMID:28892079 doi:10.1038/ncb3610