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http://purl.uniprot.org/citations/35672408http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35672408http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35672408http://www.w3.org/2000/01/rdf-schema#comment"The activity of V-ATPase is well-known to be regulated by reversible dissociation of its V1 and Vo domains in response to growth factor stimulation, nutrient sensing, and cellular differentiation. The molecular basis of its regulation by an endogenous modulator without affecting V-ATPase assembly remains unclear. Here, we discover that a lysosome-anchored protein termed (mammalian Enhancer-of-Akt-1-7 (mEAK7)) binds to intact V-ATPase. We determine cryo-EM structure of human mEAK7 in complex with human V-ATPase in native lipid-containing nanodiscs. The structure reveals that the TLDc domain of mEAK7 engages with subunits A, B, and E, while its C-terminal domain binds to subunit D, presumably blocking V1-Vo torque transmission. Our functional studies suggest that mEAK7, which may act as a V-ATPase inhibitor, does not affect the activity of V-ATPase in vitro. However, overexpression of mEAK7 in HCT116 cells that stably express subunit a4 of V-ATPase represses the phosphorylation of ribosomal protein S6. Thus, this finding suggests that mEAK7 potentially links mTOR signaling with V-ATPase activity."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.org/dc/terms/identifier"doi:10.1038/s41467-022-30899-z"xsd:string
http://purl.uniprot.org/citations/35672408http://purl.org/dc/terms/identifier"doi:10.1038/s41467-022-30899-z"xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/author"Li X."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/author"Li X."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/author"Wang R."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/author"Wang R."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/author"Xie X.S."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/author"Xie X.S."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/author"Qin Y."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/author"Qin Y."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/name"Nat. Commun."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/name"Nat Commun"xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/pages"3272"xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/pages"3272"xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/title"Molecular basis of mEAK7-mediated human V-ATPase regulation."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/title"Molecular basis of mEAK7-mediated human V-ATPase regulation."xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/volume"13"xsd:string
http://purl.uniprot.org/citations/35672408http://purl.uniprot.org/core/volume"13"xsd:string
http://purl.uniprot.org/citations/35672408http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35672408
http://purl.uniprot.org/citations/35672408http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35672408