http://purl.uniprot.org/citations/22898812 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/22898812 | http://www.w3.org/2000/01/rdf-schema#comment | "The copper-transporting ATPase ATP7B has a dual intracellular localization: the trans-Golgi network (TGN) and cytosolic vesicles. Changes in copper levels, kinase-mediated phosphorylation, and mutations associated with Wilson disease alter the steady-state distribution of ATP7B between these compartments. To identify a primary molecular event that triggers ATP7B exit from the TGN, we characterized the folding, activity, and trafficking of the ATP7B variants with mutations within the regulatory N-terminal domain (N-ATP7B). We found that structural changes disrupting the inter-domain contacts facilitate ATP7B exit from the TGN. Mutating Ser-340/341 in the N-ATP7B individually or together to Ala, Gly, Thr, or Asp produced active protein and shifted the steady-state localization of ATP7B to vesicles, independently of copper levels. The Ser340/341G mutant had a lower kinase-mediated phosphorylation under basal conditions and no copper-dependent phosphorylation. Thus, negative charges introduced by copper-dependent phosphorylation are not obligatory for ATP7B trafficking from the TGN. The Ser340/341A mutation did not alter the overall fold of N-ATP7B, but significantly decreased interactions with the nucleotide-binding domain, mimicking consequences of copper binding to N-ATP7B. We propose that structural changes that specifically alter the inter-domain contacts initiate exit of ATP7B from the TGN, whereas increased phosphorylation may be needed to maintain an open interface between the domains."xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m112.370403"xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/author | "Gupta A."xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/author | "Hasan N.M."xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/author | "Lutsenko S."xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/author | "Yu C.H."xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/author | "Dmitriev O.Y."xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/author | "Polishchuk R."xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/author | "Polishchuk E."xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/pages | "36041-36050"xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/title | "Molecular events initiating exit of a copper-transporting ATPase ATP7B from the trans-Golgi network."xsd:string |
http://purl.uniprot.org/citations/22898812 | http://purl.uniprot.org/core/volume | "287"xsd:string |
http://purl.uniprot.org/citations/22898812 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22898812 |
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