| http://purl.uniprot.org/citations/26756164 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26756164 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26756164 | http://www.w3.org/2000/01/rdf-schema#comment | "The mammalian circadian clock influences most aspects of physiology and behavior through the transcriptional control of a wide variety of genes, mostly in a tissue-specific manner. About 20 clock-controlled genes (CCGs) oscillate in virtually all mammalian tissues and are generally considered as core clock components. One of them is Ubiquitin-Specific Protease 2 (Usp2), whose status remains controversial, as it may be a cogwheel regulating the stability or activity of core cogwheels or an output effector. We report here that Usp2 is a clock output effector related to bodily Ca2+ homeostasis, a feature that is conserved across evolution. Drosophila with a whole-body knockdown of the orthologue of Usp2, CG14619 (dUsp2-kd), predominantly die during pupation but are rescued by dietary Ca2+ supplementation. Usp2-KO mice show hyperabsorption of dietary Ca2+ in small intestine, likely due to strong overexpression of the membrane scaffold protein NHERF4, a regulator of the Ca2+ channel TRPV6 mediating dietary Ca2+ uptake. In this tissue, USP2-45 is found in membrane fractions and negatively regulates NHERF4 protein abundance in a rhythmic manner at the protein level. In clock mutant animals (Cry1/Cry2-dKO), rhythmic USP2-45 expression is lost, as well as the one of NHERF4, confirming the inverse relationship between USP2-45 and NHERF4 protein levels. Finally, USP2-45 interacts in vitro with NHERF4 and endogenous Clathrin Heavy Chain. Taken together these data prompt us to define USP2-45 as the first clock output effector acting at the post-translational level at cell membranes and possibly regulating membrane permeability of Ca2+."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0145155"xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0145155"xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Martin V."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Martin V."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Koch R."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Koch R."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Staub O."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Staub O."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Gachon F."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Gachon F."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Babis M."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Babis M."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Chenaux S."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Chenaux S."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Katanaev V.L."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Katanaev V.L."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Nagoshi E."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Nagoshi E."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Pouly D."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/author | "Pouly D."xsd:string |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/26756164 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |