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http://purl.uniprot.org/citations/20460380http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20460380http://www.w3.org/2000/01/rdf-schema#comment"Because intracellular [Na(+)] is kept low by Na(+)/K(+)-ATPase, Na(+) dependence is generally considered a property of extracellular enzymes. However, we found that p94/calpain 3, a skeletal-muscle-specific member of the Ca(2+)-activated intracellular "modulator proteases" that is responsible for a limb-girdle muscular dystrophy ("calpainopathy"), underwent Na(+)-dependent, but not Cs(+)-dependent, autolysis in the absence of Ca(2+). Furthermore, Na(+) and Ca(2+) complementarily activated autolysis of p94 at physiological concentrations. By blocking Na(+)/K(+)-ATPase, we confirmed intracellular autolysis of p94 in cultured cells. This was further confirmed using inactive p94:C129S knock-in (p94CS-KI) mice as negative controls. Mutagenesis studies showed that much of the p94 molecule contributed to its Na(+)/Ca(2+)-dependent autolysis, which is consistent with the scattered location of calpainopathy-associated mutations, and that a conserved Ca(2+)-binding sequence in the protease acted as a Na(+) sensor. Proteomic analyses using Cs(+)/Mg(2+) and p94CS-KI mice as negative controls revealed that Na(+) and Ca(2+) direct p94 to proteolyze different substrates. We propose three roles for Na(+) dependence of p94; 1) to increase sensitivity of p94 to changes in physiological [Ca(2+)], 2) to regulate substrate specificity of p94, and 3) to regulate contribution of p94 as a structural component in muscle cells. Finally, this is the first example of an intracellular Na(+)-dependent enzyme."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m110.126946"xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/author"Abe K."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/author"Ono Y."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/author"Nakagawa K."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/author"Hata S."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/author"Doi N."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/author"Sorimachi H."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/author"Ojima K."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/author"Torii F."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/author"Takaya E."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/pages"22986-22998"xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/title"Skeletal muscle-specific calpain is an intracellular Na+-dependent protease."xsd:string
http://purl.uniprot.org/citations/20460380http://purl.uniprot.org/core/volume"285"xsd:string
http://purl.uniprot.org/citations/20460380http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20460380
http://purl.uniprot.org/citations/20460380http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20460380
http://purl.uniprot.org/uniprot/Q64691#attribution-C4E152BF15B1E663E1E487B018651728http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/20460380
http://purl.uniprot.org/uniprot/P16259#attribution-02366186FC359B0B3708D482E835AD23http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/20460380
http://purl.uniprot.org/uniprot/#_A0A0G2K9P9-mappedCitation-20460380http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20460380
http://purl.uniprot.org/uniprot/#_A0A0G2JVX0-mappedCitation-20460380http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20460380
http://purl.uniprot.org/uniprot/#_A0A0G2K0L5-mappedCitation-20460380http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20460380
http://purl.uniprot.org/uniprot/#_A0A8I5ZRY1-mappedCitation-20460380http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20460380