| http://purl.uniprot.org/citations/25627681 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25627681 | http://www.w3.org/2000/01/rdf-schema#comment | "The NH2-terminal region (residues 1-543) of the cardiac ryanodine receptor (RyR2) harbors a large number of mutations associated with cardiac arrhythmias and cardiomyopathies. Functional studies have revealed that the NH2-terminal region is involved in the activation and termination of Ca(2+) release. The three-dimensional structure of the NH2-terminal region has recently been solved. It is composed of three domains (A, B, and C). However, the roles of these individual domains in Ca(2+) release activation and termination are largely unknown. To understand the functional significance of each of these NH2-terminal domains, we systematically deleted these domains and assessed their impact on caffeine- or Ca(2+)-induced Ca(2+) release and store overload-induced Ca(2+) release (SOICR) in HEK293 cells. We found that all deletion mutants were capable of forming caffeine- and ryanodine-sensitive functional channels, indicating that the NH2-terminal region is not essential for channel gating. Ca(2+) release measurements revealed that deleting domain A markedly reduced the threshold for SOICR termination but had no effect on caffeine or Ca(2+) activation or the threshold for SOICR activation, whereas deleting domain B substantially enhanced caffeine and Ca(2+) activation and lowered the threshold for SOICR activation and termination. Conversely, deleting domain C suppressed caffeine activation, abolished Ca(2+) activation and SOICR, and diminished protein expression. These results suggest that domain A is involved in channel termination, domain B is involved in channel suppression, and domain C is critical for channel activation and expression. Our data shed new insights into the structure-function relationship of the NH2-terminal domains of RyR2 and the action of NH2-terminal disease mutations."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m114.618827"xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Guo W."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Mi T."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Sun B."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Wang Y."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Wang R."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Xiao Z."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Zhang J.Z."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Van Petegem F."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Chen S.R."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/author | "Jones P.P."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/pages | "7736-7746"xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/title | "Roles of the NH2-terminal domains of cardiac ryanodine receptor in Ca2+ release activation and termination."xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://purl.uniprot.org/core/volume | "290"xsd:string |
| http://purl.uniprot.org/citations/25627681 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25627681 |
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| http://purl.uniprot.org/uniprot/#_D7UNU3-mappedCitation-25627681 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25627681 |