| http://purl.uniprot.org/citations/33941685 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33941685 | http://www.w3.org/2000/01/rdf-schema#comment | "To avoid conflicting and deleterious outcomes, eukaryotic cells often confine second messengers to spatially restricted subcompartments. The smallest signaling unit is the Ca2+ nanodomain, which forms when Ca2+ channels open. Ca2+ nanodomains arising from store-operated Orai1 Ca2+ channels stimulate the protein phosphatase calcineurin to activate the transcription factor nuclear factor of activated T cells (NFAT). Here, we show that NFAT1 tethered directly to the scaffolding protein AKAP79 (A-kinase anchoring protein 79) is activated by local Ca2+ entry, providing a mechanism to selectively recruit a transcription factor. We identify the region on the N terminus of Orai1 that interacts with AKAP79 and demonstrate that this site is essential for physiological excitation-transcription coupling. NMR structural analysis of the AKAP binding domain reveals a compact shape with several proline-driven turns. Orai2 and Orai3, isoforms of Orai1, lack this region and therefore are less able to engage AKAP79 and activate NFAT. A shorter, naturally occurring Orai1 protein that arises from alternative translation initiation also lacks the AKAP79-interaction site and fails to activate NFAT1. Interfering with Orai1-AKAP79 interaction suppresses cytokine production, leaving other Ca2+ channel functions intact. Our results reveal the mechanistic basis for how a subtype of a widely expressed Ca2+ channel is able to activate a vital transcription pathway and identify an approach for generation of immunosuppressant drugs."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.2012908118"xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/author | "Lin Y.P."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/author | "Amin N."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/author | "Hediger M.A."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/author | "Tucker C.J."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/author | "Bird G.S."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/author | "Bhardwaj R."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/author | "Kar P."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/author | "Parekh A.B."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/author | "Monico C."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/pages | "e2012908118"xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/title | "The N terminus of Orai1 couples to the AKAP79 signaling complex to drive NFAT1 activation by local Ca2+ entry."xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://purl.uniprot.org/core/volume | "118"xsd:string |
| http://purl.uniprot.org/citations/33941685 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33941685 |
| http://purl.uniprot.org/citations/33941685 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33941685 |
| http://purl.uniprot.org/uniprot/#_B5B2P4-mappedCitation-33941685 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33941685 |
| http://purl.uniprot.org/uniprot/#_B7Z8Y1-mappedCitation-33941685 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33941685 |
| http://purl.uniprot.org/uniprot/#_Q13469-mappedCitation-33941685 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33941685 |
| http://purl.uniprot.org/uniprot/#_P24588-mappedCitation-33941685 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33941685 |
| http://purl.uniprot.org/uniprot/#_Q6PG46-mappedCitation-33941685 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33941685 |
| http://purl.uniprot.org/uniprot/#_Q96D31-mappedCitation-33941685 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/33941685 |