{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T02:18:48Z","timestamp":1775787528695,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2025,8,10]],"date-time":"2025-08-10T00:00:00Z","timestamp":1754784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102024\u201006525"],"award-info":[{"award-number":["RGPIN\u20102024\u201006525"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    Calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) is critical for normal cell function, and several protein networks are required for Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling. In the pancreas, regulated changes in cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    allow for the exocytosis of zymogen granules, and altered Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling underlies pancreatic pathologies. Previously, our laboratory showed a pancreas\u2010specific isoform of secretory pathway Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010ATPase 2 (also known as calcium\u2010transporting ATPase type 2C member 2; SPCA2), termed SPCA2C (gene name\n                    <jats:italic>Atp2c2c<\/jats:italic>\n                    , C\u2010terminally truncated form), affects multiple pathways involved in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis. The goal of this study was to define the SPCA2C interactome that contributes to these processes. Using proximity\u2010dependent biotin identification, BioID, we expressed SPCA2C\u2010BirA*\n                    <jats:sup>HA<\/jats:sup>\n                    in HEK293 cells with constitutive calcium release\u2010activated calcium channel protein 1 (\n                    <jats:italic>Orai1<\/jats:italic>\n                    ) expression. A total of 150 high\u2010confidence interacting proteins for SPCA2C were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analyses supported the localization of SPCA2C to the endoplasmic reticulum, and that it functions in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling and vesicular transport. Stromal interaction molecule 1 (STIM1) and coiled\u2010coil domain\u2010containing protein 47 (CCDC47; also known as PAT complex subunit CCDC47) were among several proteins we confirmed as strong interactors through co\u2010immunoprecipitation (co\u2010IP). Co\u2010expression of\n                    <jats:italic>Atp2c2c<\/jats:italic>\n                    and\n                    <jats:italic>CCDC47<\/jats:italic>\n                    in HEK\u2010Orai1\n                    <jats:sup>YFP<\/jats:sup>\n                    cells increased store\u2010operated calcium entry (SOCE) and resting cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels compared with the expression of either protein alone. We further teased out the domain determinants of CCDC47 interactions with SPCA2C, STIM1, and Orai1 using co\u2010IP and co\u2010localization experiments. CCDC47 localized with SPCA2C and the key store\u2010operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry mediators STIM1 and Orai1 but did not interact with the long SPCA2 isoform. These interactions were dependent on the presence of the CCDC47 coiled\u2010coil or accessible transmembrane domains. Overall, we define several previously unknown protein interactions for SPCA2C, and suggest that CCDC47 may be involved in the coiled\u2010coil interplay that underlies STIM1 and Orai1\u2010mediated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry.\n                  <\/jats:p>","DOI":"10.1111\/febs.70213","type":"journal-article","created":{"date-parts":[[2025,8,10]],"date-time":"2025-08-10T12:29:07Z","timestamp":1754828947000},"page":"6644-6669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Defining the interactome of the pancreas\u2010specific\n                    <scp>SPCA2<\/scp>\n                    \u00a0isoform (\n                    <scp>SPCA2C<\/scp>\n                    ) identifies unique links to store\u2010operated Ca\n                    <sup>2+<\/sup>\n                    entry"],"prefix":"10.1111","volume":"292","author":[{"given":"Petra","family":"Samardzija","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Canada"},{"name":"Department of Paediatrics, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Canada"},{"name":"Department of Oncology, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Canada"},{"name":"Children's Health Research Institute London Health Sciences Research Centre  Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa A.","family":"Fenech","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Canada"},{"name":"Department of Paediatrics, Schulich School of Medicine &amp; Dentistry University of Western Ontario  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C.","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Canada"},{"name":"Department of Paediatrics, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Canada"},{"name":"Department of Oncology, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Canada"},{"name":"Children's Health Research Institute London Health Sciences Research Centre  Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Canada"},{"name":"Department of Paediatrics, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Canada"},{"name":"Department of Oncology, Schulich School of 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