Defining the interactome of the pancreas‐specific <scp>SPCA2</scp> isoform ( <scp>SPCA2C</scp> ) identifies unique links to store‐operated Ca <sup>2+</sup> entry
Bibliographic record
Abstract
Calcium (Ca 2+ ) is critical for normal cell function, and several protein networks are required for Ca 2+ signaling. In the pancreas, regulated changes in cytosolic Ca 2+ allow for the exocytosis of zymogen granules, and altered Ca 2+ signaling underlies pancreatic pathologies. Previously, our laboratory showed a pancreas‐specific isoform of secretory pathway Ca 2+ ‐ATPase 2 (also known as calcium‐transporting ATPase type 2C member 2; SPCA2), termed SPCA2C (gene name Atp2c2c , C‐terminally truncated form), affects multiple pathways involved in Ca 2+ homeostasis. The goal of this study was to define the SPCA2C interactome that contributes to these processes. Using proximity‐dependent biotin identification, BioID, we expressed SPCA2C‐BirA* HA in HEK293 cells with constitutive calcium release‐activated calcium channel protein 1 ( Orai1 ) expression. A total of 150 high‐confidence 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 2+ signaling and vesicular transport. Stromal interaction molecule 1 (STIM1) and coiled‐coil domain‐containing protein 47 (CCDC47; also known as PAT complex subunit CCDC47) were among several proteins we confirmed as strong interactors through co‐immunoprecipitation (co‐IP). Co‐expression of Atp2c2c and CCDC47 in HEK‐Orai1 YFP cells increased store‐operated calcium entry (SOCE) and resting cytosolic Ca 2+ 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‐IP and co‐localization experiments. CCDC47 localized with SPCA2C and the key store‐operated Ca 2+ 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‐coil or accessible transmembrane domains. Overall, we define several previously unknown protein interactions for SPCA2C, and suggest that CCDC47 may be involved in the coiled‐coil interplay that underlies STIM1 and Orai1‐mediated Ca 2+ entry.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".