Defining the SPCA2C interactome identifies unique links to Store-Operated Ca <sup>2+</sup> Entry
Bibliographic record
Abstract
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 (SPCA2C) 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 Orai1 expression. In silico modeling of SPCA2C showed a highly dynamic cytosolic C-terminus, revealing a putative site for interactions and was selected for BirA* fusion. 150 candidate SPCA2C interactors were identified. Gene Ontology and KEGG Pathway analyses supported localization of SPCA2C to the endoplasmic reticulum as well as function in Ca 2+ signaling and suggested roles in vesicular transport. SPCA2C interactions with stromal interaction molecule 1 (STIM1), extended synaptotagmin-1 (ESYT1), and aspartate beta-hydroxylase (ASPH) were validated. Coiled-coil domain containing protein 47 (CCDC47) ranked as a high confidence SPCA2C-interactor which was confirmed through immunoprecipitation and co-localization with SPCA2C. CCDC47 interactions with SPCA2C, STIM1 and Orai1 were maintained following deletion of the CCDC47 luminal and cytosolic domains while deletion of only the coiled-coil domain altered CCDC47 localization and decreased interactions with STIM1 and Orai1. Overall, this study defines several novel protein interactions for SPCA2C and suggests it may be involved in affecting CCDC47, STIM1 and Orai1 function.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".