ArticleNature communications2014
Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
110 citing papers in PubMed, 156 citations in OpenAlex.
- Mechanistic insights into Orai dynamics during pore opening.Channels (Austin, Tex.) · 2026Review
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- Two-pore channel-2 controls calmodulin-dependent STIM1 inactivation.Nature communications · 2026Article
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Unraveling new functions of the Ca2+ sensor STIM1 in cell signaling.Biochemical Society transactions · 2026Review
- Multiple weak brakes act in concert to control STIM1 and store-operated calcium entry.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Orai storeoperated CaChannels (Austin, Tex.) · 2025Review
- Store-operated calcium entry-based targets for novel cancer therapeutic development.The Journal of pharmacology and experimental therapeutics · 2025Review
- Cellular calcium homeostasis and regulation of its dynamic perturbation.Quantitative plant biology · 2025Review
- A Deep Dive into the N-Terminus of STIM Proteins: Structure-Function Analysis and Evolutionary Significance of the Functional Domains.Biomolecules · 2024Review
- Synthetic Biology Meets CaCells · 2024Review
- CaPhysiological reviews · 2024Review
- Article
- An apical Phe-His pair defines the Orai1-coupling site and its occlusion within STIM1.Nature communications · 2023Article
- Upregulation of Orai Channels Contributes to Aging-Related Vascular Alterations in Rat Coronary Arteries.International journal of molecular sciences · 2023Article
- The CaBiomolecules · 2023Review
- ORAI Calcium Channels: Regulation, Function, Pharmacology, and Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2023Review
- ER-resident STIM1/2 couples CaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- STIM Proteins and Regulation of SOCE in ER-PM Junctions.Biomolecules · 2022Review
- Control of STIM and Orai function by post-translational modifications.Cell calcium · 2022Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
STIM1 and STIM2 are widely expressed endoplasmic reticulum (ER) Ca(2+) sensor proteins able to translocate within the ER membrane to physically couple with and gate plasma membrane Orai Ca(2+) channels. Although they are structurally similar, we reveal critical differences in the function of the short STIM-Orai-activating regions (SOAR) of STIM1 and STIM2. We narrow these differences in Orai1 gating to a strategically exposed phenylalanine residue (Phe-394) in SOAR1, which in SOAR2 is substituted by a leucine residue. Remarkably, in full-length STIM1, replacement of Phe-394 with the dimensionally similar but polar histidine head group prevents both Orai1 binding and gating, creating an Orai1 non-agonist. Thus, this residue is critical in tuning the efficacy of Orai activation. While STIM1 is a full Orai1-agonist, leucine-replacement of this crucial residue in STIM2 endows it with partial agonist properties, which may be critical for limiting Orai1 activation stemming from its enhanced sensitivity to store-depletion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.