Affinage

STIM2

Stromal interaction molecule 2 · UniProt Q9P246

Length
746 aa
Mass
84.0 kDa
Annotated
2026-06-10
92 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STIM2 is an ER-resident Ca2+ sensor that functions as the principal feedback regulator stabilizing basal cytosolic and ER Ca2+ levels by activating Ca2+ influx through Orai1 in response to smaller ER Ca2+ decreases than those required for STIM1 (PMID:18160041). Its lower activation threshold derives from biophysical and conformational distinctions: its EF-SAM domain is more structurally stable than that of STIM1 (PMID:18166150), and a cross-talk between N-terminal Ca2+ sensing and increased C-terminal flexibility tunes its slow/weak versus fast/potent gating of Orai, switchable by STIM1/STIM2 chimeras and point mutations (PMID:30444880, PMID:30824535). Mechanistically, STIM2 is constitutively localized at ER-PM junctions in Ca2+-replete cells, where IP3R activity and local ER Ca2+ drive formation of immobile clusters that recruit Orai1 under basal conditions (PMID:29642009, PMID:35022238). Upon mild store depletion it traps STIM1 and remodels its C-terminus to induce the active conformation, enhancing Orai1 coupling and NFAT activation at low agonist concentrations (PMID:29642009, PMID:25587190), and it scaffolds Orai1/STIM1 to the AKAP79 complex to couple Ca2+ entry to NFAT1 (PMID:32601188). STIM2 physically interacts with STIM1 and forms heteromers that modulate SOCE (PMID:16860747, PMID:20436167, PMID:22592407). Beyond CRAC channels, STIM2 differentially regulates non-CRAC store-operated channels including Imin and TRPC1 (PMID:25533457, PMID:34157631). Its activity is negatively controlled by oxidative modification at Cys313 (PMID:33086068) and by alternative splicing: the STIM2.1/β isoform inhibits SOCE through increased calmodulin affinity, impaired direct Orai1 interaction, and allosteric inhibition via heterodimer recruitment to Orai1 (PMID:25896806, PMID:26033257). STIM2 is required for store-operated Ca2+ entry and NFAT-dependent cytokine production in T cells (PMID:18327260), and is essential for capacitive Ca2+ entry and ischemia-induced neuronal Ca2+ accumulation, such that its loss is neuroprotective in cerebral ischemia (PMID:19843959). In neurons it stabilizes mushroom dendritic spines through a neuronal SOC–CaMKII axis that is compromised in Alzheimer's disease models (PMID:24698269, PMID:26275606), acts through an ER Ca2+-dependent complex with the microtubule plus-end protein EB3 (PMID:29247211), and controls AMPAR (GluA1) and NMDAR trafficking to regulate synaptic plasticity (PMID:25609091, PMID:27544849, PMID:37989792). STIM2 additionally scaffolds CaMKK2-AMPK to mediate calcium-dependent energy sensing (PMID:30335546).

Mechanistic history

Synthesis pass · year-by-year structured walk · 32 steps
  1. 2006 High

    Established that STIM2 is functionally and spatially distinct from STIM1, acting as an intracellular inhibitor of STIM1-mediated store-operated Ca2+ entry that physically partners with STIM1.

    Evidence Overexpression, immunofluorescence localization, reciprocal co-IP and Ca2+ entry assays across multiple cell lines

    PMID:16860747

    Open questions at the time
    • Did not resolve the threshold difference quantitatively
    • Step of inhibition downstream of puncta formation left mechanistically undefined
  2. 2007 High

    Defined STIM2's core physiological role as a feedback sensor that stabilizes basal Ca2+ by responding to smaller ER depletions than STIM1, answering why two STIM paralogs exist.

    Evidence Genome-wide siRNA screen of signaling proteome plus Ca2+ imaging and rescue assays

    PMID:18160041

    Open questions at the time
    • Molecular basis of the lower threshold not established
    • Did not address tissue-specific roles
  3. 2007 High

    Provided a biophysical basis for STIM2's distinct activation by showing its EF-SAM domain, despite similar Ca2+ affinity, is more stable and aggregation-resistant than STIM1.

    Evidence CD spectroscopy and aggregation assays on recombinant EF-SAM domains in vitro

    PMID:18166150

    Open questions at the time
    • In vitro domain behavior not directly linked to full-length cellular gating
    • Did not test C-terminal contributions
  4. 2007 High

    Demonstrated STIM2 activates CRAC channels through both store-operated and store-independent modes under calmodulin control, expanding its regulatory repertoire.

    Evidence Whole-cell patch-clamp with calmodulin inhibitors, 2-APB, and G418 pharmacology

    PMID:17905723

    Open questions at the time
    • CaM binding site not mapped
    • Physiological trigger of store-independent mode unclear
  5. 2008 High

    Established in vivo that STIM2 is required, alongside STIM1, for NFAT-dependent cytokine production and immune homeostasis in T cells.

    Evidence Conditional knockout mice with Ca2+ imaging, NFAT translocation, flow cytometry and cytokine readouts

    PMID:18327260

    Open questions at the time
    • Relative contribution at physiological agonist levels not dissected
    • Mechanism of NFAT coupling not yet resolved
  6. 2009 High

    Showed STIM2-specific control of neuronal capacitive Ca2+ entry has pathological consequences, with STIM2 loss conferring neuroprotection in ischemia.

    Evidence Stim2 knockout mice, neuronal Ca2+ imaging, hippocampal slices and in vivo focal cerebral ischemia

    PMID:19843959

    Open questions at the time
    • Downstream effectors of ischemic Ca2+ accumulation not identified
    • Channel composition mediating neuronal CCE not defined
  7. 2010 High

    Confirmed dynamic STIM1-STIM2 physical interaction during SOCE activation and their joint requirement in muscle Ca2+ handling and differentiation.

    Evidence FRET live imaging, endogenous reciprocal co-IP, siRNA and myoblast differentiation assays in human myotubes

    PMID:20436167

    Open questions at the time
    • Stoichiometry of heteromers not determined
    • Functional consequence of heteromerization on gating not quantified
  8. 2011 Medium

    Extended STIM2 localization and interaction networks to acidic Ca2+ stores and platelet contexts, linking it to Orai1, TRPC and SERCA3.

    Evidence Organelle fractionation, co-IP and Ca2+ imaging with bafilomycin A1 in human platelets

    PMID:21321120

    Open questions at the time
    • Direct vs indirect associations not distinguished
    • Single-lab subcellular fractionation
  9. 2011 Medium

    Showed STIM2/Orai1 complexes preferentially govern resting ER Ca2+ and leak in neurons, pharmacologically separable from STIM1/Orai1 SOCE.

    Evidence Subcellular fractionation, YFP-STIM overexpression, Fura-2 imaging and SOCE inhibitors in rat cortical neurons

    PMID:21541286

    Open questions at the time
    • Overexpression-based, endogenous behavior less defined
    • Basis of differential inhibitor sensitivity unexplained
  10. 2011 Medium

    Revealed a non-canonical cytosolic preSTIM2 from inefficient signal peptide cleavage that regulates basal Ca2+ and transcription store-independently.

    Evidence Signal peptide mutagenesis, fractionation, co-IP with ORAI1 and transcription reporter assays

    PMID:21383014

    Open questions at the time
    • Physiological abundance of preSTIM2 unclear
    • Mechanism of plasma-membrane targeting not fully defined
  11. 2012 Medium

    Linked STIM1/STIM2 ratio to physiological cell migration, showing STIM2 heteromers suppress STIM1 translocation and TRPC1-mediated influx.

    Evidence ODC manipulation of polyamines, STIM1/STIM2 co-IP, Ca2+ imaging and wound-healing migration assays

    PMID:22592407

    Open questions at the time
    • Direct transcriptional vs post-translational control by polyamines not separated
    • Single-system epithelial context
  12. 2012 Medium

    Demonstrated STIM2-specific control of basal Orai1-dependent Ca2+ entry gated by TRPC2 and PKCδ in thyroid cells.

    Evidence TRPC2 shRNA, PKCδ siRNA, STIM2 puncta imaging, Ca2+ imaging and Orai1 mutant expression in FRTL-5 cells

    PMID:23144458

    Open questions at the time
    • Mechanism by which TRPC2/PKCδ restrains STIM2 clustering unknown
    • Single cell type
  13. 2013 Medium

    Established that STIM2 preferentially mediates SOCE and Ca2+ oscillations under mild, physiological store depletion without engaging STIM1-dependent responses.

    Evidence siRNA, G418 inhibition and Ca2+ oscillation measurements across mast cells, T cells and HEK293; endogenous PLA/co-IP of STIM2-ORAI1 in neurons

    PMID:23359669 PMID:23711249

    Open questions at the time
    • Quantitative depletion threshold not defined
    • Single-lab studies
  14. 2014 Medium

    Distinguished STIM2 from STIM1 in regulating non-CRAC Imin and TRPC channels, showing the active STIM2/STIM1 ratio switches channel modes.

    Evidence Single-channel patch-clamp with selective STIM1/STIM2 activation in native HEK293 cells

    PMID:25533457

    Open questions at the time
    • Molecular determinants of channel selectivity not mapped
    • Single lab
  15. 2014 High

    Defined a neuronal STIM2-nSOC-CaMKII axis essential for mushroom spine stability and showed its disruption underlies spine loss in Alzheimer's models.

    Evidence PS1-M146V knockin mice, spine morphology, Ca2+ imaging, CaMKII assays and STIM2 overexpression rescue

    PMID:24698269 PMID:26275606

    Open questions at the time
    • Channel composition of synaptic nSOC not fully defined
    • Link between STIM2 downregulation and amyloid pathology causality incomplete
  16. 2015 High

    Identified STIM2.1/STIM2β splice isoform as a dominant inhibitor of SOCE acting via calmodulin and impaired/allosteric Orai1 interaction recruited through heterodimers.

    Evidence Reciprocal siRNA knockdown in T cells, Orai1 co-IP, calmodulin binding, mutagenesis and Orai1-STIM2β chimeras

    PMID:25896806 PMID:26033257

    Open questions at the time
    • Regulation of splice-isoform ratio in vivo not established
    • Structural basis of allosteric inhibition not resolved
  17. 2015 High

    Showed STIM2 promotes STIM1 clustering at ER-PM junctions at low stimulus intensity in vivo, with C-terminal residues required for recruitment and secretory function.

    Evidence Conditional STIM2 deletion in salivary glands, C-terminal deletion mutants, live STIM1 puncta imaging and NFAT assays

    PMID:25587190

    Open questions at the time
    • Exact recruitment interface not defined
    • How threshold integrates with STIM1 polybasic domain unclear
  18. 2015 Medium

    Uncovered a SOCE-independent neuronal function: STIM2 couples PKA to AMPAR GluA1, controlling its phosphorylation and surface trafficking.

    Evidence STIM2 KO neurons, biochemical PKA phosphorylation assays, live imaging and GluA1 surface trafficking assays

    PMID:25609091

    Open questions at the time
    • Direct STIM2-PKA-GluA1 binding architecture not defined
    • Single lab
  19. 2016 Medium

    Established STIM2 as required for stable LTP and LTD via control of GluA1 trafficking, connecting its synaptic role to plasticity.

    Evidence Stim2 conditional KO mice, LTP/LTD electrophysiology, spine imaging and GluA1 trafficking assays

    PMID:27544849

    Open questions at the time
    • Whether plasticity defect is SOCE-dependent not separated
    • Behavioral consequences not assessed here
  20. 2017 Medium

    Identified an ER Ca2+-dependent STIM2-EB3 complex acting downstream of STIM2 to maintain mushroom spines, placing microtubule dynamics in the pathway.

    Evidence Co-IP, interaction-motif mapping, epistasis via EB3/STIM2 overexpression and knockdown in hippocampal neurons

    PMID:29247211

    Open questions at the time
    • How EB3 enacts spine maintenance downstream not defined
    • Single lab
  21. 2018 High

    Resolved the mechanism of STIM2's threshold advantage: it is constitutive at ER-PM junctions and traps/remodels STIM1 to drive Orai1 coupling and NFAT at high ER-Ca2+.

    Evidence Conformational FRET sensors for STIM1/STIM2, interaction and functional Ca2+/NFAT assays

    PMID:29642009

    Open questions at the time
    • Trapping interface not structurally defined
    • Quantitative occupancy at junctions not measured
  22. 2018 High

    Defined the structural determinant of STIM2's distinct dynamics as cross-talk between N-terminal sensing and C-terminal flexibility, switchable by chimeras and single residues.

    Evidence CRISPR KOs, STIM1/STIM2 chimeras, E470G mutation, FRET sensors and Ca2+ imaging across HEK293/HCT116

    PMID:30444880 PMID:30824535

    Open questions at the time
    • High-resolution structure of the activating conformation not solved
    • How redox and splicing intersect with C-terminal flexibility not unified
  23. 2018 Medium

    Revealed a SOCE-independent metabolic role: STIM2 scaffolds CaMKK2-AMPK to selectively mediate calcium-induced AMPK activation.

    Evidence Co-IP, colocalization, STIM2 KO cells and AMPK phosphorylation under calcium vs energy stress

    PMID:30335546

    Open questions at the time
    • Direct binding regions not mapped
    • Physiological metabolic outputs not characterized
  24. 2020 High

    Showed STIM2 selectively couples Orai1 Ca2+ entry to NFAT1 by recruiting the channel to the AKAP79 complex through its polybasic domain, independent of bulk clustering.

    Evidence Co-IP, Ca2+ imaging, NFAT1 translocation, siRNA and polybasic domain-swap mutants

    PMID:32601188

    Open questions at the time
    • How AKAP79 selectivity is achieved over STIM1 not fully defined
    • Single lab
  25. 2020 High

    Identified Cys313 as STIM2's main redox sensor, providing a mechanism by which oxidative stress suppresses STIM2-mediated Orai1 gating.

    Evidence Redox proteomics, C313 mutagenesis, FLIM/FRET, patch-clamp and MD simulations

    PMID:33086068

    Open questions at the time
    • In vivo physiological redox triggers not defined
    • Interplay with splice isoform inhibition unexplored
  26. 2021 Medium

    Clarified STIM2's regulation of TRPC1, showing Orai-mediated Ca2+ entry initiates TRPC1 activation while subsequent STIM2 regulation is Ca2+-entry-independent.

    Evidence Single-channel patch-clamp, Orai1 KO/knockdown and dominant-negative Orai1 E106Q with STIM2 overexpression

    PMID:34157631

    Open questions at the time
    • Direct STIM2-TRPC1 interface not mapped
    • Overexpression-based, single lab
  27. 2022 High

    Established the upstream logic of basal STIM2 clustering: IP3R-driven local ER Ca2+, set by PIP2-PLC activity, immobilizes endogenous STIM2 at ER-PM junctions to recruit Orai1.

    Evidence Endogenous STIM2 gene-edited tagging, live imaging, IP3R manipulation, E-Syt2/3 KO, PLC inhibition and Orai1 recruitment assays

    PMID:35022238

    Open questions at the time
    • Molecular link between local Ca2+ and immobilization not defined
    • Generalizability beyond the studied cell type
  28. 2023 Medium

    Extended STIM2 partnerships to ORAI3 in mitosis, where the basal ORAI3-STIM2 complex restrains SOCE to permit mitotic progression in prostate cancer cells.

    Evidence Co-IP, cell-cycle synchronization, SOCE measurements and cell death assays in PC-3 cells

    PMID:37597301

    Open questions at the time
    • Mechanism of cell-cycle-dependent STIM2/STIM1 switch unclear
    • Single cell line
  29. 2023 Medium

    Showed STIM2 promotes NMDAR endocytosis after overactivation, providing a neuroprotective brake on excessive Ca2+ influx.

    Evidence Co-IP of STIM2-GluN2A/GluN2B, STIM2 silencing, NMDAR currents and surface trafficking in cortical neurons

    PMID:37989792

    Open questions at the time
    • Direct vs adaptor-mediated NMDAR interaction not resolved
    • Single lab
  30. 2024 Medium

    Connected STIM2 splice variants to mitochondrial Ca2+ homeostasis via MAM-localized complexes, with STIM2.1 abolishing mitochondrial Ca2+ uptake.

    Evidence siRNA, splice-variant overexpression, ISOC patch-clamp, super-resolution imaging, Rhod-2 imaging and MAM co-IPs in cardiomyocytes

    PMID:38537434

    Open questions at the time
    • Direct interaction partners within MAM not validated reciprocally
    • Single lab, cardiomyocyte-specific
  31. 2025 Medium

    Revealed an Orai-independent tumor-suppressive function: STIM2 loss raises ER Ca2+ via SERCA2, rewires metabolism and triggers the ATF4/BiP ER stress pathway, promoting CRC progression.

    Evidence CRISPR/shRNA loss-of-function, xenografts, SERCA2 rescue, ER Ca2+ and transcriptomic analyses

    PMID:40554601

    Open questions at the time
    • Mechanism by which STIM2 restrains SERCA2 not defined
    • Single lab
  32. 2025 Medium

    Showed that resting ER-PM contact definition by STIM2 in neurons depends on constitutive NMDAR activity, distinguishing STIM2 from transiently recruited STIM1.

    Evidence Single-particle tracking of endogenous STIM1/STIM2 with NMDAR and CaV1.2 pharmacology in hippocampal neurons

    PMID:40966085

    Open questions at the time
    • Molecular coupling between NMDAR activity and STIM2 confinement unknown
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How STIM2's various regulatory inputs — redox modification, alternative splicing, calmodulin, C-terminal flexibility, and junctional scaffolding partners — are integrated structurally to set its activation threshold and channel selectivity remains unresolved.
  • No high-resolution structure of the active STIM2 conformation or STIM2-Orai1 interface
  • Quantitative integration of splice/redox/CaM inputs not modeled
  • In vivo physiological triggers distinguishing STIM2 from STIM1 incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140299 molecular sensor activity 5 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 4 GO:0005739 mitochondrion 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-168256 Immune System 1
Partners
AKAP79AMPKCAMKK2EB3ORAI1ORAI3STIM1TRPC1
Complex memberships
AKAP79-Orai1-STIM signaling complexMAM Ca2+ complex (IP3R/VDAC/MCU/mitofusin-2)STIM1-STIM2 heteromerSTIM2-Orai1 complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 STIM2 functions as a feedback regulator that stabilizes basal cytosolic and ER Ca2+ levels by activating Ca2+ influx through Orai1 in response to smaller decreases in ER Ca2+ than those required for STIM1 activation. siRNA screen identified STIM2 as the strongest positive regulator of basal Ca2+ concentration. siRNA screen of human signaling proteome, Ca2+ imaging, functional rescue assays Cell High 18160041
2006 STIM2 acts as an inhibitor of STIM1-mediated store-operated Ca2+ entry (SOC). STIM2 is expressed only intracellularly (not at plasma membrane unlike STIM1), translocates into puncta upon store depletion only when coexpressed with STIM1, co-localizes with STIM1 in puncta, and physically interacts with STIM1 by co-immunoprecipitation. STIM2 inhibits SOCE at a step downstream of puncta formation. Overexpression in HEK293/PC12/A7r5/Jurkat cells, subcellular localization by immunofluorescence, co-immunoprecipitation, functional Ca2+ entry assays Current biology : CB High 16860747
2007 Biophysical characterization of STIM2 EF-SAM domain reveals a Ca2+-binding affinity (Kd ~0.5 mM) similar to STIM1, but apo-STIM2 EF-SAM is more structurally stable and does not readily aggregate compared to apo-STIM1 EF-SAM, which may account for STIM2's distinct functional properties and lower activation threshold. CD spectroscopy, biophysical characterization of recombinant EF-SAM domain in vitro Biochemical and biophysical research communications High 18166150
2007 STIM2 activates CRAC channels via two distinct modes: a store-operated mode triggered by ER Ca2+ depletion via IP3, and a store-independent mode activated by cell dialysis during whole-cell patch-clamp. Both modes are regulated by calmodulin (CaM); CaM inhibition can be reversed by 2-APB. The aminoglycoside antibiotic G418 specifically and potently inhibits STIM2-dependent CRAC channel activation. Whole-cell patch-clamp, Ca2+ imaging, pharmacological manipulation with calmodulin inhibitors and 2-APB, G418 treatment FASEB journal High 17905723
2008 STIM2 deficiency in mouse T cells and fibroblasts results in a smaller impairment of store-operated Ca2+ influx compared to STIM1 deficiency, but both STIM1 and STIM2 are required for cytokine production and nuclear translocation of NFAT. T cell-specific deletion of both STIM1 and STIM2 causes lymphoproliferative phenotype and reduced regulatory T cell numbers. Conditional knockout mice, Ca2+ imaging, NFAT nuclear translocation assays, flow cytometry, cytokine measurement Nature immunology High 18327260
2009 STIM2, but not STIM1, is essential for capacitive Ca2+ entry (CCE) and ischemia-induced cytosolic Ca2+ accumulation in neurons. Neurons from Stim2-/- mice showed increased survival under hypoxic conditions in culture and in acute hippocampal slices, and Stim2-/- mice were protected from neurological damage in focal cerebral ischemia in vivo. Stim2 knockout mice, Ca2+ imaging in neurons, hippocampal slice preparations, focal cerebral ischemia model in vivo Science signaling High 19843959
2010 STIM1 and STIM2 interact physically (FRET between CFP-STIM1 and YFP-STIM2 increases upon SOCE activation; confirmed by co-immunoprecipitation of endogenous proteins), both contribute to SOCE and myoblast differentiation, and both are required for ER Ca2+ refilling during excitation-contraction coupling in human myotubes. The two proteins co-localize into clusters during SOCE activation. FRET live cell imaging, co-immunoprecipitation of endogenous proteins, siRNA silencing, Ca2+ imaging, myoblast differentiation assays The Journal of biological chemistry High 20436167
2011 STIM1 and STIM2 are localized in acidic Ca2+ stores (lysosome-related organelles and dense granules) in human platelets. Depletion of acidic Ca2+ stores enhances STIM1-STIM2 association, association of both with Orai1, co-immunoprecipitation of STIM1 with hTRPC1 and hTRPC6, and association of Orai1 with TRPC proteins. Depletion also enhances STIM2-SERCA3 association. Immunomagnetic sorting of organelle fractions, co-immunoprecipitation, Ca2+ imaging with bafilomycin A1 (vacuolar H+-ATPase inhibitor) The Journal of biological chemistry Medium 21321120
2011 In rat cortical neurons, thapsigargin-induced ER store depletion redistributes endogenous STIM1 and STIM2 to membrane fractions and increases STIM1/ORAI1 and STIM2/ORAI1 complexes. STIM1/ORAI1 mainly activates SOCE, whereas STIM2/ORAI1 regulates resting ER Ca2+ levels and Ca2+ leakage; SOCE inhibitors ML-9 and 2-APB affect STIM1/ORAI1 but not STIM2/ORAI1. Subcellular fractionation, YFP-STIM overexpression, Ca2+ imaging with Fura-2, pharmacological inhibitors PloS one Medium 21541286
2011 A cytosolic preSTIM2 protein is produced by inefficient signal peptide cleavage. This preSTIM2 localizes to the inner leaflet of the plasma membrane where it interacts with ORAI1 to regulate basal Ca2+ concentration and Ca2+-dependent gene transcription in a store-independent manner. A third peptide fragment from the STIM2 signal peptide is released into cytosol and regulates gene transcription in a Ca2+-independent manner. Signal peptide mutagenesis, subcellular fractionation, co-immunoprecipitation with ORAI1, Ca2+ imaging, transcription reporter assays The Journal of biological chemistry Medium 21383014
2012 Polyamines regulate intestinal epithelial restitution by altering the STIM1/STIM2 ratio. Increased polyamines stimulate STIM1 but inhibit STIM2 expression, while polyamine depletion decreases STIM1 and increases STIM2. Induced STIM1/STIM2 heteromers (by polyamine depletion or STIM2 overexpression) suppress STIM1 membrane translocation, reduce TRPC1-mediated Ca2+ influx, and inhibit cell migration. ODC overexpression, ODC inhibitor treatment, co-immunoprecipitation of STIM1/STIM2 complexes, Ca2+ imaging, cell migration wound-healing assay American journal of physiology. Cell physiology Medium 22592407
2013 Endogenous STIM2 forms a calcium-sensitive, thapsigargin-insensitive complex with ORAI1 in cortical neurons. The number of STIM2-ORAI1 complexes increases when intracellular Ca2+ is decreased by BAPTA-AM or low-calcium medium but does not increase with thapsigargin. This indicates that small drops in ER Ca2+ (triggered by decreased intracellular Ca2+) are sufficient to initiate STIM2-ORAI1 complex formation in neurons. Co-immunoprecipitation, Proximity Ligation Assay (PLA), Ca2+ imaging with Fura-2 Journal of neurochemistry Medium 23711249
2013 STIM2 drives Ca2+ oscillations in mast cells, T cells, and HEK293 cells by mediating store-operated Ca2+ entry at low levels of store depletion (mild ER Ca2+ reduction). siRNA silencing of STIM2 or inhibition by G418 suppresses SOCE and Ca2+ oscillations at low agonist concentrations without interfering with STIM1-mediated signals at full store depletion, indicating STIM2 is preferentially activated by physiological low-level stimulation. siRNA silencing, G418 pharmacological inhibition, Ca2+ oscillation measurements in multiple cell types The Journal of physiology Medium 23359669
2014 STIM2-mediated neuronal store-operated Ca2+ influx (nSOC) is required for stabilization of mushroom dendritic spines in hippocampal neurons through continuous activation of CaMKII. The STIM2-nSOC-CaMKII pathway is compromised in PS1-M146V knockin AD neurons, aging neurons, and sporadic AD brains due to STIM2 downregulation. STIM2 overexpression rescues synaptic nSOC, CaMKII activity, and mushroom spine loss. PS1 knockin mouse model, spine morphology analysis, Ca2+ imaging, CaMKII activity assay, STIM2 overexpression rescue Neuron High 24698269
2014 STIM2 in native HEK293 cells specifically regulates endogenous non-CRAC Imin channels (a store-operated channel distinct from CRAC), whereas STIM1 blocks Imin channel activation. Changes in the ratio of active STIM2 to STIM1 can switch Imin channel regulation between store-operated and store-independent modes. STIM1 and STIM2 also differ in regulation of other channels: TRPC3-containing INS channels are induced by STIM1, and TRPC1-composed Imax channels are activated by both. Single-channel patch-clamp recordings, STIM1/STIM2 selective activation, overexpression studies The Journal of biological chemistry Medium 25533457
2015 STIM2.1, an alternatively spliced isoform retaining an additional exon in the channel-activating domain region, is an inhibitor of SOCE. STIM2.1 shows impaired interaction with Orai1 and prevents Orai1 activation, but shows increased affinity towards calmodulin compared to STIM2.2. Knockdown of STIM2.1 increases SOCE in naive CD4+ T cells while STIM2.2 knockdown decreases SOCE. siRNA knockdown in naive T cells, Orai1 co-immunoprecipitation, calmodulin binding assays, Ca2+ imaging Nature communications High 25896806
2015 STIM2β (equivalent to STIM2.1), a conserved alternatively spliced isoform of STIM2, is a potent inhibitor of SOCE. Although STIM2β does not strongly bind Orai1 by itself, it is recruited to Orai1 channels by forming heterodimers with other STIM isoforms. Mutational analysis and Orai1-STIM2β chimeras indicate it inhibits SOCE through a sequence-specific allosteric interaction with Orai1. Overexpression and mutagenesis, heterodimer formation assay, Orai1-STIM2β chimeric constructs, Ca2+ entry measurements The Journal of cell biology High 26033257
2015 STIM2 enhances agonist-mediated SOCE by promoting STIM1 clustering at ER-PM junctions at low stimulus intensities. STIM2 lacking five C-terminal amino acids failed to promote STIM1 puncta formation at low agonist concentrations. Coexpression of STIM2 with STIM1ΔK (lacking polybasic region) resulted in co-clustering, suggesting STIM2 recruits STIM1 to ER-PM junctions when ER Ca2+ stores are mildly depleted. STIM2 knockout in mouse salivary glands diminished fluid secretion and SOCE in acinar cells stimulated with low muscarinic agonist concentrations. Conditional STIM2 deletion in salivary glands, C-terminal deletion mutants of STIM2, live cell imaging of STIM1 puncta, Ca2+ imaging, NFAT nuclear translocation assay Science signaling High 25587190
2015 STIM2 regulates PKA-dependent phosphorylation of the AMPA receptor subunit GluA1 and controls GluA1 surface delivery (both exocytosis and endocytosis). cAMP triggers rapid migration of STIM2 to ER-PM contact sites and promotes GluA1 recruitment to these junctions and STIM2 localization in dendritic spines. STIM2 regulates GluA1 phosphorylation by coupling PKA to AMPARs in a SOCE-independent manner. Biochemical assays, live-cell imaging, STIM2 KO neurons, PKA phosphorylation assays, surface GluA1 trafficking assays Molecular biology of the cell Medium 25609091
2015 Expression of STIM2 protects hippocampal mushroom spines from Aβ42 oligomer-induced toxicity by rescuing CaMKII activity. Aβ42 oligomer application (in vitro and in vivo by hippocampal injection) reduces mushroom spines and synaptic CaMKII activity; STIM2 overexpression rescues both. In vitro hippocampal cultures with Aβ42 oligomers, in vivo Aβ42 injection into hippocampus, dendritic spine morphology analysis, CaMKII activity measurement, STIM2 overexpression Molecular neurodegeneration Medium 26275606
2016 STIM2 is required for stable expression of both LTP and LTD at CA3-CA1 hippocampal synapses. Stim2 cKO mice showed altered dendritic spine density/shape in CA1, reduced surface delivery of GluA1 in response to LTP-inducing stimuli, and impaired GluA1 endocytosis following chemically-induced LTD. Stim2 conditional KO mice, electrophysiology (LTP and LTD induction), dendritic spine imaging, GluA1 surface trafficking assays Neurobiology of learning and memory Medium 27544849
2017 STIM2 forms an ER Ca2+-dependent complex with microtubule plus-end binding protein EB3 via a Ser-x-Ile-Pro amino acid motif. Disruption of STIM2-EB3 interaction results in loss of mushroom spines in hippocampal neurons. EB3 overexpression rescues mushroom spine deficiency in PS1-M146V-KI AD neurons and rescues spine loss caused by STIM2 depletion, whereas STIM2 overexpression cannot rescue spines after EB3 knockdown. Co-immunoprecipitation, STIM2-EB3 interaction domain mapping, EB3 and STIM2 overexpression/knockdown, dendritic spine morphology in hippocampal neurons Scientific reports Medium 29247211
2018 STIM2 is constitutively localized within ER-PM junctions in Ca2+-replete cells and induces the activated conformation of STIM1 by trapping STIM1 and triggering remodeling of STIM1 C-terminus, causing STIM1/Orai1 coupling in cells with relatively high ER-[Ca2+]. This enhancement of Orai1 function controls NFAT activation at low agonist concentrations. Conformational FRET sensors for STIM1 and STIM2, protein interaction studies, functional Ca2+ entry and NFAT activation assays Cell reports High 29642009
2018 STIM2 interacts directly with AMPK and CaMKK2. Increased intracellular calcium promotes colocalization and interaction of AMPK with STIM2. STIM2 deficiency attenuates calcium-induced but not energy stress-induced AMPK activation, acting as a scaffold for CaMKK2-AMPK signaling. Co-immunoprecipitation, co-localization microscopy, STIM2 knockout cells, AMPK phosphorylation assays with calcium vs. energy stress stimuli FASEB journal Medium 30335546
2018 Cross-talk between N-terminal Ca2+-sensing and C-terminal flexibility of STIM2 determines its distinct activation dynamics. The increased flexibility of the STIM2 C-terminus (compared to STIM1) contributes to its selective store-independent activation by 2-APB. STIM1/STIM2 chimeric constructs and the E470G mutation in STIM1 (equivalent to a STIM2 residue) can switch STIM2 from slow/weak to fast/potent Orai channel activator, and vice versa. CRISPR/Cas9 knockouts, STIM1/STIM2 chimeric constructs, point mutagenesis, FRET-based activity sensors, Ca2+ imaging PLoS biology High 30444880
2019 Cross-talk between N-terminal and C-terminal domains of STIM2 determines its enhanced sensitivity compared to STIM1. The increased flexibility of the STIM2 C-terminus contributes to store-independent activation by 2-APB, but coordination of N-terminal sensitivity with C-terminal flexibility is required for specific STIM2 store-independent activation. STIM1 variants with enhanced C-terminal flexibility alone were insufficient to support store-independent activation. CRISPR/Cas9 STIM1-/-, STIM2-/-, and STIM1/2-/- knockouts in HEK293 and HCT116 cells, STIM1/STIM2 chimeras, C-terminal stabilizing/disrupting variants, Ca2+ imaging The Journal of biological chemistry High 30824535
2020 STIM2 recruits Orai1/STIM1 to the AKAP79 signaling complex at ER-PM junctions, coupling Orai1 Ca2+ entry to NFAT1 activation. STIM2 knockdown had little effect on Orai1/STIM1 clustering or global Ca2+ increases but significantly attenuated NFAT1 activation and AKAP79-Orai1 assembly. The polybasic domain of STIM2 (replacing that of STIM1ΔK) eliminated the requirement of STIM2 for NFAT1 activation. Co-immunoprecipitation, Ca2+ imaging, NFAT1 nuclear translocation assay, siRNA knockdown, domain-swap mutants (STIM1ΔK, polybasic domain chimeras) Proceedings of the National Academy of Sciences of the United States of America High 32601188
2020 Oxidative stress modifies STIM2 at cysteine 313, the main redox sensor of STIM2. Oxidative modifications of C313 alter STIM2 activation dynamics and hinder STIM2-mediated gating of ORAI1, suppressing SOCE. Mutation of C313 abolishes the oxidative suppression of SOCE. MD simulations indicate C313 oxidation affects the STIM2 activation conformation. Redox proteomics (in vitro and in vivo), C313 mutagenesis, FLIM/FRET microscopy, patch-clamp, molecular dynamics simulations Cell reports High 33086068
2021 STIM2 regulates TRPC1 channel activity at partial store depletion conditions. STIM2 overexpression increases both basal TRPC1 activity and number of silent TRPC1 channels at the plasma membrane. After store depletion, STIM2 directly activates TRPC1 even without calcium entry; however, this effect is abrogated by co-expression with non-permeable Orai1 E106Q mutant, indicating Ca2+ entry through Orai triggers TRPC1 activation, while subsequent STIM2-mediated regulation is independent of Ca2+ entry. Single-channel patch-clamp recordings, Orai1 knockout/knockdown, dominant-negative Orai1 E106Q, STIM2 overexpression Cell calcium Medium 34157631
2022 IP3R function and local ER Ca2+ are the main drivers of immobile STIM2 cluster formation at ER-PM junctions under basal conditions. Endogenous STIM2 is constitutively present in mobile and immobile clusters; immobile clusters associate with ER-PM junctions and recruit Orai1 under basal conditions. ER-PM junction formation (via E-Syt2/3) is required but not sufficient for STIM2 clustering. Ambient PIP2-PLC activity determines IP3R function, STIM2 immobilization, and basal Ca2+ entry. Endogenous STIM2 fluorescent tagging via gene editing, live cell imaging, IP3R functional manipulation, E-Syt2/3 knockout, PLC inhibition, Orai1 recruitment assays Proceedings of the National Academy of Sciences of the United States of America High 35022238
2024 In cardiomyocytes (NRVMs), STIM2 splice variants differentially regulate SOCE: STIM2.1 suppresses Orai1-mediated SOCE while STIM2.2 enhances SOCE also involving TRPC1 and TRPC4. STIM2 is present in mitochondria-associated ER membranes (MAMs) and interacts with IP3Rs, VDAC, MCU, and mitofusin-2. STIM2.1 overexpression abolishes mitochondrial Ca2+ uptake, linking STIM2 to mitochondrial Ca2+ homeostasis. siRNA knockdown, overexpression of splice variants, SOCE patch-clamp (ISOC), super-resolution confocal microscopy, Rhod-2 mitochondrial Ca2+ imaging, co-immunoprecipitation of MAM complexes Cell calcium Medium 38537434
2023 STIM2 regulates NMDA receptor endocytosis in cortical neurons. Short-term NMDAR overactivation increased STIM2-GluN2A and STIM2-GluN2B interactions. STIM2 silencing inhibited post-activation NMDAR translocation from the plasma membrane and synaptic spines and increased NMDAR currents, suggesting STIM2 promotes NMDAR endocytosis after overactivation to protect against excessive Ca2+ influx. Co-immunoprecipitation, STIM2 siRNA silencing, NMDAR current measurements, NMDAR surface trafficking assays, immunofluorescence in primary cortical neurons Cellular and molecular life sciences : CMLS Medium 37989792
2023 ORAI3 and STIM2 interact under basal conditions in PC-3 prostate cancer cells. STIM2 expression increases during M phase while STIM1 expression and SOCE amplitude decrease. The ORAI3-STIM2 complex allows successful progression through mitosis by preventing mitotic catastrophe; ORAI3 silencing increased SOCE and induced mitotic arrest-related death. Co-immunoprecipitation of ORAI3-STIM2, cell cycle synchronization, SOCE measurements, cell death assays Cell calcium Medium 37597301
2025 STIM2 loss in colorectal cancer cells causes SERCA2-dependent increase in ER Ca2+ content, transcriptional and metabolic rewiring, and activates the ATF4/BiP ER stress response pathway independently of Orai channels. STIM2-deficient CRC xenografts showed increased tumor size, invasion, and metastasis. CRISPR/shRNA STIM2 loss-of-function, xenograft tumor models, SERCA2 rescue experiments, ER Ca2+ measurements, transcriptomic analysis, Orai-independent ER stress pathway assessment Science signaling Medium 40554601
2025 In hippocampal neurons, a substantial fraction of STIM2 (but not STIM1) defines ER-PM contacts under resting conditions and is dependent on constitutive NMDAR activity. STIM1 is only transiently recruited to ER-PM junctions during strong NMDAR activation. STIM2 clusters are not enriched at KV2.1-organized junctions, and their activity-dependent confinement is independent of CaV1.2 activity. Single-particle tracking of endogenous STIM1 and STIM2, pharmacological NMDAR and CaV1.2 manipulation, live cell imaging in hippocampal neurons Cell reports Medium 40966085
2012 STIM2, but not STIM1, is required for TRPC2-independent regulation of basal Ca2+ entry in rat thyroid FRTL-5 cells. Knockdown of TRPC2 causes STIM2 to arrange into puncta in resting cells (not seen in controls) and enhances basal Ca2+ entry. PKCδ knockdown mimics TRPC2 loss by increasing STIM2 punctum formation. Basal Ca2+ entry in TRPC2-knockdown cells is dependent on Orai1. shRNA knockdown of TRPC2, siRNA knockdown of PKCδ, immunofluorescence (STIM2 puncta), Ca2+ imaging, Orai1 mutant expression The Journal of biological chemistry Medium 23144458

Source papers

Stage 0 corpus · 92 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels. Cell 593 18160041
2008 Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T cell activation and tolerance. Nature immunology 501 18327260
2014 Reduced synaptic STIM2 expression and impaired store-operated calcium entry cause destabilization of mature spines in mutant presenilin mice. Neuron 234 24698269
2009 STIM2 regulates capacitive Ca2+ entry in neurons and plays a key role in hypoxic neuronal cell death. Science signaling 229 19843959
2011 The calcium sensors STIM1 and STIM2 control B cell regulatory function through interleukin-10 production. Immunity 221 21530328
2006 STIM2 is an inhibitor of STIM1-mediated store-operated Ca2+ Entry. Current biology : CB 210 16860747
2007 Biophysical characterization of the EF-hand and SAM domain containing Ca2+ sensory region of STIM1 and STIM2. Biochemical and biophysical research communications 135 18166150
2007 STIM2 protein mediates distinct store-dependent and store-independent modes of CRAC channel activation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 134 17905723
2011 Differential roles for STIM1 and STIM2 in store-operated calcium entry in rat neurons. PloS one 120 21541286
2015 A STIM2 splice variant negatively regulates store-operated calcium entry. Nature communications 108 25896806
2010 T-cell-specific deletion of STIM1 and STIM2 protects mice from EAE by impairing the effector functions of Th1 and Th17 cells. European journal of immunology 106 21061435
2015 Upregulated expression of STIM2, TRPC6, and Orai2 contributes to the transition of pulmonary arterial smooth muscle cells from a contractile to proliferative phenotype. American journal of physiology. Cell physiology 104 25673771
2014 A reciprocal shift in transient receptor potential channel 1 (TRPC1) and stromal interaction molecule 2 (STIM2) contributes to Ca2+ remodeling and cancer hallmarks in colorectal carcinoma cells. The Journal of biological chemistry 101 25143380
2015 Alternative splicing converts STIM2 from an activator to an inhibitor of store-operated calcium channels. The Journal of cell biology 96 26033257
2013 STIM1 and STIM2-mediated Ca(2+) influx regulates antitumour immunity by CD8(+) T cells. EMBO molecular medicine 93 23922331
2011 Evolutionary origins of STIM1 and STIM2 within ancient Ca2+ signaling systems. Trends in cell biology 88 21288721
2014 Inverse regulation of melanoma growth and migration by Orai1/STIM2-dependent calcium entry. Pigment cell & melanoma research 87 24472175
2015 STIM2 enhances receptor-stimulated Ca²⁺ signaling by promoting recruitment of STIM1 to the endoplasmic reticulum-plasma membrane junctions. Science signaling 86 25587190
2014 STIM1, STIM2, and Orai1 regulate store-operated calcium entry and purinergic activation of microglia. Glia 76 25471906
2011 STIM2 Contributes to Enhanced Store-operated Ca Entry in Pulmonary Artery Smooth Muscle Cells from Patients with Idiopathic Pulmonary Arterial Hypertension. Pulmonary circulation 76 21709766
2011 STIM1 and STIM2 are located in the acidic Ca2+ stores and associates with Orai1 upon depletion of the acidic stores in human platelets. The Journal of biological chemistry 73 21321120
2018 STIM2 Induces Activated Conformation of STIM1 to Control Orai1 Function in ER-PM Junctions. Cell reports 68 29642009
2010 Human muscle economy myoblast differentiation and excitation-contraction coupling use the same molecular partners, STIM1 and STIM2. The Journal of biological chemistry 67 20436167
2015 STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity. Molecular neurodegeneration 66 26275606
2017 Role of STIM2 in cell function and physiopathology. The Journal of physiology 62 28087881
2012 Polyamines regulate intestinal epithelial restitution through TRPC1-mediated Ca²+ signaling by differentially modulating STIM1 and STIM2. American journal of physiology. Cell physiology 62 22592407
2017 STIM1 and STIM2 cooperatively regulate mouse neutrophil store-operated calcium entry and cytokine production. Blood 60 28724541
2015 Downregulation of STIM2 improves neuronal survival after traumatic brain injury by alleviating calcium overload and mitochondrial dysfunction. Biochimica et biophysica acta 59 26300487
2015 STIM2 regulates PKA-dependent phosphorylation and trafficking of AMPARs. Molecular biology of the cell 55 25609091
2018 STIM2 (Stromal Interaction Molecule 2)-Mediated Increase in Resting Cytosolic Free Ca2+ Concentration Stimulates PASMC Proliferation in Pulmonary Arterial Hypertension. Hypertension (Dallas, Tex. : 1979) 54 29358461
2014 CD4⁺ and CD8⁺ T cell-dependent antiviral immunity requires STIM1 and STIM2. The Journal of clinical investigation 54 25157823
2013 STIM2 drives Ca2+ oscillations through store-operated Ca2+ entry caused by mild store depletion. The Journal of physiology 54 23359669
2012 STIM1 and STIM2 protein deficiency in T lymphocytes underlies development of the exocrine gland autoimmune disease, Sjogren's syndrome. Proceedings of the National Academy of Sciences of the United States of America 54 22904194
2011 Stromal interaction molecule 2 (STIM2) is frequently overexpressed in colorectal tumors and confers a tumor cell growth suppressor phenotype. Molecular carcinogenesis 54 22125164
2013 Native STIM2 and ORAI1 proteins form a calcium-sensitive and thapsigargin-insensitive complex in cortical neurons. Journal of neurochemistry 53 23711249
2010 Differential roles of STIM1, STIM2 and Orai1 in the control of cell proliferation and SOCE amplitude in HEK293 cells. Cell calcium 50 20172609
2018 STIM2 interacts with AMPK and regulates calcium-induced AMPK activation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 48 30335546
2017 Stim2-Eb3 Association and Morphology of Dendritic Spines in Hippocampal Neurons. Scientific reports 46 29247211
2009 STIM1 but not STIM2 is an essential regulator of Ca2+ influx-mediated NADPH oxidase activity in neutrophil-like HL-60 cells. Biochemical pharmacology 43 19433064
2017 STIM1 and STIM2 differently regulate endogenous Ca2+ entry and promote TGF-β-induced EMT in breast cancer cells. Biochemical and biophysical research communications 40 28479254
2020 STIM2 targets Orai1/STIM1 to the AKAP79 signaling complex and confers coupling of Ca2+ entry with NFAT1 activation. Proceedings of the National Academy of Sciences of the United States of America 38 32601188
2019 Cross-talk between N-terminal and C-terminal domains in stromal interaction molecule 2 (STIM2) determines enhanced STIM2 sensitivity. The Journal of biological chemistry 38 30824535
2022 Functional communication between IP3R and STIM2 at subthreshold stimuli is a critical checkpoint for initiation of SOCE. Proceedings of the National Academy of Sciences of the United States of America 33 35022238
2020 Oxidative Stress-Induced STIM2 Cysteine Modifications Suppress Store-Operated Calcium Entry. Cell reports 33 33086068
2018 Identification of molecular determinants that govern distinct STIM2 activation dynamics. PLoS biology 32 30444880
2016 STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses. Neurobiology of learning and memory 32 27544849
2013 Calcium signaling in B cells: regulation of cytosolic Ca2+ increase and its sensor molecules, STIM1 and STIM2. Molecular immunology 32 24246800
2021 STIM2 Mediates Excessive Store-Operated Calcium Entry in Patient-Specific iPSC-Derived Neurons Modeling a Juvenile Form of Huntington's Disease. Frontiers in cell and developmental biology 31 33604336
2014 STIM1 and STIM2 proteins differently regulate endogenous store-operated channels in HEK293 cells. The Journal of biological chemistry 31 25533457
2020 Mossy cell synaptic dysfunction causes memory imprecision via miR-128 inhibition of STIM2 in Alzheimer's disease mouse model. Aging cell 29 32222058
2011 A cytosolic STIM2 preprotein created by signal peptide inefficiency activates ORAI1 in a store-independent manner. The Journal of biological chemistry 29 21383014
2018 The distinct role of STIM1 and STIM2 in the regulation of store-operated Ca2+ entry and cellular function. Journal of cellular physiology 26 30317585
2015 Cooperative and alternate functions for STIM1 and STIM2 in macrophage activation and in the context of inflammation. Immunity, inflammation and disease 26 26417434
2019 STIM2 knockdown protects against ischemia/reperfusion injury through reducing mitochondrial calcium overload and preserving mitochondrial function. Life sciences 25 31200000
2018 STIM1 and STIM2 Mediate Cancer-Induced Inflammation in T Cell Acute Lymphoblastic Leukemia. Cell reports 25 30208327
2020 Functional role of TRPC6 and STIM2 in cytosolic and endoplasmic reticulum Ca2+ content in resting estrogen receptor-positive breast cancer cells. The Biochemical journal 20 32794568
2018 Interplay between ER Ca2+ Binding Proteins, STIM1 and STIM2, Is Required for Store-Operated Ca2+ Entry. International journal of molecular sciences 17 29783744
2022 Kinetics of early and late molecular recurrences after first-line imatinib cessation in chronic myeloid leukemia: updated results from the STIM2 trial. Haematologica 16 35615931
2020 PGRMC1 Inhibits Progesterone-Evoked Proliferation and Ca2+ Entry Via STIM2 in MDA-MB-231 Cells. International journal of molecular sciences 16 33076541
2019 Pivotal role of STIM2, but not STIM1, in IL-4 production by IL-3-stimulated murine basophils. Science signaling 15 30967512
2016 Inhibition of store-operated calcium entry by sub-lethal levels of proteasome inhibition is associated with STIM1/STIM2 degradation. Cell calcium 15 26960935
2012 Canonical transient receptor potential channel 2 (TRPC2) as a major regulator of calcium homeostasis in rat thyroid FRTL-5 cells: importance of protein kinase C δ (PKCδ) and stromal interaction molecule 2 (STIM2). The Journal of biological chemistry 15 23144458
2021 Role of STIM2 and Orai proteins in regulating TRPC1 channel activity upon calcium store depletion. Cell calcium 14 34157631
2010 STIM1, but not STIM2, is required for proper agonist-induced Ca2+ signaling. Cell calcium 14 20801505
2023 Pivotal role of the ORAI3-STIM2 complex in the control of mitotic death and prostate cancer cell cycle progression. Cell calcium 11 37597301
2018 STIM1 Knockout Enhances PDGF-Mediated Ca2+ Signaling through Upregulation of the PDGFR⁻PLCγ⁻STIM2 Cascade. International journal of molecular sciences 11 29912163
2025 Loss of STIM1 and STIM2 in Salivary Glands Disrupts ANO1 Function but Does Not Induce Sjogren's Disease. Function (Oxford, England) 9 39479800
2025 Loss of STIM2, but not of STIM1, drives colorectal cancer metastasis through metabolic reprogramming and the ATF4 ER stress pathway. Science signaling 9 40554601
2022 STIM2 promotes the invasion and metastasis of breast cancer cells through the NFAT1/TGF-β1 pathway. Cellular and molecular biology (Noisy-le-Grand, France) 9 35818214
2024 STIM2 variants regulate Orai1/TRPC1/TRPC4-mediated store-operated Ca2+ entry and mitochondrial Ca2+ homeostasis in cardiomyocytes. Cell calcium 7 38537434
2023 Loss of STIM2 in colorectal cancer drives growth and metastasis through metabolic reprogramming and PERK-ATF4 endoplasmic reticulum stress pathway. bioRxiv : the preprint server for biology 7 37873177
2023 STIM2 regulates NMDA receptor endocytosis that is induced by short-term NMDA receptor overactivation in cortical neurons. Cellular and molecular life sciences : CMLS 6 37989792
2021 A Novel Modulator of STIM2-Dependent Store-Operated Ca2+ Channel Activity. Acta naturae 6 33959394
2025 Activity-dependent localization and dynamics of STIM1 and STIM2 at ER-PM contacts in hippocampal neurons. Cell reports 5 40966085
2022 Modification of STIM2 by m6A RNA methylation inhibits metastasis of cholangiocarcinoma. Annals of translational medicine 5 35282134
2022 [Resveratrol pretreatment improves mitochondrial function and alleviates myocardial ischemia-reperfusion injury by up-regulating mi R-20b-5p to inhibit STIM2]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 5 36164909
2023 Lack of Stim2 Affects Vision-Dependent Behavior and Sensitivity to Hypoxia. Zebrafish 4 37590563
2020 STIM2: Redox-sensor and effector of the (tumor) microenvironment. Cell calcium 4 33387846
2024 STIM2 is involved in the regulation of apoptosis and the cell cycle in normal and malignant monocytic cells. Molecular oncology 3 38234211
2024 Loss of Stim2 in zebrafish induces glaucoma-like phenotype. Scientific reports 3 39424970
2016 Deficient for endoplasmic reticulum calcium sensors Stim1 and Stim2 affects aberrant antibody affinity maturation in B cells. Oncotarget 3 27572320
2014 Differential role of STIM1 and STIM2 during transient inward (T in) current generation and the maturation process in the Xenopus oocyte. BMC physiology 3 25399338
2023 STIM2 Suppression Blocks Glial Activation to Alleviate Brain Ischemia Reperfusion Injury via Inhibition of Inflammation and Pyroptosis. Molecular biotechnology 2 37572222
2025 Role of store-operated Ca2+ entry and STIM2 in retinal neurodegeneration during glaucoma. Frontiers in aging neuroscience 1 41079995
2024 Loss of STIM1 and STIM2 in salivary glands disrupts ANO1 function but does not induce Sjogren's disease. bioRxiv : the preprint server for biology 1 38260625
2022 "Functional communication between IP3R and STIM2 at subthreshold stimuli is a critical checkpoint for initiation of SOCE". Cell calcium 1 35395520
2021 STIM1, STIM2, and PDI Participate in Cellular Fate Decisions in Low Energy Availability Induced by 3-NP in Male Rats. Neurotoxicity research 1 34173958
2026 Alternatively spliced STIM2.3 is an evolutionarily late store-operated Ca2+ entry regulator expressed in brain. Journal of cell science 0 41766388
2025 Modelling the role of STIM1 and STIM2 in oscillations in T-lymphocytes. Bulletin of mathematical biology 0 41335264
2025 Store-operated Ca2+ entry mediated by STIM1 and STIM2 regulates salivary secretion and KCa channels in salivary gland. Biochemical and biophysical research communications 0 41344216
2022 Erratum to modification of STIM2 by m6A RNA methylation inhibits metastasis of cholangiocarcinoma. Annals of translational medicine 0 36111026
2014 [Roles of STIM2 and TRPC3 in the CaR mediated Ca2+ entry and NO generation in human umbilical vein endothelial cells]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 0 25330669

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