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Showing ATP2A2 — SERCA2 is a alias.

ATP2A2

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 · UniProt P16615

Length
1042 aa
Mass
114.8 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP2A2 encodes SERCA2, a sarco/endoplasmic reticulum P-type Ca2+-ATPase that pumps cytosolic Ca2+ into the ER/SR lumen through an E1/E2 transport cycle, thereby controlling intracellular Ca2+ homeostasis across keratinocytes, cardiomyocytes, neurons, β-cells, and endothelium (PMID:12975374, PMID:11387203). The pump exists as kinetically distinct SERCA2a and SERCA2b isoforms; rapid-kinetic analysis defined the partial reactions of the catalytic cycle and showed that Darier disease mutations uncouple Ca2+ translocation from ATP hydrolysis or block specific phosphoenzyme transitions (PMID:12975374). SERCA2 activity is tuned by a network of direct protein partners and post-translational modifications: phospholamban acts as a reversible inhibitor whose phosphorylation relieves suppression to accelerate cardiac relaxation (PMID:9202840), PDE3A binds the actuator domain to constrain a local cAMP pool (PMID:25593322, PMID:36876489), AKAP18δ anchors CaMKIIδ at the SERCA2-PLN complex to bidirectionally control Ca2+ reuptake (PMID:34814703), JNK2 phosphorylates and activates the pump (PMID:33334123), luminal calumenin inhibits it in the E1 state (PMID:19740751), HAX-1 controls its protein level (PMID:18971376), and MFN2 tethers it to mitochondria to govern mitochondrial Ca2+ supply (PMID:37738362). The pump is further regulated by redox and covalent modifications—activating S-glutathiolation of Cys-674 (PMID:22472004) versus inhibitory serotonylation (PMID:32116663), Ser-663 phosphorylation (PMID:37291092), O-GlcNAcylation (PMID:32375037), and K460/K541 ubiquitination driving Sigmar1/Hrd1-Sel1L-dependent ERAD (PMID:35611810)—and at the transcriptional level by PPAR-γ, TFAM/TFB2M, ERK/NF-κB repression, and a thyroid hormone receptor/FOG-2 axis (PMID:22240811, PMID:21113058, PMID:25008120, PMID:18658259). Loss-of-function mutations in ATP2A2 cause Darier disease, in which mutant SERCA2 aggregation and ER stress, ERK/MAPK hyperactivation, and disrupted sphingolipid signaling impair desmosome/adherens junction assembly and keratinocyte adhesion (PMID:10080178, PMID:24390139, PMID:37561594). SERCA2 haploinsufficiency separately predisposes to squamous cell tumors without loss of heterozygosity and produces neuropsychiatric phenotypes through prolonged cytosolic Ca2+ transients and enhanced dopamine signaling (PMID:11389134, PMID:16204033, PMID:34104969).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 High

    Established the genetic basis linking SERCA2 to an epidermal disease, defining the pump as essential for keratinocyte adhesion and differentiation rather than only muscle Ca2+ handling.

    Evidence Mutation screening of ATP2A2 across Darier disease families, identifying 13 mutations in functional domains

    PMID:10080178

    Open questions at the time
    • Did not resolve how individual mutations alter pump catalysis
    • Did not establish the downstream signaling defect in keratinocytes
  2. 2003 High

    Resolved how disease mutations impair pump function at the level of the catalytic cycle, distinguishing SERCA2a/2b kinetics and assigning specific partial-reaction defects to mutants.

    Evidence Heterologous expression with steady-state and transient kinetic, Ca2+ transport, and phosphorylation assays in HEK-293 cells

    PMID:12975374

    Open questions at the time
    • 3/10 mutants not mechanistically explained
    • No high-resolution structural model of mutant transitions
  3. 2001 High

    Demonstrated in vivo consequences of reduced pump dosage—tumor predisposition and altered Ca2+ transient kinetics buffered by compensatory adaptations—showing haploinsufficiency is a primary initiating event.

    Evidence Atp2a2+/- mouse models with histopathology, Ca2+ imaging, exocytosis assays, and Western blot

    PMID:11387203 PMID:11389134

    Open questions at the time
    • Mechanism connecting reduced pump to neoplasia not defined here
    • Compensatory pathways may differ across tissues
  4. 2008 High

    Identified HAX-1 as a direct partner controlling SERCA2 protein level and ER Ca2+ stores, linking pump abundance to apoptosis resistance.

    Evidence Reciprocal Co-IP with deletion mapping, transfection, and viability assays in HEK-293 cells

    PMID:18971376

    Open questions at the time
    • Mechanism by which HAX-1 lowers SERCA2 levels unresolved
    • Physiological relevance in non-transfected tissue untested
  5. 2009 High

    Defined a luminal, conformation-selective inhibitory interaction (calumenin), broadening regulation of SERCA2 beyond the cytosolic face.

    Evidence GST pulldown, Co-IP, calumenin knockdown, and oxalate-supported Ca2+ uptake in HL-1 cells

    PMID:19740751

    Open questions at the time
    • Structural basis of E1-state preference not determined
    • In vivo significance not tested
  6. 2012 High

    Showed redox modification activates the pump, establishing Cys-674 S-glutathiolation as a NO/VEGF-responsive activating switch governing endothelial Ca2+ and migration.

    Evidence C674S mutagenesis, 45Ca2+ uptake, S-glutathione adduct detection, glutaredoxin-1 overexpression, and migration assays

    PMID:22472004

    Open questions at the time
    • Whether C674 modification operates similarly in other cell types not addressed
    • Crosstalk with other PTMs at the same residue unexplored
  7. 2012 Medium

    Connected SERCA2-controlled ER Ca2+ to sphingolipid signaling as a mediator of keratinocyte adhesion defects, providing a downstream pathway for Darier disease.

    Evidence SERCA2b siRNA and thapsigargin in keratinocytes with sphingolipid pathway inhibitors and adhesion/differentiation readouts

    PMID:22277942

    Open questions at the time
    • Causal link between sphingosine and adhesion proteins correlative
    • Single lab without genetic SERCA2 model
  8. 2011 Medium

    Reframed Darier disease pathogenesis around mutant protein aggregation and ER stress rather than Ca2+ depletion per se.

    Evidence Expression of DD mutants in primary human keratinocytes with solubility, ubiquitination, ER stress, and apoptosis assays plus knockdown

    PMID:22045735

    Open questions at the time
    • Aggregation vs depletion contributions not fully separated for all mutants
    • Single-lab primary cell system
  9. 2014 High

    Demonstrated SERCA2 loss recapitulates the DD adhesion phenotype via ER retention of junctional proteins and constitutive ER stress, with pharmacological rescue.

    Evidence DD keratinocytes and thapsigargin in normal keratinocytes with immunostaining, dispase dissociation, and Miglustat rescue

    PMID:24390139

    Open questions at the time
    • Signaling intermediary between ER stress and junction assembly not yet identified
    • Chemical inhibition may not fully mimic genetic loss
  10. 2015 High

    Placed SERCA2 within a phosphorylation-dependent PDE3A1/AKAP18 signalosome that compartmentalizes cAMP to control phospholamban and pump activity.

    Evidence Co-IP, gel filtration, recombinant interaction assays, S-to-A mutagenesis, and SR Ca2+ uptake

    PMID:25593322

    Open questions at the time
    • Stoichiometry and spatial organization of the signalosome not resolved
    • Functional consequences in vivo not tested here
  11. 2010 Medium

    Identified TFAM and TFB2M as direct nuclear transcriptional regulators of Serca2, expanding control beyond muscle-specific enhancers.

    Evidence ChIP, fluorescence correlation spectroscopy, and promoter-mutation luciferase reporters in cardiac myocytes

    PMID:21113058

    Open questions at the time
    • Mechanism of nuclear localization of mitochondrial factors unclear
    • Physiological inducers of this regulation not defined
  12. 2012 Medium

    Defined a PPAR-γ/CDK5 transcriptional axis governing SERCA2b in β-cells, linking pump expression to metabolic ER-stress protection.

    Evidence Luciferase reporter, EMSA, ChIP, CDK5 inhibition, and insulin secretion/Ca2+ assays

    PMID:22240811

    Open questions at the time
    • In vivo relevance of Ser-273 phosphorylation to SERCA2 not tested
    • Single lab
  13. 2014 Medium

    Established an ERK→NF-κB pathway that transcriptionally represses SERCA2 during cardiac hypertrophy, complementing the ERK-driven adhesion defects later seen in skin.

    Evidence Neonatal rat ventricular myocyte hypertrophy model with ERK/NF-κB inhibitors, RT-PCR, and promoter reporter

    PMID:25008120

    Open questions at the time
    • Direct NF-κB binding site on SERCA2 promoter not mapped
    • Pharmacological dissection only
  14. 2020 Medium

    Expanded the PTM repertoire controlling SERCA2 across tissues—activating O-GlcNAcylation in β-cells, inhibitory TG2-mediated serotonylation in vascular smooth muscle, and calcineurin/NFAT-coupled C674 signaling in aneurysm—each tying pump regulation to a disease context.

    Evidence OGT-KO mice and O-GlcNAc proteomics; TG2 silencing/KO with activity and Ca2+ assays; C674S knock-in with calcineurin inhibitors and aneurysm model

    PMID:32035136 PMID:32116663 PMID:32375037

    Open questions at the time
    • Modification site mapping incomplete for some PTMs
    • Crosstalk among coexisting modifications unresolved
  15. 2021 High

    Defined AKAP18δ as a dual CaM/CaMKIIδ regulator at the SERCA2-PLN complex and JNK2 as a CaMKII-independent activating kinase, refining kinase control of Ca2+ reuptake and arrhythmogenesis.

    Evidence Peptide arrays, Co-IP, PLA, SPR, FRET CaMKII assays, and SR Ca2+ imaging; Co-IP and ATPase assays with optical mapping for JNK2

    PMID:33334123 PMID:34814703

    Open questions at the time
    • JNK2 phosphorylation site on SERCA2 not identified
    • Integration of opposing AKAP18δ-N/-C activities in vivo incompletely defined
  16. 2021 Medium

    Demonstrated neuronal SERCA2 haploinsufficiency slows Ca2+ decay and elevates accumbal dopamine, providing a mechanism for the neuropsychiatric phenotype associated with reduced pump dosage.

    Evidence Brain-specific conditional Atp2a2 heterozygous KO mice with ER Ca2+ uptake, neuronal Ca2+ imaging, in vivo microdialysis, and behavior

    PMID:34104969

    Open questions at the time
    • Link between Ca2+ kinetics and dopamine release mechanistically indirect
    • Cell types responsible not isolated
  17. 2022 Medium

    Identified Sigmar1 as a direct partner targeting SERCA2 for Hrd1/Sel1L ERAD via K460/K541 ubiquitination, defining a degradative control branch with osteoclast consequences.

    Evidence IP-MS, Co-IP, site-directed mutagenesis, ubiquitination assays, Sigmar1 KO mice, and osteoclast differentiation

    PMID:35611810

    Open questions at the time
    • Trigger that initiates Sigmar1-driven degradation unclear
    • Single-lab validation
  18. 2023 High

    Tied SERCA2 oxidation/inactivation to endothelial and cardiac ischemia-reperfusion injury, with Ser-663 phosphorylation and XO-mediated oxidation as inhibitory events causing Ca2+ overload.

    Evidence Human ischemic hearts, SERCA2-KO mice, mutagenesis, and cytosolic/mitochondrial Ca2+ and CaMKII assays

    PMID:35836807 PMID:37291092

    Open questions at the time
    • Kinase responsible for S663 phosphorylation not identified
    • Therapeutic translation of preventing modification untested
  19. 2023 High

    Showed MFN2 directly couples SERCA2 to ER-mitochondria contact, regulating mitochondrial Ca2+ supply and survival in CD8+ T cells.

    Evidence Co-IP, PLA, Mfn2 ablation in CD8+ T cells, SERCA2-KO mice, and mitochondrial Ca2+/metabolism measurements

    PMID:37738362

    Open questions at the time
    • Structural basis of the MFN2-SERCA2 interface unknown
    • Generalizability beyond T cells untested
  20. 2023 Medium

    Linked SERCA2-dependent ER Ca2+ to prohormone processing, autophagy, and feedback transcription, broadening pump function into secretory and degradative cell biology.

    Evidence β-cell-specific SERCA2 KO with proinsulin processing analysis; LC3B LIR-motif Co-IP and Ca2+/CaMKK/CREB feedback in TNBC cells

    PMID:36561988 PMID:37537395

    Open questions at the time
    • Direct vs indirect contributions of SERCA2 to autophagosome formation unresolved
    • Feedback loop characterized in single cancer model
  21. 2023 High

    Demonstrated SERCA2 loss drives neurodegenerative and epidermal pathology that is rescuable, with ERK signaling positioned downstream of SERCA2 loss in keratinocyte adhesion failure.

    Evidence CRISPR SERCA2-KO keratinocytes with omics, organotypic epidermis, and MEK inhibitor rescue; retinal Ca2+ imaging with SERCA2 gene delivery and pharmacological activation

    PMID:37561594 PMID:39615485

    Open questions at the time
    • How ER Ca2+ loss activates ERK not mechanistically defined
    • Durability of gene-delivery rescue not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the diverse activating and inhibitory PTMs and partner interactions are integrated to set SERCA2 activity in a given cell, and what structural transitions couple specific modifications to defined catalytic steps.
  • No structural model linking PTMs to E1/E2 transitions
  • Hierarchy and crosstalk among regulators undefined
  • Tissue-specific dominance of regulatory branches unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0016787 hydrolase activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-382551 Transport of small molecules 4 R-HSA-1643685 Disease 3 R-HSA-397014 Muscle contraction 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
AKAP18ΔCALUHAX1LC3BMFN2PDE3APLNSIGMAR1
Complex memberships
SERCA2-phospholamban complexSERCA2/AKAP18δ/PDE3A1 signalosome

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Mutations in ATP2A2 (encoding SERCA2, a sarco/endoplasmic reticulum Ca2+-ATPase) cause Darier disease; frameshift, in-frame, splice-site, and missense mutations in functional domains were identified, establishing that SERCA2 loss-of-function disrupts a Ca2+-signalling pathway regulating keratinocyte cell-to-cell adhesion and differentiation. Mutation screening of ATP2A2 gene in DD families; identification of 13 mutations in functional domains Nature genetics High 10080178
2003 Steady-state and rapid kinetic analyses of SERCA2a and SERCA2b isoforms revealed: SERCA2b has 10-fold lower Ca2+ dissociation rate from E1Ca2 (true high Ca2+ affinity) and slower dephosphorylation than SERCA2a; both SERCA2 isoforms show 2-fold slower E2→E1Ca2 transition than SERCA1a. Ten Darier disease mutants were functionally characterized: uncoupling of Ca2+ translocation from ATP hydrolysis and/or altered partial reaction rates (E1~P→E2-P block, E2-P→E2 rate reduction, or loss of phosphorylation) account for loss of function in 7/10 mutants. Heterologous expression in HEK-293 cells; steady-state and transient kinetic analyses; radioactive Ca2+ transport and phosphorylation assays The Journal of biological chemistry High 12975374
2001 Mice heterozygous for a null Atp2a2 allele (SERCA2 haploinsufficiency) develop squamous cell tumors of forestomach, esophagus, oral mucosa, tongue, and skin, without loss of heterozygosity, establishing that reduced SERCA2 Ca2+ pump levels predispose keratinocytes to neoplasia as a primary initiating event. Atp2a2+/- mouse model; Western blot; histopathology; comparison with age/sex-matched wild-type controls The Journal of biological chemistry High 11389134
2001 In SERCA2+/- mice, reduced SERCA2 causes shorter cytosolic Ca2+ transients (due to compensatory upregulation of specific plasma membrane Ca2+ pump isoforms) and ~50% reduction in Ca2+ oscillation frequency, yet agonist-stimulated exocytosis is preserved through adaptive upregulation of Ca2+ sensors synaptotagmins I and III, making exocytosis ~10-fold more sensitive to Ca2+. SERCA2+/- mouse model; Ca2+ imaging; exocytosis assays; Western blot for synaptotagmins and plasma membrane Ca2+ pumps The EMBO journal High 11387203
2008 HAX-1 (anti-apoptotic protein) binds directly to SERCA2 via residues 575–594 of SERCA2's nucleotide-binding domain interacting with HAX-1 C-terminal domain (aa 203–245). Overexpression of HAX-1 downregulates SERCA2 protein levels, reduces ER Ca2+ stores, and promotes cell survival after hypoxia/reoxygenation or thapsigargin treatment; conversely, SERCA2 overexpression abrogates HAX-1's pro-survival effect. Co-immunoprecipitation; deletion mapping; transfection in HEK-293 cells; immunofluorescence; cell viability assays Molecular biology of the cell High 18971376
2009 Calumenin (a luminal EF-hand Ca2+-binding protein) interacts with SERCA2 via its residues 132–222 binding to SERCA2 luminal domain L4 (aa 853–892). The interaction is favored in the E1 conformation of SERCA2 (reduced by thapsigargin, vanadate, or ATP). Calumenin knockdown increases SERCA2 Ca2+ sensitivity and enhances Ca2+ transient amplitude in cardiomyocytes. GST pulldown; co-immunoprecipitation; calumenin knockdown in HL-1 cells; oxalate-supported Ca2+ uptake assay; immunocytochemistry The Journal of biological chemistry High 19740751
2012 VEGF activates SERCA2b via •NO-mediated S-glutathiolation of cysteine-674, which stimulates ER Ca2+ uptake and is required for VEGF-induced endothelial cell Ca2+ influx and migration. A C674S SERCA2b mutant is unresponsive to VEGF/•NO-stimulated migration and Ca2+ uptake, and overexpression of glutaredoxin-1 (which reverses S-glutathiolation) blocks these effects. 45Ca2+ uptake assay; SERCA2b C674S mutagenesis; adenoviral overexpression; immunochemical detection of S-glutathione adducts; SERCA2 knockdown; Ca2+ imaging Antioxidants & redox signaling High 22472004
2015 Phosphodiesterase 3A1 (PDE3A1) interacts with SERCA2 in a phosphorylation-dependent manner: PKA phosphorylation of PDE3A1 at Ser-292/Ser-293 (unique N-terminal site) promotes its incorporation into a SERCA2/AKAP18 signalosome in human sarcoplasmic reticulum, where it controls a local cAMP pool regulating phospholamban phosphorylation and SERCA2 activity. Deletion of the PDE3A1/2 N-terminus blocks SERCA2 interaction. Co-immunoprecipitation; gel filtration chromatography; immunohistochemistry; recombinant protein interaction assays; serine-to-alanine mutagenesis; SR Ca2+ uptake assay The Journal of biological chemistry High 25593322
2023 SERCA2 phosphorylation at serine 663 is increased in ischemic human and mouse hearts. Preventing S663 phosphorylation significantly increases SERCA2 activity and protects against cytosolic and mitochondrial Ca2+ overload and cell death, establishing S663 phosphorylation as a negative regulator of SERCA2 activity and a pathophysiological event in cardiac ischemia-reperfusion. Phosphorylation analysis in human ischemic hearts; mutagenesis; SERCA2 activity assays; cytosolic/mitochondrial Ca2+ measurements; cell death assays Nature communications High 37291092
2023 PDE3A binds directly to SERCA2 via PDE3A amino acids 277–402 interacting with SERCA2 actuator domain (aa 169–216). Disruption of this interaction with a peptide disruptor (OptF) increases SERCA2 activity independently of PLB and PKA, reduces cardiac mortality after aortic banding in mice, and has no effect in cardiomyocyte-specific SERCA2-inactivated mice, confirming the mechanism is SERCA2-dependent. Surface plasmon resonance; proximity ligation assay; peptide arrays; immunoprecipitation; SR Ca2+ uptake in cardiomyocytes and HEK293 vesicles; rAAV9 in vivo gene delivery; echocardiography; cardiac MRI Circulation High 36876489
2021 AKAP18δ anchors CaMKIIδ to SERCA2-PLN and RYR complexes via two distinct regions: AKAP18δ-N inhibits CaMKIIδ (and binds CaM), while AKAP18δ-C activates CaMKIIδ by lowering the Ca2+ threshold and inducing CaM trapping. AKAP18δ-C facilitates faster Ca2+ reuptake via SERCA2, while AKAP18δ-N has opposite effects, defining AKAP18δ as both a CaM-KAP and a CaMKII regulator at SERCA2-PLN. Peptide arrays; co-immunoprecipitation; pulldown; proximity ligation; FRET-based CaMKII activity assay; SR vesicle Ca2+ imaging; surface plasmon resonance; AlphaScreen; adenovirus/AAV transduction Circulation research High 34814703
2020 JNK2 (but not JNK1) associates with and phosphorylates SERCA2, increasing SERCA2 ATPase maximal rate (without altering Ca2+ affinity) and SR Ca2+ content load. This JNK2-driven SERCA2 activation is CaMKII-independent and, combined with JNK2-CaMKII-driven SR Ca2+ leak, exacerbates atrial arrhythmogenicity. Co-immunoprecipitation; biochemical phosphorylation assay; confocal Ca2+ imaging; SERCA2 ATPase activity assay; optical mapping in intact hearts; JNK-specific inhibition Circulation research High 33334123
2023 MFN2 (mitofusin-2) interacts with ER-embedded SERCA2, enhancing mitochondria-ER contact and facilitating mitochondrial Ca2+ influx required for mitochondrial metabolism. MFN2 also stimulates SERCA2 ER Ca2+ retrieval activity, preventing excessive mitochondrial Ca2+ accumulation and apoptosis in CD8+ T cells. The beneficial effects were largely prevented in SERCA2-knockout mice. Co-immunoprecipitation; proximity ligation assay; genetic ablation of Mfn2 in CD8+ T cells; SERCA2-knockout mice; mitochondrial Ca2+ and metabolism measurements Science immunology High 37738362
2014 Darier disease keratinocytes display constitutive ER stress with impaired membrane localization of desmosomal cadherins (Dsg3, Dsc3), desmoplakin, E-cadherin, and catenins (retained in ER), and reduced intercellular adhesion strength. SERCA2 inhibition by thapsigargin in normal keratinocytes recapitulates these abnormalities, establishing SERCA2 loss-of-function as the cause of ER stress and defective desmosome/adherens junction formation in DD. Immunostaining; co-immunostaining with ER markers; dispase mechanical dissociation assay; thapsigargin treatment of normal keratinocytes; Miglustat pharmacological rescue The Journal of investigative dermatology High 24390139
2012 SERCA2b loss-of-function (via thapsigargin inhibition or siRNA) in keratinocytes increases sphingosine levels and decreases sphingosine kinase (SPHK1) expression. Inhibiting sphingosine lyase rescues defects in keratinocyte differentiation, E-cadherin localization, desmoplakin translocation, and ER Ca2+ sequestration caused by SERCA2 inhibition, linking SERCA2-controlled ER Ca2+ to sphingolipid signaling in keratinocyte adhesion. SERCA2b siRNA knockdown; thapsigargin inhibition; sphingolipid pathway inhibitors; immunofluorescence; Ca2+ sequestration assay The Journal of investigative dermatology Medium 22277942
2011 SERCA2 mutant proteins associated with Darier disease are less soluble, aggregate, and are more polyubiquitinated in keratinocytes. Aggregated SERCA2 mutants (not ER Ca2+ depletion per se) initiate ER stress. Mutant SERCA2 aggregates in primary human keratinocytes cause cell rounding, detachment, and apoptosis; conversely, SERCA2 knockdown renders cells resistant to apoptosis. Expression of DD mutants in primary human keratinocytes; solubility/aggregation assays; ubiquitination assay; ER stress markers; cell death/apoptosis assays; SERCA2 knockdown Journal of cell science Medium 22045735
2005 Haploinsufficiency of Atp2a2 predisposes mice to squamous cell tumors via a novel mechanism not involving loss of heterozygosity (tumor cells retain the wild-type allele and express SERCA2 protein), absence of ras mutations, and upregulation of wild-type K-ras. Affected epithelium shows overexpression of hyperactivation-associated keratins as early as 2 months of age. Laser capture microdissection; immunoblot; immunohistochemistry; ras mutation analysis; Atp2a2+/- mouse model Cancer research Medium 16204033
2009 Reduced SERCA2 abundance (53% reduction) in inducible cardiomyocyte-specific knockout mice decreases SR Ca2+ content, Ca2+ transient amplitude and decay, and reduces the propensity for arrhythmogenic Ca2+ wave development (waves in 31% KO vs 57% WT cardiomyocytes) and ventricular extrasystoles. Inducible cardiomyocyte-specific Serca2 gene disruption; Fluo-5F Ca2+ imaging; whole-cell voltage clamp; in vivo ECG Cardiovascular research Medium 20019150
2012 PPAR-γ directly binds a PPAR response element in the proximal SERCA2 gene promoter (−259 bp region) and transactivates SERCA2b expression in pancreatic β-cells. CDK5-induced phosphorylation of PPAR-γ at Ser-273 reduces SERCA2 expression; pioglitazone (PPAR-γ agonist) prevents this by blocking CDK5-mediated PPAR-γ phosphorylation, restoring SERCA2b levels and protecting against ER stress-induced β-cell death. Luciferase reporter assay; EMSA; chromatin immunoprecipitation; CDK5 inhibitor (roscovitine); Ca2+ imaging; insulin secretion assay Molecular endocrinology Medium 22240811
2010 Mitochondrial transcription factors TFAM and TFB2M bind to the −122 to −114 nt (TFAM) and −122 to −117 nt (TFB2M) regions of the Serca2 gene promoter in the nucleus of cardiac myocytes, directly regulating SERCA2 gene transcription. Mutation of these binding sites reduces Serca2 transcription. Chromatin immunoprecipitation; fluorescence correlation spectroscopy; luciferase reporter with promoter mutations; immunostaining (nuclear localization); overexpression in cardiac myocytes Cardiovascular research Medium 21113058
2020 SERCA2 is O-GlcNAcylated in mouse and human β-cells (identified via OGT-dependent modification), and pharmacological SERCA2 activation rescues palmitate-stimulated insulin secretion in OGT-deficient islets, establishing O-GlcNAcylation of SERCA2 as a mechanism coupling nutrient sensing to β-cell ER Ca2+ function and lipid-potentiated insulin secretion. β-cell-specific OGT knockout mice; O-GlcNAc proteomics; pharmacological SERCA2 activation (CDN1163); insulin secretion assay; in vivo hyperinsulinemic clamp Cell reports Medium 32375037
2020 TG2 (transglutaminase 2) mediates serotonylation of SERCA2 (covalent modification by serotonin) under hypoxia, inhibiting SERCA2 activity and increasing intracellular Ca2+ via TRPC6. TG2 gene silencing or knockout prevents hypoxia-induced SERCA2 serotonylation and attenuates pulmonary vascular remodeling and hypertension in vivo. Co-immunoprecipitation; SERCA2 activity assay; TG2 gene silencing/overexpression; TG2 vascular smooth muscle-specific knockout mice; Fluo-4AM Ca2+ measurement Frontiers in pharmacology Medium 32116663
2020 Inactivation of SERCA2 cysteine 674 (C674S knock-in mice) causes intracellular Ca2+ accumulation that activates calcineurin, promoting nuclear translocation of NFAT and NFκB, resulting in smooth muscle cell phenotypic modulation and accelerating angiotensin II-induced aortic aneurysm development. Calcineurin inhibition reverses SMC modulation. SERCA2 C674S knock-in mouse model; calcineurin inhibitors; NFAT/NFκB nuclear translocation assay; angiotensin II aneurysm model; intracellular Ca2+ measurement Journal of molecular and cellular cardiology Medium 32035136
2022 Sigma-1 receptor (Sigmar1) interacts with SERCA2 at residue Q615, and promotes SERCA2 proteasomal degradation through Hrd1/Sel1L-dependent ER-associated degradation (ERAD), with ubiquitination of SERCA2 at K460 and K541 mediating degradation. This Sigmar1-SERCA2 axis attenuates osteoclastogenesis. IP-mass spectrometry; co-immunoprecipitation; site-directed mutagenesis; ubiquitination assay; Sigmar1 agonist/antagonist treatment; Sigmar1 KO mice; osteoclast differentiation assay EMBO molecular medicine Medium 35611810
2021 Brain-specific heterozygous loss of Atp2a2 in mice results in decreased ER Ca2+ uptake activity, slower cytosolic Ca2+ decay after neuronal depolarization, and elevated extracellular dopamine levels in the nucleus accumbens (measured by in vivo dialysis), linking SERCA2 haploinsufficiency in neurons to enhanced dopamine signaling and behavioral abnormalities. Brain-specific conditional Atp2a2 heterozygous KO mice; ER Ca2+ uptake assay in brain membranes; neuronal Ca2+ imaging; in vivo microdialysis; behavioral testing Human molecular genetics Medium 34104969
1997 The relative ratio of phospholamban to SERCA2 is a critical determinant of myocardial contractility: cardiac muscles with lower PLB:SERCA2 ratios (atria vs. ventricle, 4.2-fold lower) show 3-fold faster rates of force development and relaxation; phospholamban knockout hearts (no PLB) show enhanced contractility parameters, establishing PLB as a reversible inhibitor of SERCA2 whose relief by phosphorylation regulates diastolic relaxation. Comparison of atrial vs. ventricular contractility; phospholamban knockout mouse hearts; isolated work-performing heart left-ventricular pressure measurements; Western blot for PLB and SERCA2 Basic research in cardiology Medium 9202840
2014 ERK1/2 activation during cardiac hypertrophy represses SERCA2 transcription via nuclear factor-κB (NFκB); pharmacological ERK inhibitors preserve SERCA2 mRNA during hypertrophy, and ERK activation alone is sufficient to reduce SERCA2 mRNA, establishing an ERK→NFκB→SERCA2 repression pathway. Neonatal rat ventricular myocyte hypertrophy model; pharmacological ERK inhibitors; NFκB inhibitors; RT-PCR; SERCA2 promoter reporter assay Journal of molecular and cellular cardiology Medium 25008120
2023 SERCA2-deficient β-cells (βS2KO mice) have reduced ER Ca2+ levels and show decreased expression of active proinsulin processing enzymes PC1/3 and PC2, mis-localization of proinsulin and proPC2 to the ERGIC/cis-Golgi, and increased circulating proinsulin, establishing that SERCA2 regulates prohormone trafficking and processing enzyme maturation through ER Ca2+ homeostasis. β-cell-specific SERCA2 KO mice; Ca2+ imaging; RNA-seq; immunofluorescence; proinsulin processing assays; SERCA2-deficient INS-1 cells Diabetologia Medium 37537395
2023 SERCA2 interacts with LC3B via an LIR motif, facilitating WIPI2-independent autophagosome formation in triple-negative breast cancer cells. Autophagy-mediated SERCA2 degradation triggers transcriptional upregulation of SERCA2 through a Ca2+/CaMKK/CREB-1 feedback loop. Co-immunoprecipitation; LIR motif analysis; autophagy flux assays; SERCA2 knockdown/overexpression; Ca2+/CaMKK pathway inhibition; CREB reporter assay Acta pharmaceutica Sinica. B Medium 36561988
2013 FE65 interacts with SERCA2 in human brain tissue, validated by pulldown/mass spectrometry and co-immunoprecipitation. FE65 knockout neurons show upregulation of SERCA2, and FE65 knockdown in HEK293T cells increases sensitivity to thapsigargin, suggesting FE65 modulates intracellular Ca2+ homeostasis via SERCA2. Pulldown/mass spectrometry from human brain tissue; co-immunoprecipitation; FE65/FE65L1 double KO mouse proteomics; FE65 siRNA knockdown; thapsigargin sensitivity assay Molecular & cellular proteomics Low 24284412
2008 FOG-2 (friend of GATA-2) physically interacts with thyroid hormone receptor-α1 and abrogates T3-mediated SERCA2 promoter activity and expression; cardiac-specific FOG-2 overexpression in mice reduces SERCA2 transcript and protein levels, depresses cardiac function, and activates fetal gene program. Co-immunoprecipitation of FOG-2 with TR-α1; luciferase reporter assay of SERCA2 promoter; FOG-2 transgenic mice; Western blot; RT-PCR Circulation research Medium 18658259
2023 SERCA2 loss in retinal neurons occurs in ocular hypertension and optic nerve crush injury in mice and patients with primary open-angle glaucoma. Pharmacological SERCA2 activation or neuron-specific SERCA2 gene delivery rescues single-cell cytosolic Ca2+ clearance dynamics, reduces ER stress, promotes neuronal survival, and restores visual function in injured mice. Two-photon microscopy Ca2+ imaging; rAAV-mediated SERCA2 neuron-specific gene delivery; pharmacological SERCA2 activation; ER stress markers; retinal ganglion cell survival assay; visual behavior testing Cell reports. Medicine Medium 39615485
2022 SERCA2 oxidation (via xanthine oxidase activation) and inactivation is a key intermediary in ischemia/reperfusion-induced endothelial dysfunction: DAPA inhibits XO-mediated SERCA2 oxidation, preventing cytoplasmic Ca2+ overload and CaMKII activation, and the protective effects of DAPA on microvascular integrity are largely abrogated in SERCA2-knockout mice. SERCA2 knockout mice; human coronary artery endothelial cells; hypoxia/reoxygenation model; Western blot for SERCA2 oxidation; CaMKII activity assay; Ca2+ imaging Theranostics Medium 35836807
1998 The SERCA2 gene contains a muscle-specific enhancer in its distal promoter (−1467 to −1105 bp). An E box/AT-rich element at −1115 bp is critical for maximal enhancer activity and binds a muscle-induced nuclear protein complex; CArG and MCAT elements within this region also bind specific nuclear factors and contribute to overall SERCA2 promoter activation in muscle cells. Deletion analysis; heterologous TK promoter assay in Sol8 muscle cells; gel mobility shift assay; mutagenesis of cis-elements Nucleic acids research Medium 9461473
2021 Cardiac troponin I (cTnI, encoded by TNNI3) translocates to the nucleus in cardiomyocytes and directly binds to the Atp2a2 promoter region (−239 to −889 bp) at a CCAT motif. TNNI3 gain-of-function increases and loss-of-function decreases SERCA2 mRNA and protein levels, and increases Atp2a2 promoter activity in a luciferase reporter assay. ChIP-seq; luciferase reporter assay; TNNI3 siRNA knockdown and overexpression; Western blot; Ca2+ transient measurement Genes & diseases Low 36157491
2023 SERCA2 depletion in CRISPR/Cas9-generated human keratinocytes lacking SERCA2 causes excess MAPK/ERK signaling and deficiency of desmosomal and cytoskeletal proteins, weakening intercellular adhesion. MEK inhibition rescues adhesive protein expression and keratinocyte sheet integrity even in SERCA2-depleted or SERCA2-inhibited cells, positioning ERK signaling downstream of SERCA2 loss in Darier disease pathogenesis. CRISPR/Cas9 SERCA2 knockout in human keratinocytes; organotypic epidermis; RNA-seq; proteomics; immunostaining; MEK inhibitor treatment; dispase sheet integrity assay JCI insight High 37561594

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nature genetics 578 10080178
2005 Modulating sarco(endo)plasmic reticulum Ca2+ ATPase 2 (SERCA2) activity: cell biological implications. Cell calcium 182 16105684
1999 Spectrum of novel ATP2A2 mutations in patients with Darier's disease. Human molecular genetics 132 10441323
1999 ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes. Human molecular genetics 124 10441325
2003 Dissection of the functional differences between sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 1 and 2 isoforms and characterization of Darier disease (SERCA2) mutants by steady-state and transient kinetic analyses. The Journal of biological chemistry 110 12975374
2000 Mosaicism for ATP2A2 mutations causes segmental Darier's disease. The Journal of investigative dermatology 108 11121153
2022 SGLT2 inhibitor dapagliflozin reduces endothelial dysfunction and microvascular damage during cardiac ischemia/reperfusion injury through normalizing the XO-SERCA2-CaMKII-coffilin pathways. Theranostics 106 35836807
2012 PPAR-γ activation restores pancreatic islet SERCA2 levels and prevents β-cell dysfunction under conditions of hyperglycemic and cytokine stress. Molecular endocrinology (Baltimore, Md.) 103 22240811
2008 The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its protein levels to promote cell survival. Molecular biology of the cell 92 18971376
2001 Squamous cell tumors in mice heterozygous for a null allele of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 Ca2+ pump. The Journal of biological chemistry 91 11389134
2015 Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2. The Journal of biological chemistry 84 25593322
1997 The relative phospholamban and SERCA2 ratio: a critical determinant of myocardial contractility. Basic research in cardiology 83 9202840
2001 Darier disease--novel mutations in ATP2A2 and genotype-phenotype correlation. Experimental dermatology 81 11168576
2023 Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8+ T cell metabolic fitness and function in tumors. Science immunology 79 37738362
2008 Lentiviral vector-mediated SERCA2 gene transfer protects against heart failure and left ventricular remodeling after myocardial infarction in rats. Molecular therapy : the journal of the American Society of Gene Therapy 78 18388909
2016 SERCA2 Deficiency Impairs Pancreatic β-Cell Function in Response to Diet-Induced Obesity. Diabetes 74 27489309
2001 Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2(+/-) mice. The EMBO journal 60 11387203
2005 Haploinsufficiency of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 Ca2+ pump, predisposes mice to squamous cell tumors via a novel mode of cancer susceptibility. Cancer research 59 16204033
2014 SERCA2 dysfunction in Darier disease causes endoplasmic reticulum stress and impaired cell-to-cell adhesion strength: rescue by Miglustat. The Journal of investigative dermatology 57 24390139
2018 The SERCA2: A Gatekeeper of Neuronal Calcium Homeostasis in the Brain. Cellular and molecular neurobiology 55 29663107
2009 Multiple and diverse coexpression, location, and regulation of additional SERCA2 and SERCA3 isoforms in nonfailing and failing human heart. Journal of molecular and cellular cardiology 54 19962989
2006 New perspectives on the role of SERCA2's Ca2+ affinity in cardiac function. Biochimica et biophysica acta 54 17005265
2006 Alterations in the ATP2A2 gene in correlation with colon and lung cancer. Cancer genetics and cytogenetics 54 17116488
2017 Mendelian Disorders of Cornification Caused by Defects in Intracellular Calcium Pumps: Mutation Update and Database for Variants in ATP2A2 and ATP2C1 Associated with Darier Disease and Hailey-Hailey Disease. Human mutation 53 28035777
2012 Redox regulation of SERCA2 is required for vascular endothelial growth factor-induced signaling and endothelial cell migration. Antioxidants & redox signaling 52 22472004
2009 Characterization of calumenin-SERCA2 interaction in mouse cardiac sarcoplasmic reticulum. The Journal of biological chemistry 52 19740751
2013 Drug-to-antibody ratio (DAR) by UV/Vis spectroscopy. Methods in molecular biology (Clifton, N.J.) 50 23913153
2022 A homogeneous high-DAR antibody-drug conjugate platform combining THIOMAB antibodies and XTEN polypeptides. Chemical science 49 35414872
2009 Reduced SERCA2 abundance decreases the propensity for Ca2+ wave development in ventricular myocytes. Cardiovascular research 48 20019150
2010 Mitochondrial transcription factors TFAM and TFB2M regulate Serca2 gene transcription. Cardiovascular research 47 21113058
2021 AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR. Circulation research 43 34814703
2020 JNK2, a Newly-Identified SERCA2 Enhancer, Augments an Arrhythmic [Ca2+]SR Leak-Load Relationship. Circulation research 43 33334123
2016 Immunogenicity and Protective Efficacy of the DAR-901 Booster Vaccine in a Murine Model of Tuberculosis. PloS one 40 27997597
2005 Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1. The British journal of dermatology 40 15840101
2023 SERCA2 phosphorylation at serine 663 is a key regulator of Ca2+ homeostasis in heart diseases. Nature communications 38 37291092
2005 Effects of drugs and anticytokine antibodies on expression of ATP2A2 and ATP2C1 in cultured normal human keratinocytes. The British journal of dermatology 37 15888147
2001 Exclusion of the Darier's disease gene, ATP2A2, as a common susceptibility gene for bipolar disorder. Molecular psychiatry 36 11244492
2004 Increased inhibition of SERCA2 by phospholamban in the type I diabetic heart. Molecular and cellular biochemistry 35 15362510
2022 Sigma-1 receptor attenuates osteoclastogenesis by promoting ER-associated degradation of SERCA2. EMBO molecular medicine 34 35611810
2014 Epigenetic switch at atp2a2 and myh7 gene promoters in pressure overload-induced heart failure. PloS one 34 25181347
2012 SERCA2-controlled Ca²+-dependent keratinocyte adhesion and differentiation is mediated via the sphingolipid pathway: a therapeutic target for Darier's disease. The Journal of investigative dermatology 34 22277942
2011 Protein aggregation of SERCA2 mutants associated with Darier disease elicits ER stress and apoptosis in keratinocytes. Journal of cell science 33 22045735
2013 Amyloid beta a4 precursor protein-binding family B member 1 (FE65) interactomics revealed synaptic vesicle glycoprotein 2A (SV2A) and sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) as new binding proteins in the human brain. Molecular & cellular proteomics : MCP 31 24284412
2004 Mutational analysis of the ATP2A2 gene in two Darier disease families with intrafamilial variability. The British journal of dermatology 31 15099360
2020 Islet O-GlcNAcylation Is Required for Lipid Potentiation of Insulin Secretion through SERCA2. Cell reports 30 32375037
1998 A novel E box/AT-rich element is required for muscle-specific expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene. Nucleic acids research 29 9461473
2007 Phenylephrine hypertrophy, Ca2+-ATPase (SERCA2), and Ca2+ signaling in neonatal rat cardiac myocytes. American journal of physiology. Cell physiology 28 17287366
2003 The MKK6-p38 MAPK pathway prolongs the cardiac contractile calcium transient, downregulates SERCA2, and activates NF-AT. Cardiovascular research 28 12829175
2019 DEL-1 ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle through SIRT1/SERCA2-mediated ER stress suppression. Biochemical pharmacology 27 31778646
2020 Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling. Frontiers in pharmacology 26 32116663
2015 Somatic ATP2A2 mutation in a case of papular acantholytic dyskeratosis: mosaic Darier disease. Journal of cutaneous pathology 26 26154588
2001 Novel mutations of ATP2A2 gene in Japanese patients of Darier's disease. Journal of dermatological science 26 11390201
2021 Brain-specific heterozygous loss-of-function of ATP2A2, endoplasmic reticulum Ca2+ pump responsible for Darier's disease, causes behavioral abnormalities and a hyper-dopaminergic state. Human molecular genetics 25 34104969
2023 Targeting SERCA2 in organotypic epidermis reveals MEK inhibition as a therapeutic strategy for Darier disease. JCI insight 24 37561594
2020 LncRNA MEG3-210 regulates endometrial stromal cells migration, invasion and apoptosis through p38 MAPK and PKA/SERCA2 signalling via interaction with Galectin-1 in endometriosis. Molecular and cellular endocrinology 24 32446846
2006 Five mutations of ATP2A2 gene in Chinese patients with Darier's disease and a literature review of 86 cases reported in China. Archives of dermatological research 24 16552539
2014 Extracellular signal-regulated kinase activation during cardiac hypertrophy reduces sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) transcription. Journal of molecular and cellular cardiology 23 25008120
2023 Cadmium Disrupted ER Ca2+ Homeostasis by Inhibiting SERCA2 Expression and Activity to Induce Apoptosis in Renal Proximal Tubular Cells. International journal of molecular sciences 22 36983052
2021 LncEDCH1 improves mitochondrial function to reduce muscle atrophy by interacting with SERCA2. Molecular therapy. Nucleic acids 22 35024244
2022 Toxoplasma gondii phosphatidylserine flippase complex ATP2B-CDC50.4 critically participates in microneme exocytosis. PLoS pathogens 21 35325010
2020 Inactivation of cysteine 674 in the SERCA2 accelerates experimental aortic aneurysm. Journal of molecular and cellular cardiology 21 32035136
2018 HIF-1 regulation of miR-29c impairs SERCA2 expression and cardiac contractility. American journal of physiology. Heart and circulatory physiology 21 30575439
2010 Silencing calcineurin A subunit reduces SERCA2 expression in cardiac myocytes. American journal of physiology. Heart and circulatory physiology 21 21057045
1996 Molecular cloning and analysis of the human cardiac sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) gene promoter. Journal of molecular and cellular cardiology 21 8930809
2023 Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure. Circulation 20 36876489
2005 High frequency of partial DIIIa and DAR alleles found in sickle cell disease patients suggests increased risk of alloimmunization to RhD. Transfusion medicine (Oxford, England) 20 15713129
2004 Dispersion of ventricular mRNA of RyR2 and SERCA2 associated with arrhythmogenesis in rats. Acta pharmacologica Sinica 20 15169625
2024 Rescuing SERCA2 pump deficiency improves bone mechano-responsiveness in type 2 diabetes by shaping osteocyte calcium dynamics. Nature communications 19 38291059
2022 Highly expressed SERCA2 triggers tumor cell autophagy and is a druggable vulnerability in triple-negative breast cancer. Acta pharmaceutica Sinica. B 19 36561988
2013 Low density lipoproteins promote unstable calcium handling accompanied by reduced SERCA2 and connexin-40 expression in cardiomyocytes. PloS one 19 23516438
2002 Mutation analysis of the ATP2A2 gene in Taiwanese patients with Darier's disease. The British journal of dermatology 19 12072062
1975 New Late Gene, dar, Involved in DNA Replication of Bacteriophage T4 I. Isolation, Characterization, and Genetic Location. Journal of virology 19 16789147
2024 Incidence of catheter-associated urinary tract infections by Gram-negative bacilli and their ESBL and carbapenemase production in specialized hospitals of Bahir Dar, northwest Ethiopia. Antimicrobial resistance and infection control 18 38273339
2023 Association of Somatic ATP2A2 Damaging Variants With Grover Disease. JAMA dermatology 18 37195706
2021 Inactivation of SERCA2 Cys674 accelerates aortic aneurysms by suppressing PPARγ. British journal of pharmacology 18 33591571
2019 CD4+ T cell cytokine responses to the DAR-901 booster vaccine in BCG-primed adults: A randomized, placebo-controlled trial. PloS one 18 31120957
2016 Loss of function mutations in ATP2A2 and psychoses: A case report and literature survey. Psychiatry and clinical neurosciences 18 27106560
2023 SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells. Diabetologia 17 37537395
2020 Different Degrees of 5'-to-3' DAR Interactions Modulate Zika Virus Genome Cyclization and Host-Specific Replication. Journal of virology 17 31826997
2024 Novel SERCA2 inhibitor Diphyllin displays anti-tumor effect in non-small cell lung cancer by promoting endoplasmic reticulum stress and mitochondrial dysfunction. Cancer letters 16 38909775
2022 Lathyrol promotes ER stress-induced apoptosis and proliferation inhibition in lung cancer cells by targeting SERCA2. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 16 36521248
2020 SMN-deficiency disrupts SERCA2 expression and intracellular Ca2+ signaling in cardiomyocytes from SMA mice and patient-derived iPSCs. Skeletal muscle 16 32384912
2012 Cyclooxygenase-2 inhibition restores ultraviolet B-induced downregulation of ATP2A2/SERCA2 in keratinocytes: possible therapeutic approach of cyclooxygenase-2 inhibition for treatment of Darier disease. The British journal of dermatology 16 22413864
2011 SERCA2 regulates non-CF and CF airway epithelial cell response to ozone. PloS one 16 22096575
2002 Expression of sarco/endo-plasmic reticulum Ca2+-ATPase type 2 isoforms (SERCA2) in normal human skin and mucosa, and Darier's disease skin. The British journal of dermatology 16 12366411
1997 Modulation of SERCA2 expression by thyroid hormone and norepinephrine in cardiocytes: role of contractility. The American journal of physiology 16 9139974
2022 The substitution of SERCA2 redox cysteine 674 promotes pulmonary vascular remodeling by activating IRE1α/XBP1s pathway. Acta pharmaceutica Sinica. B 15 35646520
2019 Pre-treatment and acquired HIV drug resistance in Dar es Salaam, Tanzania in the era of tenofovir and routine viral load monitoring. The Journal of antimicrobial chemotherapy 15 31273377
2015 Hypoxia-driven sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) downregulation depends on low-density lipoprotein receptor-related protein 1 (LRP1)-signalling in cardiomyocytes. Journal of molecular and cellular cardiology 15 25968337
2013 Malondialdehyde and 4-hydroxynonenal adducts are not formed on cardiac ryanodine receptor (RyR2) and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) in diabetes. Molecular and cellular biochemistry 15 23354458
2004 Identification of mutations in the ATP2A2 gene in patients with Darier's disease from Hungary. Experimental dermatology 15 15186327
2024 Melatonin protects RPE cells from necroptosis and NLRP3 activation via promoting SERCA2-related intracellular Ca2+ homeostasis. Phytomedicine : international journal of phytotherapy and phytopharmacology 14 39341129
2022 Healthcare Workers' Knowledge and Resource Availability for Care of Sickle Cell Disease in Dar es Salaam, Tanzania. Frontiers in genetics 14 35222514
2011 Regulation and rate limiting mechanisms of Ca2+ ATPase (SERCA2) expression in cardiac myocytes. Molecular and cellular biochemistry 14 21964539
2024 Endoplasmic reticulum stress-related deficits in calcium clearance promote neuronal dysfunction that is prevented by SERCA2 gene augmentation. Cell reports. Medicine 13 39615485
2023 Cardiac Plin5 interacts with SERCA2 and promotes calcium handling and cardiomyocyte contractility. Life science alliance 13 36717246
2021 Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes. Genes & diseases 13 36157491
2008 Increased FOG-2 in failing myocardium disrupts thyroid hormone-dependent SERCA2 gene transcription. Circulation research 13 18658259
2012 Acrokeratosis verruciformis of Hopf showing P602L mutation in ATP2A2 and overlapping histopathological features with Darier disease. The American Journal of dermatopathology 12 22814319
1995 Modulation of SERCA2 activity: regulated splicing and interaction with phospholamban. Bioscience reports 12 8825033

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