Affinage

ATP2A2

Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 · UniProt P16615

Round 2 corrected
Length
1042 aa
Mass
114.8 kDa
Annotated
2026-04-28
130 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP2A2 encodes SERCA2, a P-type Ca²⁺-ATPase that actively transports cytosolic Ca²⁺ into the sarcoplasmic/endoplasmic reticulum lumen, functioning as a master regulator of intracellular Ca²⁺ homeostasis across muscle and non-muscle cell types (PMID:2844796, PMID:9891028). SERCA2 activity is tuned by an extensive network of direct regulators: inhibited by phospholamban (whose stoichiometric ratio to SERCA2 sets contractile kinetics), calumenin binding at luminal loop L4, PDE3A1 docking at the actuator domain, serotonylation by TG2, and phosphorylation at Ser663, while being activated by S-glutathiolation at Cys674, SUMOylation at Lys480/Lys585, JNK2-mediated phosphorylation, and O-GlcNAcylation (PMID:2146166, PMID:9202840, PMID:19740751, PMID:36876489, PMID:15489859, PMID:21900893, PMID:33334123, PMID:37291092). Haploinsufficiency of ATP2A2 causes Darier disease through disrupted keratinocyte adhesion and differentiation, predisposes to squamous cell carcinogenesis, impairs cardiac contractility, disrupts pancreatic β-cell insulin processing, and produces a hyperdopaminergic neuropsychiatric phenotype (PMID:10080178, PMID:11389134, PMID:10587333, PMID:37537395, PMID:34104969). SERCA2 is further integrated into supramolecular signaling complexes via AKAP18δ-CaMKIIδ scaffolding at the SR and MFN2-mediated coupling at mitochondria-ER contact sites, and its turnover is controlled by Sigmar1-dependent Hrd1/Sel1L ERAD (PMID:34814703, PMID:37738362, PMID:35611810).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1988 High

    Molecular cloning established that a single ATP2A2 gene produces two isoforms—cardiac SERCA2a and ubiquitous SERCA2b—through alternative splicing, resolving the molecular basis of tissue-specific Ca²⁺ pump expression.

    Evidence cDNA cloning and sequencing of human kidney SERCA2 transcripts with Southern blot and immunological validation

    PMID:2844796

    Open questions at the time
    • Functional differences between SERCA2a and SERCA2b catalytic properties not yet compared
    • Regulatory elements governing isoform-specific splicing unknown
  2. 1990 High

    Co-expression experiments demonstrated that phospholamban directly inhibits SERCA2 by lowering Ca²⁺ affinity, establishing the first regulatory partner of the pump and the principle that SERCA2 activity is modulated by protein–protein interaction.

    Evidence COS-1 cell co-transfection with Ca²⁺-transport assays in microsomes

    PMID:2146166

    Open questions at the time
    • Structural basis of PLB–SERCA2 interaction unknown
    • Whether the PLB:SERCA2 stoichiometry has physiological consequences untested
  3. 1997 High

    The physiological significance of PLB:SERCA2 stoichiometry was demonstrated by showing that chambers with lower PLB:SERCA2 ratios contract faster, and PLB knockout enhances contractility, proving that this ratio is a primary determinant of cardiac Ca²⁺ handling kinetics.

    Evidence Comparison of atrial vs. ventricular contractile parameters and PLB knockout mouse hearts

    PMID:9202840

    Open questions at the time
    • Whether stoichiometric regulation is dynamic under stress conditions unclear
    • Other endogenous SERCA2 inhibitors not yet identified
  4. 1999 High

    Three convergent studies established SERCA2 as essential in vivo: loss-of-function mutations caused Darier disease in humans, heterozygous knockout impaired cardiac function in mice, and SERCA2a gene transfer rescued contractile dysfunction in failing human cardiomyocytes, linking pump deficiency to skin, cardiac, and disease phenotypes.

    Evidence Human mutation screening in Darier families; SERCA2+/− mouse cardiovascular measurements; adenoviral SERCA2a delivery to failing human cardiomyocytes with Ca²⁺ and contractility readouts

    PMID:10080178 PMID:10587333 PMID:9891028

    Open questions at the time
    • Molecular mechanism linking ER Ca²⁺ depletion to keratinocyte acantholysis unknown
    • Whether all Darier mutations act through haploinsufficiency vs. toxic gain-of-function unresolved
  5. 2000 High

    Analysis of SERCA2+/− mice revealed compensatory remodeling—upregulation of PMCA isoforms, Na⁺/Ca²⁺ exchanger, and altered PLB phosphorylation—that partially buffers reduced pump activity, establishing the principle that cells adapt Ca²⁺-handling networks when SERCA2 is diminished.

    Evidence SERCA2 heterozygous knockout mice with confocal Ca²⁺ imaging, myocyte contractility, exocytosis assays, and synaptotagmin isoform Western blotting

    PMID:10970890 PMID:11387203

    Open questions at the time
    • Whether compensatory mechanisms fail under chronic stress not tested
    • Mechanisms triggering compensatory gene expression changes unknown
  6. 2001 High

    SERCA2 haploinsufficiency was found to predispose to squamous cell tumors without loss of heterozygosity, establishing SERCA2 as a haploinsufficient tumor suppressor that alters epithelial tumorigenic potential through Ca²⁺ signaling perturbation.

    Evidence Aged Atp2a2+/− mice with histopathology; laser capture microdissection showing retained wild-type allele; ras mutation and p53 analysis

    PMID:11389134 PMID:16204033

    Open questions at the time
    • Downstream oncogenic pathways activated by partial SERCA2 loss not fully defined
    • Whether tumor suppressor role extends to human epithelial cancers not established
  7. 2004 High

    Identification of Cys674 S-glutathiolation as a redox-sensitive activating switch resolved how NO signals through SERCA2 to relax arteries, and showed that irreversible Cys674 oxidation in atherosclerosis abolishes this regulation.

    Evidence Reconstituted purified SERCA2 in vesicles; C674S mutagenesis; mass spectrometry of oxidized Cys674 in atherosclerotic tissue

    PMID:15489859

    Open questions at the time
    • Other Cys residues that may undergo regulatory oxidation not surveyed
    • Whether Cys674 oxidation is reversible in early disease stages unknown
  8. 2008 High

    Calumenin was identified as a luminal SERCA2 inhibitor that binds the L4 loop (residues 853–892) preferentially in the E1 state, revealing that SERCA2 is regulated from both cytoplasmic and luminal sides.

    Evidence GST-pulldown domain mapping; oxalate-supported Ca²⁺ uptake assays; calumenin knockdown in HL-1 cells

    PMID:19740751

    Open questions at the time
    • Physiological conditions that modulate calumenin–SERCA2 interaction not defined
    • Whether calumenin and PLB regulation are synergistic or independent unclear
  9. 2011 High

    Two discoveries expanded the regulatory landscape: SUMOylation at K480/K585 was shown essential for SERCA2a stability and ATPase activity (reduced in heart failure, rescued by SUMO1 gene therapy), and Darier disease missense mutants were found to aggregate, trigger ER stress, and cause apoptosis, revealing a toxic gain-of-function mechanism beyond haploinsufficiency.

    Evidence Site-directed mutagenesis of K480/K585; AAV-SUMO1 delivery in pressure-overload mice; DD mutant expression in keratinocytes with solubility, ubiquitination, and ER stress assays

    PMID:21900893 PMID:22045735

    Open questions at the time
    • SUMO E3 ligase responsible for SERCA2a SUMOylation not identified
    • Which DD mutations act through aggregation vs. pure loss-of-function not systematically classified
  10. 2012 High

    SERCA2b inhibition was shown to disrupt keratinocyte adhesion through sphingolipid pathway perturbation—increasing sphingosine and decreasing SPHK1—with rescue by sphingolipid lyase inhibition, providing a mechanistic link between ER Ca²⁺ depletion and Darier disease pathology.

    Evidence Thapsigargin and siRNA SERCA2b inhibition; sphingolipid analysis; rescue of E-cadherin and desmoplakin localization by sphingolipid lyase inhibitor

    PMID:22277942

    Open questions at the time
    • Whether sphingolipid pathway is perturbed in Darier patient skin not confirmed
    • Direct Ca²⁺-sensing mechanism controlling SPHK1 expression unknown
  11. 2015 High

    PDE3A1 was identified as a SERCA2 signalosome component: PKA-dependent phosphorylation of PDE3A1 at Ser292/293 promotes its incorporation into SERCA2/AKAP18 complexes, establishing a mechanism by which local cAMP pools control PLB phosphorylation and SERCA2 activity.

    Evidence Reciprocal co-IP of endogenous proteins from human SR; deletion mutant and mutagenesis mapping; gel filtration chromatography

    PMID:25593322

    Open questions at the time
    • Whether PDE3A1 directly modulates SERCA2 activity independent of cAMP hydrolysis not tested at this time
  12. 2016 High

    SERCA2 was established as critical for pancreatic β-cell function: heterozygous loss impaired glucose-stimulated Ca²⁺ mobilization, insulin secretion, and β-cell mass under metabolic stress, and pharmacological SERCA2 activation rescued β-cell death.

    Evidence SERCA2+/− mice on high-fat diet; Ca²⁺ imaging in islets; insulin secretion assays; SERCA2 activator treatment

    PMID:27489309

    Open questions at the time
    • Specific SERCA2 activator mechanism of action not characterized
    • Whether SERCA2 dysfunction contributes to human type 2 diabetes not directly shown
  13. 2020 High

    Multiple new regulatory modifications and downstream consequences were uncovered: JNK2 directly phosphorylates SERCA2 to increase Vmax; O-GlcNAcylation modulates β-cell insulin hypersecretion; TG2-mediated serotonylation inhibits SERCA2 promoting pulmonary vascular remodeling; and Cys674 inactivation activates calcineurin/NFAT signaling driving aneurysm and hypertension through ER stress pathways.

    Evidence Co-IP and ATPase assays (JNK2); OGT β-cell knockout with SERCA2 activation rescue; TG2 conditional knockout with hemodynamics; C674S knock-in mice with calcineurin, IRE1α, and renal pathway analyses

    PMID:31758704 PMID:32035136 PMID:32116663 PMID:32375037 PMID:33334123

    Open questions at the time
    • JNK2 phosphorylation site on SERCA2 not mapped
    • O-GlcNAcylation sites not identified by mutagenesis
    • Serotonylation site not confirmed by mutagenesis
  14. 2021 High

    The AKAP18δ scaffold was shown to bidirectionally regulate CaMKIIδ activity at SERCA2 through distinct N- and C-terminal domains, and brain-specific SERCA2 haploinsufficiency was found to produce a hyperdopaminergic phenotype with behavioral abnormalities, extending SERCA2 physiology to neuropsychiatric function.

    Evidence Peptide arrays, SPR, FRET-based CaMKII assays, AAV injection in mice (AKAP18δ); conditional brain Atp2a2+/− mice with in vivo microdialysis and behavioral testing

    PMID:34104969 PMID:34814703

    Open questions at the time
    • How SERCA2 haploinsufficiency leads specifically to dopamine elevation mechanistically unclear
    • Whether AKAP18δ scaffold architecture differs between cardiac and neuronal SERCA2 pools unknown
  15. 2022 High

    Sigma-1 receptor was identified as a SERCA2 binding partner that promotes its ubiquitin-dependent degradation via Hrd1/Sel1L ERAD at K460/K541, and PDE3A was shown to directly inhibit SERCA2 through actuator domain binding (aa 169–216) independently of its catalytic activity, with disruptor peptides rescuing SERCA2 function in failing hearts.

    Evidence IP-MS; co-IP with mutagenesis of Q615, K460/K541 (Sigmar1-SERCA2); 2-color dSTORM, SPR, peptide arrays, and AAV9 disruptor peptide delivery reducing cardiac mortality (PDE3A-SERCA2)

    PMID:35611810 PMID:36876489

    Open questions at the time
    • Whether Sigmar1-mediated SERCA2 degradation is regulated by ligands in vivo unknown
    • Structural basis of PDE3A actuator domain inhibition not resolved
  16. 2023 High

    Ser663 was identified as a pathophysiological inhibitory phosphosite elevated in ischemic hearts, MFN2 was shown to enhance SERCA2 activity at MAMs for mitochondrial Ca²⁺ transfer in CD8⁺ T cells, and β-cell SERCA2 loss was found to mislocalize proinsulin processing enzymes, revealing new site-specific regulation, subcellular coupling, and organelle-level consequences of pump dysfunction.

    Evidence Phosphoproteomics of ischemic human hearts with S663 mutagenesis; MFN2-SERCA2 co-IP with conditional Mfn2 ablation in CD8⁺ T cells; β-cell SERCA2 knockout with proinsulin/proPC2 localization and RNA-seq

    PMID:37291092 PMID:37537395 PMID:37738362

    Open questions at the time
    • Kinase responsible for Ser663 phosphorylation not identified
    • Structural basis of MFN2-SERCA2 interaction at MAMs unknown
    • Whether proinsulin trafficking defects occur in human SERCA2-deficient β-cells not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the identity of the kinase(s) phosphorylating Ser663, the specific O-GlcNAcylation and serotonylation sites on SERCA2, the structural basis of the PDE3A–actuator domain inhibitory interaction, and the mechanism by which partial SERCA2 loss selectively elevates dopamine in the brain.
  • Ser663 kinase identity unknown
  • O-GlcNAcylation and serotonylation sites unmapped by mutagenesis
  • No high-resolution structure of SERCA2–PDE3A or SERCA2–AKAP18δ complexes
  • Mechanism linking SERCA2 haploinsufficiency to dopaminergic hyperactivity unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 6 GO:0005215 transporter activity 5
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005886 plasma membrane 1
Pathway
R-HSA-382551 Transport of small molecules 7 R-HSA-397014 Muscle contraction 6 R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 2 R-HSA-9612973 Autophagy 1
Partners
AKAP18CALUCAMK2DMAPK9MFN2PDE3APLNSIGMAR1
Complex memberships
SERCA2/AKAP18δ/CaMKIIδ signalosomeSERCA2/PDE3A1/AKAP18 signalosomeSERCA2/PLB complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 Molecular cloning of human kidney cDNAs revealed that the cardiac Ca2+-ATPase (ATP2A2/SERCA2) gene produces two alternatively spliced products: SERCA2a (identical to cardiac muscle Ca2+-ATPase) and SERCA2b (with the carboxyl-terminal 4 amino acids replaced by an extended 49-amino-acid sequence), with SERCA2b being the most abundant isoform in non-muscle tissues. cDNA cloning, Southern blotting, sequencing, and immunological characterization of microsomal fractions The Journal of biological chemistry High 2844796
1990 Co-expression of SERCA2 with phospholamban in COS-1 cells demonstrated that phospholamban directly inhibits SERCA2 by lowering its Ca2+ affinity, establishing functional interaction between the two proteins. Transient transfection of COS-1 cells, Ca2+-transport assays in microsomes FEBS letters High 2146166
1997 The relative ratio of phospholamban to SERCA2 is a critical determinant of myocardial contractility; atrial muscles with a 4.2-fold lower phospholamban:SERCA2 ratio exhibit threefold faster contraction/relaxation rates than ventricular muscles, and phospholamban knockout hearts show enhanced contractility, demonstrating that phospholamban:SERCA2 stoichiometry directly regulates pump-dependent Ca2+ handling. Comparison of atrial vs. ventricular contractile parameters; phospholamban knockout mouse hearts; isolated work-performing heart preparations Basic research in cardiology High 9202840
1999 Loss-of-function mutations in ATP2A2 (encoding SERCA2) cause Darier disease, demonstrating that SERCA2-mediated Ca2+ signaling is essential for keratinocyte cell-to-cell adhesion and differentiation. Thirteen mutations including frameshift deletions, splice-site mutations, and missense mutations in functional domains were identified. Mutation screening of ATP2A2 in Darier disease families; identification of 13 mutations in functional domains Nature genetics High 10080178
1999 Heterozygous null mutation in the SERCA2 gene reduces SERCA2 mRNA by ~45%, protein and maximal Ca2+ uptake velocity by ~35%, and impairs cardiac contractility and relaxation, demonstrating that two functional copies of SERCA2 are required for normal cardiac Ca2+ sequestration and function. Gene targeting in mice; RNase protection, Western blotting, biochemical Ca2+ uptake assays, in vivo cardiovascular pressure measurements The Journal of biological chemistry High 9891028
1999 Gene transfer of SERCA2a into failing human cardiomyocytes restores pump activity, increases contraction and relaxation velocity, decreases diastolic Ca2+, increases systolic Ca2+, and normalizes the frequency response, establishing that SERCA2a deficiency directly underlies contractile dysfunction in heart failure. Adenoviral gene transfer into isolated human failing cardiomyocytes; Ca2+ imaging, contractility measurements Circulation High 10587333
2000 Disruption of one SERCA2 allele in mice reduces SR Ca2+ stores and Ca2+ release by ~30–60%, decreases myocyte shortening/relengthening rates by ~40%, and triggers compensatory reductions in phospholamban (by ~40%) with increased basal phosphorylation of PLB at Ser-16 and Thr-17 (~2-fold), along with upregulation of the Na+-Ca2+ exchanger, revealing adaptive mechanisms that partially compensate for reduced SERCA2 levels. SERCA2 heterozygous knockout mice; confocal Ca2+ imaging, myocyte contractility measurements, Western blotting, electrophysiology The Journal of biological chemistry High 10970890
2000 Somatic (mosaic) mutations in ATP2A2 cause segmental Darier disease following Blaschko's lines, confirming that postzygotic ATP2A2 mutations restricted to affected skin are sufficient to produce acantholytic dyskeratosis. Mutation analysis of affected skin vs. unaffected skin and leukocytes; identification of nonsense (Y894X) and missense (G769R) mutations present only in affected tissue The Journal of investigative dermatology High 11121153
2001 Haploinsufficiency of Atp2a2 (SERCA2) predisposes mice to squamous cell tumors of the forestomach, esophagus, oral mucosa, tongue, and skin, with 13/14 heterozygous mice developing tumors versus none in wild-type controls, establishing that perturbation of Ca2+ homeostasis via SERCA2 reduction can serve as a primary initiating event in squamous cell carcinogenesis. Aged Atp2a2+/- mice; histopathology, Western blot analysis of SERCA2 in affected tissues The Journal of biological chemistry High 11389134
2001 In SERCA2+/- mice, the shorter Ca2+ transient evoked by agonist stimulation is due to upregulation of specific plasma membrane Ca2+ pump isoforms; Ca2+ oscillation frequency is reduced ~50%, but agonist-stimulated exocytosis is preserved through compensatory increases in Ca2+ sensitivity of exocytosis mediated by altered levels of Ca2+ sensors synaptotagmins I and III. SERCA2+/- mouse model; Ca2+ imaging, exocytosis assays, Western blotting of synaptotagmin isoforms The EMBO journal High 11387203
2004 S-Glutathiolation of SERCA2 at Cys674 by NO-derived peroxynitrite directly activates SERCA Ca2+-uptake activity and mediates arterial relaxation; mutation of Cys674 to serine abolishes this activation, and irreversible oxidation of Cys674 to sulfonic acid in atherosclerosis prevents NO-dependent SERCA activation and arterial relaxation. Purified SERCA reconstituted in phospholipid vesicles; site-directed mutagenesis (C674S); Ca2+-uptake assays; mass spectrometry of oxidized Cys674 in atherosclerotic tissue Nature medicine High 15489859
2005 Atp2a2 haploinsufficiency causes squamous cell tumorigenesis via a novel mechanism not involving loss of heterozygosity (wild-type allele retained in tumors), without ras mutations, but with upregulated K-ras expression, establishing a cancer susceptibility mode based on global change in tumorigenic potential of keratinized epithelium. Laser capture microdissection of tumor cells; PCR for wild-type allele; ras mutation analysis; immunohistochemistry; Western blot; p53 analysis Cancer research High 16204033
2008 Calumenin, a multiple EF-hand Ca2+-binding protein located in the cardiac SR lumen, directly interacts with SERCA2 and inhibits SERCA2-mediated Ca2+ uptake; the interaction is favored in the E1 state of SERCA2, and the binding regions are residues 132-222 of calumenin and 853-892 of SERCA2 luminal loop L4. Co-immunoprecipitation; GST-pulldown with calumenin deletion fragments and SERCA2 luminal domains; oxalate-supported Ca2+ uptake assays; calumenin knockdown in HL-1 cells The Journal of biological chemistry High 19740751
2010 Mitochondrial transcription factors TFAM and TFB2M bind to the -122 to -114 nt region of the Serca2 gene promoter in rat neonatal cardiomyocytes (demonstrated by ChIP and fluorescence correlation spectroscopy), and their overexpression prevents stress-induced decreases in SERCA2a mRNA, revealing that these factors coordinate transcription of both mitochondrial metabolic genes and the SERCA2 gene. Chromatin immunoprecipitation (ChIP); fluorescence correlation spectroscopy; promoter mutation analysis; adenoviral overexpression; rat myocardial infarction model Cardiovascular research High 21113058
2011 SERCA2a is SUMOylated at lysines 480 and 585, and this SUMOylation is essential for maintaining SERCA2a ATPase activity and stability; SUMO1 levels and SERCA2a SUMOylation are reduced in failing hearts, and AAV-mediated SUMO1 restoration improves SERCA2a function and cardiac performance comparably to SERCA2a gene delivery. Site-directed mutagenesis of K480 and K585; adeno-associated virus gene delivery; in vitro ATPase assays; cardiomyocyte Ca2+ decay measurements; pressure-overload mouse model Nature High 21900893
2011 SERCA2 protein aggregation is triggered by Darier disease-associated missense mutations; these mutant proteins are less soluble, aggregate, become polyubiquitinated, and when transduced into primary keratinocytes, elicit ER stress and induce apoptosis and cell detachment, establishing a gain-of-toxic-function pathogenic mechanism distinct from simple haploinsufficiency. Expression of DD-associated SERCA2 mutants; solubility assays; polyubiquitination assays; adenoviral transduction into primary human keratinocytes; ER stress markers; apoptosis assays Journal of cell science High 22045735
2012 SERCA2b-controlled ER Ca2+ sequestration regulates keratinocyte adhesion and differentiation via the sphingolipid signaling pathway: SERCA2b inhibition increases sphingosine levels and decreases sphingosine kinase (SPHK1) expression, and inhibiting sphingolipid lyase rescues defects in keratinocyte differentiation, E-cadherin localization, and desmoplakin translocation caused by SERCA2 inhibition. SERCA2b inhibition with thapsigargin and siRNA; sphingolipid pathway analysis; rescue experiments with sphingolipid lyase inhibitor; immunofluorescence of E-cadherin and desmoplakin The Journal of investigative dermatology High 22277942
2015 Phosphodiesterase 3A1 (PDE3A1) directly interacts with SERCA2 in human cardiac SR; phosphorylation of PDE3A1 by PKA at Ser-292/Ser-293 (unique to PDE3A1) promotes its incorporation into SERCA2/AKAP18 signalosomes; PDE3A co-immunoprecipitates with SERCA2, cav3, PKARII, PP2A, and AKAP18; and deletion of the PDE3A1 N-terminus blocks SERCA2 interaction, placing PDE3A1 as a regulator of a discrete cAMP pool controlling PLB phosphorylation and SERCA2 activity. Co-immunoprecipitation of endogenous proteins from human SR; gel filtration chromatography; recombinant protein co-IP; deletion mutants; site-directed mutagenesis; PKA phosphorylation assays; immunohistochemistry The Journal of biological chemistry High 25593322
2016 SERCA2 deficiency in pancreatic beta cells impairs ER Ca2+ homeostasis, glucose-induced Ca2+ mobilization, insulin secretion, proinsulin processing, and beta-cell mass under high-fat diet conditions; pharmacological SERCA2 activation rescues tunicamycin-induced beta-cell death, establishing SERCA2 as critical for the beta-cell compensatory response to obesity. SERCA2 heterozygous mice on high-fat diet; Ca2+ imaging in islets; insulin secretion assays; beta-cell mass quantification; ER stress markers; SERCA2 activator treatment Diabetes High 27489309
2020 JNK2 (but not JNK1) directly associates with and phosphorylates SERCA2, increasing SERCA2 ATPase activity (maximal rate without altering Ca2+ affinity) and SR Ca2+ content in a CaMKII-independent manner, thereby exacerbating an arrhythmic SR Ca2+ leak-load relationship in aged and alcohol-exposed hearts. Confocal Ca2+ imaging; biochemical SERCA2 ATPase activity assays; co-immunoprecipitation; dual Ca2+/voltage optical mapping in intact hearts; JNK2-specific inhibition; CaMKII inhibitor controls Circulation research High 33334123
2020 O-GlcNAcylation of SERCA2 in pancreatic beta cells, mediated by OGT, is required for lipid-stimulated insulin hypersecretion; SERCA2 was identified as a beta-cell O-GlcNAcylated protein in mice and humans, and pharmacological SERCA2 activation rescues impaired palmitate-stimulated insulin secretion in OGT-deficient islets. OGT-specific beta-cell knockout mice; in vivo and in vitro insulin secretion assays; identification of O-GlcNAcylated SERCA2 by proteomic approaches; pharmacological SERCA2 activation Cell reports Medium 32375037
2020 TG2-mediated serotonylation of SERCA2 inhibits SERCA2 activity, leading to increased cytosolic Ca2+ and store-operated Ca2+ entry via TRPC6; hypoxia enhances TG2 expression and activity promoting SERCA2 serotonylation both in vitro and in vivo, and vascular smooth muscle-specific Tgm2 knockout prevents hypoxia-induced pulmonary vascular remodeling. Co-immunoprecipitation; TG2 gene silencing/overexpression; SERCA2 activity assays; Fluo-4AM Ca2+ measurements; tissue-specific conditional TG2 knockout mice; hemodynamic measurements Frontiers in pharmacology Medium 32116663
2020 Inactivation of SERCA2 Cys674 (C674S knock-in, representing irreversible oxidation) causes intracellular Ca2+ accumulation that activates calcineurin, promoting nuclear translocation of NFAT and NF-κB, resulting in smooth muscle cell phenotypic modulation and acceleration of angiotensin II-induced aortic aneurysm. SERCA2 C674S heterozygous knock-in mice; aortic aneurysm model; calcineurin inhibition; NFAT/NFκB nuclear translocation assays; SMC phenotypic marker Western blots Journal of molecular and cellular cardiology High 32035136
2020 Inactivation of SERCA2 Cys674 in the kidney (C674S knock-in mice) promotes hypertension by inducing ER stress and upregulating soluble epoxide hydrolase (sEH), which together suppress dopamine D1 receptor expression, impairing Na+/K+-ATPase regulation and sodium excretion. SERCA2 C674S heterozygous knock-in mice; blood pressure measurement; urine sodium/volume analysis; ER stress marker Western blots; D1 receptor expression; Na+/K+-ATPase activity assays British journal of pharmacology Medium 31758704
2021 AKAP18δ anchors CaMKIIδ at SERCA2-PLN and RYR via two distinct regions: an N-terminal region (AKAP18δ-N) inhibits CaMKIIδ by binding a region homologous to CaMKII inhibitor peptide and the Thr17-PLN region, while a C-terminal region (AKAP18δ-C) activates CaMKIIδ by lowering the Ca2+ threshold for kinase activation and inducing CaM trapping; AKAP18δ-C facilitates faster Ca2+ reuptake by SERCA2. Peptide arrays; cell-permeant peptide technology; immunoprecipitations; pull-downs; FRET-based CaMKII activity assays; SR vesicle fluorescence imaging; surface plasmon resonance; AAV injection in mice Circulation research High 34814703
2021 Brain-specific heterozygous loss of Atp2a2 (SERCA2) in mice causes slower cytosolic Ca2+ decay after neuronal depolarization (due to decreased ER Ca2+ uptake), behavioral abnormalities including altered novelty responses and impaired fear memory, and elevated extracellular dopamine in the nucleus accumbens, establishing that SERCA2 haploinsufficiency in brain produces a hyperdopaminergic state. Brain-specific conditional Atp2a2 heterozygous knockout mice; ER Ca2+ uptake assays; neuronal Ca2+ imaging after depolarization; behavioral testing; in vivo microdialysis for dopamine Human molecular genetics High 34104969
2022 Sigma-1 receptor (Sigmar1) interacts with SERCA2 (with Q615 as the critical binding residue) and promotes SERCA2 degradation through Hrd1/Sel1L-dependent ER-associated degradation (ERAD), with ubiquitination of SERCA2 at K460 and K541 targeting it for proteasomal degradation; this mechanism attenuates osteoclastogenesis. IP-mass spectrometry; co-immunoprecipitation; mutagenesis of SERCA2 Q615 and K460/K541; ERAD inhibition; proteasome inhibitor experiments; Sigmar1 knockout and overexpression in mice EMBO molecular medicine High 35611810
2022 SERCA2 oxidation and inactivation by xanthine oxidase (XO) during cardiac ischemia/reperfusion leads to cytoplasmic Ca2+ overload, CaMKII activation, and cofilin phosphorylation causing F-actin depolymerization and endothelial dysfunction; SGLT2 inhibitor dapagliflozin inhibits this XO-SERCA2-CaMKII-cofilin pathway, and its protective effects are lost in SERCA2-knockout mice. SERCA2 knockout mice subjected to ischemia/reperfusion; human coronary artery endothelial cells with hypoxia/reoxygenation; XO activity measurements; SERCA2 oxidation assays; CaMKII and cofilin phosphorylation; endothelial function assays Theranostics High 35836807
2022 SERCA2 interacts with LC3B via an LIR motif to facilitate WIPI2-independent autophagosome formation, promoting autophagy in triple-negative breast cancer cells; autophagy-mediated SERCA2 degradation induces SERCA2 transcriptional upregulation through a Ca2+/CaMKK/CREB-1 feedback loop. Co-immunoprecipitation of SERCA2 with LC3B; LIR motif identification; autophagy flux assays; Ca2+ imaging; CaMKK inhibition; CREB-1 reporter assays; in vitro and in vivo tumor models Acta pharmaceutica Sinica. B Medium 36561988
2023 SERCA2 phosphorylation at serine 663 is increased in ischemic human and mouse hearts; preventing serine 663 phosphorylation significantly increases SERCA2 activity and protects against cell death by counteracting cytosolic and mitochondrial Ca2+ overload, establishing serine 663 as a pathophysiological regulatory site of SERCA2 activity. Phosphoproteomic analysis of ischemic human hearts; mutagenesis preventing S663 phosphorylation; SERCA2 ATPase activity assays; Ca2+ homeostasis measurements in human cell lines; infarct size analysis Nature communications High 37291092
2023 MFN2 interacts with ER-embedded SERCA2 at mitochondria-ER contact sites (MAMs) to enhance SERCA2 ER Ca2+ retrieval activity, facilitating mitochondrial Ca2+ influx required for efficient mitochondrial metabolism in CD8+ T cells while preventing excessive mitochondrial Ca2+ accumulation and apoptosis. Co-immunoprecipitation of MFN2 and SERCA2; Mfn2 genetic ablation in CD8+ T cells; mitochondria-ER contact site imaging; mitochondrial Ca2+ measurements; metabolic assays; tumor models Science immunology High 37738362
2023 SERCA2 deficiency in beta cells impairs spatial regulation of prohormone trafficking, causing mis-location of proinsulin and proPC2 to the ERGIC/cis-Golgi, and decreases expression of active forms of proinsulin processing enzymes PC1/3 and PC2, linking ER Ca2+ depletion to defective insulin maturation. Beta-cell-specific SERCA2 knockout mice; RNA-seq; Ca2+ imaging; proinsulin processing assays; immunofluorescence of proinsulin and proPC2 localization; INS-1 SERCA2-deficient cell line Diabetologia High 37537395
2023 PDE3A directly binds to amino acids 169-216 within the actuator domain of SERCA2 via PDE3A amino acids 277-402, and this interaction inhibits SERCA2 activity independently of PDE3A catalytic activity; disruption of the SERCA2/PDE3A interaction by disruptor peptides increases SERCA2 activity in normal and failing cardiomyocytes and reduces cardiac mortality after aortic banding in mice. 2-color dSTORM; proximity ligation assay; co-immunoprecipitation; peptide arrays; surface plasmon resonance; HEK293 vesicle Ca2+ uptake assays; AAV9 gene delivery in mice; serial echocardiography; cardiac MRI Circulation High 36876489
1998 An E box/AT-rich element at -1115 bp is critical for muscle-specific enhancer activity of the SERCA2 gene promoter; gel mobility shift studies show this element specifically binds a protein induced during myogenesis, and it acts together with CArG and MCAT elements to regulate SERCA2 transcription. Deletion analysis; reporter gene assays in Sol8 myotubes; gel mobility shift assays; mutagenesis of cis-acting elements Nucleic acids research Medium 9461473
1996 The human SERCA2 gene promoter contains a TATA-like box, CAAT-box, three Sp1 sites, a CACCC-box, OTF-1 binding sequence, and two putative thyroid response elements; sequences from -263 to +170 bp are necessary for maximal transcriptional activity and sequences from -125 to +170 bp are essential for basal activity in cardiomyocytes and myotubes. Genomic cloning; 5' deletion reporter constructs; transfection into neonatal rat cardiomyocytes and C2C12 myotubes; luciferase assays Journal of molecular and cellular cardiology Medium 8930809
2021 Cardiac troponin I (cTnI) translocates to the nucleus in cardiomyocytes and binds to the Atp2a2 promoter in the -239 to -889 region at a 'CCAT' motif, positively regulating SERCA2a expression; TNNI3 gain/loss causes dose-dependent Atp2a2 mRNA and protein changes, and increasing cTnI increases SERCA2a promoter activity in luciferase assays. ChIP-sequencing; luciferase reporter assays; TNNI3 siRNA and overexpression; Western blotting; Ca2+ transient measurements Genes & diseases Medium 36157491
2022 Substitution of SERCA2 Cys674 (C674S knock-in) activates the IRE1α/XBP1s ER stress pathway in pulmonary artery smooth muscle cells, accelerating cell cycle and proliferation, leading to pulmonary vascular remodeling resembling pulmonary hypertension; this is reversed by IRE1α/XBP1s pathway inhibitor 4μ8C. SERCA2 C674S heterozygous knock-in mice; IRE1α/XBP1s pathway analysis; cell cycle assays; PASMC proliferation assays; right ventricular systolic pressure measurements Acta pharmaceutica Sinica. B Medium 35646520

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Biological insights from 108 schizophrenia-associated genetic loci. Nature 5878 25056061
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2015 Gene essentiality and synthetic lethality in haploid human cells. Science (New York, N.Y.) 657 26472760
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
1999 Mutations in ATP2A2, encoding a Ca2+ pump, cause Darier disease. Nature genetics 576 10080178
2004 S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide. Nature medicine 541 15489859
2006 Hsp90 cochaperone Aha1 downregulation rescues misfolding of CFTR in cystic fibrosis. Cell 517 17110338
2004 Biology, structure and mechanism of P-type ATPases. Nature reviews. Molecular cell biology 447 15071553
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2012 Modulation of cardiac contractility by the phospholamban/SERCA2a regulatome. Circulation research 429 22679139
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2008 A genome-wide association study identifies protein quantitative trait loci (pQTLs). PLoS genetics 390 18464913
1999 Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a. Circulation 386 10587333
2018 DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. Cell 379 29656893
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1988 Molecular cloning of cDNAs from human kidney coding for two alternatively spliced products of the cardiac Ca2+-ATPase gene. The Journal of biological chemistry 332 2844796
2014 A quantitative chaperone interaction network reveals the architecture of cellular protein homeostasis pathways. Cell 325 25036637
2011 SUMO1-dependent modulation of SERCA2a in heart failure. Nature 320 21900893
1999 Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) gene. The Journal of biological chemistry 213 9891028
2005 Modulating sarco(endo)plasmic reticulum Ca2+ ATPase 2 (SERCA2) activity: cell biological implications. Cell calcium 181 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
1999 ATP2A2 mutations in Darier's disease: variant cutaneous phenotypes are associated with missense mutations, but neuropsychiatric features are independent of mutation class. Human molecular genetics 122 10441324
2000 Mosaicism for ATP2A2 mutations causes segmental Darier's disease. The Journal of investigative dermatology 108 11121153
2000 Disruption of a single copy of the SERCA2 gene results in altered Ca2+ homeostasis and cardiomyocyte function. The Journal of biological chemistry 107 10970890
2022 SGLT2 inhibitor dapagliflozin reduces endothelial dysfunction and microvascular damage during cardiac ischemia/reperfusion injury through normalizing the XO-SERCA2-CaMKII-coffilin pathways. Theranostics 99 35836807
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 83 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
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
2023 Mitochondria-ER contact mediated by MFN2-SERCA2 interaction supports CD8+ T cell metabolic fitness and function in tumors. Science immunology 75 37738362
2016 SERCA2 Deficiency Impairs Pancreatic β-Cell Function in Response to Diet-Induced Obesity. Diabetes 74 27489309
1995 Reciprocal changes in the postnatal expression of the sarcolemmal Na+-Ca(2+)-exchanger and SERCA2 in rat heart. Journal of molecular and cellular cardiology 64 8523431
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
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
2013 Gender differences in HIV disease progression and treatment outcomes among HIV patients one year after starting antiretroviral treatment (ART) in Dar es Salaam, Tanzania. BMC public health 52 23320567
2009 Characterization of calumenin-SERCA2 interaction in mouse cardiac sarcoplasmic reticulum. The Journal of biological chemistry 52 19740751
2019 Newborn screening for sickle cell disease: an innovative pilot program to improve child survival in Dar es Salaam, Tanzania. International health 48 31145786
2013 Drug-to-antibody ratio (DAR) by UV/Vis spectroscopy. Methods in molecular biology (Clifton, N.J.) 48 23913153
2022 A homogeneous high-DAR antibody-drug conjugate platform combining THIOMAB antibodies and XTEN polypeptides. Chemical science 45 35414872
2010 Mitochondrial transcription factors TFAM and TFB2M regulate Serca2 gene transcription. Cardiovascular research 45 21113058
2020 JNK2, a Newly-Identified SERCA2 Enhancer, Augments an Arrhythmic [Ca2+]SR Leak-Load Relationship. Circulation research 41 33334123
2021 AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR. Circulation research 40 34814703
2016 Immunogenicity and Protective Efficacy of the DAR-901 Booster Vaccine in a Murine Model of Tuberculosis. PloS one 40 27997597
1990 Co-expression of slow-twitch/cardiac muscle Ca2(+)-ATPase (SERCA2) and phospholamban. FEBS letters 38 2146166
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
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
2023 SERCA2 phosphorylation at serine 663 is a key regulator of Ca2+ homeostasis in heart diseases. Nature communications 32 37291092
2022 Sigma-1 receptor attenuates osteoclastogenesis by promoting ER-associated degradation of SERCA2. EMBO molecular medicine 31 35611810
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
2008 Calumenin interacts with SERCA2 in rat cardiac sarcoplasmic reticulum. Molecules and cells 30 18562801
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
2005 PKC-independent signal transduction pathways increase SERCA2 expression in adult rat cardiomyocytes. Journal of molecular and cellular cardiology 28 16236312
2003 The MKK6-p38 MAPK pathway prolongs the cardiac contractile calcium transient, downregulates SERCA2, and activates NF-AT. Cardiovascular research 28 12829175
2002 Correlates of plasma HIV-1 RNA viral load among HIV-1-seropositive women in Dar es Salaam, Tanzania. Journal of acquired immune deficiency syndromes (1999) 27 12131569
2017 The costs of providing antiretroviral therapy services to HIV-infected individuals presenting with advanced HIV disease at public health centres in Dar es Salaam, Tanzania: Findings from a randomised trial evaluating different health care strategies. PloS one 26 28234969
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
2020 Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling. Frontiers in pharmacology 25 32116663
2019 DEL-1 ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle through SIRT1/SERCA2-mediated ER stress suppression. Biochemical pharmacology 25 31778646
2010 Understanding women's experiences of distress during pregnancy in Dar es Salaam, Tanzania. Tanzania journal of health research 24 20737827
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
2020 Inactivation of Cys674 in SERCA2 increases BP by inducing endoplasmic reticulum stress and soluble epoxide hydrolase. British journal of pharmacology 23 31758704
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 23 32446846
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
2007 Time course of changes in the expression of DHPR, RyR(2), and SERCA2 after myocardial infarction in the rat left ventricle. Molecular and cellular biochemistry 23 17516033
2017 Early marriage and cultural constructions of adulthood in two slums in Dar es Salaam. Culture, health & sexuality 22 29111880
2016 Renal abnormalities among HIV infected children at Muhimbili National Hospital (MNH)-Dar es Salaam, Tanzania. BMC nephrology 22 27000018
2010 Characterization of in vivo pharmacokinetic properties of the dopamine D1 receptor agonist DAR-0100A in nonhuman primates using PET with [11C] NNC112 and [11C] raclopride. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 22 20571519
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 21 36983052
2022 Toxoplasma gondii phosphatidylserine flippase complex ATP2B-CDC50.4 critically participates in microneme exocytosis. PLoS pathogens 21 35325010
2021 LncEDCH1 improves mitochondrial function to reduce muscle atrophy by interacting with SERCA2. Molecular therapy. Nucleic acids 21 35024244
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
2022 DAR-PCR: a new tool for efficient retrieval of unknown flanking genomic DNA. AMB Express 20 36224448
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
2023 Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure. Circulation 19 36876489
2013 Low density lipoproteins promote unstable calcium handling accompanied by reduced SERCA2 and connexin-40 expression in cardiomyocytes. PloS one 19 23516438
2011 Risk factors for mortality among HIV-positive patients with and without active tuberculosis in Dar es Salaam, Tanzania. Antiviral therapy 19 22293579
2002 Mutation analysis of the ATP2A2 gene in Taiwanese patients with Darier's disease. The British journal of dermatology 19 12072062
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 Association of Somatic ATP2A2 Damaging Variants With Grover Disease. JAMA dermatology 17 37195706
2022 Highly expressed SERCA2 triggers tumor cell autophagy and is a druggable vulnerability in triple-negative breast cancer. Acta pharmaceutica Sinica. B 17 36561988
2021 Inactivation of SERCA2 Cys674 accelerates aortic aneurysms by suppressing PPARγ. British journal of pharmacology 17 33591571
2020 Different Degrees of 5'-to-3' DAR Interactions Modulate Zika Virus Genome Cyclization and Host-Specific Replication. Journal of virology 17 31826997
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 16 38273339
2015 Prevalence and risk factors of cervical squamous intraepithelial lesions among HIV-infected women in Dar es Salaam, Tanzania. International journal of STD & AIDS 16 25957324
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
1997 Modulation of SERCA2 expression by thyroid hormone and norepinephrine in cardiocytes: role of contractility. The American journal of physiology 16 9139974
2023 SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells. Diabetologia 15 37537395
2022 Lathyrol promotes ER stress-induced apoptosis and proliferation inhibition in lung cancer cells by targeting SERCA2. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 36521248
2020 Metoprolol alleviates arginine vasopressin-induced cardiomyocyte hypertrophy by upregulating the AKT1-SERCA2 cascade in H9C2 cells. Cell & bioscience 15 32489586
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 Evaluating the SERCA2 and VEGF mRNAs as Potential Molecular Biomarkers of the Onset and Progression in Huntington's Disease. PloS one 15 25915065
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
2004 Identification of mutations in the ATP2A2 gene in patients with Darier's disease from Hungary. Experimental dermatology 15 15186327
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 14 38909775
2022 Healthcare Workers' Knowledge and Resource Availability for Care of Sickle Cell Disease in Dar es Salaam, Tanzania. Frontiers in genetics 14 35222514
2022 The substitution of SERCA2 redox cysteine 674 promotes pulmonary vascular remodeling by activating IRE1α/XBP1s pathway. Acta pharmaceutica Sinica. B 14 35646520
2018 Loss of ATP2A2 Allows Herpes Simplex Virus 1 Infection of a Human Epidermis Model by Disrupting Innate Immunity and Barrier Function. The Journal of investigative dermatology 14 29870688
2011 Regulation and rate limiting mechanisms of Ca2+ ATPase (SERCA2) expression in cardiac myocytes. Molecular and cellular biochemistry 14 21964539
2021 Intranuclear cardiac troponin I plays a functional role in regulating Atp2a2 expression in cardiomyocytes. Genes & diseases 13 36157491