Gene Symbol: Atp2a2
Description: ATPase, Ca++ transporting, cardiac muscle, slow twitch 2
Alias: 9530097L16Rik, D5Wsu150e, SERCA2, SERCA2B, Serca2a, mKIAA4195, sarcoplasmic/endoplasmic reticulum calcium ATPase 2, SERCA2a isoform, SR Ca(2+)-ATPase 2, calcium pump 2, calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform, endoplasmic reticulum class 1/2 Ca(2+) ATPase, sarco/endoplasmic reticulum Ca2+-ATPase 2
Species: mouse
Products:     Atp2a2

Top Publications

  1. Stokke M, Hougen K, Sjaastad I, Louch W, Briston S, Enger U, et al. Reduced SERCA2 abundance decreases the propensity for Ca2+ wave development in ventricular myocytes. Cardiovasc Res. 2010;86:63-71 pubmed publisher
    To describe the overall role of reduced sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) for Ca(2+) wave development...
  2. Louch W, Hougen K, Mørk H, Swift F, Aronsen J, Sjaastad I, et al. Sodium accumulation promotes diastolic dysfunction in end-stage heart failure following Serca2 knockout. J Physiol. 2010;588:465-78 pubmed publisher
    ..from complete loss of SR Ca(2+) release between 4- and 7-week KO, due to loss of a small remaining pool of SERCA2. Declining SR Ca(2+) release was partly offset by increased L-type Ca(2+) current, which was facilitated by AP ..
  3. Ji Y, Lalli M, Babu G, Xu Y, Kirkpatrick D, Liu L, et al. Disruption of a single copy of the SERCA2 gene results in altered Ca2+ homeostasis and cardiomyocyte function. J Biol Chem. 2000;275:38073-80 pubmed
    A mouse model carrying a null mutation in one copy of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase isoform 2 (SERCA2) gene, in which SERCA2 protein levels are reduced by approximately 35%, was used to investigate the effects of decreased ..
  4. Asahi M, Otsu K, Nakayama H, Hikoso S, Takeda T, Gramolini A, et al. Cardiac-specific overexpression of sarcolipin inhibits sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2a) activity and impairs cardiac function in mice. Proc Natl Acad Sci U S A. 2004;101:9199-204 pubmed
    Sarcolipin (SLN) inhibits the cardiac sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA2a) by direct binding and is superinhibitory if it binds through phospholamban (PLN)...
  5. Periasamy M, Reed T, Liu L, Ji Y, Loukianov E, Paul R, et al. Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) gene. J Biol Chem. 1999;274:2556-62 pubmed
    ..Ca2+-ATPase isoform 2 (SERCA2) gene encodes both SERCA2a, the cardiac sarcoplasmic reticulum Ca2+ pump, and SERCA2b, which is expressed in all tissues...
  6. He A, Ma Q, Cao J, von Gise A, Zhou P, Xie H, et al. Polycomb repressive complex 2 regulates normal development of the mouse heart. Circ Res. 2012;110:406-15 pubmed publisher
    ..Our study reveals a previously undescribed role of EZH2 in regulating heart formation and shows that perturbation of the epigenetic landscape early in cardiogenesis has sustained disruptive effects at later developmental stages. ..
  7. Kho C, Lee A, Jeong D, Oh J, Chaanine A, Kizana E, et al. SUMO1-dependent modulation of SERCA2a in heart failure. Nature. 2011;477:601-5 pubmed publisher
    The calcium-transporting ATPase ATP2A2, also known as SERCA2a, is a critical ATPase responsible for Ca(2+) re-uptake during excitation-contraction coupling...
  8. Luciani D, Gwiazda K, Yang T, Kalynyak T, Bychkivska Y, Frey M, et al. Roles of IP3R and RyR Ca2+ channels in endoplasmic reticulum stress and beta-cell death. Diabetes. 2009;58:422-32 pubmed publisher
    ..Our results also suggest the involvement of mitochondria in beta-cell apoptosis associated with dysfunctional beta-cell ER Ca(2+) homeostasis and ER stress. ..
  9. Andersson K, Finsen A, Sjåland C, Winer L, Sjaastad I, Odegaard A, et al. Mice carrying a conditional Serca2(flox) allele for the generation of Ca(2+) handling-deficient mouse models. Cell Calcium. 2009;46:219-25 pubmed publisher
    ..In heterozygous Serca2(wt/flox)MLC-2v(wt/Cre) mice, the expression of SERCA2a and SERCA2b proteins were reduced in the heart and slow skeletal muscle, in accordance with the expression ..

More Information


  1. Hiranandani N, Raman S, Kalyanasundaram A, Periasamy M, Janssen P. Frequency-dependent contractile strength in mice over- and underexpressing the sarco(endo)plasmic reticulum calcium-ATPase. Am J Physiol Regul Integr Comp Physiol. 2007;293:R30-6 pubmed ultrathin trabeculae isolated from hearts of mice overexpressing SERCA (transgenic, TG), underexpressing SERCA2a (heterozygous knockout, Het), and their respective wild-type (WT) littermates...
  2. Swift F, Franzini Armstrong C, Øyehaug L, Enger U, Andersson K, Christensen G, et al. Extreme sarcoplasmic reticulum volume loss and compensatory T-tubule remodeling after Serca2 knockout. Proc Natl Acad Sci U S A. 2012;109:3997-4001 pubmed publisher
    ..Indeed, major reduction in sarcoplasmic reticulum (SR) function in mice with Serca2 knockout (KO) is compensated by enhanced plasmalemmal Ca(2+) fluxes...
  3. Babu G, Bhupathy P, Timofeyev V, Petrashevskaya N, Reiser P, Chiamvimonvat N, et al. Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility. Proc Natl Acad Sci U S A. 2007;104:17867-72 pubmed
    Sarcolipin is a novel regulator of cardiac sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and is expressed abundantly in atria...
  4. Andersson K, Birkeland J, Finsen A, Louch W, Sjaastad I, Wang Y, et al. Moderate heart dysfunction in mice with inducible cardiomyocyte-specific excision of the Serca2 gene. J Mol Cell Cardiol. 2009;47:180-7 pubmed publisher
    ..We investigated heart function in adult mice with an inducible cardiomyocyte-specific excision of the Atp2a2 (Serca2) gene (SERCA2 KO)...
  5. Liu X, Zhang Z, Andersson K, Husberg C, Enger U, Ræder M, et al. Cardiomyocyte-specific disruption of Serca2 in adult mice causes sarco(endo)plasmic reticulum stress and apoptosis. Cell Calcium. 2011;49:201-7 pubmed publisher
    Reduced sarco(endo)plasmic reticulum (SR) Ca(2+) ATPase (SERCA2) contributes to the impaired cardiomyocyte Ca(2+) homeostasis observed in heart failure...
  6. Wang Y, Bruce A, Tu C, Ma K, Zeng L, Zheng P, et al. Protein aggregation of SERCA2 mutants associated with Darier disease elicits ER stress and apoptosis in keratinocytes. J Cell Sci. 2011;124:3568-80 pubmed publisher
    Mutations in sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) underlie Darier disease (DD), a dominantly inherited skin disorder characterized by loss of keratinocyte adhesion (acantholysis) and abnormal keratinization (..
  7. Hawkins C, Xu A, Narayanan N. Sarcoplasmic reticulum calcium pump in cardiac and slow twitch skeletal muscle but not fast twitch skeletal muscle undergoes phosphorylation by endogenous and exogenous Ca2+/calmodulin-dependent protein kinase. Characterization of optimal conditions . J Biol Chem. 1994;269:31198-206 pubmed
    ..of the Ca2+ pump is isoform-specific since heart and slow twitch muscle express the same Ca(2+)-ATPase isoform (SERCA2a), which is distinct from that of fast twitch muscle (SERCA1)...
  8. Huang H, Joseph L, Gurin M, Thorp E, Morrow J. Extracellular signal-regulated kinase activation during cardiac hypertrophy reduces sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) transcription. J Mol Cell Cardiol. 2014;75:58-63 pubmed publisher
    Pathologic cardiac hypertrophy can lead to heart failure, but the mechanisms involved are poorly understood. SERCA2 is critical for normal cardiac calcium handling and function and SERCA2 mRNA and protein levels are reduced by cardiac ..
  9. Zhou T, Li J, Zhao P, Liu H, Jia D, Jia H, et al. Palmitoyl acyltransferase Aph2 in cardiac function and the development of cardiomyopathy. Proc Natl Acad Sci U S A. 2015;112:15666-71 pubmed publisher
    ..These findings establish Aph2 as a critical in vivo regulator of cardiac function and reveal roles for protein palmitoylation in the development of other organs including eyes. ..
  10. Zhao Y, Chen Y, Miao G, Zhao H, Qu W, Li D, et al. The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation. Mol Cell. 2017;67:974-989.e6 pubmed publisher
    ..Our study provides mechanistic insights into the establishment and disassociation of ER-IM contacts and reveals that VMP1 modulates SERCA activity to control ER contacts. ..
  11. Zhu Y, Gramolini A, Walsh M, Zhou Y, Slorach C, Friedberg M, et al. Tbx5-dependent pathway regulating diastolic function in congenital heart disease. Proc Natl Acad Sci U S A. 2008;105:5519-24 pubmed publisher
    ..Tbx5 dosage modulates expression of the sarco(endo)plasmic reticulum Ca(2+)-ATPase isoform 2a encoded by Atp2a2 and Tbx5 haploinsufficiency in ventricular myocytes results in impaired Ca(2+) uptake dynamics and Ca(2+) ..
  12. Lipskaia L, Bobe R, Chen J, Turnbull I, Lopez J, Merlet E, et al. Synergistic role of protein phosphatase inhibitor 1 and sarco/endoplasmic reticulum Ca2+ -ATPase in the acquisition of the contractile phenotype of arterial smooth muscle cells. Circulation. 2014;129:773-85 pubmed publisher
    ..Gene transfer of constitutively active I-1 is a promising therapeutic strategy for preventing vascular proliferative disorders. ..
  13. Lang S, Benedix J, Fedeles S, Schorr S, Schirra C, Schäuble N, et al. Different effects of Sec61?, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cells. J Cell Sci. 2012;125:1958-69 pubmed publisher
    ..By contrast, silencing the SEC62 gene inhibited only post-translational transport of a signal-peptide-containing precursor protein. ..
  14. Ericsson M, Sjåland C, Andersson K, Sjaastad I, Christensen G, Sejersted O, et al. Exercise training before cardiac-specific Serca2 disruption attenuates the decline in cardiac function in mice. J Appl Physiol (1985). 2010;109:1749-55 pubmed publisher
    In the heart, function of the sarco(endo)plasmic Ca(2+)-ATPase (SERCA2) is closely linked to contractility, cardiac function, and aerobic fitness...
  15. Shanmugam M, Li D, Gao S, Fefelova N, Shah V, Voit A, et al. Cardiac specific expression of threonine 5 to alanine mutant sarcolipin results in structural remodeling and diastolic dysfunction. PLoS ONE. 2015;10:e0115822 pubmed publisher
    ..Furthermore, our studies suggest that alteration in SLN function can cause abnormal Ca2+ handling and subsequent cardiac remodeling and dysfunction. ..
  16. Feng Y, Valley M, Lazar J, Yang A, Bronson R, Firestein S, et al. SRp38 regulates alternative splicing and is required for Ca(2+) handling in the embryonic heart. Dev Cell. 2009;16:528-38 pubmed publisher
    ..Taken together, our results demonstrate that SRp38 regulates cardiac-specific alternative splicing of triadin pre-mRNA and, reflecting this, is essential for proper Ca(2+) handling during embryonic heart development. ..
  17. Hsu D, Donohue P, Alberts G, Winkles J. Fibroblast growth factor-1 induces phosphofructokinase, fatty acid synthase and Ca(2+)-ATPase mRNA expression in NIH 3T3 cells. Biochem Biophys Res Commun. 1993;197:1483-91 pubmed
    ..phosphofructokinase (PFK), fatty acid synthase (FAS) and sarco(endo)plasmic reticulum Ca(2+)-ATPase type 2 (SERCA2)--are described in this report...
  18. Prasad V, Boivin G, Miller M, Liu L, Erwin C, Warner B, et al. 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 Res. 2005;65:8655-61 pubmed
    ..mutation in one copy of the Atp2a2 or ATP2A2 gene, encoding sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2), leads to squamous cell tumors in mice and to Darier disease in humans, a skin disorder that also involves ..
  19. Arvanitis D, Vafiadaki E, Fan G, Mitton B, Gregory K, Del Monte F, et al. Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase. Am J Physiol Heart Circ Physiol. 2007;293:H1581-9 pubmed
    ..may mediate part of its regulatory effects by binding directly to sarco(endo)plasmic reticulum Ca-ATPase type 2 (SERCA2) in cardiac muscle, which is confirmed by coimmunostaining observed under confocal microscopy...
  20. Rouf R, Greytak S, Wooten E, Wu J, Boltax J, Picard M, et al. Increased FOG-2 in failing myocardium disrupts thyroid hormone-dependent SERCA2 gene transcription. Circ Res. 2008;103:493-501 pubmed publisher
    ..b>SERCA2 transcript and protein levels were reduced in FOG-2 transgenic hearts, and FOG-2 overexpression impaired T3-..
  21. Tsika R, Schramm C, Simmer G, Fitzsimons D, Moss R, Ji J. Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype. J Biol Chem. 2008;283:36154-67 pubmed publisher
    ..These novel in vivo data support a role for TEAD-1 in modulating slow muscle gene expression. ..
  22. Boardman N, Aronsen J, Louch W, Sjaastad I, Willoch F, Christensen G, et al. Impaired left ventricular mechanical and energetic function in mice after cardiomyocyte-specific excision of Serca2. Am J Physiol Heart Circ Physiol. 2014;306:H1018-24 pubmed publisher
    ..b>SERCA2 is a major ATP consumer in excitation-contraction coupling but is regarded to contribute to energetically ..
  23. Heinis F, Andersson K, Christensen G, Metzger J. Prominent heart organ-level performance deficits in a genetic model of targeted severe and progressive SERCA2 deficiency. PLoS ONE. 2013;8:e79609 pubmed publisher
    The cardiac SERCA2 Ca(2+) pump is critical for maintaining normal Ca(2+) handling in the heart. Reduced SERCA2a content and blunted Ca(2+) reuptake are frequently observed in failing hearts and evidence implicates poor cardiac Ca(2+) ..
  24. Tyser R, Miranda A, Chen C, Davidson S, Srinivas S, Riley P. Calcium handling precedes cardiac differentiation to initiate the first heartbeat. elife. 2016;5: pubmed publisher
    ..NCX1 blockade impacted on CaMKII signalling to down-regulate cardiac gene expression, leading to impaired differentiation and failed crescent maturation. ..
  25. Stoykov I, Zandieh Doulabi B, Moorman A, Christoffels V, Wiersinga W, Bakker O. Expression pattern and ontogenesis of thyroid hormone receptor isoforms in the mouse heart. J Endocrinol. 2006;189:231-45 pubmed
  26. Jiao Q, Takeshima H, Ishikawa Y, Minamisawa S. Sarcalumenin plays a critical role in age-related cardiac dysfunction due to decreases in SERCA2a expression and activity. Cell Calcium. 2012;51:31-9 pubmed publisher
    ..Thus we uncovered the important role of SAR in maintaining Ca(2+) transport activity of SERCA2a and cardiac function in the senescent population.
  27. Zhou L, Burnett A, Huang P, Becker L, Kuppusamy P, Kass D, et al. Lack of nitric oxide synthase depresses ion transporting enzyme function in cardiac muscle. Biochem Biophys Res Commun. 2002;294:1030-5 pubmed
  28. Revuelta López E, Cal R, Herraiz Martínez A, De Gonzalo Calvo D, Nasarre L, Roura S, et al. Hypoxia-driven sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) downregulation depends on low-density lipoprotein receptor-related protein 1 (LRP1)-signalling in cardiomyocytes. J Mol Cell Cardiol. 2015;85:25-36 pubmed publisher
    The maintenance of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) activity is crucial for cardiac function and SERCA2 is dramatically reduced in the heart exposed to hypoxic/ischemic conditions...
  29. Scharf M, Neef S, FREUND R, Geers Knörr C, Franz Wachtel M, Brandis A, et al. Mitogen-activated protein kinase-activated protein kinases 2 and 3 regulate SERCA2a expression and fiber type composition to modulate skeletal muscle and cardiomyocyte function. Mol Cell Biol. 2013;33:2586-602 pubmed publisher
    ..Elevated SERCA2a gene expression caused by a decreased ratio of transcription factor Egr-1 to Sp1 was associated with accelerated ..
  30. Mei Y, Thompson M, Shiraishi Y, Cohen R, Tong X. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase C674 promotes ischemia- and hypoxia-induced angiogenesis via coordinated endothelial cell and macrophage function. J Mol Cell Cardiol. 2014;76:275-82 pubmed publisher
    ..This study highlights the hitherto unrecognized interaction of two ER proteins, SERCA 2 C674 and ERO1, which mediate the EC and macrophage angiogenic response to ischemia/hypoxia. ..
  31. Kim Y, Kim S, Yatani A, Huang Y, Castelli G, Vatner D, et al. Mechanism of enhanced cardiac function in mice with hypertrophy induced by overexpressed Akt. J Biol Chem. 2003;278:47622-8 pubmed
    ..0 +/- 0.3 versus 7.2 +/- 0.3 pA/pF, p < 0.01). Sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) protein levels were increased (p < 0.05) by 6...
  32. Toral Ojeda I, Aldanondo G, Lasa Elgarresta J, Lasa Fernández H, Fernandez Torron R, Lopez de Munain A, et al. Calpain 3 deficiency affects SERCA expression and function in the skeletal muscle. Expert Rev Mol Med. 2016;18:e7 pubmed publisher
    ..Interestingly, SERCA2 protein was patently reduced in muscles from LGMD2A patients, while it was normally expressed in other forms of ..
  33. Wang Q, Wang D, Yan G, Qiao Y, Sun L, Zhu B, et al. SERCA2a was serotonylated and may regulate sino-atrial node pacemaker activity. Biochem Biophys Res Commun. 2016;480:492-497 pubmed publisher, we screened the cardiomyocytes proteins and found that sarco(endo)plasmic reticulum Ca ATPase type 2a (SERCA2a) can be serotonylated...
  34. Furtado M, Wilmanns J, Chandran A, Tonta M, Biben C, Eichenlaub M, et al. A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels. Differentiation. 2016;91:29-41 pubmed publisher
  35. Earls L, Bayazitov I, Fricke R, Berry R, Illingworth E, Mittleman G, et al. Dysregulation of presynaptic calcium and synaptic plasticity in a mouse model of 22q11 deletion syndrome. J Neurosci. 2010;30:15843-55 pubmed publisher
    ..calcium kinetics in CA3 presynaptic terminals and upregulated sarco(endo)plasmic reticulum calcium-ATPase type 2 (SERCA2). SERCA inhibitors rescued synaptic phenotypes of Df(16)1/+ mice...
  36. Ikeda K, Kang Q, Yoneshiro T, Camporez J, Maki H, Homma M, et al. UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis. Nat Med. 2017;23:1454-1465 pubmed publisher
    ..involves enhanced ATP-dependent Ca2+ cycling by sarco/endoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) and ryanodine receptor 2 (RyR2)...
  37. Mederle K, Gess B, Pluteanu F, Plackic J, Tiefenbach K, Grill A, et al. The angiotensin receptor-associated protein Atrap is a stimulator of the cardiac Ca2+-ATPase SERCA2a. Cardiovasc Res. 2016;110:359-70 pubmed publisher
    ..Sequencing by MALDI-MS of the isolated complexes showed that Atrap interacts with the cardiac Ca(2+)-ATPase SERCA2a. The interaction between Atrap and SERCA2a was confirmed by co-immunoprecipitation and by surface plasmon ..
  38. Stokke M, Briston S, Jølle G, Manzoor I, Louch W, Øyehaug L, et al. Ca(2+) wave probability is determined by the balance between SERCA2-dependent Ca(2+) reuptake and threshold SR Ca(2+) content. Cardiovasc Res. 2011;90:503-12 pubmed publisher
    ..SERCA2 knockout mice (KO) were used 6 days after cardio-specific gene deletion, with left ventricular SERCA2a abundance reduced by 54 ± 9% compared with SERCA2(flox/flox) controls (FF) (P < 0.05)...
  39. Hillestad V, Kramer F, Golz S, Knorr A, Andersson K, Christensen G. Long-term levosimendan treatment improves systolic function and myocardial relaxation in mice with cardiomyocyte-specific disruption of the Serca2 gene. J Appl Physiol (1985). 2013;115:1572-80 pubmed publisher
    ..After induction of Serca2 gene disruption, these mice develop marked diastolic dysfunction as well as impaired contractility...
  40. Rog Zielinska E, Thomson A, Kenyon C, Brownstein D, Moran C, Szumska D, et al. Glucocorticoid receptor is required for foetal heart maturation. Hum Mol Genet. 2013;22:3269-82 pubmed publisher
  41. Lee A, Jeong D, Mitsuyama S, Oh J, Liang L, Ikeda Y, et al. The role of SUMO-1 in cardiac oxidative stress and hypertrophy. Antioxid Redox Signal. 2014;21:1986-2001 pubmed publisher
    ..shown to play a critical role in the dysfunction of the cardiac isoform of sarcoplasmic reticulum calcium ATPase (SERCA2a) pump in the setting of heart failure...
  42. Iversen P, Andersson K, Finsen A, Sjaastad I, von Lueder T, Sejersted O, et al. Separate mechanisms cause anemia in ischemic vs. nonischemic murine heart failure. Am J Physiol Regul Integr Comp Physiol. 2010;298:R808-14 pubmed publisher
    ..protein calsequestrin (CSQ) or to induced cardiac disruption of the sarcoplasmic reticulum Ca(2+)-ATPase 2 gene (SERCA2 KO). Hematopoiesis was analyzed by colony formation of CD34(+) bone marrow cells. Hemoglobin concentration was 14...
  43. Ravier M, Daro D, Roma L, Jonas J, Cheng Xue R, Schuit F, et al. Mechanisms of control of the free Ca2+ concentration in the endoplasmic reticulum of mouse pancreatic ?-cells: interplay with cell metabolism and [Ca2+]c and role of SERCA2b and SERCA3. Diabetes. 2011;60:2533-45 pubmed publisher
    Sarco-endoplasmic reticulum Ca(2+)-ATPase 2b (SERCA2b) and SERCA3 pump Ca(2+) in the endoplasmic reticulum (ER) of pancreatic ?-cells...
  44. Domenighetti A, Wang Q, Egger M, Richards S, Pedrazzini T, Delbridge L. Angiotensin II-mediated phenotypic cardiomyocyte remodeling leads to age-dependent cardiac dysfunction and failure. Hypertension. 2005;46:426-32 pubmed
    ..In TG hearts, chronic Ang II exposure induced downregulation of the sarcoplasmic reticulum calcium pump (SERCA2) and diminution of Ca2+ transients, indicative of an underlying disturbance in calcium homeostasis...
  45. Jaisser F, Beggah A. The nongastric H+-K+-ATPases: molecular and functional properties. Am J Physiol. 1999;276:F812-24 pubmed
    ..Extensive studies will be required in the future to better understand the physiological role of these H-K-ATPases, especially in disease processes including ionic or acid-base disorders. ..
  46. Ver Heyen M, Heymans S, Antoons G, Reed T, Periasamy M, Awede B, et al. Replacement of the muscle-specific sarcoplasmic reticulum Ca(2+)-ATPase isoform SERCA2a by the nonmuscle SERCA2b homologue causes mild concentric hypertrophy and impairs contraction-relaxation of the heart. Circ Res. 2001;89:838-46 pubmed
    ..Gene targeting in mice successfully disrupted the splicing mechanism responsible for generating the SERCA2a isoform. Homozygous SERCA2a(-/-) mice displayed a complete loss of SERCA2a mRNA and protein resulting in a switch to ..
  47. Wakai T, Zhang N, Vangheluwe P, Fissore R. Regulation of endoplasmic reticulum Ca(2+) oscillations in mammalian eggs. J Cell Sci. 2013;126:5714-24 pubmed publisher
    ..We also examined the expression of SERCA2b protein and found that it was expressed throughout oocyte maturation and attained a conspicuous cortical cluster ..
  48. Stefanovic B, Stefanovic L, Schnabl B, Bataller R, Brenner D. TRAM2 protein interacts with endoplasmic reticulum Ca2+ pump Serca2b and is necessary for collagen type I synthesis. Mol Cell Biol. 2004;24:1758-68 pubmed
    ..The C-terminal part of TRAM2 interacts with the Ca(2+) pump of the ER, SERCA2b, as demonstrated in a Saccharomyces cerevisiae two-hybrid screen and by immunoprecipitations in human cells...
  49. Radzyukevich T, Moseley A, Shelly D, Redden G, Behbehani M, Lingrel J, et al. The Na(+)-K(+)-ATPase alpha2-subunit isoform modulates contractility in the perinatal mouse diaphragm. Am J Physiol Cell Physiol. 2004;287:C1300-10 pubmed
    ..They further indicate that the alpha2-isoform contributes significantly less at rest than expected from its proportional content but can modulate contractility during muscle contraction. ..
  50. Land S, Louch W, Niederer S, Aronsen J, Christensen G, Sjaastad I, et al. Beta-adrenergic stimulation maintains cardiac function in Serca2 knockout mice. Biophys J. 2013;104:1349-56 pubmed publisher
    Previous studies on Serca2 knockout (KO) mice showed that cardiac function is sustained in vivo for several weeks after knockout, whereas SERCA protein levels decrease and calcium dynamics are significantly impaired...
  51. Shintani Y, Drexler H, Kioka H, Terracciano C, Coppen S, Imamura H, et al. Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2. EMBO Rep. 2014;15:438-45 pubmed publisher
    ..Here, we identify the calcium-transporting ATPase, SERCA2 (also known as Atp2a2), as a key molecule for the alternative TLR9 signalling pathway...
  52. Franco D, Campione M, Kelly R, Zammit P, Buckingham M, Lamers W, et al. Multiple transcriptional domains, with distinct left and right components, in the atrial chambers of the developing heart. Circ Res. 2000;87:984-91 pubmed
    ..Furthermore, this work will allow the contribution of each of these myocardial components to be studied in congenitally malformed hearts, such as those with abnormal venous return. ..
  53. Kruithof B, van den Hoff M, Tesink Taekema S, Moorman A. Recruitment of intra- and extracardiac cells into the myocardial lineage during mouse development. Anat Rec A Discov Mol Cell Evol Biol. 2003;271:303-14 pubmed
    ..pattern of expression of alpha-Sma and of the myocardial markers sarcoplasmatic reticulum calcium ATPase (Serca2a), alpha-myosin heavy chain (Mhc), and beta-Mhc were examined...
  54. Haghighi K, Gregory K, Kranias E. Sarcoplasmic reticulum Ca-ATPase-phospholamban interactions and dilated cardiomyopathy. Biochem Biophys Res Commun. 2004;322:1214-22 pubmed
    ..A large body of evidence points to the central role of abnormal Ca handling by SR proteins, Ca-ATPase pump (SERCA2a) and phospholamban (PLN), in pathophysiological heart conditions, compromising the contractile state of the ..
  55. Pelled D, Lloyd Evans E, Riebeling C, Jeyakumar M, Platt F, Futerman A. Inhibition of calcium uptake via the sarco/endoplasmic reticulum Ca2+-ATPase in a mouse model of Sandhoff disease and prevention by treatment with N-butyldeoxynojirimycin. J Biol Chem. 2003;278:29496-501 pubmed
    ..This study suggests a mechanistic link among GM2 accumulation, reduced SERCA activity, and neuronal cell death, which may be of significance for delineating the neuropathophysiology of Sandhoff disease...
  56. McFadden D, Barbosa A, Richardson J, Schneider M, Srivastava D, Olson E. The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage-dependent manner. Development. 2005;132:189-201 pubmed
    ..These findings demonstrate that Hand factors play pivotal and partially redundant roles in cardiac morphogenesis, cardiomyocyte differentiation and cardiac-specific transcription. ..
  57. Lai L, Leone T, Zechner C, Schaeffer P, Kelly S, Flanagan D, et al. Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev. 2008;22:1948-61 pubmed publisher
    ..We conclude that PGC-1alpha and PGC-1beta share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT. ..
  58. Wang J, Silva J, Gustafsson C, Rustin P, Larsson N. Increased in vivo apoptosis in cells lacking mitochondrial DNA gene expression. Proc Natl Acad Sci U S A. 2001;98:4038-43 pubmed
    ..It would therefore be of interest to determine whether manipulation of respiratory chain function can be used to inhibit or enhance apoptosis in these conditions. ..
  59. Rohman M, Emoto N, Takeshima Y, Yokoyama M, Matsuo M. Decreased mAKAP, ryanodine receptor, and SERCA2a gene expression in mdx hearts. Biochem Biophys Res Commun. 2003;310:228-35 pubmed
    ..Therefore, dystrophin deficiency may cause an impairment of SR Ca(2+) homeostasis and E-C coupling in mdx hearts, in part, by decreased gene expression of molecules involved in SR Ca(2+) handling. ..
  60. Tong J, Qi Y, Wang X, Yu L, Su C, Xie W, et al. Cell micropatterning reveals the modulatory effect of cell shape on proliferation through intracellular calcium transients. Biochim Biophys Acta Mol Cell Res. 2017;1864:2389-2401 pubmed publisher
    ..of the inositol 1,4,5-triphosphate receptor 1 (IP3R1) and sarco/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), two major calcium cycling proteins in the endoplasmic reticulum (ER), were increased with an increase in NSI as ..
  61. Ver Heyen M, Reed T, Blough R, Baker D, Zilberman A, Loukianov E, et al. Structure and organization of the mouse Atp2a2 gene encoding the sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2) isoforms. Mamm Genome. 2000;11:159-63 pubmed
  62. Sari F, Watanabe K, Widyantoro B, Thandavarayan R, Harima M, Kodama M, et al. Sex differences play a role in cardiac endoplasmic reticulum stress (ERS) and ERS-initiated apoptosis induced by pressure overload and thapsigargin. Cardiovasc Pathol. 2011;20:281-90 pubmed publisher
    ..Our data suggest that sex differences affected the response of myocardial tissues in dealing with cardiac ERS and further result of ERS, apoptosis, at least in part through the regulation of SERCA2, CHOP, Ire1? and TRAF2.
  63. Zhou H, Black S, Benson T, Weintraub N, Chen W. Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Is Not Required for Brown Adipogenesis but Regulates Brown Adipose Tissue Development and Function. Mol Cell Biol. 2016;36:2027-38 pubmed publisher
  64. Zhao X, Shin D, Liu L, Shull G, Muallem S. Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2(+/-) mice. EMBO J. 2001;20:2680-9 pubmed
    Darier's disease (DD) is a high penetrance, autosomal dominant mutation in the ATP2A2 gene, which encodes the SERCA2 Ca2+ pump...
  65. Wei H, Li Z, Wang X, Wang J, Pang W, Yang G, et al. microRNA-151-3p regulates slow muscle gene expression by targeting ATP2a2 in skeletal muscle cells. J Cell Physiol. 2015;230:1003-12 pubmed publisher
    ..Further investigation into the underlying mechanisms revealed for the first time that miR-151-3p directly targets ATP2a2, a gene encoding for a slow skeletal and cardiac muscle specific Ca(2+) ATPase, SERCA2 thus downregulating slow ..
  66. Ericsson M, Andersson K, Amundsen B, Torp S, Sjaastad I, Christensen G, et al. High-intensity exercise training in mice with cardiomyocyte-specific disruption of Serca2. J Appl Physiol (1985). 2010;108:1311-20 pubmed publisher
    Several lines of evidence indicate that the sarco(endo)plasmic reticulum ATPase type 2 (SERCA2) is essential for maintaining myocardial calcium handling and cardiac pump function...
  67. Sjåland C, Lunde P, Swift F, Munkvik M, Ericsson M, Lunde M, et al. Slowed relaxation and preserved maximal force in soleus muscles of mice with targeted disruption of the Serca2 gene in skeletal muscle. J Physiol. 2011;589:6139-55 pubmed publisher
    ..In this study, we present a new mouse model with targeted disruption of the Serca2 gene in skeletal muscle (skKO) to investigate the functional consequences of reduced SERCA2 expression in skeletal ..
  68. Sprenger J, Perera R, Steinbrecher J, Lehnart S, Maier L, Hasenfuss G, et al. In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease. Nat Commun. 2015;6:6965 pubmed publisher
    ..In particular, we uncover the existence of a phosphodiesterase-dependent receptor-microdomain communication, which is affected in hypertrophy, resulting in reduced β-adrenergic receptor-cAMP signalling to SERCA. ..
  69. Seth M, Li T, Graham V, Burch J, Finch E, Stiber J, et al. Dynamic regulation of sarcoplasmic reticulum Ca(2+) stores by stromal interaction molecule 1 and sarcolipin during muscle differentiation. Dev Dyn. 2012;241:639-47 pubmed publisher
    ..These results suggest that SOCE regulates SR/ER specialization and that SLN and STIM1 act in opposing fashions to govern SOCE during myogenesis. ..
  70. Johnson J, Kono T, Tong X, Yamamoto W, Zarain Herzberg A, Merrins M, et al. Pancreatic and duodenal homeobox protein 1 (Pdx-1) maintains endoplasmic reticulum calcium levels through transcriptional regulation of sarco-endoplasmic reticulum calcium ATPase 2b (SERCA2b) in the islet β cell. J Biol Chem. 2014;289:32798-810 pubmed publisher
    ..The sarco-endoplasmic reticulum Ca(2+) ATPase 2b (SERCA2b) pump maintains a steep Ca(2+) gradient between the cytosol and ER lumen...
  71. Shirai M, Osugi T, Koga H, Kaji Y, Takimoto E, Komuro I, et al. The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis. J Clin Invest. 2002;110:177-84 pubmed
    ..5 expression in cardiomyocytes. Thus, our data show that a mammalian PcG gene can play a key role in organogenesis by helping to maintain the expression of a selector gene. ..
  72. Park S, Zhou Y, Lee J, Lee J, Ozcan U. Sarco(endo)plasmic reticulum Ca2+-ATPase 2b is a major regulator of endoplasmic reticulum stress and glucose homeostasis in obesity. Proc Natl Acad Sci U S A. 2010;107:19320-5 pubmed publisher
    ..Here, we show that SERCA2b protein and mRNA levels are dramatically reduced in the liver of obese mice and restoration of SERCA2b in the ..
  73. Moore C, Omikorede O, Gomez E, Willars G, Herbert T. PERK activation at low glucose concentration is mediated by SERCA pump inhibition and confers preemptive cytoprotection to pancreatic ?-cells. Mol Endocrinol. 2011;25:315-26 pubmed publisher
  74. Suarez J, Scott B, Dillmann W. Conditional increase in SERCA2a protein is able to reverse contractile dysfunction and abnormal calcium flux in established diabetic cardiomyopathy. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1439-45 pubmed publisher
    ..heart is impaired sarcoplasmic reticulum function with reduced sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) pump activity, leading to disturbed intracellular calcium handling...
  75. Vangheluwe P, Schuermans M, Raeymaekers L, Wuytack F. Tight interplay between the Ca2+ affinity of the cardiac SERCA2 Ca2+ pump and the SERCA2 expression level. Cell Calcium. 2007;42:281-9 pubmed
    ..In SERCA2b/b mice, the normal SERCA2a isoform is replaced by SERCA2b, displaying a higher Ca2+ affinity...
  76. Ya J, Erdtsieck Ernste E, de Boer P, van Kempen M, Jongsma H, Gros D, et al. Heart defects in connexin43-deficient mice. Circ Res. 1998;82:360-6 pubmed
  77. Morissette M, Susser S, Stammers A, O Hara K, Gardiner P, Sheppard P, et al. Differential regulation of the fiber type-specific gene expression of the sarcoplasmic reticulum calcium-ATPase isoforms induced by exercise training. J Appl Physiol (1985). 2014;117:544-55 pubmed publisher
    ..monophosphate-activated protein kinase (AMPK)-?2 on sarcoplasmic reticulum calcium-ATPase (SERCA) 1a and SERCA2a in different skeletal muscle fiber types has yet to be elucidated...
  78. Kuwahara K, Saito Y, Takano M, Arai Y, Yasuno S, Nakagawa Y, et al. NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function. EMBO J. 2003;22:6310-21 pubmed
    ..Our results indicate NRSF to be a key transcriptional regulator of the fetal cardiac gene program and suggest an important role for NRSF in maintaining normal cardiac structure and function. ..
  79. Wang W, Barnabei M, Asp M, Heinis F, Arden E, Davis J, et al. Noncanonical EF-hand motif strategically delays Ca2+ buffering to enhance cardiac performance. Nat Med. 2013;19:305-12 pubmed publisher
    ..Strategic design of new EF-hand motif domains to modulate intracellular Ca(2+) signaling could benefit many biological systems with abnormal Ca(2+) handling, including the diseased heart. ..
  80. Toki H, Minowa O, Inoue M, Motegi H, Karashima Y, Ikeda A, et al. Novel allelic mutations in murine Serca2 induce differential development of squamous cell tumors. Biochem Biophys Res Commun. 2016;476:175-182 pubmed publisher
    Dominant mutations in the Serca2 gene, which encodes sarco(endo)plasmic reticulum calcium-ATPase, predispose mice to gastrointestinal epithelial carcinoma [1-4] and humans to Darier disease (DD) [14-17]...
  81. Raeymaekers L, Vandecaetsbeek I, Wuytack F, Vangheluwe P. Modeling Ca2+ dynamics of mouse cardiac cells points to a critical role of SERCA's affinity for Ca2+. Biophys J. 2011;100:1216-25 pubmed publisher
    The SERCA2a isoform of the sarco/endoplasmic reticulum Ca(2+) pumps is specifically expressed in the heart, whereas SERCA2b is the ubiquitously expressed variant...