Affinage

ATP2B4

Plasma membrane calcium-transporting ATPase 4 · UniProt P23634

Length
1241 aa
Mass
137.9 kDa
Annotated
2026-06-09
38 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP2B4 (PMCA4) is a plasma-membrane Ca2+-extrusion ATPase that acts as the dominant pump clearing cytosolic Ca2+ in multiple cell types and, in parallel, serves as a membrane scaffold organizing Ca2+-signaling microdomains (PMID:15178683, PMID:21965681, PMID:28714864). Its primary transcript is alternatively spliced into PMCA4a and PMCA4b, which differ in their C-terminal regulatory domain and show distinct tissue distributions and basal activities (PMID:1531651); during sperm maturation an a/b isoform switch tunes Ca2+ turnover (PMID:21187283). In sperm, PMCA4 localizes to the principal piece alongside CatSper, and its loss causes Ca2+ overload and failure of hyperactivated motility, producing male infertility (PMID:15178683), while it also forms a Ca2+-dependent quaternary complex with eNOS, nNOS, and Caveolin1 that restrains nitrosative stress (PMID:28247940). In cardiomyocytes it tethers nNOS to a caveolar microdomain, where its delocalization shifts local cGMP/cAMP balance to raise contractility (PMID:21965681, PMID:23880607). Beyond pumping, PMCA4 couples Ca2+ handling to proliferation and differentiation programs: its efflux activity drives G1-phase progression in vascular smooth muscle through splice-variant-specific control of Cyclin D1 and AP-2β (PMID:24448801), and in cancer cells it restrains migration, EMT via an NFATc1–ZEB1 axis, and macropinocytosis, and modulates apoptosis and DNA-damage responses (PMID:32860837, PMID:31963119, PMID:38597132, PMID:42185253). An erythroid-specific enhancer and regulatory non-coding variants set ATP2B4 expression in red blood cells, controlling RBC Ca2+ homeostasis (PMID:28714864, PMID:35563239, PMID:28216081). A familial spastic paraplegia-associated R268Q missense mutation reduces Ca2+ extrusion capacity, linking PMCA4 dysfunction to disease (PMID:25798335).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 High

    Established that a single ATP2B4 gene generates distinct regulatory isoforms, explaining how one pump could be functionally tailored to different tissues.

    Evidence cDNA cloning, RT-PCR/Southern blot and genomic intron-exon sequencing identifying PMCA4a/PMCA4b splice variants and their tissue distribution

    PMID:1531651

    Open questions at the time
    • Functional consequences of the truncated C-terminal regulatory domain not directly tested
    • Isoform-specific regulators not identified
  2. 2001 High

    First loss-of-function evidence that PMCA4 controls a cell-fate outcome, linking its Ca2+ handling to TNF-induced death pathways.

    Evidence Retrovirus-insertion mutagenesis in L929 cells with intracellular Ca2+, lysosome exocytosis and acidic-compartment volume readouts

    PMID:11713265

    Open questions at the time
    • Mechanism linking Ca2+ elevation to VAC inhibition incompletely defined
    • Single cell-line context
  3. 2004 High

    Defined PMCA4 as the dominant Ca2+ extrusion pump in sperm and established its requirement for hyperactivated motility and male fertility.

    Evidence Pmca4-/- mice with sperm motility assays, IHC localization to the principal piece, and ultrastructural analysis

    PMID:15178683

    Open questions at the time
    • Relationship to CatSper-mediated Ca2+ entry not mechanistically resolved
    • Does not address PMCA4's scaffolding roles
  4. 2011 High

    Revealed a non-pumping, scaffolding function whereby PMCA4 spatially confines nNOS to set local second-messenger balance and contractility.

    Evidence PMCA4-/- mice with FRET cAMP/cGMP sensors, subcellular fractionation, nNOS activity and channel/RyR phosphorylation assays plus in vivo physiology

    PMID:21965681

    Open questions at the time
    • Structural basis of nNOS tethering not defined
    • Whether scaffolding requires pump activity not separated
  5. 2010 Medium

    Showed compartmentalization of PMCA4 within sperm membrane microdomains and an isoform switch during epididymal maturation, connecting localization to Ca2+ turnover demands.

    Evidence Detergent-resistant membrane fractionation, Ca2+-ATPase activity assays, isoform-specific IHC and qPCR across testis/epididymis/sperm

    PMID:20050939 PMID:21187283

    Open questions at the time
    • Functional consequence of isoform switch inferred, not directly tested
    • Regulators driving the switch unknown
  6. 2014 High

    Demonstrated that PMCA4 Ca2+ efflux, not just its presence, drives cell-cycle progression, with splice variants engaging different downstream effectors.

    Evidence PMCA4-knockout VSMCs with thymidine incorporation, splice-variant and pump-dead rescue, microarray and Western blot

    PMID:24448801

    Open questions at the time
    • Connection between Ca2+ efflux and AP-2β/Cyclin D1 transcription not fully mapped
    • Restricted to VSMC context
  7. 2013 Medium

    Provided a tool to monitor Ca2+ near the pump, confirming PMCA4 shapes local Ca2+ dynamics under β-adrenergic input in cardiomyocytes.

    Evidence PMCA4-GCaMP2 fusion biosensor with pump-inactive control in rat cardiomyocytes and live-cell imaging

    PMID:23880607

    Open questions at the time
    • Quantitative size of the microdomain not defined
    • Single-lab biosensor approach
  8. 2016 Medium

    Identified a Ca2+-independent signaling role through direct CD147 binding that suppresses T-cell IL-2 expression.

    Evidence AP-MS interaction discovery, CD147 domain-mapping constructs, siRNA and IL-2 assays in human T cells

    PMID:26729804

    Open questions at the time
    • Molecular basis of the Ca2+-independent effect undefined
    • Single-lab interaction
  9. 2017 High

    Linked PMCA4 to nitrosative-stress control in sperm via a Ca2+-dependent multiprotein NOS complex and established regulatory variation governing RBC Ca2+ homeostasis and malaria-relevant biology.

    Evidence Co-IP/FRET of PMCA4-eNOS-nNOS-Caveolin1 with NOS/peroxynitrite assays in Pmca4-/- sperm; erythroid enhancer CRISPR deletion and Atp2b4-/- mice; haplotype-linked RBC PMCA4b quantification and Ca2+ extrusion assays

    PMID:28216081 PMID:28247940 PMID:28714864

    Open questions at the time
    • Stoichiometry and assembly order of the NOS complex unknown
    • Mechanism connecting RBC Ca2+ to malaria susceptibility not directly shown in these studies
  10. 2015 Medium

    Connected a disease-associated missense mutation to reduced pump function, providing a mechanistic basis for a PMCA4-linked neurological phenotype.

    Evidence Overexpression of WT vs R268Q PMCA4 in SH-SY5Y cells with fura-2 Ca2+ imaging after depolarization and SERCA inhibition

    PMID:25798335

    Open questions at the time
    • Causality in patient neurons not established
    • Single overexpression model
  11. 2020 Medium

    Extended PMCA4 into cancer cell behavior, defining it as a suppressor of migration, EMT, and proliferation through Ca2+ clearance and NFATc1-ZEB1 signaling, with pathway-driven downregulation in vascular disease.

    Evidence siRNA/overexpression with epistasis (NFATc1/ZEB1 knockdown, cyclosporine A), Ca2+ clearance, migration/apoptosis assays, MEK/ERK inhibitors, and in vivo rat PAH and nude-mouse metastasis models

    PMID:31963119 PMID:32860837 PMID:32966125

    Open questions at the time
    • Whether effects depend on pump activity vs scaffolding not uniformly resolved
    • Single-lab studies per tissue
  12. 2022 Medium

    Confirmed non-coding malaria-associated variants functionally tune ATP2B4 expression and RBC Ca2+, and identified exosomal miR-4261 as a post-transcriptional regulator.

    Evidence CRISPR deletion of the regulatory region in K562 cells with expression/Ca2+ readouts; dual-luciferase reporter and exosome transfer assays for miR-4261 targeting

    PMID:35563239 PMID:36091107

    Open questions at the time
    • miR-4261 finding rests on single luciferase/transfer experiment
    • Downstream pathophysiology of RBC Ca2+ overload inferred
  13. 2024 Medium

    Showed PMCA4 pump activity is required for a specific stage of macropinocytosis, broadening its role into vesicle-mediated uptake.

    Evidence ATP2B4 CRISPR knockout with live-cell macropinocytosis imaging, Ca2+ oscillation measurement, and PDZ-binding and pump-dead mutant rescue in A431 cells

    PMID:38597132

    Open questions at the time
    • How Ca2+ oscillations drive ruffle closure not detailed
    • Single cell-line context
  14. 2025 Medium

    Identified a PMCA4/GAT3/calmodulin lipid-raft complex coupling Ca2+ microdomains to CaMKII-CREB signaling and glioma invasion.

    Evidence Co-IP, lipid raft fractionation with Ca2+ measurement, siRNA knockdown, and CaMKII/CREB phosphorylation and migration assays in glioma cells

    PMID:40580687

    Open questions at the time
    • Direct vs calmodulin-bridged PMCA4-GAT3 interaction not resolved
    • Abstract-level mechanistic detail
  15. 2026 Medium

    Uncovered a nuclear-relevant function in which PMCA4 stabilizes ELAVL1 to maintain histone H1.0, controlling chromatin compaction and radiosensitivity.

    Evidence CRISPR knockout, TurboID proximity-labeling MS, IP, micrococcal nuclease and RNA-seq assays, and in vivo xenograft radiotherapy

    PMID:42185253

    Open questions at the time
    • Mechanism by which a plasma-membrane pump stabilizes ELAVL1 unclear
    • Single-lab novel finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how PMCA4 partitions between its Ca2+-pumping and scaffolding functions across tissues, and what structural features dictate its assembly into the various NOS, CD147, GAT3, and ELAVL1 complexes.
  • No structural model of PMCA4 partner complexes
  • Pump-activity vs scaffolding contributions not separated in most disease contexts
  • Mechanism linking membrane pump to nuclear/chromatin effects unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0060090 molecular adaptor activity 3 GO:0140657 ATP-dependent activity 3 GO:0016787 hydrolase activity 1
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1640170 Cell Cycle 1 R-HSA-5653656 Vesicle-mediated transport 1
Partners
CALMODULINCAV1CD147ELAVL1ENOSGAT3NNOS
Complex memberships
PMCA4-eNOS-nNOS-Caveolin1 quaternary complexPMCA4/GAT3/calmodulin lipid-raft complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 PMCA4 (ATP2B4) is localized to the principal piece of the sperm tail, co-localizing with the CatSper Ca2+ channel, and its loss in Pmca4-/- mice causes failure to achieve hyperactivated sperm motility and male infertility despite normal spermatogenesis; increased mitochondrial condensation in null sperm indicated Ca2+ overload, consistent with PMCA4's role as the dominant Ca2+ extrusion pump in sperm. Gene knockout (Pmca4-/- mice), immunoblotting, immunohistochemistry, sperm motility assays, ultrastructural analysis The Journal of biological chemistry High 15178683
1992 PMCA4 primary transcripts are alternatively spliced to produce at least two isoforms (PMCA4a and PMCA4b); PMCA4b contains an inserted exon after the calmodulin-binding domain that shifts the reading frame, truncating the C-terminal regulatory domain; each splice variant shows distinct tissue distribution with PMCA4a present in all tissues and PMCA4b restricted to excitable tissues. RT-PCR/Southern blot of cDNA, cDNA cloning and sequencing, genomic sequencing of intron-exon boundaries The Journal of biological chemistry High 1531651
2001 PMCA4 is required for TNF-induced cell death in L929 cells; retrovirus-insertion mutagenesis of PMCA4 caused abnormally elevated intracellular Ca2+ following TNF stimulation, which promoted lysosome exocytosis and inhibited the TNF-induced increase in volume of acidic compartments (VAC), thereby conferring resistance to TNF-induced death. Retrovirus-insertion random mutagenesis screen, intracellular Ca2+ measurement, lysosome volume assays, pharmacological rescue (sucrose-mediated VAC increase) Molecular and cellular biology High 11713265
2011 PMCA4 acts as a structural scaffold that tethers neuronal NOS (nNOS) to a caveolar microdomain in cardiomyocytes; in PMCA4-/- hearts >36% of membrane-associated nNOS is delocalized to the cytosol, reducing microdomain cGMP, decreasing PDE2 activity, elevating local cAMP, increasing L-type Ca2+ channel activity and ryanodine receptor phosphorylation, and thereby increasing cardiac contractility. PMCA4 knockout mice, in vivo cardiac contractility measurements, subcellular fractionation, nNOS activity assays, FRET-based cAMP/cGMP sensors, L-type Ca2+ channel and ryanodine receptor phosphorylation assays The Journal of biological chemistry High 21965681
2017 ATP2B4 is the primary Ca2+ extrusion pump in red blood cells; an erythroid-specific enhancer drives its expression, and CRISPR-Cas9 deletion of this enhancer reduces ATP2B4 expression and causes abnormally elevated intracellular Ca2+ in erythroid cells; Atp2b4-/- mice display increased mean corpuscular hemoglobin concentration (MCHC). CRISPR-Cas9 enhancer deletion, eQTL mapping in erythroblasts, Atp2b4 knockout mice, intracellular Ca2+ measurement The Journal of clinical investigation High 28714864
2014 Ca2+ efflux activity of PMCA4 is required for G1-phase progression in vascular smooth muscle cells (VSMCs); PMCA4 knockout VSMCs show impaired DNA synthesis and G1 arrest; PMCA4a and PMCA4b splice variants differentially regulate downstream mediators (AP-2β and p15/Cyclin D1 respectively) of cell cycle progression; a PMCA4b mutant with only 10% of normal Ca2+ efflux activity cannot rescue G1 arrest. PMCA4 knockout mouse-derived VSMCs, [3H]thymidine incorporation, electroporation of splice-variant expression constructs, microarray, Western blot The Journal of biological chemistry High 24448801
2017 PMCA4 physically associates with eNOS and nNOS in sperm; Co-IP and FRET show PMCA4 forms a quaternary complex with eNOS, nNOS, and Caveolin1 in a Ca2+-dependent manner; in Pmca4-/- sperm, NOS activity and peroxynitrite levels are elevated ~2-fold, causing increased apoptosis in germ cells and asthenospermia. Co-immunoprecipitation, FRET (fluorescence resonance energy transfer), NOS activity assay, peroxynitrite measurement, germ cell apoptosis assay in Pmca4-/- mice Journal of cellular physiology High 28247940
2016 CD147 interacts with PMCA4 via its transmembrane domain and Ig-like domain II; this interaction is required for CD147-dependent inhibition of IL-2 expression in T cells via a calcium-independent mechanism; CD147 does not control membrane localization of PMCA4. Affinity purification with mass spectrometry, CD147 domain-mapping constructs, siRNA knockdown of CD147 and PMCA4, IL-2 production assays in human T cells Journal of immunology Medium 26729804
2015 The familial spastic paraplegia-associated R268Q missense mutation in PMCA4 reduces Ca2+ extrusion capacity; SH-SY5Y neuroblastoma cells overexpressing R268Q PMCA4 show significantly higher cytosolic Ca2+ surge after depolarization and elevated steady-state Ca2+ after SERCA inhibition compared with wild-type PMCA4. Overexpression of WT and R268Q mutant PMCA4 in SH-SY5Y cells, fura-2 Ca2+ imaging by confocal microscopy, KCl depolarization and thapsigargin treatment Brain and behavior Medium 25798335
2010 During sperm maturation in the bovine epididymis, PMCA4 splice variants switch from predominantly PMCA4b in testis/caput/corpus to predominantly PMCA4a in cauda epididymidis; PMCA4a (which has higher basal activity and is more effective at returning Ca2+ to resting levels) is transferred to sperm membranes in the cauda, suggesting this isoform switch facilitates the higher Ca2+ turnover needed for sperm to traverse the female genital tract. Quantitative PCR, immunohistochemistry with isoform-specific antibody, Western blotting of testis/epididymis/sperm fractions The Journal of biological chemistry Medium 21187283
2013 PMCA4 is correctly targeted to the plasma membrane and co-localizes with caveolin-3 in cardiomyocytes; a PMCA4-GCaMP2 fusion construct directly monitors local Ca2+ dynamics near the pump, showing higher signal amplitude and faster decay than a pump-inactive mutant; β-adrenergic stimulation specifically enhances Ca2+ signals near active PMCA4. Adenoviral expression of PMCA4-GCaMP2 fusion protein in neonatal and adult rat cardiomyocytes, live-cell fluorescence imaging, small-molecule inhibitor screen Journal of molecular and cellular cardiology Medium 23880607
2020 PMCA4 inhibition in gastric cancer cells increases ZEB1 expression and promotes nuclear accumulation of NFATc1; EMT induced by PMCA4 knockdown is prevented by knockdown of NFATc1 or ZEB1, or by cyclosporine A treatment, placing PMCA4 upstream of an NFATc1-ZEB1 signaling axis that controls epithelial-mesenchymal transition. siRNA knockdown and overexpression of PMCA4 in GC cell lines, NFATc1 and ZEB1 knockdown, cyclosporine A pharmacological inhibition, in vivo lung metastasis assay in nude mice, E-cadherin/vimentin Western blot Biochimica et biophysica acta. Molecular cell research Medium 32860837
2020 PDGF-BB signaling through MEK/ERK downregulates PMCA4 protein abundance in pulmonary arterial smooth muscle cells; PMCA4 suppression attenuates Ca2+ clearance after Ca2+ entry, promotes cell proliferation, and increases cell migration via focal adhesion formation; knockdown of PMCA4 in rats increases right ventricular systolic pressure and pulmonary artery wall thickness. PDGF-BB stimulation with MEK/ERK inhibitors, siRNA knockdown of PMCA4, intracellular Ca2+ clearance assay, proliferation and migration assays, focal adhesion staining, in vivo rat PAH models (MCT/hypoxia), RVSP measurement American journal of physiology. Cell physiology Medium 32966125
2020 PMCA4 knockdown in MIA PaCa-2 pancreatic cancer cells reduces cytosolic Ca2+ clearance, decreases cell migration, and sensitizes cells to apoptosis without affecting cell growth or major metabolic parameters. siRNA knockdown of PMCA4, intracellular Ca2+ clearance assay, cell migration assay, apoptosis assay, Seahorse XF metabolic analysis Cancers Medium 31963119
2024 ATP2B4 (PMCA4) is required for EGF-induced macropinocytosis in A431 cells; ATP2B4 knockout inhibits ruffle closure and macropinosome formation without affecting ruffle formation, and reduces EGF-stimulated Ca2+ oscillations; this function depends on PMCA4 Ca2+ pump activity and is independent of C-terminal PDZ domain-binding motif interactions. ATP2B4 CRISPR knockout, live-cell imaging of macropinocytosis, Ca2+ oscillation measurement, expression of PDZ-binding mutant and pump-dead constructs Genes to cells Medium 38597132
2010 PMCA4 is present in both detergent-resistant membrane (lipid raft/DRM) and detergent-soluble fractions of bovine sperm; it co-localizes with caveolin in the midpiece; Ca2+-ATPase activity in detergent-soluble fractions is more strongly enhanced by the seminal vesicle protein PDC-109 than in DRM fractions, indicating functional compartmentalization of PMCA4 in sperm membranes. Detergent-resistant membrane fractionation, Ca2+-ATPase activity assays, immunocytochemistry, lipid overlay experiments International journal of andrology Medium 20050939
2022 CRISPR/Cas9-mediated deletion of an ATP2B4 regulatory region containing five malaria-associated SNPs decreased ATP2B4 transcript and protein levels and increased intracellular Ca2+ concentration in K562 cells, demonstrating that these non-coding variants functionally regulate ATP2B4 expression. CRISPR/Cas9 regulatory region deletion in K562 cells, RT-qPCR, Western blot, intracellular Ca2+ measurement International journal of molecular sciences Medium 35563239
2017 A minor haplotype in the predicted second promoter region of ATP2B4 correlates with significantly reduced PMCA4b protein levels in erythrocytes and lower Ca2+ extrusion capacity; no coding missense mutations were found, indicating the mechanism is transcriptional/regulatory rather than structural. Flow cytometry with specific antibody to quantify PMCA4b in erythrocytes, Western blot of RBC membranes, Ca2+ extrusion assays, sequencing of ATP2B4 coding regions and promoter Cell calcium Medium 28216081
2026 ATP2B4 stabilizes ELAVL1 (HuR), which in turn maintains mRNA stability of histone H1.0; loss of ATP2B4 in pancreatic cancer cells causes histone H1.0 downregulation, chromatin decompaction, increased DNA damage, and enhanced radiosensitivity; this mechanism was identified by TurboID proximity labeling mass spectrometry and immunoprecipitation. CRISPR knockout, TurboID-based proximity labeling mass spectrometry, immunoprecipitation, micrococcal nuclease assay, RNA sequencing, drug rescue assays, in vivo xenograft radiotherapy experiments Cell death discovery Medium 42185253
2025 PMCA4 and GAT3 interact within lipid raft microdomains in glioma cells; PMCA4 knockdown increases resting Ca2+ and Ca2+ accumulation in lipid rafts, impairing glioma cell migration and invasion; GAT3 interacts with calmodulin (a key PMCA4 regulator), and long-term GABA treatment disrupts the PMCA4/GAT3 complex; GABA-stimulated Ca2+ events in lipid rafts drive CaMKII-dependent CREB phosphorylation at Ser133. PMCA4 siRNA knockdown, Co-IP of GAT3/PMCA4/calmodulin, lipid raft fractionation with Ca2+ measurement, cell migration/invasion assays, CaMKII/CREB phosphorylation assays, parvalbumin Ca2+ chelator expression in rafts Cell calcium Medium 40580687
2022 MM-derived exosomal miR-4261 is transferred to red blood cells and directly targets ATP2B4, downregulating PMCA4 expression; this causes calcium overload in RBCs, confirmed by dual-luciferase reporter assay establishing the miR-4261/ATP2B4 targeting relationship. Dual-luciferase reporter assay, Western blot, immunofluorescence, Transwell exosome transfer assay, atomic absorption spectroscopy for Ca2+ Frontiers in oncology Low 36091107

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Targeted ablation of plasma membrane Ca2+-ATPase (PMCA) 1 and 4 indicates a major housekeeping function for PMCA1 and a critical role in hyperactivated sperm motility and male fertility for PMCA4. The Journal of biological chemistry 271 15178683
1992 Analysis of the tissue-specific distribution of mRNAs encoding the plasma membrane calcium-pumping ATPases and characterization of an alternately spliced form of PMCA4 at the cDNA and genomic levels. The Journal of biological chemistry 109 1531651
2001 Resistance to tumor necrosis factor-induced cell death mediated by PMCA4 deficiency. Molecular and cellular biology 66 11713265
2011 Plasma membrane calcium pump (PMCA4)-neuronal nitric-oxide synthase complex regulates cardiac contractility through modulation of a compartmentalized cyclic nucleotide microdomain. The Journal of biological chemistry 62 21965681
2017 An erythroid-specific ATP2B4 enhancer mediates red blood cell hydration and malaria susceptibility. The Journal of clinical investigation 50 28714864
2017 Exome sequencing identified rare variants in genes HSPG2 and ATP2B4 in a family segregating developmental dysplasia of the hip. BMC medical genetics 30 28327142
2017 Decreased calcium pump expression in human erythrocytes is connected to a minor haplotype in the ATP2B4 gene. Cell calcium 27 28216081
2014 PMCA4 (ATP2B4) mutation in familial spastic paraplegia. PloS one 27 25119969
2015 PMCA4 (ATP2B4) mutation in familial spastic paraplegia causes delay in intracellular calcium extrusion. Brain and behavior 25 25798335
2014 Calcium efflux activity of plasma membrane Ca2+ ATPase-4 (PMCA4) mediates cell cycle progression in vascular smooth muscle cells. The Journal of biological chemistry 25 24448801
2017 Plasma membrane calcium ATPase 4 (PMCA4) co-ordinates calcium and nitric oxide signaling in regulating murine sperm functional activity. Journal of cellular physiology 24 28247940
2016 Association of CD147 and Calcium Exporter PMCA4 Uncouples IL-2 Expression from Early TCR Signaling. Journal of immunology (Baltimore, Md. : 1950) 22 26729804
2013 Development and characterization of a novel fluorescent indicator protein PMCA4-GCaMP2 in cardiomyocytes. Journal of molecular and cellular cardiology 21 23880607
2022 Identification of ATP2B4 Regulatory Element Containing Functional Genetic Variants Associated with Severe Malaria. International journal of molecular sciences 20 35563239
2014 Investigation of the association between ATP2B4 and ATP5B genes with colorectal cancer. Gene 20 24583174
2006 Plasma membrane calcium ATPase (PMCA4): a housekeeper for RT-PCR relative quantification of polytopic membrane proteins. BMC molecular biology 20 16978418
2010 Switch of PMCA4 splice variants in bovine epididymis results in altered isoform expression during functional sperm maturation. The Journal of biological chemistry 19 21187283
2010 Local signals with global impacts and clinical implications: lessons from the plasma membrane calcium pump (PMCA4). Biochimica et biophysica acta 18 21167220
2020 Plasma Membrane Ca2+ ATPase Isoform 4 (PMCA4) Has an Important Role in Numerous Hallmarks of Pancreatic Cancer. Cancers 17 31963119
2010 Arrangement of PMCA4 in bovine sperm membrane fractions. International journal of andrology 16 20050939
2020 The calcium pump PMCA4 prevents epithelial-mesenchymal transition by inhibiting NFATc1-ZEB1 pathway in gastric cancer. Biochimica et biophysica acta. Molecular cell research 15 32860837
2007 Expression and localization of PMCA4 in rat testis and epididymis. Histochemistry and cell biology 12 18057950
2020 PDGF/MEK/ERK axis represses Ca2+ clearance via decreasing the abundance of plasma membrane Ca2+ pump PMCA4 in pulmonary arterial smooth muscle cells. American journal of physiology. Cell physiology 11 32966125
2016 Calcium Extrusion Pump PMCA4: A New Player in Renal Calcium Handling? PloS one 11 27101128
2020 Molecular and Electrophysiological Analyses of ATP2B4 Gene Variants in Bilateral Adrenal Hyperaldosteronism. Hormones & cancer 9 32002807
2023 ATP2B4 regulatory genetic variants are associated with mild malaria. Malaria journal 6 36849945
2022 Exosomal MiR-4261 mediates calcium overload in RBCs by downregulating the expression of ATP2B4 in multiple myeloma. Frontiers in oncology 6 36091107
2023 Genetic variations in human ATP2B4 gene alter Plasmodium falciparum in vitro growth in RBCs from Gambian adults. Malaria journal 5 36604655
2020 Plasma membrane Ca2+ ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca2+ homeostasis in mice. European journal of immunology 5 33098669
2024 ATP2B4 is an essential gene for epidermal growth factor-induced macropinocytosis in A431 cells. Genes to cells : devoted to molecular & cellular mechanisms 3 38597132
2023 Primary Cutaneous Epithelioid Mesenchymal Tumor With a Novel ATP2B4::GLI1 Gene Fusion. The American Journal of dermatopathology 2 37506273
2023 Dynamic elementomics of single-cell ICP-MS-derived signals in normal and calcium pump PMCA4-deficient mouse epididymal sperm during capacitation. Metallomics : integrated biometal science 2 37740571
2017 A New Baltic Population-Specific Human Genetic Marker in the PMCA4 Gene. Human heredity 1 29131013
2026 FOXM1 inhibitor, RCM‑1, enhances venetoclax mediated apoptosis through downregulation of ATP2B4 in rhabdomyosarcoma. International journal of oncology 0 41789627
2026 Sodium pentachlorophenol induces inflammatory damage via the ATP2B4/Ca2+/ROS signaling axis in mouse testes. Pesticide biochemistry and physiology 0 41831900
2026 MiR-4261 targeted YWHAE/CAST/GPX1 impairs the calcium regulatory function of PMCA4 in erythrocytes of myeloma. Indian journal of pathology & microbiology 0 41983776
2026 ATP2B4 driven chromatin compaction exacerbates pancreatic cancer radiotherapy resistance. Cell death discovery 0 42185253
2025 GAT3-dependent regulation of glioma invasiveness via a lipid raft-associated PMCA4 Ca2+ transporter and a downstream CaMKII/CREB signaling - implications for compartmentalized signaling in glioma tumors. Cell calcium 0 40580687

Missed literature

Know a paper Affinage missed for ATP2B4? Flag it for the maintainers and the community.

No submissions yet.