Affinage

ATP2B1

Plasma membrane calcium-transporting ATPase 1 · UniProt P20020

Length
1220 aa
Mass
134.7 kDa
Annotated
2026-06-09
59 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP2B1 (PMCA1) is a plasma membrane Ca2+-ATPase that extrudes cytosolic Ca2+ to maintain intracellular calcium homeostasis, a function essential for embryonic development since homozygous knockout is embryolethal in mice (PMID:15178683). Across multiple cell types its Ca2+-clearing activity sets the basal calcium tone that downstream effectors require: tissue-specific deletion in vascular smooth muscle elevates intracellular Ca2+ and blood pressure with upregulated L-type Ca2+ channels (PMID:22311909, PMID:29046519), deletion in intestinal epithelium abolishes active calcium absorption and vitamin D-responsive calcium handling (PMID:26392310), deletion in B cells raises basal and ER Ca2+ and abrogates B-cell development (PMID:33098669), and deletion in CD4+ T cells drives T-cell hyperactivation and colitis (PMID:38507609). By keeping cytosolic Ca2+ low, ATP2B1 gates calcium/calmodulin-dependent signaling — its loss in endothelial cells alters eNOS activity and NO production (PMID:24805951, PMID:29416109) and feeds the calmodulin/eNOS/Akt insulin-sensitivity axis (PMID:29104511) — and supports Norrin/WNT7-FZD4/β-catenin signaling by suppressing calcineurin/NFAT (PMID:40777252). Its pump activity is inhibited by phosphorylation-independent binding of 14-3-3epsilon (PMID:18029012) and by a calreticulin–calmodulin–p38MAPK feedback loop under mechanical stress (PMID:35976579), and basolateral targeting in hair cells is directed by a Leu-Ile motif in the 'b'-tail splice variant (PMID:16803870). De novo and biallelic missense variants reduce Ca2+ export and mislocalize the protein away from the plasma membrane, causing a neurodevelopmental disorder, in one case with primary hypoparathyroidism (PMID:35358416, PMID:37926713, PMID:41853798).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2004 High

    Established that PMCA1 is not redundant with other PMCA isoforms but performs an essential, non-substitutable developmental function.

    Evidence Targeted null knockout in mice scored for embryonic lethality

    PMID:15178683

    Open questions at the time
    • Does not identify which developmental process or cell lineage requires PMCA1
    • Heterozygotes appear normal, leaving dose-sensitivity in adults unaddressed
  2. 2000 Medium

    Addressed how PMCA1 expression is hormonally controlled, showing tissue-specific transcriptional downregulation of its promoter by 1,25-dihydroxyvitamin D3.

    Evidence Luciferase reporter assays with promoter deletions plus EMSA in osteosarcoma vs. kidney cell lines

    PMID:11062020

    Open questions at the time
    • Candidate VDRE did not bind VDR/RXRalpha, so the responsible element is unmapped
    • Mechanism of tissue specificity not resolved
  3. 2006 Medium

    Defined how PMCA1 achieves correct polarized targeting, identifying a Leu-Ile motif in the 'b'-tail splice variant that drives basolateral sorting.

    Evidence Splice-variant localization and motif dissection in mammalian hair cells

    PMID:16803870

    Open questions at the time
    • Trafficking machinery recognizing the motif not identified
    • Generality beyond hair cells untested
  4. 2007 Medium

    Identified a direct protein regulator of PMCA1, showing 14-3-3epsilon binds and inhibits its Ca2+-pumping activity independent of phosphorylation.

    Evidence Reciprocal Co-IP and GST pulldown plus aequorin Ca2+ assay in HeLa/CHO cells

    PMID:18029012

    Open questions at the time
    • Binding site on PMCA1 not mapped
    • Physiological context of the inhibition in vivo unknown
  5. 2012 High

    Causally linked ATP2B1 to blood pressure, showing VSMC-specific loss raises intracellular Ca2+, vasoconstriction, and blood pressure.

    Evidence VSMC conditional KO with telemetric BP, Ca2+ measurement, and vascular ring assays

    PMID:22311909

    Open questions at the time
    • Did not distinguish whether elevated Ca2+ acts via channels or compensatory transporter changes
    • Endothelial contribution not separated
  6. 2017 Medium

    Placed L-type Ca2+ channel upregulation downstream of VSMC ATP2B1 loss as the primary hypertensive mechanism.

    Evidence VSMC KO with pharmacological dissection (CCB vs ARB vs alpha-blocker) and channel expression analysis

    PMID:29046519

    Open questions at the time
    • Mechanism coupling reduced pump activity to channel upregulation unknown
    • nNOS unchanged, leaving endothelial axis unaddressed here
  7. 2014 High

    Connected ATP2B1 to endothelial NO signaling, showing haploinsufficiency reduces eNOS Ser-1177 phosphorylation and NO production.

    Evidence Heterozygous KO mice with vascular relaxation assays, eNOS western blot, and NO measurement

    PMID:24805951

    Open questions at the time
    • Direction of Ca2+ effect on eNOS not reconciled with later HUVEC data
    • Endothelial vs smooth muscle contributions to BP not separated
  8. 2017 Medium

    Mapped the endothelial Ca2+/calmodulin/eNOS/Akt pathway controlled by ATP2B1, where silencing raises Ca2+ and increases eNOS activity and insulin-induced Akt signaling.

    Evidence siRNA knockdown in HUVECs with BAPTA-AM, W7, and L-NAME epistasis and Ca2+/NO/Akt readouts

    PMID:29104511 PMID:29416109

    Open questions at the time
    • Cell-culture results show increased eNOS activity, opposite to the in vivo haploinsufficiency phenotype
    • In vivo relevance of the insulin-sensitivity arm not tested
  9. 2015 High

    Established ATP2B1 as the intestinal calcium-extrusion step required for active, vitamin D-responsive calcium absorption and bone mineralization.

    Evidence Villin-Cre intestinal KO with active Ca2+ transport, DXA, and hormone measurements

    PMID:26392310

    Open questions at the time
    • Does not explain how vitamin D normally upregulates the pump given promoter repression data
    • Renal contribution not addressed
  10. 2018 Medium

    Extended ATP2B1's role to systemic calcium homeostasis, linking haploinsufficiency to hypocalcemia, hypercalciuria, and altered PTH.

    Evidence Heterozygous KO mice with serum/urinary calcium, PTH, BMD, and tissue expression measurement

    PMID:29950683

    Open questions at the time
    • Direct role in parathyroid PTH secretion vs secondary effect not resolved
    • Increased BMD here contrasts with reduced BMD in intestinal KO
  11. 2017 Medium

    Showed ATP2B1 loss drives arterial structural remodeling that precedes age-dependent hypertension.

    Evidence Longitudinal BP and pressure myography in heterozygous KO mice across ages

    PMID:28795531

    Open questions at the time
    • Causal chain from Ca2+ elevation to remodeling not defined
    • Cell type responsible for remodeling not isolated
  12. 2020 High

    Identified PMCA1 as the sole PMCA isoform required for B-cell Ca2+ handling and development, distinguishing it from PMCA4.

    Evidence B-cell conditional KO with FACS, isoform-specific western blot, Ca2+ assays, and PMCA4 KO comparison

    PMID:33098669

    Open questions at the time
    • Stage at which Ca2+ overload blocks development not pinpointed
    • Downstream Ca2+-sensitive effectors in B cells not identified
  13. 2024 Medium

    Extended the immune role to T cells, showing CD4+ T-cell ATP2B1 loss causes hyperactivation and colitis.

    Evidence CD4+ T-cell conditional KO with T-cell FACS, cytokine qRT-PCR, and colon histology

    PMID:38507609

    Open questions at the time
    • Ca2+ measurements in the KO T cells not reported in this entry
    • Whether colitis is T-cell-intrinsic vs microbiome-dependent untested
  14. 2022 Medium

    Defined a stress-responsive inhibitory loop in which calreticulin suppresses PMCA1 via calmodulin and a p38MAPK feedback arm, linking pump inhibition to Ca2+ overload and apoptosis.

    Evidence Mechanical stretch of myoblasts with CRT/PMCA1 gain/loss-of-function and pathway inhibitors

    PMID:35976579

    Open questions at the time
    • Whether CRT acts directly or via CaM on the pump not biochemically resolved
    • Relevance beyond stretched myoblasts unknown
  15. 2022 High

    Established de novo ATP2B1 missense variants as a cause of neurodevelopmental disorder through reduced Ca2+ export and plasma-membrane mislocalization.

    Evidence Ca2+ imaging, confocal localization, and structural modeling of nine variants in HEK293T cells

    PMID:35358416

    Open questions at the time
    • Neuronal cell-type consequences not modeled
    • Genotype-phenotype correlation across variants not established
  16. 2023 Medium

    Demonstrated a biallelic loss-of-function presentation combining neurodevelopmental malformation with primary hypoparathyroidism.

    Evidence Trio exome sequencing with fibroblast splicing analysis, Ca2+ extrusion assay, and immunoblotting

    PMID:37926713

    Open questions at the time
    • Single case limits genotype-phenotype generalization
    • Mechanism of hypoparathyroidism in this patient not dissected
  17. 2026 Medium

    Confirmed impaired trafficking and calcium dyshomeostasis as the core pathomechanism with an additional de novo variant.

    Evidence Confocal imaging of tagged constructs and Fluo-4 Ca2+ measurement in HEK293T cells

    PMID:41853798

    Open questions at the time
    • Single variant in heterologous cells
    • Mechanism of retention/mislocalization not defined
  18. 2024 Medium

    Revealed an antiviral angle, showing SARS-CoV-2 downregulates ATP2B1 via PI3K/Akt/FOXO3 and that maintaining the pump pharmacologically limits viral replication.

    Evidence Caloxin-derivative PI-7 treatment, Ca2+ measurement, infection assays, and pathway analysis

    PMID:38816514

    Open questions at the time
    • How intracellular Ca2+ supports viral replication mechanistically unclear
    • PI-7 specificity for ATP2B1 not fully delineated
  19. 2025 Medium

    Connected ATP2B1 to developmental angiogenic signaling, identifying it as an FZD4 proximity partner whose Ca2+-lowering activity sustains Norrin/WNT7-FZD4/β-catenin signaling by restraining calcineurin/NFAT.

    Evidence BioID, endothelial conditional KO with retinal phenotyping, β-catenin assays, ionomycin/calcineurin pharmacology, and Gpr124 epistasis (preprint)

    PMID:40777252

    Open questions at the time
    • Preprint, not peer-reviewed
    • Direct vs indirect FZD4 association not biochemically resolved
  20. 2026 Medium

    Linked ATP2B1 surface expression to hematopoietic stem cell function, marking LT-HSCs with superior self-renewal and a TFEB-endolysosomal program.

    Evidence Surface sorting, in vivo xenograft repopulation, scMultiome, and immunofluorescence

    PMID:42085155

    Open questions at the time
    • Whether ATP2B1 is functionally required or merely a marker not established
    • Mechanistic link between Ca2+ extrusion and the TFEB axis untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how reduced ATP2B1 Ca2+-pump activity produces opposite eNOS/NO outcomes between cultured endothelial cells and intact vessels, and how a single Ca2+-extrusion defect is translated into the divergent tissue phenotypes (hypertension, calcium malabsorption, immune dysregulation, neurodevelopmental disease) by distinct downstream Ca2+ effectors.
  • No unified model reconciling cell-autonomous Ca2+ rise with tissue-specific signaling outputs
  • Direct structural basis of variant-induced mislocalization not solved
  • Endothelial vs smooth-muscle contributions to NO/blood-pressure phenotype not cleanly separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140657 ATP-dependent activity 3 GO:0016787 hydrolase activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
GO:0005215 transporter activity 3
Partners
CALRFZD4YWHAE

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Homozygous knockout of Atp2b1 (PMCA1) causes embryolethality in mice, indicating an essential housekeeping or developmental function. Heterozygous knockout shows no overt phenotype. PMCA1 is distinct from PMCA4 in this essential role. Targeted gene knockout (null mutation) in mice; embryonic lethality readout The Journal of biological chemistry High 15178683
2006 A Leu-Ile motif in 'b'-tail splice variants of PMCA1 promotes basolateral sorting in hair cells, whereas apical targeting of PMCA2 depends on the size of the A-site-spliced insert. PMCA1 is localized to the basolateral plasma membrane of hair cells, while PMCA2 is localized to stereocilia. Subcellular localization studies and molecular dissection of targeting motifs in mammalian hair cells; splice-variant expression analysis Journal of cell science Medium 16803870
2007 14-3-3epsilon protein interacts with PMCA1 (and PMCA3) and inhibits their Ca2+-pumping activity. The interaction is phosphorylation-independent and was confirmed by co-immunoprecipitation in HeLa cells and GST-pulldown with fusion proteins. Co-expression of 14-3-3epsilon with PMCA1 in CHO cells decreased the ability of cells to restore basal Ca2+ concentration after an InsP3-induced Ca2+ transient. Co-immunoprecipitation in HeLa cells; GST pulldown with fusion proteins; aequorin-based Ca2+ measurement in CHO cells co-expressing 14-3-3epsilon and PMCA1 Cell calcium Medium 18029012
2000 The 1.7-kb promoter region of the human PMCA1 gene mediates transcriptional downregulation by 1,25-dihydroxyvitamin D3 in ROS 17/2.8 osteosarcoma cells but not MDBK cells, demonstrating tissue-specific sensitivity. EMSA analysis showed that a candidate VDRE sequence in the PMCA1 promoter did not interact with VDR or RXRalpha, suggesting any positive regulatory VDRE lies outside the 1.7-kb core promoter. Luciferase reporter gene assays with promoter deletion constructs; EMSA with nuclear extracts from COS-1 cells expressing hVDR and hRXRalpha Biochemical and biophysical research communications Medium 11062020
2012 Vascular smooth muscle cell (VSMC)-specific knockout of ATP2B1 in mice causes significantly elevated blood pressure (measured by tail-cuff and radiotelemetry), increased intracellular calcium concentration in VSMCs under basal and phenylephrine-stimulated conditions, and increased phenylephrine-induced vasoconstriction. Na+-Ca2+ exchanger isoform 1 expression was decreased and ATP2B4 expression was increased in KO VSMCs. Cre-loxP conditional knockout in VSMCs; radiotelemetry and tail-cuff blood pressure measurement; intracellular calcium measurement in cultured VSMCs; vascular ring contraction assays Hypertension (Dallas, Tex. : 1979) High 22311909
2013 Systemic siRNA-mediated silencing of Atp2b1 in mice via tail vein injection elevated blood pressure, increased mesenteric artery wall:lumen ratio, enhanced myogenic responses to pressure, and increased contractile responses to phenylephrine, demonstrating that ATP2B1 regulates blood pressure through control of vascular calcium and contractility. In vivo siRNA knockdown via tail vein injection; blood pressure measurement; vascular morphometry; myogenic and contractile response assays Journal of hypertension Medium 23666421
2014 Systemic heterozygous ATP2B1 null mice exhibit elevated blood pressure, increased phenylephrine-induced vasoconstriction (abolished by NOS inhibitor), attenuated acetylcholine-induced vasorelaxation, reduced phosphorylation of eNOS at Ser-1177, and decreased nitric oxide production in endothelial cells and aorta. Neural NOS expression in VSMCs was not significantly different. This demonstrates that ATP2B1 haploinsufficiency impairs endothelial NOS activity and NO production. Heterozygous KO mice; radiotelemetric BP measurement; vascular ring contraction/relaxation assays with NOS inhibitor; eNOS phosphorylation by western blot; NO measurement in cultured endothelial cells and aorta Journal of hypertension High 24805951
2015 Intestinal epithelial cell-specific knockout of Pmca1 (Atp2b1) in mice results in reduced bone mineral density, impaired active intestinal calcium transport, and failure to upregulate calcium absorption in response to 1,25-dihydroxyvitamin D3, demonstrating that intestinal PMCA1 is required for active calcium absorption and vitamin D-responsive calcium homeostasis. Villin-Cre intestinal conditional knockout; bone mineral density by DXA; active intestinal calcium transport assay; PTH and 1,25(OH)2D3 measurements; urinary phosphorus measurement Biochemical and biophysical research communications High 26392310
2017 VSMC-specific ATP2B1 KO mice show enhanced blood pressure reduction with a single injection of nicardipine (L-type Ca2+ channel blocker) compared to ARB or alpha-blocker, and L-type calcium channel mRNA and protein are upregulated in KO VSMCs. Long-term amlodipine (CCB) but not ARB significantly decreased BP in KO vs. control mice. Neural NOS expression and urinary NO production were unchanged. This places ATP2B1 upstream of L-type Ca2+ channel upregulation as the primary mechanism of hypertension in these mice. VSMC conditional KO mice; drug treatment with CCB, ARB, alpha-blocker; radiotelemetric BP measurement; quantitative RT-PCR and western blot for L-type Ca2+ channel and nNOS Hypertension research : official journal of the Japanese Society of Hypertension Medium 29046519
2017 ATP2B1 gene silencing in HUVECs elevates intracellular Ca2+ concentration, increases eNOS activity and NO production under basal conditions via the Ca2+/calmodulin pathway, as confirmed by BAPTA-AM (calcium chelator) and W7 (calmodulin antagonist) abolishing the effect. siRNA knockdown in HUVECs; intracellular Ca2+ measurement; NO and eNOS activity assays; pharmacological inhibition with BAPTA-AM, W7 Hypertension research : official journal of the Japanese Society of Hypertension Medium 29416109
2017 ATP2B1 gene silencing in HUVECs elevates intracellular Ca2+ and increases insulin-induced Akt activation (insulin sensitivity) via the Ca2+/calmodulin/eNOS/Akt signaling pathway. The enhanced insulin sensitivity was abolished by BAPTA-AM, W7 (calmodulin antagonist), and L-NAME (eNOS inhibitor), demonstrating the pathway: elevated Ca2+ → calmodulin → eNOS → Akt. siRNA knockdown in HUVECs; insulin-stimulated Akt phosphorylation by western blot; pharmacological inhibition with BAPTA-AM, W7, L-NAME; intracellular Ca2+ measurement International journal of biological sciences Medium 29104511
2017 Heterozygous PMCA1 null mice develop elevated blood pressure at ≥12 months of age (not at 6 or 9 months), preceded by eutrophic remodelling of small mesenteric arteries (decreased lumen diameter, increased wall thickness) and increased mesenteric artery intrinsic tone and global intracellular calcium at both 6 and 18 months. Structural arterial changes precede the BP elevation. Heterozygous PMCA1 KO mice; conscious BP measurement at multiple ages; pressure myography of mesenteric arteries; intracellular Ca2+ measurement Aging cell Medium 28795531
2018 Systemic heterozygous ATP2B1+/- mice exhibit hypocalcemia, reduced renal and intestinal ATP2B1 expression, hypercalciuria, lower intact-PTH levels, and increased bone mineral density. This demonstrates that ATP2B1 is required not only for intracellular Ca2+ regulation but also for systemic calcium homeostasis and PTH secretion. Heterozygous KO mice; serum and urinary calcium/PTH measurement; bone mineral density measurement; RT-PCR for tissue ATP2B1 expression Hypertension research : official journal of the Japanese Society of Hypertension Medium 29950683
2020 Conditional knockout of Pmca1 (Atp2b1) in B cells results in greatly reduced numbers of splenic follicular B cells, marginal zone B cells, and peritoneal B-1a cells, elevated basal Ca2+ levels, elevated ER Ca2+ stores, and reduced Ca2+ clearance. PMCA4 KO B cells showed normal Ca2+ handling and normal B-cell development. Human and mouse naïve B cells express only PMCA1 (not PMCA4), in contrast to T cells. This demonstrates that PMCA1 is the sole isoform required for B-cell Ca2+ signaling and development. B-cell conditional KO mice (Cre-loxP); FACS analysis of B-cell populations; western blot for PMCA1/4; Ca2+ measurement in B cells European journal of immunology High 33098669
2022 Nine de novo missense variants of ATP2B1, when introduced into HEK293T cells, all lead to significantly decreased Ca2+ export capacity compared to wild-type, as measured by Ca2+ imaging. The same variant set also causes incorrect intracellular localization of ATP2B1 (mislocalization away from plasma membrane). 3D structural modeling predicted destabilizing effects of the variants on the protein. Ca2+ imaging in transfected HEK293T cells; confocal microscopy for subcellular localization; 3D structural protein modeling American journal of human genetics High 35358416
2022 In stretched myoblasts, calreticulin (CRT) inhibits PMCA1 activity via suppressing calmodulin (CaM), while reduced PMCA1 activity promotes CRT expression through the p38MAPK pathway, forming a positive feedback loop (CRT-CaM-PMCA1-p38MAPK-CRT) that causes Ca2+ overload and apoptosis. PMCA1 overexpression attenuated stretch-induced Ca2+ accumulation and apoptosis; PMCA1 knockdown aggravated them. Mechanical stretch of myoblasts; CRT knockdown/overexpression; PMCA1 knockdown/overexpression; p38MAPK inhibitor; CaM inhibitor; intracellular Ca2+ measurement; apoptosis assay Apoptosis : an international journal on programmed cell death Medium 35976579
2023 Biallelic ATP2B1 variants (compound heterozygous: splice-site causing NMD + missense p.Val980Leu) cause a neurodevelopmental malformation syndrome with primary hypoparathyroidism. The correctly-spliced mRNA encoding p.Val980Leu caused decreased cellular Ca2+ extrusion in functional assays, and immunoblotting showed reduced fibroblast ATP2B1 protein. Trio exome sequencing; RT-PCR on fibroblast mRNA showing aberrant splicing and NMD; Ca2+ extrusion functional assay; immunoblotting for ATP2B1 European journal of human genetics : EJHG Medium 37926713
2024 A caloxin-derivative compound (PI-7) targeting ATP2B1 reduces intracellular Ca2+ levels and impairs SARS-CoV-2 infection and replication. During SARS-CoV-2 infection, PI3K/Akt signaling is activated, leading to FOXO3 inactivation and transcriptional downregulation of ATP2B1 (and ATP2A1), increasing intracellular Ca2+. Pharmacological maintenance of ATP2B1 expression by PI-7 reduces the intracellular Ca2+ pool and negatively influences SARS-CoV-2 replication. Pharmacological inhibition with caloxin-derivative PI-7; intracellular Ca2+ measurement; SARS-CoV-2 infection assay; PI3K/Akt/FOXO3 pathway analysis; ATP2B1 expression measurement EMBO reports Medium 38816514
2024 CD4+ T cell-specific knockout of ATP2B1 in mice causes colitis with diarrhea, colonic wall thickening, crypt distortion, and shorter colon, accompanied by increased T-bet (Th1 marker) and GATA3 (Th2 marker) expression in blood CD4+ T cells, and increased TNF-α and gp91 in colon. This demonstrates that ATP2B1-mediated Ca2+ removal from CD4+ T cells is required to prevent T cell hyperactivation and colitis. CD4+ T cell-specific Cre-loxP KO mice; FACS analysis of T-cell populations; qRT-PCR for T-bet, GATA3, TNF-α, gp91; colon histology Inflammatory bowel diseases Medium 38507609
2025 ATP2B1 (PMCA1) was identified as a proximity interactor of Frizzled4 (FZD4) in endothelial cells by proximity biotinylation. ATP2B1 depletion increased endothelial cell Ca2+ and significantly attenuated Norrin/Frizzled4-induced β-catenin signaling. These effects were recapitulated by ionomycin-mediated Ca2+ elevation and suppressed by calcineurin/NFAT inhibition. Endothelial-specific Atp2b1 deletion caused retinal vascular defects consistent with compromised Norrin/FZD4 signaling. In developing brain, WNT7A/B pathway loss-of-function phenotypes in Gpr124 KO mice were exacerbated by additional endothelial Atp2b1 deletion. Proximity biotinylation (BioID); endothelial conditional KO; retinal vascular phenotyping; β-catenin signaling assay; ionomycin and calcineurin/NFAT inhibitor pharmacology; genetic epistasis with Gpr124 KO bioRxiv : the preprint server for biologypreprint Medium 40777252
2026 ATP2B1+ (PMCA1-expressing) CD49f+ LT-HSCs exhibit superior long-term repopulation and self-renewal capacities in vivo compared to ATP2B1- LT-HSCs, as assessed in xenograft assays. ATP2B1+ LT-HSCs show enrichment for a self-renewal program including the TFEB-endolysosomal axis by scMultiome and immunofluorescence. Immunophenotypic sorting by ATP2B1 cell-surface expression; single-cell clonogenic assays; in vivo xenograft repopulation assay; scMultiome molecular profiling; immunofluorescence microscopy Proceedings of the National Academy of Sciences of the United States of America Medium 42085155
2026 A novel de novo ATP2B1 missense variant (p.Thr714Pro) causes profound cytoplasmic mislocalization of the PMCA1 protein (as shown by confocal imaging of mScarlet-tagged constructs in HEK293T cells) and a 2.07-fold increase in basal intracellular Ca2+ levels (measured by Fluo-4 AM), confirming that impaired plasma membrane trafficking and calcium dyshomeostasis are the core pathomechanisms of ATP2B1-associated neurodevelopmental disorder. Confocal imaging of mScarlet-tagged WT and mutant ATP2B1 in transfected HEK293T cells; Fluo-4 AM intracellular Ca2+ measurement; whole-exome sequencing Experimental biology and medicine (Maywood, N.J.) Medium 41853798

Source papers

Stage 0 corpus · 59 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
2010 Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project. Hypertension (Dallas, Tex. : 1979) 82 20921432
2012 Mice lacking hypertension candidate gene ATP2B1 in vascular smooth muscle cells show significant blood pressure elevation. Hypertension (Dallas, Tex. : 1979) 79 22311909
2009 Genetic variations in ATP2B1, CSK, ARSG and CSMD1 loci are related to blood pressure and/or hypertension in two Korean cohorts. Journal of human hypertension 65 19960030
2006 Molecular determinants for differential membrane trafficking of PMCA1 and PMCA2 in mammalian hair cells. Journal of cell science 58 16803870
2011 Coexpression and estrogen-mediated regulation of TRPV6 and PMCA1 in the human endometrium during the menstrual cycle. Molecular reproduction and development 42 21400627
1995 Cellular and regional expression of transcripts of the plasma membrane calcium pump PMCA1 in rabbit intestine. The American journal of physiology 40 7631790
2015 Deletion of the intestinal plasma membrane calcium pump, isoform 1, Atp2b1, in mice is associated with decreased bone mineral density and impaired responsiveness to 1, 25-dihydroxyvitamin D3. Biochemical and biophysical research communications 35 26392310
2020 Silencing of ATP2B1-AS1 contributes to protection against myocardial infarction in mouse via blocking NFKBIA-mediated NF-κB signalling pathway. Journal of cellular and molecular medicine 30 32155320
2007 Inhibitory interaction of the 14-3-3 proteins with ubiquitous (PMCA1) and tissue-specific (PMCA3) isoforms of the plasma membrane Ca2+ pump. Cell calcium 26 18029012
2013 Silencing of Atp2b1 increases blood pressure through vasoconstriction. Journal of hypertension 22 23666421
2014 Impaired nitric oxide production and increased blood pressure in systemic heterozygous ATP2B1 null mice. Journal of hypertension 21 24805951
2012 Polymorphism near the ATP2B1 gene is associated with hypertension risk in East Asians: a meta-analysis involving 15 909 cases and 18 529 controls. Blood pressure 21 22229515
2012 Common variants in the ATP2B1 gene are associated with hypertension and arterial stiffness in Chinese population. Molecular biology reports 20 23079715
2022 De novo variants in ATP2B1 lead to neurodevelopmental delay. American journal of human genetics 18 35358416
2017 The effects of anti-hypertensive drugs and the mechanism of hypertension in vascular smooth muscle cell-specific ATP2B1 knockout mice. Hypertension research : official journal of the Japanese Society of Hypertension 17 29046519
2013 ATP2B1 and blood pressure: from associations to pathophysiology. Current opinion in nephrology and hypertension 17 23324996
2021 ATP2B1-AS1 Promotes Cerebral Ischemia/Reperfusion Injury Through Regulating the miR-330-5p/TLR4-MyD88-NF-κB Signaling Pathway. Frontiers in cell and developmental biology 16 34712659
2000 The promoter region of the human PMCA1 gene mediates transcriptional downregulation by 1,25-dihydroxyvitamin D(3). Biochemical and biophysical research communications 15 11062020
2017 Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries. Aging cell 14 28795531
2017 ATP2B1 gene Silencing Increases Insulin Sensitivity through Facilitating Akt Activation via the Ca2+/calmodulin Signaling Pathway and Ca2+-associated eNOS Activation in Endothelial Cells. International journal of biological sciences 13 29104511
2024 Targeting ATP2B1 impairs PI3K/Akt/FOXO signaling and reduces SARS-COV-2 infection and replication. EMBO reports 11 38816514
2020 5-Hydroxy-l-tryptophan Promotes the Milk Calcium Level via the miR-99a-3p/ATP2B1 Axis in Goat Mammary Epithelial Cells. Journal of agricultural and food chemistry 11 32054265
2022 Long non-coding ribonucleic acid ATP2B1-AS1 modulates endothelial permeability through regulating the miR-4729-IQGAP2 axis in diabetic retinopathy. Journal of diabetes investigation 10 34935307
2016 Gender-Specific Association of ATP2B1 Variants with Susceptibility to Essential Hypertension in the Han Chinese Population. BioMed research international 10 26933664
2000 PMCA1 mRNA expression in rat aortic myocytes: a real-time RT-PCR study. Biochemical and biophysical research communications 10 11027585
2018 ATP2B1 Gene Silencing Increases NO Production Under Basal Conditions Through the Ca2+/calmodulin/eNOS Signaling Pathway in Endothelial Cells. Hypertension research : official journal of the Japanese Society of Hypertension 9 29416109
2016 Interaction according to urinary sodium excretion level on the association between ATP2B1 rs17249754 and incident hypertension: the Korean genome epidemiology study. Clinical and experimental hypertension (New York, N.Y. : 1993) 9 27149052
2023 Biallelic ATP2B1 variants as a likely cause of a novel neurodevelopmental malformation syndrome with primary hypoparathyroidism. European journal of human genetics : EJHG 7 37926713
2021 ATP2B1 gene polymorphisms rs2681472 and rs17249754 are associated with susceptibility to hypertension and blood pressure levels: A systematic review and meta-analysis. Medicine 7 33847678
2018 Reduced secretion of parathyroid hormone and hypocalcemia in systemic heterozygous ATP2B1-null hypertensive mice. Hypertension research : official journal of the Japanese Society of Hypertension 7 29950683
2022 Low expression and Hypermethylation of ATP2B1 in Intrahepatic Cholangiocarcinoma Correlated With Cold Tumor Microenvironment. Frontiers in oncology 6 35875160
2021 CYP17A1-ATP2B1 SNPs and Gene-Gene and Gene-Environment Interactions on Essential Hypertension. Frontiers in cardiovascular medicine 6 34722659
2022 Intensive stretch-activated CRT-PMCA1 feedback loop promoted apoptosis of myoblasts through Ca2+ overloading. Apoptosis : an international journal on programmed cell death 5 35976579
2021 Endogenous neuroprotective mechanism of ATP2B1 in transcriptional regulation of ischemic preconditioning. American journal of translational research 5 33841647
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
2018 Association between ATP2B1 and CACNB2 polymorphisms and high blood pressure in a population of Lithuanian children and adolescents: a cross-sectional study. BMJ open 5 29982197
2017 People with the major alleles of ATP2B1 rs17249754 increases the risk of hypertension in high ratio of sodium and potassium, and low calcium intakes. Journal of human hypertension 5 28934190
2024 ATP2B1 gene polymorphisms associated with resistant hypertension in the Japanese population. Journal of clinical hypertension (Greenwich, Conn.) 4 38430457
2019 Evaluation of Single-Nucleotide Polymorphisms of Transcription Factor 7-Like 2 and ATP2B1 Genes as Cardiovascular Risk Predictors in Chronic Kidney Disease. International journal of applied & basic medical research 4 31681547
2014 [Association between polymorphism of ATP2B1 gene, its interaction with smoking and essential hypertension -a case-control study]. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 4 25059375
2024 Regulation of overexpression lncRNA ATP2B1-AS1 on lung adenocarcinoma progression. Journal of cardiothoracic surgery 3 38347625
2023 ATP2B1-AS1 exacerbates sepsis-induced cell apoptosis and inflammation by regulating miR-23a-3p/TLR4 axis. Allergologia et immunopathologia 3 36916084
2019 Association of ATP2B1 gene polymorphism with incidence of eclampsia. European review for medical and pharmacological sciences 3 31858526
2000 Development of a real-time RT-PCR assay for plasma membrane calcium ATPase isoform 1 (PMCA1) mRNA levels in a human breast epithelial cell line. Journal of pharmacological and toxicological methods 3 11395329
2025 ATP2B1 variants associated with generalized epilepsy without neurodevelopmental disorders and the underlying mechanism. Seizure 2 40834682
2023 Association between polymorphism and haplotype of ATP2B1 gene and skeletal fluorosis in Han population. International journal of environmental health research 2 37211801
2021 ATP2B1 genotypes rs2070759 and rs2681472 polymorphisms and risk of hypertension in Saudi population. Nucleosides, nucleotides & nucleic acids 2 34486947
2018 Association of ATP2B1 common variants with asymptomatic intracranial and extracranial large artery stenosis in hypertension patients. Clinical and experimental hypertension (New York, N.Y. : 1993) 2 29902063
2007 Plasma membrane Ca2+-ATPase isoforms in frog crista ampullaris: identification of PMCA1 and PMCA2 specific splice variants. Hearing research 2 17336006
2026 ATP2B1 expression identifies human hematopoietic stem cells with superior repopulation and self-renewal. Proceedings of the National Academy of Sciences of the United States of America 1 42085155
2024 Lack of ATP2B1 in CD4+ T Cells Causes Colitis. Inflammatory bowel diseases 1 38507609
2023 The Protective Effect of Polymorphisms rs2681472 and rs17249754 of the ATP2B1 Gene Against Coronary Artery Disease and Hypertension is Abolished by Tobacco Smoking. Kardiologiia 1 37815139
2022 ATP2B1 gene rs71454161, rs73196661 and rs73196675 polymorphisms in eclampsia. European review for medical and pharmacological sciences 1 35253182
2026 A novel de novo ATP2B1 variant causes autosomal dominant intellectual developmental disorder 66 by disrupting calcium homeostasis via impaired membrane trafficking. Experimental biology and medicine (Maywood, N.J.) 0 41853798
2026 Association of ATP2B1 and STK39 gene variants with blood pressure levels in patients with essential hypertension. Laboratory medicine 0 42160625
2025 The Calcium Pump ATP2B1/PMCA1 Regulates CNS Vascular Development by Facilitating Norrin- and WNT7A/B-induced Frizzled4 signaling. bioRxiv : the preprint server for biology 0 40777252
2021 Association between ATP2B1 gene polymorphism and the onset of cerebral infarction. European review for medical and pharmacological sciences 0 34109602
2019 Association between ATP2B1 gene polymorphism and the onset of cerebral infarction. European review for medical and pharmacological sciences 0 31173308

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