Affinage

ATP1A1

Sodium/potassium-transporting ATPase subunit alpha-1 · UniProt P05023

Length
1023 aa
Mass
112.9 kDa
Annotated
2026-06-09
72 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP1A1 encodes the catalytic α1 subunit of the Na+/K+-ATPase, an ATP-driven plasma-membrane ion pump whose activity governs cation gradients, membrane potential, and—in mutant or ligand-bound states—intracellular signaling (PMID:23416519, PMID:24082052, PMID:30388404). Somatic and germline missense mutations impair pump function and reduce Na+ and K+ binding affinities, producing abnormal cation permeabilities and membrane depolarization; structural modeling localizes representative substitutions (e.g. Gly99Arg) to the gateway of the ion-binding pocket (PMID:24082052, PMID:30388404). This pump dysfunction underlies aldosterone-producing adrenal adenoma through inappropriate depolarization and autonomous aldosterone secretion (PMID:23416519, PMID:24082052), and additional pathogenic variants cause renal hypomagnesemia with seizures (PMID:30388404), axonal Charcot-Marie-Tooth neuropathy where ATP1A1 localizes to the axolemma and Schmidt-Lanterman incisures (PMID:29499166), hereditary spastic paraplegia (PMID:31705535), and a neurodevelopmental phenotype with intellectual disability (PMID:38504481). CMT-causing variants act not through haploinsufficiency—protein-null heterozygosity is tolerated in mice and humans—but require a malfunctioning dominant protein product, in some cases destabilized by proteasomal degradation (PMID:31373411, PMID:37659504). Beyond ion transport, ATP1A1 functions as a signaling receptor: cardiotonic steroids or natural-product ligands bind it (with a defined binding site at residue T804 and resistance residues Gly98/Gly99) to trigger Src kinase activation, EGFR transactivation, and downstream ERK/AKT and Ca2+ signaling that regulates cell proliferation, junctional integrity, and EMT (PMID:28203706, PMID:31114755, PMID:34681640, PMID:39227746, PMID:39754293). This Src-coupled receptor function is exploited by multiple viruses—coronaviruses, RSV, PEDV, and PRRSV—which engage ATP1A1 as an attachment/entry factor driving macropinocytic and caveolae-mediated uptake (PMID:25653449, PMID:31381610, PMID:36835408, PMID:41773865). ATP1A1 also acts as an unconventional secretion factor, recruiting FGF2 at the inner plasma-membrane leaflet via a direct cytoplasmic-domain interaction (PMID:25533462), and mediates heterocellular tumor-fibroblast contact through homophilic ATP1A1 binding that promotes invasion (PMID:35618735). ATP1A1 protein abundance is controlled by ubiquitin-dependent turnover involving GPR37, TRIM8/LAPTM4B, and UBQLN4, linking its stability to AKT/mTOR and lysosomal signaling (PMID:39730361, PMID:40665639, PMID:41362742).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2004 Medium

    Tested whether the α1 isoform is individually essential, establishing functional redundancy among Na/K-ATPase isoforms during early development.

    Evidence Targeted Atp1a1 knockout mouse embryos assessed for compaction and cavitation

    PMID:15147760

    Open questions at the time
    • Does not address tissue-specific requirements later in development
    • No assessment of adult phenotype from this null allele
  2. 2012 Medium

    Placed Atp1a1 upstream of RhoA in regulating neuroepithelial permeability, separating its ion-transport role in CSF production from its developmental signaling role.

    Evidence Morpholino knockdown and RhoA epistasis in zebrafish brain ventricle development

    PMID:22683378

    Open questions at the time
    • Mechanism linking pump activity to RhoA is undefined
    • Ortholog model; human relevance not tested
  3. 2013 High

    Established the disease mechanism for aldosterone-producing adenoma: hotspot mutations cause loss of pump activity and reduced K+ affinity, depolarizing adrenal cells to drive autonomous aldosterone secretion.

    Evidence Pump activity and ATPase assays, patch-clamp electrophysiology in adrenal cells, structural modeling, exome sequencing

    PMID:23416519 PMID:24082052

    Open questions at the time
    • Does not explain how depolarization couples to CYP11B2/aldosterone transcription mechanistically
    • Tumor proliferation link not addressed
  4. 2014 High

    Defined a non-pump function: ATP1A1 directly recruits FGF2 to the inner membrane leaflet for unconventional secretion, independent of β-subunits.

    Evidence Genome-wide RNAi screen plus direct in vitro binding affinity measurement

    PMID:25533462

    Open questions at the time
    • Structural basis of the FGF2 interaction not resolved
    • How recruitment couples to membrane translocation unknown
  5. 2015 High

    Identified ATP1A1 as a host entry factor for enveloped viruses and showed cardiotonic-steroid-triggered Src signaling can block entry, separating signaling from ion-transport function.

    Evidence siRNA silencing, cardiotonic steroid treatment, Src inhibitor rescue, viral infection and EM across multiple viruses

    PMID:25653449

    Open questions at the time
    • Direct viral-ATP1A1 binding not mapped here
    • How Src signaling blocks fusion mechanistically unclear
  6. 2017 Medium

    Demonstrated dose-dependent receptor signaling: low ouabain activates Src-EGFR-ERK-CREB to strengthen junctions, while pump-inhibitory doses act oppositely.

    Evidence Primary Sertoli cell culture, ouabain dosing, signaling inhibitors, TER measurements

    PMID:28203706

    Open questions at the time
    • Endogenous ligand for signaling-dose activation unknown
    • Single cell type
  7. 2018 High

    Extended the pathogenic mechanism to abnormal cation permeabilities and to axonal CMT neuropathy, with direct evidence of axolemmal localization.

    Evidence Heterologous expression and Xenopus oocyte electrophysiology of patient mutants, peripheral nerve immunostaining, exome sequencing

    PMID:29499166 PMID:30388404

    Open questions at the time
    • How abnormal cation leak versus pump loss differentially drives renal vs neuronal phenotypes unresolved
    • Cell-type vulnerability basis unknown
  8. 2019 Medium

    Showed ATP1A1 drives macropinocytic viral entry via clustering-dependent Src/EGFR-Tyr845 signaling, and that some CMT variants act via proteasomal protein loss rather than mRNA loss.

    Evidence Genome-wide siRNA screen, phosphorylation assays, imaging, inhibitors in airway cells; proteasome inhibitor and mRNA analysis in patient cells; iPSC neuronal differentiation

    PMID:31114755 PMID:31373411 PMID:31381610 PMID:31705535 PMID:31707753

    Open questions at the time
    • Whether degradation-prone variants act dominant-negatively or by simple loss not fully separated
    • HSP variant mechanism only partially characterized
  9. 2021 Medium

    Linked APA mutations to proliferative signaling by showing the L104R mutant raises intracellular Ca2+ and Src phosphorylation, connecting pump dysfunction to tumor growth.

    Evidence Mutant transfection in HAC15 cells, proliferation, Ca2+ fluorescence, Src phosphorylation, transcriptomics

    PMID:34681640

    Open questions at the time
    • Direct causal chain from Ca2+/Src to proliferation not isolated
    • Single cell line
  10. 2022 Medium

    Revealed ATP1A1 as a homophilic heterocellular adhesion/signaling molecule driving tumor EMT through fibroblast NF-κB and activin A secretion.

    Evidence Co-IP/pulldown, calcium imaging, NF-κB reporters, activin A neutralization, invasion assays

    PMID:35618735

    Open questions at the time
    • Structural basis of homophilic trans-binding unresolved
    • Single tumor model context
  11. 2023 Medium

    Established ubiquitin-dependent control of ATP1A1 abundance (GPR37, TRIM8/LAPTM4B) coupling its stability to AKT/mTOR and lysosomal signaling, and confirmed that disease requires a dominant malfunctioning product, not haploinsufficiency.

    Evidence Co-IP, ubiquitination assays, knockdowns in cancer cells; Atp1a1+/- mouse longitudinal phenotyping and human protein-null carrier

    PMID:36835408 PMID:36871182 PMID:37407874 PMID:37659504 PMID:39730361 PMID:41362742

    Open questions at the time
    • Hierarchy among competing E3/stabilizing factors unknown
    • Physiological contexts where each turnover pathway dominates undefined
  12. 2024 High

    Mapped a defined small-molecule binding site (T804) on ATP1A1 through a resistance mutation, establishing it as a druggable target whose engagement drives cytotoxicity.

    Evidence Forward genetic chemical mutagenesis screen, hydrogen-bond modeling, T804A mutagenesis, in vivo xenografts

    PMID:39227746

    Open questions at the time
    • Downstream pathway from T804 ligand binding not detailed here
    • Generality across other cardiotonic ligands not tested
  13. 2025 Medium

    Identified additional ligand binding determinants (Gly98/Gly99) and a lncRNA (DARS-AS1) that competes with UBQLN4 to stabilize ATP1A1 and enhance pump activity, linking abundance control to metastasis.

    Evidence Affinity chromatography and resistance mapping for odoamide; ChIRP/MS, docking, NKA enzymatic assays and xenografts for lncDARS-AS1

    PMID:39754293 PMID:40665639

    Open questions at the time
    • Whether multiple ligand-binding residues form a single common pocket unresolved
    • How enhanced pump activity drives metastasis mechanistically unclear
  14. 2026 Medium

    Showed ATP1A1 cooperates with GJA5 in atrial conduction, linking ion flux to arrhythmogenesis.

    Evidence Combined siRNA knockdown in 3D iPSC-derived atrial tissue with electrophysiology and in silico modeling

    PMID:41868610

    Open questions at the time
    • Direct molecular interaction with GJA5 not established
    • Mechanism of conduction heterogeneity undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single protein partitions between its canonical ion-pump function and its Src-coupled receptor, FGF2-recruitment, and homophilic adhesion functions—and what governs that switch in vivo—remains unresolved.
  • No structural model distinguishing signaling-competent from pumping conformations
  • Endogenous physiological ligands for signaling-dose activation unidentified
  • Tissue determinants of disease-variant selectivity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 4 GO:0005215 transporter activity 4 GO:0060089 molecular transducer activity 4 GO:0140657 ATP-dependent activity 4 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-382551 Transport of small molecules 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
EGFRFGF2FXYD1GPR37LAPTM4BSRCTRIM8UBQLN4
Complex memberships
Na+/K+-ATPase (α1/β heterodimer)

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 Somatic hotspot mutations in ATP1A1 (encoding the Na+/K+-ATPase α1 subunit) cause loss of pump activity and strongly reduced affinity for potassium, leading to inappropriate membrane depolarization in adrenal cells and autonomous aldosterone secretion. In vitro functional pump activity assays, electrophysiological ex vivo studies on primary adrenal adenoma cells, exome sequencing Nature genetics High 23416519
2013 The ATP1A1 Gly99Arg mutation (somatic, found in APA) severely impairs ATPase activity, reduces apparent Na+ affinity for phosphorylation and K+ affinity for dephosphorylation (indicating decreased Na+ and K+ binding), and causes membrane depolarization when overexpressed in adrenal cells; structural modeling indicates the substitution interferes with the gateway to the ion binding pocket. In vitro ATPase activity assays, whole-cell patch-clamp electrophysiology in HAC15 adrenal cells, structural homology modeling, CYP11B2 expression assays Hypertension (Dallas, Tex. : 1979) High 24082052
2015 ATP1A1 is required for coronavirus (MHV, FIPV, MERS-CoV) and VSV entry into host cells; cardiotonic steroid binding to ATP1A1 (at nanomolar concentrations that do not inhibit ion transport) activates Src signaling that inhibits virus entry at an early stage, causing virion accumulation near the cell surface and reduced membrane fusion. Gene silencing (siRNA), cardiotonic steroid (ouabain, bufalin) treatment, Src kinase inhibitor rescue experiments, viral infection assays, electron microscopy of virion localization Journal of virology High 25653449
2014 ATP1A1 (α1-chain of Na/K-ATPase), but not the β1- or β3-chains (ATP1B1/ATP1B3), is required for efficient unconventional secretion of FGF2; in the absence of β-chains, a direct protein-protein interaction between the cytoplasmic domain of ATP1A1 and FGF2 occurs with submicromolar affinity, suggesting ATP1A1 acts as a recruitment factor for FGF2 at the inner leaflet of the plasma membrane. Unbiased RNAi screen, siRNA knockdown of individual Na/K-ATPase subunits, direct binding assay (cytoplasmic domain of ATP1A1 with FGF2, affinity measurement) The Journal of biological chemistry High 25533462
2018 De novo mutations in ATP1A1 (catalytic α1 subunit of Na+/K+-ATPase) cause not only loss of pump function but also abnormal cation permeabilities leading to membrane depolarization, underlying renal hypomagnesemia and refractory seizures. Heterologous expression systems (functional characterization of mutant Na+/K+-ATPase α1 subunits), electrophysiology, whole-exome sequencing American journal of human genetics High 30388404
2018 Missense mutations in ATP1A1 cause autosomal-dominant CMT2 (axonal peripheral neuropathy); two-electrode voltage clamp in Xenopus oocytes demonstrated significant reduction in Na+ current activity in some ouabain-insensitive ATP1A1 mutants, indicating loss-of-function of the Na+/K+ pump. ATP1A1 localizes to the axolemma of myelinated sensory and motor axons and to Schmidt-Lanterman incisures. Two-electrode voltage clamp in Xenopus oocytes, immunostaining of peripheral nerve axons, whole-exome/genome sequencing across seven countries American journal of human genetics High 29499166
2019 ATP1A1 is required for macropinocytic entry of RSV into respiratory epithelial cells; RSV triggers clustering of ATP1A1 in the plasma membrane (dependent on viral attachment glycoprotein G), activating c-Src kinase signaling that transactivates EGFR at Tyr845, culminating in macropinosome formation and RSV uptake. Genome-wide siRNA screen, knockdown validation, live-cell imaging, phosphorylation assays (c-Src, EGFR Tyr845), pharmacological inhibitors (ouabain, PST2238), primary human airway epithelial cell validation PLoS pathogens High 31381610
2012 In zebrafish brain ventricle development, Atp1a1 (Na,K-ATPase α subunit) regulates neuroepithelial permeability and CSF production downstream; RhoA acts downstream of Atp1a1 (and its regulatory subunit Fxyd1) in neuroepithelium formation and permeability modulation, while CSF production requires Atp1a1 but not Fxyd1 or RhoA. Morpholino knockdown in zebrafish, overexpression, RhoA epistasis experiments, ouabain pharmacological inhibition, intracellular Na+ measurements Developmental biology Medium 22683378
2017 ATP1A1 in Sertoli cells regulates tight junctions (claudin 11) and gap junctions (connexin 43) through the Src-EGFR-ERK1/2-CREB signaling pathway; 50 nM ouabain (signaling dose) activates this pathway and increases transepithelial electrical resistance, while 1 mM ouabain (pump-inhibitory dose) has opposite effects; Src and MAPK pathway inhibitors abolish ouabain-induced junctional regulation. Primary Sertoli cell culture, ouabain treatment, signaling inhibitors, immunoblotting, transepithelial electrical resistance measurements, immunofluorescence, mass spectrometry Biology of reproduction Medium 28203706
2022 ATP1A1 overexpressed in tumor cells binds homophilically to ATP1A1 on fibroblasts (heterocellular contact), inducing calcium oscillations, NF-κB activation, and activin A secretion in fibroblasts, which promotes EMT in tumor cells and myofibroblast activation; silencing ATP1A1 or neutralizing activin A suppresses tumor invasion. Co-immunoprecipitation/pulldown, siRNA silencing, calcium imaging, NF-κB reporter assays, activin A neutralization, invasion assays, primary tumor analysis Nature communications Medium 35618735
2019 ATP1A1 knockdown in glioma stem cells inhibits ERK1/2 and AKT pathway activation through suppression of Src phosphorylation, reducing cell proliferation, survival, and causing G1 arrest; rescue of ATP1A1 expression restores proliferation, placing ATP1A1 upstream of Src in this signaling axis. siRNA knockdown, ATP1A1 re-expression rescue, Western blotting for p-Src/p-ERK1/2/p-AKT, cell cycle analysis, apoptosis assays in primary human GSCs Frontiers in oncology Medium 31114755
2021 ATP1A1 L104R mutation (APA-associated) stimulates cell proliferation and increases intracellular Ca2+ (measured by Fluo-4), enhances Src phosphorylation, and increases NKA expression in adrenal cells; low-concentration ouabain further potentiates Src phosphorylation in mutant cells. HAC15 cell transfection with mutant ATP1A1, cell proliferation assays, DNA content analysis, S-phase measurement, Ca2+ fluorescence (Fluo-4), Src phosphorylation (Western blot), transcriptome analysis, immunohistochemistry International journal of molecular sciences Medium 34681640
2019 ATP1A1 mutations causing intermediate CMT disease lead to proteasomal degradation of the ATP1A1 protein (loss-of-function), without affecting mRNA levels; the mutations (p.S207F and p.G877S) downregulate protein levels by promoting proteasomal turnover. Whole-exome sequencing, Western blot of protein levels, RT-PCR for mRNA, proteasome inhibitor experiments in patient-derived cells Human mutation Medium 31373411
2023 GPR37 interacts with ATP1A1 and promotes its ubiquitination-induced proteasomal degradation, thereby limiting activation of the AKT/mTOR signaling pathway; GPR37 knockdown stabilizes ATP1A1 and increases AKT/mTOR activity. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, Western blotting for AKT/mTOR pathway components, ESCC cell functional assays Cell death & disease Medium 39730361
2025 LncDARS-AS1 directly binds ATP1A1 protein, preventing its interaction with UBQLN4 and subsequent proteasomal degradation, thereby enhancing Na+/K+-ATPase activity and promoting osteosarcoma metastasis; digoxin targeting NKA inhibits tumor growth. ChIRP, mass spectrometry, molecular docking, molecular dynamics simulations, ion-sensitive fluorescent indicators, enzymatic NKA assays, siRNA silencing, in vivo xenograft models Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 40665639
2024 Periplogenin (PPG) directly binds ATP1A1 at residue T804 (forming a hydrogen bond); T804A substitution abolishes PPG binding and confers resistance to PPG's cytotoxic activity both in vitro and in vivo in xenograft models. Forward genetic chemical mutagenesis screen, next-generation sequencing, in vitro hydrogen bond modeling, T804A mutagenesis, in vivo xenograft comparison of wild-type vs. T804A DU145 cells Scientific reports High 39227746
2023 ATP1A1 serves as a receptor/attachment factor for PEDV; the CT structural domain of ATP1A1 interacts with PEDV S1 protein; knockdown or inhibition of ATP1A1 significantly reduces PEDV attachment; ATP1A1 co-localizes with PEDV S1 at the cell surface in early infection. Virus overlay protein binding assay (VOPBA), mass spectrometry, siRNA knockdown, overexpression, co-localization (immunofluorescence), antibody blocking assay, ouabain/PST2238 inhibitor treatment International journal of molecular sciences Medium 36835408
2023 ATP1A1-linked CMT disease requires a malfunctioning (dominant-negative or gain-of-abnormal-function) protein product from one allele; haploinsufficiency (protein-null heterozygosity) alone is not sufficient to cause disease in Atp1a1+/- mice up to 18 months, and a human carrier of a protein-null truncation variant (p.Y148*) was phenotypically normal. Atp1a1+/- heterozygous knockout mouse neuromuscular phenotyping (up to 18 months, with exercise), clinical phenotyping of human protein-null variant carrier Biochimica et biophysica acta. Molecular cell research Medium 37659504
2019 The ATP1A1 Pro600Ala mutation (CMT2-causing) is associated with defective in vitro neuronal differentiation of patient-derived iPSCs; ATP1A1 protein is undetectable in the few neurons derived from CMT iPSCs, and electrophysiological properties of derived neurons are less mature compared to controls. Patient-specific iPSC generation, neural differentiation assays, immunostaining for ATP1A1, electrophysiology of derived neurons Journal of the peripheral nervous system : JPNS Medium 31707753
2022 In a pancreatic ductal adenocarcinoma context, resibufogenin (RB) binds ATP1A1, activating Na+-K+-ATPase as a signaling receptor that triggers the intracellular MAPK/ERK pathway and Ca2+-mediated Src/FAK/Paxillin focal adhesion pathway, leading to G2/M arrest and inhibition of invasion. Drug-target binding assays, MAPK/ERK pathway analysis, Ca2+ measurement, Src/FAK/Paxillin phosphorylation assays, cell cycle analysis, invasion assays in GBM cell lines Frontiers in pharmacology Medium 35656311
2017 shRNA screen identified ATP1A1 knockdown as conferring sensitivity to aurilide B (a mitochondria-mediated apoptosis inducer); combined ATP1A1 inhibition with ouabain potentiated aurilide B sensitivity, suggesting ATP1A1 regulates mitochondria-mediated apoptosis. Genome-wide pooled shRNA screen with deep sequencing, ouabain combination treatment, cell viability assays Scientific reports Low 28515454
2023 ATP1A1 regulates tumor progression in colon cancer through the ERK5 signaling pathway; ATP1A1 knockdown suppresses cell proliferation, migration, and invasion and induces apoptosis, with microarray revealing altered expression of EGFR, MAP2K5, MAPK7, FOS, MYC, and BAD. siRNA knockdown in HT29 and Caco2 cells, microarray gene expression profiling, cell proliferation/migration/invasion/apoptosis assays Annals of surgical oncology Low 37407874
2022 In ATP1A1 mutant APA, the VDR gene promoter is hypomethylated compared to non-functioning adenoma, leading to high VDR expression; VDR suppression abrogates ATP1A1 mutation-mediated cell proliferation in HAC15 cells, placing VDR downstream of ATP1A1 mutation in the proliferative signaling cascade. DNA methylation analysis, qPCR, siRNA VDR knockdown in HAC15 cells transfected with mutant ATP1A1, cell proliferation assays Molecular and cellular endocrinology Low 35257799
2017 ATP1A1 overexpression in RCC cells inhibits proliferation and migration by increasing ROS production and suppressing the Raf/MEK/ERK signaling pathway, while downregulation of ATP1A1 promotes cancer development. Exogenous overexpression, CCK-8 proliferation assay, Boyden chamber migration assay, flow cytometry for apoptosis and ROS, Western blotting for Raf/MEK/ERK pathway Clinical proteomics Low 28484360
2023 LAPTM4B interacts with ATP1A1 and prevents its TRIM8-mediated K63-linked ubiquitination and proteasomal degradation, stabilizing ATP1A1 to enhance lysosomal acidification and promote EGFR-TKI resistance in NSCLC. Co-immunoprecipitation, ubiquitination assays (K63-linkage-specific), siRNA knockdown, Western blotting, lysosomal pH assays, clinical sample analysis International journal of biological sciences Medium 41362742
2025 ATP1A1 is required for PRRSV-2 attachment and internalization; PRRSV glycoprotein GP4 interacts with the fourth extracellular region (ER4) of ATP1A1 (dependent on GP4 C-terminus); ATP1A1-Src signaling activates EGFR and caveolin-1 to enable viral uptake via macropinocytosis and caveolae/raft-mediated endocytosis; internalized virions traffic to ATP1A1/CD163-positive early endosomes for uncoating. siRNA knockdown, overexpression, co-localization imaging, signaling inhibitor assays, GP4-ER4 interaction mapping, synthetic peptide competition, nanobody targeting, multiple PRRSV lineage testing mBio Medium 41773865
2025 ATP1A1 directly binds odoamide (marine natural product); mutations at Gly98 and Gly99 of ATP1A1 confer resistance to odoamide cytotoxicity; ATP1A1 was identified as the specific binding protein by affinity chromatography with an odoamide probe, and odoamide-induced apoptotic cell death is critically dependent on interaction with ATP1A1. Affinity chromatography with odoamide probe, mass spectrometry, resistance mutation mapping (Gly98/Gly99), cell viability assays, JFCR39 cancer panel fingerprinting, gene expression profiling Chembiochem : a European journal of chemical biology Medium 39754293
2004 Mouse embryos homozygous for a null mutation in the Na/K-ATPase α1-subunit (Atp1a1) are able to undergo compaction and cavitation (blastocyst formation), demonstrating that the α1-isozyme is not strictly required for trophectoderm fluid transport during preimplantation development; other Na/K-ATPase isoforms provide functional redundancy. Targeted gene disruption (Atp1a1 knockout mice), embryo development analysis from heterozygous matings, morphological assessment of compaction and cavitation Mechanisms of development Medium 15147760
2023 Calcium oxalate crystal deposition decreases ATP1A1 expression in renal cells and activates the ATP1A1/Src/ROS/p38/JNK/NF-κB signaling pathway; overexpression of ATP1A1 or treatment with pNaKtide (specific inhibitor of ATP1A1/Src complex) inhibits this signaling cascade and reduces crystal-cell adhesion and stone formation. In vitro crystal deposition experiments, in vivo mouse models, ATP1A1 overexpression, pNaKtide treatment, Western blotting for Src/ROS/p38/JNK/NF-κB Redox biology Medium 36871182
2023 ATP1A1 loss-of-function variant Gly903Arg (p.G903R) causes significantly reduced HEK cell viability in an ouabain resistance assay, demonstrating loss of ATPase function; variant is associated with developmental delay, intellectual disability, and autism. Whole-exome/genome sequencing, ouabain resistance/cell viability assay in transfected HEK cells with ouabain-insensitive ATP1A1 constructs Annals of clinical and translational neurology Medium 38504481
2019 Hereditary spastic paraplegia (HSP) is caused by a de novo ATP1A1 variant (p.L337P); functional studies in heterologous expression systems and homology modeling provide evidence for pathogenicity of this variant affecting Na+/K+-ATPase function. Whole-exome sequencing, functional characterization in heterologous expression systems, homology modeling Clinical genetics Low 31705535
2026 Combined knockdown of ATP1A1 (Na/K-ATPase) and GJA5 (connexin 40) in iPSC-derived atrial myocardium induces significant beat irregularity and increased conduction heterogeneity, establishing these two factors as cooperative drivers of arrhythmogenesis; this is consistent with an inflammation-driven AF mechanism where both intercellular connectivity and ion flux are disrupted. siRNA knockdown in 3D iPSC-derived atrial myocardium tissue model, sharp electrode recordings, calcium imaging, multi-electrode assays, lentiviral overexpression, pharmacological modulation, in silico modeling Frontiers in immunology Medium 41868610

Source papers

Stage 0 corpus · 72 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. Nature genetics 448 23416519
2013 Somatic ATP1A1, ATP2B3, and KCNJ5 mutations in aldosterone-producing adenomas. Hypertension (Dallas, Tex. : 1979) 135 24082052
2015 ATP1A1-mediated Src signaling inhibits coronavirus entry into host cells. Journal of virology 99 25653449
2018 Germline De Novo Mutations in ATP1A1 Cause Renal Hypomagnesemia, Refractory Seizures, and Intellectual Disability. American journal of human genetics 75 30388404
2004 Deletion of the Na/K-ATPase alpha1-subunit gene (Atp1a1) does not prevent cavitation of the preimplantation mouse embryo. Mechanisms of development 69 15147760
2018 Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2. American journal of human genetics 63 29499166
2010 A novel SNP of the ATP1A1 gene is associated with heat tolerance traits in dairy cows. Molecular biology reports 51 20336380
2014 A direct role for ATP1A1 in unconventional secretion of fibroblast growth factor 2. The Journal of biological chemistry 48 25533462
2019 The alpha-1 subunit of the Na+,K+-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells. PLoS pathogens 41 31381610
2019 Genotype-structure-phenotype relationships diverge in paralogs ATP1A1, ATP1A2, and ATP1A3. Neurology. Genetics 38 30842972
2021 Diseases caused by mutations in the Na+/K+ pump α1 gene ATP1A1. American journal of physiology. Cell physiology 37 34232746
2012 Multiple roles for the Na,K-ATPase subunits, Atp1a1 and Fxyd1, during brain ventricle development. Developmental biology 34 22683378
2007 Association of ATP1A1 and dear single-nucleotide polymorphism haplotypes with essential hypertension: sex-specific and haplotype-specific effects. Circulation research 34 17446437
2022 Homophilic ATP1A1 binding induces activin A secretion to promote EMT of tumor cells and myofibroblast activation. Nature communications 31 35618735
2017 A quantitative shRNA screen identifies ATP1A1 as a gene that regulates cytotoxicity by aurilide B. Scientific reports 28 28515454
2017 Downregulation of ATP1A1 promotes cancer development in renal cell carcinoma. Clinical proteomics 24 28484360
2023 Meta-data analysis of kidney stone disease highlights ATP1A1 involvement in renal crystal formation. Redox biology 22 36871182
2017 Abnormal expression of ATP1A1 and ATP1A2 in breast cancer. F1000Research 22 28529692
2021 ATP1A1 de novo Mutation-Related Disorders: Clinical and Genetic Features. Frontiers in pediatrics 20 33968856
2001 Altered Na+-K+ pump activity and plasma lipids in salt-hypertensive Dahl rats: relationship to Atp1a1 gene. Physiological genomics 18 11459925
2017 The ubiquitous isoform of Na/K-ATPase (ATP1A1) regulates junctional proteins, connexin 43 and claudin 11 via Src-EGFR-ERK1/2-CREB pathway in rat Sertoli cells. Biology of reproduction 17 28203706
2019 ATP1A1 Integrates AKT and ERK Signaling via Potential Interaction With Src to Promote Growth and Survival in Glioma Stem Cells. Frontiers in oncology 16 31114755
2016 Overexpression of ATPase Na+/+ transporting alpha 1 polypeptide, ATP1A1, correlates with clinical diagnosis and progression of esophageal squamous cell carcinoma. Oncotarget 16 27845894
2010 Association of ATP1A1 gene polymorphism with heat tolerance traits in dairy cattle. Genetics and molecular research : GMR 16 20467982
2019 ATP1A1 mutations cause intermediate Charcot-Marie-Tooth disease. Human mutation 15 31373411
2022 Resibufogenin Targets the ATP1A1 Signaling Cascade to Induce G2/M Phase Arrest and Inhibit Invasion in Glioma. Frontiers in pharmacology 14 35656311
2019 Hereditary spastic paraplegia is a novel phenotype for germline de novo ATP1A1 mutation. Clinical genetics 14 31705535
2021 Comparative Expression Profiling and Sequence Characterization of ATP1A1 Gene Associated with Heat Tolerance in Tropically Adapted Cattle. Animals : an open access journal from MDPI 13 34438824
2023 Bufalin Inhibits Tumorigenesis and SREBP-1-Mediated Lipogenesis in Hepatocellular Carcinoma via Modulating the ATP1A1/CA2 Axis. The American journal of Chinese medicine 11 36655687
2015 Association of ATP1A1 gene polymorphism with thermotolerance in Tharparkar and Vrindavani cattle. Veterinary world 11 27047171
2021 ATP1A1 Mutant in Aldosterone-Producing Adenoma Leads to Cell Proliferation. International journal of molecular sciences 10 34681640
2020 Enhanced genome editing in human iPSCs with CRISPR-CAS9 by co-targeting ATP1a1. PeerJ 10 32391204
2024 ATP1A1 is a promising new target for melanoma treatment and can be inhibited by its physiological ligand bufalin to restore targeted therapy efficacy. Cancer cell international 9 38178183
2023 The Alpha-1 Subunit of the Na+/K+-ATPase (ATP1A1) Is a Host Factor Involved in the Attachment of Porcine Epidemic Diarrhea Virus. International journal of molecular sciences 9 36835408
2023 Functional Analysis and Clinical Importance of ATP1A1 in Colon Cancer. Annals of surgical oncology 9 37407874
2022 Molecular characterization of alpha subunit 1 of sodium pump (ATP1A1) gene in Camelus dromedarius: its differential tissue expression potentially interprets the role in osmoregulation. Molecular biology reports 9 35235155
2021 Downregulation of ATP1A1 Expression by Panax notoginseng (Burk.) F.H. Chen Saponins: A Potential Mechanism of Antitumor Effects in HepG2 Cells and In Vivo. Frontiers in pharmacology 9 34690763
2011 The effect of ovary storage and in vitro maturation on mRNA levels in bovine oocytes; a possible impact of maternal ATP1A1 on blastocyst development in slaughterhouse-derived oocytes. The Journal of reproduction and development 9 21959748
2008 The Atp1a1 gene from inbred Dahl salt sensitive rats does not contain the A1079T missense transversion. Hypertension (Dallas, Tex. : 1979) 9 18285611
2023 Bioactive C21 Steroidal Glycosides from Euphorbia kansui Promoted HepG2 Cell Apoptosis via the Degradation of ATP1A1 and Inhibited Macrophage Polarization under Co-Cultivation. Molecules (Basel, Switzerland) 8 36985801
2022 De Novo ATP1A1 Variants in an Early-Onset Complex Neurodevelopmental Syndrome. Neurology 8 35110381
2014 Somatic mutations of the ATP1A1 gene and aldosterone-producing adenomas. Molecular and cellular endocrinology 8 25496839
2012 Polymorphisms of the ATP1A1 gene associated with mastitis in dairy cattle. Genetics and molecular research : GMR 8 22535401
2023 Normalization of the ATP1A1 Signalosome Rescinds Epigenetic Modifications and Induces Cell Autophagy in Hepatocellular Carcinoma. Cells 7 37830582
2019 Differential expression and characterization of ATP1A1 exon17 gene by high resolution melting analysis and RT-PCR in Indian goats. Molecular biology reports 7 31414310
2019 Insights into the pathogenesis of ATP1A1-related CMT disease using patient-specific iPSCs. Journal of the peripheral nervous system : JPNS 7 31707753
2023 The phenotypic spectrum of pathogenic ATP1A1 variants expands: the novel p.P600R substitution causes demyelinating Charcot-Marie-Tooth disease. Journal of neurology 6 36738336
2019 Association between a novel G94A single nucleotide polymorphism in ATP1A1 gene and type 2 diabetes mellitus among Egyptian patients. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences 6 31523248
2024 Intracranial aneurysm circulating exosome-derived LncRNA ATP1A1-AS1 promotes smooth muscle cells phenotype switching and apoptosis. Aging 5 38728254
2015 A functional 12T-insertion polymorphism in the ATP1A1 promoter confers decreased susceptibility to hypertension in a male Sardinian population. PloS one 5 25615575
2009 Differential expression of P-type ATPases in intestinal epithelial cells: identification of putative new atp1a1 splice-variant. Biochemical and biophysical research communications 5 19900414
2025 ATP1A1-Driven Intercellular Contact Between Dental Pulp Stem Cell and Endothelial Cell Enhances Vasculogenic Activity. International dental journal 4 40628202
2024 The natural compound periplogenin suppresses the growth of prostate carcinoma cells by directly targeting ATP1A1. Scientific reports 4 39227746
2024 GPR37-enhanced ubiquitination of ATP1A1 inhibits tumor progression and radiation resistance in esophageal squamous cell carcinoma. Cell death & disease 4 39730361
2023 ATP1A1/BCL2L1 predicts the response of myelomonocytic and monocytic acute myeloid leukemia to cardiac glycosides. Leukemia 4 37904054
2022 Hypomethylation associated vitamin D receptor expression in ATP1A1 mutant aldosterone-producing adenoma. Molecular and cellular endocrinology 4 35257799
2023 Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures. Neural regeneration research 3 38767491
2022 LncRNA ATP1A1-AS1 inhibits cell proliferation and promotes cell apoptosis in thyroid carcinoma by regulating the miR-620/IRF2BP2 axis. The American journal of the medical sciences 3 36002076
2025 Target Identification of Marine Natural Product Odoamide:Odoamide Induces Apoptotic Cell Death by Targeting ATPase Na+/K+ Transporting Subunit Alpha 1 (ATP1A1). Chembiochem : a European journal of chemical biology 2 39754293
2025 LncDARS-AS1 Regulates ATP1A1 Stability and Enhances Na+/K+ ATPase Activity to Promote Osteosarcoma Metastasis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 40665639
2023 Silencing of ATP1A1 attenuates cell membrane disruption by nanosecond electric pulses. Biochemical and biophysical research communications 2 37566922
2023 ATP1A1-linked diseases require a malfunctioning protein product from one allele. Biochimica et biophysica acta. Molecular cell research 2 37659504
2009 RAD51D- and FANCG-dependent base substitution mutagenesis at the ATP1A1 locus in mammalian cells. Mutation research 2 19427512
2025 pNaktide reverses metabolic reprogramming and disease progression of ATP1A1-deficiency clear cell renal cell carcinoma. Cancer gene therapy 1 41057666
2024 Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism. Annals of clinical and translational neurology 1 38504481
2002 Targeting of A701G nucleotide at the human ATP1A1 locus using a RNA/DNA chimera. Nucleosides, nucleotides & nucleic acids 1 12537020
2026 LAPTM4B Confers Resistance to EGFR-TKIs by Suppressing the Proteasomal Degradation of ATP1A1 in Non-small Cell Lung Cancer. International journal of biological sciences 0 41362742
2026 ATP1A1 enhances porcine reproductive and respiratory syndrome virus type 2 attachment and internalization. mBio 0 41773865
2026 GJA5 and ATP1A1 perturbations recapitulate inflammation-related beat irregularities in iPSC-based atrial myocardium tissue model. Frontiers in immunology 0 41868610
2026 Low Shear Stress Promotes Atherosclerosis by Mediating Pathological Accumulation of Endothelial Lipid Droplets via the KLF4/TFEB/ATP1A1 Axis. Journal of cardiovascular development and disease 0 42188099
2023 ATP1A1 -linked diseases require a malfunctioning protein product from one allele. bioRxiv : the preprint server for biology 0 37090550
2023 Auditory Neuropathy Spectrum Disorder Progressing with Motor and Sensory Neuropathy Caused by an ATP1A1 Variant. Internal medicine (Tokyo, Japan) 0 37558483

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