Last update 01 Nov 2024

ATP1A1

Last update 01 Nov 2024

Basic Info

Synonyms

ATP1A1, ATPase Na+/K+ transporting subunit alpha 1, ATPase, Na+/K+ transporting, alpha 1 polypeptide

+ [4]

Introduction

This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.

Drugs associated with ATP1A1

Digitoxin

Target

ATP1A1

Mechanism

Sodium/potassium-transporting ATPase alpha-1 chain inhibitors

Active Org.

Zhejiang Jinhua CONBA Bio-Pharm Co., Ltd.

Originator Org.-

Active Indication

Arrhythmias, Cardiac [+1]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date31 Dec 1951

Digitoxin/Escin

Target

ATP1A1

Mechanism

Sodium/potassium-transporting ATPase alpha-1 chain inhibitors

Active Org.-

Originator Org.-

Active Indication-

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Ouabain

Target

ATP1A1

Mechanism

Sodium/potassium-transporting ATPase alpha-1 chain inhibitors

Active Org.-

Originator Org.-

Active Indication

Heart Failure

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ATP1A1

EUCTR2013-005326-38-AT / Unknown statusPhase 4IIT

A multicenter, randomized, double-blind, placebo-controlled study to demonstrate that digitoxin reduces a composite of overall mortality and hospitalization for worsening heart failure in patients with chronic heart failure and reduced ejection fraction - DIGIT-HF

Start Date28 May 2018

Sponsor / Collaborator

Hannover Medical School

NCT00782288 / CompletedPhase 2IIT

Phase II Study of Digitoxin to Treat Cystic Fibrosis

This study will measure the inflammatory effects of digitoxin on IL-8 and neutrophil counts in induced sputum in stable Cystic Fibrosis (CF) patients and the pharmacokinetics of digitoxin in serum.
Funding Source-FDA OOPD

Start Date01 Aug 2010

Sponsor / Collaborator

National Jewish Health, Inc.

EUCTR2006-005493-52-SE / Not yet recruitingPhase 2IIT

A pilot phase II study of digitoxin for Androgen-Independent Prostate Cancer (AIPC)

Start Date04 Mar 2007

Sponsor / Collaborator-

100 Clinical Results associated with ATP1A1

100 Translational Medicine associated with ATP1A1

0 Patents (Medical) associated with ATP1A1

490

Literatures (Medical) associated with ATP1A1

01 Jan 2025·Neural Regeneration Research

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

Article

Author: Xie, Jiayu ; Ling, Shengan ; Wen, Dongjing ; He, Jin ; Chen, Wenfeng ; Wang, Xinrui ; Yuan, Yao ; Hong, Jingmei ; Zhuang, Xudong ; Du, Xiaoyue ; Yu, Lingqi

JOURNAL/nrgr/04.03/01300535-202501000-00034/figure1/v/2024-05-29T114527Z/r/image-tiff Certain amino acids changes in the human Na+/K+-ATPase pump, ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1), cause Charcot-Marie-Tooth disease type 2 (CMT2) disease and refractory seizures. To develop in vivo models to study the role of Na+/K+-ATPase in these diseases, we modified the Drosophila gene homolog, Atpα, to mimic the human ATP1A1 gene mutations that cause CMT2. Mutations located within the helical linker region of human ATP1A1 (I592T, A597T, P600T, and D601F) were simultaneously introduced into endogenous DrosophilaAtpα by CRISPR/Cas9-mediated genome editing, generating the AtpαTTTF model. In addition, the same strategy was used to generate the corresponding single point mutations in flies (AtpαI571T, AtpαA576T, AtpαP579T, and AtpαD580F). Moreover, a deletion mutation (Atpαmut) that causes premature termination of translation was generated as a positive control. Of these alleles, we found two that could be maintained as homozygotes (AtpαI571T and AtpαP579T). Three alleles (AtpαA576T, AtpαP579 and AtpαD580F) can form heterozygotes with the Atpαmut allele. We found that the Atpα allele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila. Flies heterozygous for AtpαTTTF mutations have motor performance defects, a reduced lifespan, seizures, and an abnormal neuronal morphology. These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

01 Dec 2024·Cellular and Molecular Life Sciences

Uncovering key steps in FGF12 cellular release reveals a common mechanism for unconventional FGF protein secretion

Article

Author: Kalka, Marta ; Sochacka, Martyna ; Zakrzewska, Malgorzata ; Krowarsch, Daniel ; Karelus, Radoslaw ; Chorazewska, Aleksandra ; Opalinski, Lukasz ; Biadun, Martyna

AbstractFGF12 belongs to a subfamily of FGF proteins called FGF homologous factors (FHFs), which until recently were thought to be non-signaling intracellular proteins. Our recent studies have shown that although they lack a conventional signal peptide for secretion, they can reach the extracellular space, especially under stress conditions. Here, we unraveled that the long “a” isoform of FGF12 is secreted in a pathway involving the A1 subunit of Na(+)/K(+) ATPase (ATP1A1), Tec kinase and lipids such as phosphatidylinositol and phosphatidylserine. Further, we showed that the short “b” isoform of FGF12, which binds ATP1A1 and phosphatidylserine less efficiently, is not secreted from cells. We also indicated regions in the FGF12a protein sequence that are crucial for its secretion, including N-terminal fragment and specific residues, and proposed that liquid-liquid phase separation may be important in this process. Our results strongly suggest that the mechanism of this process is very similar for all unconventionally secreted FGF proteins.

15 Oct 2024·Cancer Research

Targeting the Sodium–Potassium Pump as a Therapeutic Strategy in Acute Myeloid Leukemia

Article

Author: Alexe, Gabriela ; Oellerich, Thomas ; Khalid, Delan ; Schneider, Constanze ; Stegmaier, Kimberly ; Scheich, Sebastian ; Spaink, Hermes ; Merickel, Lucy A. ; Meyer, Ashleigh ; Dharia, Neekesh V. ; Häupl, Björn ; Staudt, Louis M.

AbstractTissue-specific differences in the expression of paralog genes, which are not essential in most cell types due to the buffering effect of the partner pair, can make for highly selective gene dependencies. To identify selective paralogous targets for acute myeloid leukemia (AML), we integrated the Cancer Dependency Map with numerous datasets characterizing protein–protein interactions, paralog relationships, and gene expression in cancer models. In this study, we identified ATP1B3 as a context-specific, paralog-related dependency in AML. ATP1B3, the β-subunit of the sodium–potassium pump (Na/K-ATP pump), interacts with the α-subunit ATP1A1 to form an essential complex for maintaining cellular homeostasis and membrane potential in all eukaryotic cells. When ATP1B3’s paralog ATP1B1 is poorly expressed, elimination of ATP1B3 leads to the destabilization of the Na/K-ATP pump. ATP1B1 expression is regulated through epigenetic silencing in hematopoietic lineage cells through histone and DNA methylation in the promoter region. Loss of ATP1B3 in AML cells induced cell death in vitro and reduced leukemia burden in vivo, which could be rescued by stabilizing ATP1A1 through overexpression of ATP1B1. Thus, ATP1B3 is a potential therapeutic target for AML and other hematologic malignancies with low expression of ATP1B1.Significance: ATP1B3 is a lethal selective paralog dependency in acute myeloid leukemia that can be eliminated to destabilize the sodium–potassium pump, inducing cell death.

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ATP1A1

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