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FLASH GENE
Symbol ATP1A1 contributors: mct - updated : 21-02-2018
HGNC name ATPase, Na+/K+ transporting, alpha 1 polypeptide
HGNC id 799
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
conjugated PhosphoP
HOMOLOGY
interspecies homolog to murine Atp1a1 (96.9pc)
homolog to rattus Atp1a1 (96.8pc)
Homologene
FAMILY
  • cation transport ATPase (P-type) family
  • type IIC subfamily
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    basic FUNCTION
  • catalyzes the hydrolysis of ATP coupled with exchange of Na+/K+ ions across the plasma membrane, thus creating the electrochemical gradient of Ca2+ and K+ ions, providing the energy for active transport of various nutrients
  • roles for the Na,K-ATPase subunits, ATP1A1 and FXYD1, during brain ventricle development
  • osmotic balance and cell volume stability
  • might interact with and regulate SRC activity in a conformation-dependent manner
  • new role for ATP1A1 as a regulator of RAB27A targeting and activation
  • has an important role in synaptic transmission and memory formation
  • important role of ATP1A1 in oxidative stress and oxidative stress-related disease
  • is the catalytic alpha subunit of a P-type Na+,K+-ATPase ion pump that establishes Na+ and K+ gradients across cell membranes
  • generates the electrochemical driving force that powers essential functions, such as neuronal firing, muscle contraction, and transepithelial ion transport (pMID: 30388404)
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS active transport
    text Na+, K+ pump
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • catalytic component of the active enzyme (composed of an alpha and a beta subunit)
  • complexing with ATP1B1 and maybe others
    • INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
  • ATP binding
  • Mg2+, K+, Na+
    • protein
  • ATP1B1
  • binding the HLA class II histocompatibility antigen DR1
  • binds to the N-ter of the inositol 1,4,5-trisphosphate receptor and can trigger an antiapoptotic calcium signal (Zhang 2006)
  • FXYD1 has recently been recognized as a critical regulator of ATP1A1 in the heart
  • ZNRF1 and ZNRF2 can ubiquitylate the cytoplasmic loop encompassing the nucleotide-binding and phosphorylation regions of the ATP1A1 subunit
  • may be a key player in dynamic regulation of cellular SRC activity and the capability of normal conformation transition is essential for both pumping and signaling functions of ATP1A1
  • role for MAPK14 in mediating cross-talk between apical Na(+) entry via SCNN1G and its basolateral exit via ATP1A1, which may allow principal cells to maintain intracellular Na(+) concentrations within narrow limits in collecting duct principal cells
  • ATP1A1 plays an essential role in RAB27A-dependent melanosome transport
  • ATP1A1 is a recruitment factor for FGF2 at the inner leaflet of plasma membranes that may control phosphatidylinositol 4,5-bisphosphate-dependent membrane translocation as part of the unconventional secretory pathway of FGF2
  • role of beta-amyloid as a novel physiological regulator of ATP1A1
  • ouabain stimulates ATP1A1 in renal proximal tubule cells through an angiotensin/AGTR1-dependent mechanism and that this pathway contributes to cardiac glycoside associated hypertension
  • increase of ATP1A1 activity is dependent on activation of the SRC pathway
  • GPNMB promotes glioma growth via ATP1A1, ATP1A2, ATP1A3, ATP1A4
    • cell & other
    REGULATION
    Other phosphorylation on tyr10 modulates pumping activity
    phosphorylation of AP-2 mu2 subunit is essential for Na+/K+-ATPase endocytosis in response to a variety of signals, such as dopamine or ROS (Chen 2006)
    ASSOCIATED DISORDERS
    corresponding disease(s) DICMT2 , HOMGSMR2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in aldosterone-producing adenomas (APAs)
    tumoral     --over  
    is strongly associated with the presence and severity of ESCC (esophageal squamous cell carcinoma)
    constitutional somatic mutation      
    in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension
    Susceptibility
    Variant & Polymorphism SNP
  • genetic variations are associated with bipolar disorders suggesting a role of the enzyme in the etiology of the disease (Goldstein 2009)
    • Candidate gene
  • for interacting hypertension susceptibility locus
    • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    targeting ATP1A1 is a novel approach to the treatment of hepatocellular carcinoma
    ANIMAL & CELL MODELS
  • Dahl salt-sensitive (S) rats bearing Dahl salt-resistant wildtype ATP1A1 cDNA exhibited less rat salt-sensitive hypertension, less hypersensitive renal disease, and longer life span compared with Dahl S controls
  • hearts from heterozygous ATP1A1 mice (with a targeted disruption in the gene) are hyponcontractile