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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
Corresponding disease
DICMT2 dominant intermediate Charcot-Marie-Tooth neuropathy 2
HOMGSMR2 hypomagnesemia, seizures, and mental retardation 2
Location 1p13.1      Physical location : 116.915.794 - 116.947.394
Synonym name
  • Na+/K+ ATPase 1
  • sodium-potassium-ATPase, alpha 1 polypeptide
  • Na, K-ATPase catalytic subunit alpha-A protein
  • sodium pump 1
  • Na, K-ATPase, alpha-A catalytic polypeptide
    • Synonym symbol(s) MGC3285, MGC51750, NKAalpha1
    EC.number 3.6.1.9/ 3.6.3.9
    DNA
    TYPE functioning gene
    STRUCTURE 31.56 kb     23 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 3754 112 1023 - Chehab (1987)
  • isoform a
  • preproprotein
    • 23 - 3778 - 1023 - -
  • isoform c
    • 23 - 3587 - 992 - -
  • isoform d
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain    
     spinal cordanterior horn    Homo sapiens
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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