Reactome: A Curated Pathway Database

ATP1A:ATP1B:FXYD exchanges Na+ for K+

Stable Identifier
Homo sapiens
The Na+/K+-transporting ATPase trimer exchanges sodium for potassium
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The sodium/potassium-transporting ATPase (ATP1A:ATP1B:FXYD) is composed of three subunits - alpha (catalytic part), beta and gamma. The trimer catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane, creating the electrochemical gradient which provides energy for the active transport of various nutrients.
Four human genes encode the catalytic alpha subunits, ATP1A1-4 (Kawakami et al, 1986; Shull et al, 1989; Ovchinnikov et al, 1988; Keryanov and Gardner, 2002). Defects in ATP1A2 cause alternating hemiplegia of childhood (AHC) (Swoboda et al, 2004). Another defect in ATP1A2 causes familial hemiplegic migraine type 2 (FHM2) (Vanmolkot et al, 2003). Defects in ATP1A3 are the cause of dystonia type 12 (DYT12) (de Carvalho Aguiar et al, 2004).

Three human genes encode the non-catalytic beta subunits, ATP1B1-3. The beta subunits are thought to mediate the number of sodium pumps transported to the plasma membrane (Lane et al, 1989; Ruiz et al, 1996; Malik et al, 1996). FXYD proteins belong to a family of small membrane proteins that are auxiliary gamma subunits of Na-K-ATPase. At least six members of this family, FYD1-4, 6 and 7, have been shown to regulate Na-K-ATPase activity (Geering 2006, Choudhury et al. 2007). Defects in FXYD2 are the cause of hypomagnesemia type 2 (HOMG2) (Meij et al, 2000). ATP1A1-4 and ATP1B1-4 play a minor role during phase 2, since they begin to restore ion concentrations. The high concentration of intracellular calcium starts contraction of those cells, which is sustained in the plateau phase.

Literature References
PubMed ID Title Journal Year
15174025 Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation Ann Neurol 2004
12953268 Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions Ann Neurol 2003
17357072 A genetic association study of chromosome 11q22-24 in two different samples implicates the FXYD6 gene, encoding phosphohippolin, in susceptibility to schizophrenia Am. J. Hum. Genet. 2007
2559024 Characterization of two genes for the human Na,K-ATPase beta subunit Genomics 1989
2430951 Primary structure of the alpha-subunit of human Na,K-ATPase deduced from cDNA sequence J Biochem 1986
12119109 Physical mapping and characterization of the human Na,K-ATPase isoform, ATP1A4 Gene 2002
11062458 Dominant isolated renal magnesium loss is caused by misrouting of the Na(+),K(+)-ATPase gamma-subunit Nat Genet 2000
2477373 Characterization of the human Na,K-ATPase alpha 2 gene and identification of intragenic restriction fragment length polymorphisms J Biol Chem 1989
2838329 Family of human Na+, K+-ATPase genes. Structure of the gene for the catalytic subunit (alpha III-form) and its relationship with structural features of the protein FEBS Lett 1988
8918259 Expression and synthesis of the Na,K-ATPase beta 2 subunit in human retinal pigment epithelium Gene 1996
15260953 Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism Neuron 2004
8798450 Identification of the mammalian Na,K-ATPase 3 subunit J Biol Chem 1996
Participant Of
This entity is regulated by:
Title Physical Entity Activity
sodium:potassium-exchanging ATPase activity of ATP1A:ATP1B:FXYD [plasma membrane] ATP1A:ATP1B:FXYD [plasma membrane] sodium:potassium-exchanging ATPase activity (0005391)
Orthologous Events