[FXYD proteins: novel regulators of Na,K-ATPase]

Med Sci (Paris). 2006 Jun-Jul;22(6-7):633-8. doi: 10.1051/medsci/20062267633.
[Article in French]


Members of the FXYD protein family are small membrane proteins which are characterized by an FXYD motif, two conserved glycines and a serine residue. FXYD proteins show a tissue-specific distribution. Recent evidence suggests that 6 out of 7 FXYD proteins, FXYD1 (phospholemman), FXYD2 (gamma subunit of Na,K-ATPase), FXYD3 (Mat-8), FXYD4 (CHIF), FXYD5 (Ric) and FXYD7 associate with Na,K-ATPase and modulate its transport properties e.g. its Na+ and/or its K+ affinity in a distinct way. These results highlight the complex regulation of Na+ and K+ transport which is necessary to ensure proper tissue functions such as renal Na+-reabsorption, muscle contractility and neuronal excitability. Moreover, mutation of a conserved glycine residue into an arginine residue in FXYD2 has been linked to cases of human hypomagnesemia indicating that dysregulation of Na,K-ATPase by FXYD proteins may be implicated in pathophysiological states. A better characterization of this novel regulatory mechanism of Na,K-ATPase may help to better understand its role in physiological and pathophysiological conditions.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arginine
  • Biological Transport
  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Conserved Sequence
  • Glycine
  • Homeostasis
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Potassium / metabolism
  • Sequence Alignment
  • Sodium / metabolism
  • Sodium-Potassium-Exchanging ATPase / chemistry
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Calcium-Binding Proteins
  • Membrane Proteins
  • phospholamban
  • Arginine
  • Sodium
  • Sodium-Potassium-Exchanging ATPase
  • Potassium
  • Glycine