FXYD proteins: new tissue-specific regulators of the ubiquitous Na,K-ATPase

Sci STKE. 2003 Jan 21;2003(166):RE1. doi: 10.1126/stke.2003.166.re1.


Maintenance of the Na+ and K+ gradients between the intracellular and extracellular milieus of animal cells is a prerequisite for basic cellular homeostasis and for functions of specialized tissues. The Na,K-ATPase, an oligomeric P-type adenosine triphosphatase (ATPase), is composed of a catalytic alpha subunit and a regulatory beta subunit and is the main player that fulfils these tasks. A variety of regulatory mechanisms are necessary to guarantee appropriate Na,K-ATPase expression and activity adapted to changing physiological demands. Recently, a regulatory mechanism was defined that is mediated by interaction of Na,K-ATPase with small proteins of the FXYD family, which possess a single transmembrane domain and so far have been considered as channels or regulators of ion channels. The mammalian FXYD proteins FXYD1 through FXYD7 exhibit tissue-specific distribution. Phospholemman (FXYD1) in heart and skeletal muscle, the gamma subunit of Na,K-ATPase (FXYD2) and corticosteroid hormone-induced factor (FXYD4, also known as CHIF) in the kidney, and FXYD7 in the brain associate preferentially with the widely expressed Na,K-ATPase alpha1-beta1 isozyme and modulate its transport activity in a way that conforms to tissue-specific requirements. Thus, tissue- and isozyme-specific interaction of Na,K-ATPase with FXYD proteins contributes to proper handling of Na+ and K+ by the Na,K-ATPase, and ensures correct function in such processes as renal Na+-reabsorption, muscle contraction, and neuronal excitability.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / physiology*
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / physiology*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / physiology*
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / physiology*
  • Organ Specificity / physiology
  • Sodium-Potassium-Exchanging ATPase / biosynthesis
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Sodium-Potassium-Exchanging ATPase / physiology*


  • FXYD3 protein, human
  • Fxyd3 protein, mouse
  • Fxyd7 protein, mouse
  • Membrane Glycoproteins
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • corticosteroid hormone-induced factor
  • FXYD2 protein, human
  • Sodium-Potassium-Exchanging ATPase