Table 1.
Summary of FXYD protein characteristics
FXYD proteinOther nameExpression patternEffects on NKAPosttranslational modifications and effects on NKAPhysiological/pathological role
FXYD1 PLM Expresses in multiple tissue types ↓Sodium affinity (Crambert et al., 2002; Despa et al., 2005; Bossuyt et al., 2009; Meyer et al., 2020) Phosphorylation at Ser63, Ser68, and Ser69 PLM is required for the sympathetic simulation of the NKA in cardiomyocytes (Despa et al., 2005) 
↑NKA activity (Fuller et al., 2009; Despa et al., 2005), glutathionylation at Cys42 ↑NKA activity (Bibert et al., 2011), palmitoylation at Cys40 and Cys42 
↓NKA activity (Tulloch et al., 2011; Hilgemann et al., 2013) 
FXYD2 γ Subunit Restricted to kidney and pancreas ↓Sodium affinity (Béguin et al., 1997; Arystarkhova et al., 1999, 2002a; Therien et al., 1999; Meyer et al., 2020) Unknown Unknown 
FXYD3 Mammary tumor (Mat-8) Restricted to tissues rich in smooth muscle, skin, and salivary gland Mixed results (Crambert et al., 2005; Bibert et al., 2006; Wujak et al., 2016) Glutathionylation at Cys40 and Cys42 Unknown 
↑NKA activity (Bibert et al., 2006) 
FXYD4 CHIF Restricted to kidney, inducible in colon with corticosteroid ↑Sodium affinity and Vmax (Béguin et al., 2001; Meyer et al., 2020) Unknown CHIF increases sodium reabsorption in the colon and kidneys during sodium deprivation (Aizman et al., 2002) 
FXYD5 Related ion channel, dysadherin Expressed in multiple tissue types and almost completely absent in brain tissue ↑Sodium affinity and Vmax, ↓potassium affinity (Lubarski et al., 2007; Mathias et al., 2008) Palmitoylation and glycosylation Dysadherin increases cancer invasiveness (Ino et al., 2002) 
FXYD6 Phosphohippolin  Expressed in multiple tissue types ↓Sodium affinity (Delprat et al., 2007b; Meyer et al., 2020) Unknown Unknown 
FXYD7 N/A Brain ↓Potassium affinity, ↑sodium affinity (Béguin et al., 2002; Meyer et al., 2020) Glycosylation at Thr5 and Thr9 Unknown 
↑FXYD7 stabilization and translocation to the plasma membrane (Moshitzky et al., 2012) 
FXYD proteinOther nameExpression patternEffects on NKAPosttranslational modifications and effects on NKAPhysiological/pathological role
FXYD1 PLM Expresses in multiple tissue types ↓Sodium affinity (Crambert et al., 2002; Despa et al., 2005; Bossuyt et al., 2009; Meyer et al., 2020) Phosphorylation at Ser63, Ser68, and Ser69 PLM is required for the sympathetic simulation of the NKA in cardiomyocytes (Despa et al., 2005) 
↑NKA activity (Fuller et al., 2009; Despa et al., 2005), glutathionylation at Cys42 ↑NKA activity (Bibert et al., 2011), palmitoylation at Cys40 and Cys42 
↓NKA activity (Tulloch et al., 2011; Hilgemann et al., 2013) 
FXYD2 γ Subunit Restricted to kidney and pancreas ↓Sodium affinity (Béguin et al., 1997; Arystarkhova et al., 1999, 2002a; Therien et al., 1999; Meyer et al., 2020) Unknown Unknown 
FXYD3 Mammary tumor (Mat-8) Restricted to tissues rich in smooth muscle, skin, and salivary gland Mixed results (Crambert et al., 2005; Bibert et al., 2006; Wujak et al., 2016) Glutathionylation at Cys40 and Cys42 Unknown 
↑NKA activity (Bibert et al., 2006) 
FXYD4 CHIF Restricted to kidney, inducible in colon with corticosteroid ↑Sodium affinity and Vmax (Béguin et al., 2001; Meyer et al., 2020) Unknown CHIF increases sodium reabsorption in the colon and kidneys during sodium deprivation (Aizman et al., 2002) 
FXYD5 Related ion channel, dysadherin Expressed in multiple tissue types and almost completely absent in brain tissue ↑Sodium affinity and Vmax, ↓potassium affinity (Lubarski et al., 2007; Mathias et al., 2008) Palmitoylation and glycosylation Dysadherin increases cancer invasiveness (Ino et al., 2002) 
FXYD6 Phosphohippolin  Expressed in multiple tissue types ↓Sodium affinity (Delprat et al., 2007b; Meyer et al., 2020) Unknown Unknown 
FXYD7 N/A Brain ↓Potassium affinity, ↑sodium affinity (Béguin et al., 2002; Meyer et al., 2020) Glycosylation at Thr5 and Thr9 Unknown 
↑FXYD7 stabilization and translocation to the plasma membrane (Moshitzky et al., 2012) 

Expression patterns were obtained from the GTEx Portal. N/A, not applicable.

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