FXYD1
Domain
The cytoplasmic domain is sufficient to regulate sodium/potassium-transporting ATPase activity.
Function
Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na(+) out of the cell and K(+) into the cell. Inhibits NKA activity in its unphosphorylated state and stimulates activity when phosphorylated. Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1. Contributes to female sexual development by maintaining the excitability of neurons which secrete gonadotropin-releasing hormone.
Post-translational modifications
Major plasma membrane substrate for cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in several different tissues (By similarity). Phosphorylated in response to insulin and adrenergic stimulation (By similarity). Phosphorylation at Ser-88 stimulates sodium/potassium-transporting ATPase activity while the unphosphorylated form inhibits sodium/potassium-transporting ATPase activity (By similarity). Phosphorylation increases tetramerization, decreases binding to ATP1A1 and reduces inhibition of ATP1A1 activity (By similarity). Phosphorylation at Ser-83 leads to greatly reduced interaction with ATP1A1, ATP1A2 and ATP1A3 (By similarity). May be phosphorylated by DMPK (PubMed:10811636).
Palmitoylation increases half-life and stability and is enhanced upon phosphorylation at Ser-88 by PKA.
Sequence Similarities
Belongs to the FXYD family.
Tissue Specificity
Highest expression in skeletal muscle and heart. Moderate levels in brain, placenta, lung, liver, pancreas, uterus, bladder, prostate, small intestine and colon with mucosal lining. Very low levels in kidney, colon and small intestine without mucosa, prostate without endothelial lining, spleen, and testis.
Cellular localization
- Cell membrane
- Sarcolemma
- Single-pass type I membrane protein
- Apical cell membrane
- Single-pass type I membrane protein
- Membrane
- Caveola
- Cell membrane
- Sarcolemma
- T-tubule
- Detected in the apical cell membrane in brain. In myocytes, localizes to sarcolemma, t-tubules and intercalated disks.
Alternative names
PLM, FXYD1, Phospholemman, FXYD domain-containing ion transport regulator 1, Sodium/potassium-transporting ATPase subunit FXYD1