FXYD1

This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator. Mouse FXYD5 has been termed RIC (Related to Ion Channel). FXYD2, also known as the gamma subunit of the Na,K-ATPase, regulates the properties of that enzyme. FXYD1 (phospholemman), FXYD2 (gamma), FXYD3 (MAT-8), FXYD4 (CHIF), and FXYD5 (RIC) have been shown to induce channel activity in experimental expression systems. Transmembrane topology has been established for two family members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the membrane. The protein encoded by this gene is a plasma membrane substrate for several kinases, including protein kinase A, protein kinase C, NIMA kinase, and myotonic dystrophy kinase. It is thought to form an ion channel or regulate ion channel activity. Transcript variants with different 5' UTR sequences have been described in the literature. [provided by RefSeq, Jul 2008]

Full Name

FXYD Domain Containing Ion Transport Regulator 1

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.

Biological Process

Chloride transport Source: ProtInc
Muscle contraction Source: ProtInc
Negative regulation of protein glutathionylation Source: UniProtKB
Positive regulation of sodium ion export across plasma membrane Source: UniProtKB
Potassium ion transport Source: UniProtKB-KW
Regulation of cardiac muscle cell membrane potential Source: BHF-UCL
Regulation of heart contraction Source: BHF-UCL
Regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
Sodium ion transport Source: UniProtKB-KW

Cellular Location

Sarcolemma; Apical cell membrane; T-tubule; Caveola. Detected in the apical cell membrane in brain. In myocytes, localizes to sarcolemma, t-tubules and intercalated disks.

Topology

Extracellular: 21-35
Helical: 36-56
Cytoplasmic: 57-92

PTM

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.