1.A.27.1.1
Phospholemman (PLM; FXYD1) forms anion channels and regulates L-type Ca²⁺ channels as well as several other cation transport systems in cardiac myocytes (Zhang et al. 2015), most importantly the Na⁺,K⁺-ATPase (Pavlovic et al. 2013). Palmitoylation of the mammalian Na⁺ pump's accessory subunit PLM by the cell surface palmitoyl acyl transferase DHHC5 leads to pump inhibition, possibly by altering the relationship between the pump's catalytic α-subunit and specifically bound membrane lipids (Howie et al. 2018). PLM is also regulated by phosphorylation and glutathionylation (Pavlovic et al. 2013). and phosphorylation couteracts the inhibitory effect of palmitoylation (Cheung et al. 2013). The human ortholog has UniProt acc #O00168 and is 89% identical to the dog protein, with all of the difference occurring in the first 20 aas. Palmitoylation affects the regulation of cardiac electrophysiology, by modifying the sodium-calcium exchanger, phospholemman and the cardiac sodium pump, as well as the voltage-gated sodium channel (Essandoh et al. 2020). The conserved FXYD motif is found in this protein as residues 29-32.