Protein Domain : Phospholamban IPR005984

Type	Family
Description	Phospholamban (PLB) is a small protein (52 amino acids) that regulates the affinity of the cardiac sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) for calcium. PLB is present in cardiac myocytes, in slow-twitch and smooth muscle and is expressed also in aorta endothelial cells in which it could play a role in tissue relaxation. The phosphorylation/dephosphorylation of phospholamban removes and restores, respectively, its inhibitory activity on SERCA2a. It has in fact been shown that phospholamban, in its non-phosphorylated form, binds to SERCA2a and inhibits this pump by lowering its affinity for Ca 2+, whereas the phosphorylated form does not exert the inhibition. PLB is phosphorylated at two sites, namely at Ser-16 for a cAMP-dependent phosphokinase and at Thr-17 for a Ca2+/calmodulin-dependent phosphokinase, phosphorylation at Ser-16 being a prerequisite for the phosphorylation at Thr-17. The structure of a 36-amino-acid-long N-terminal fragment of human phospholamban phosphorylated at Ser-16 and Thr-17 and Cys36Ser mutated was determined from nuclear magnetic resonance data. The peptide assumes a conformation characterised by two α-helices connected by an irregular strand, which comprises the amino acids from Arg-13 to Pro-21. The proline is in a trans conformation. The two phosphate groups on Ser-16 and Thr-17 are shown to interact preferably with the side chains of Arg-14 and Arg-13, respectively [].Mutations of the phospholamban gene cause cardiomyopathy, such as Cardiomyopathy, dilated 1P (CMD1P) [ , ] and Cardiomyopathy, familial hypertrophic 18 (CMH18) [].
Short Name	PLB