Recombinant Human Phospholamban (PLN)

Function

Reversibly inhibits the activity of ATP2A2/SERCA2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+) (PubMed:28890335). Binds preferentially to the ATP-bound E1 conformational form of ATP2A2 which predominates at low Ca(2+) concentrations during the diastolic phase of the cardiac cycle (By similarity). Inhibits ATP2A2 Ca(2+) affinity by disrupting its allosteric activation by ATP (By similarity). Modulates the contractility of the heart muscle in response to physiological stimuli via its effects on ATP2A2. Modulates calcium re-uptake during muscle relaxation and plays an important role in calcium homeostasis in the heart muscle. The degree of ATP2A2 inhibition depends on the oligomeric state of PLN. ATP2A2 inhibition is alleviated by PLN phosphorylation (By similarity). Also inhibits the activity of ATP2A3/SERCA3 (By similarity). Controls intracellular Ca(2+) levels in elongated spermatids and may play a role in germ cell differentiation (By similarity). In the thalamic reticular nucleus of the brain, plays a role in the regulation of sleep patterns and executive functioning (By similarity)

Subcellular Location

Endoplasmic reticulum membrane (Single-pass membrane protein); Sarcoplasmic reticulum membrane (Single-pass membrane protein); Mitochondrion membrane (Single-pass membrane protein); Membrane (Single-pass membrane protein)

Disease Association

Cardiomyopathy, dilated, 1P (CMD1P) : A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. [The disease is caused by variants affecting the gene represented in this entry] | Cardiomyopathy, familial hypertrophic, 18 (CMH18) : A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Heart muscle (at protein level)

Subunit

Homopentamer (PubMed:16043693, PubMed:16897780). Can also form heterooligomers with other sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) regulators ARLN, ERLN, SLN and STRIT1/DWORF (PubMed:36523160). Monomer (By similarity). Interacts with HAX1 (PubMed:17241641). Interacts as a monomer with ATP2A2; the interaction decreases ATP2A2 Ca(2+) affinity (PubMed:28890335, PubMed:36523160). Interacts with VMP1; VMP1 competes with PLN and SLN to prevent them from forming an inhibitory complex with ATP2A2 (PubMed:28890335). Interacts with S100A1 in a Ca(2+)-dependent manner (PubMed:12804600)

• Fujii J. et al. Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6. — J. Biol. Chem. (1991)
• Salvatore C.A. et al. Cloning of human cardiac phospholamban. (MAR-)
• McTiernan C.F. et al. The human phospholamban gene: structure and expression. — J. Mol. Cell. Cardiol. (1999)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Minamisawa S. et al. Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy. — Biochem. Biophys. Res. Commun. (2003)
• Kiewitz R. et al. Ca2+ -dependent interaction of S100A1 with the sarcoplasmic reticulum Ca2+ -ATPase2a and phospholamban in the human heart. — Biochem. Biophys. Res. Commun. (2003)
• Kaliman P. et al. Myotonic dystrophy protein kinase phosphorylates phospholamban and regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum. — J. Biol. Chem. (2005)
• Rose A.J. et al. Ca2+-calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise. — J. Physiol. (Lond.) (2006)