PLN
PLN (phospholamban, also known as PLB or CMD1P) is a small membrane protein that reversibly inhibits the sarcoplasmic reticulum Ca(2+)-ATPase ATP2A2/SERCA2 in cardiac muscle. It is a key regulator of calcium re-uptake and diastolic function in the heart. Browse Assay Genie's current range of PLN research reagents below, or read on for the biology behind the target.
PLN reversibly inhibits the activity of ATP2A2/SERCA2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+). It binds preferentially to the ATP-bound E1 conformation of ATP2A2, which predominates at low Ca(2+) concentrations during the diastolic phase of the cardiac cycle, and it lowers Ca(2+) affinity by disrupting the allosteric activation of the pump by ATP. The degree of inhibition depends on the oligomeric state of PLN, and the protein is found as a pentamer. Through these effects on ATP2A2, PLN modulates calcium re-uptake during muscle relaxation and the contractility of the heart in response to physiological stimuli. It also inhibits ATP2A3/SERCA3.
PLN is a major substrate for cAMP-dependent protein kinase in cardiac muscle. In its unphosphorylated state it inhibits the sarcoplasmic reticulum Ca(2+)-ATPase; phosphorylation relieves this inhibition. The resulting activation of the Ca(2+) pump enhances muscle relaxation rates, contributing to the inotropic response elicited in the heart by beta-agonists. UniProt places the protein in the phospholamban family, and HGNC lists the PLN gene in the regulins group. It localises to the endoplasmic reticulum, sarcoplasmic reticulum and mitochondrion membranes. The mouse and rat orthologs are both named Pln.
Beyond the heart, PLN controls intracellular Ca(2+) levels in elongated spermatids and may play a role in germ cell differentiation. In the thalamic reticular nucleus of the brain it contributes to the regulation of sleep patterns and executive functioning. Mutations in the PLN gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure, and also of familial hypertrophic cardiomyopathy. The alias CMD1P reflects this link to dilated cardiomyopathy.
PLN regulates calcium re-uptake into the sarcoplasmic reticulum during relaxation and is central to calcium homeostasis in heart muscle.
Mutations in PLN cause inherited dilated cardiomyopathy with refractory congestive heart failure and familial hypertrophic cardiomyopathy.
PLN is a major substrate of cAMP-dependent protein kinase, linking beta-agonist stimulation to faster relaxation and the inotropic response.
PLN controls Ca(2+) in elongated spermatids and, in the thalamic reticular nucleus, helps regulate sleep patterns and executive functioning.
PLN inhibits the cardiac sarcoplasmic reticulum Ca(2+)-ATPase ATP2A2/SERCA2 by lowering its apparent affinity for Ca(2+). Phosphorylation of PLN relieves this inhibition, speeding calcium re-uptake and muscle relaxation. In this way PLN modulates cardiac contractility and diastolic function.
PLN is the HGNC symbol for phospholamban. Aliases include PLB and CMD1P, the latter reflecting the link between PLN mutations and dilated cardiomyopathy. No previous HGNC names are listed. UniProt records the protein as Phospholamban, and HGNC places it in the regulins gene group.
Mutations in the PLN gene cause inherited dilated cardiomyopathy with refractory congestive heart failure, and also familial hypertrophic cardiomyopathy. Orthologs exist in mouse and rat, both named Pln; check the datasheet of any product for its validated reactivity.
Other SERCA pumps, regulins, calcium-handling proteins and kinases linked to cardiac relaxation, with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P26678; product specifications from Assay Genie datasheets.