PLN

PLN is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase in cardiac muscle. The encoded protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca(2+)-ATPase in the unphosphorylated state, but inhibition is relieved upon phosphorylation of the protein. The subsequent activation of the Ca(2+) pump leads to enhanced muscle relaxation rates, thereby contributing to the inotropic response elicited in heart by beta-agonists. The encoded protein is a key regulator of cardiac diastolic function.

Phospholamban

Reversibly inhibits the activity of ATP2A2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca2+ (PubMed:28890335).
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.

Adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart processIEA:Ensembl
Blood circulation1 PublicationNAS:ProtInc
Cardiac muscle tissue developmentIEA:Ensembl
Muscle cell cellular homeostasisIEA:Ensembl
Negative regulation of ATP-dependent activityManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of ATPase-coupled calcium transmembrane transporter activityManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of calcium ion bindingManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of calcium ion importBy SimilarityISS:BHF-UCL
Negative regulation of calcium ion import into sarcoplasmic reticulumISS:UniProtKB
Negative regulation of calcium ion transmembrane transporter activityManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of calcium ion transportManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of catalytic activityBy SimilarityISS:BHF-UCL
Negative regulation of heart rateManual Assertion Based On ExperimentIMP:BHF-UCL
Notch signaling pathwayIEA:Ensembl
Regulation of ATPase-coupled calcium transmembrane transporter activityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of calcium ion transportManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cardiac muscle cell contraction1 PublicationIC:BHF-UCL
Regulation of cardiac muscle cell membrane potential1 PublicationIC:BHF-UCL
Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ionIEA:Ensembl
Regulation of cytosolic calcium ion concentration1 PublicationIC:BHF-UCL
Regulation of heart contractionManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of relaxation of cardiac muscle1 PublicationIC:BHF-UCL
Regulation of ryanodine-sensitive calcium-release channel activityIEA:Ensembl
Regulation of the force of heart contraction1 PublicationIC:BHF-UCL
Regulation of the force of heart contraction by cardiac conductionIEA:Ensembl
Relaxation of cardiac muscleManual Assertion Based On ExperimentTAS:BHF-UCL

Endoplasmic reticulum membrane
Sarcoplasmic reticulum membrane
Mitochondrion membrane
Membrane
Colocalizes with HAX1 at the endoplasmic reticulum (PubMed:17241641).
Colocalizes with DMPK a the sarcoplasmic reticulum (PubMed:15598648).

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.
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.

Cytoplasmic: 1-31
Helical: 32-52

Phosphorylation by PKA abolishes the inhibition of ATP2A2-mediated calcium uptake. Phosphorylated at Thr-17 by CaMK2, and in response to beta-adrenergic stimulation. Phosphorylation by DMPK may stimulate sarcoplasmic reticulum calcium uptake in cardiomyocytes.
Palmitoylated by ZDHHC16, promoting formation of the homopentamer.