The protein encoded by this gene 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. Mutations in this gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure. [provided by RefSeq, Jul 2008].
Function:
Phospholamban has been postulated to regulate the activity of the calcium pump of cardiac sarcoplasmic reticulum.
Subunit:
Homopentamer. Interacts with HAX1.
Subcellular Location:
Mitochondrion membrane. Sarcoplasmic reticulum.
Tissue Specificity:
Heart.
Post-translational modifications:
Phosphorylated at Thr-17 by CaMK2, and in response to beta-adrenergic stimulation. Phosphorylation by DMPK may stimulate sarcoplasmic reticulum calcium uptake in cardiomyocytes.
DISEASE:
Defects in PLN are the cause of cardiomyopathy dilated type 1P (CMD1P) [MIM:609909]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Defects in PLN are the cause of cardiomyopathy familial hypertrophic type 18 (CMH18) [MIM:613874]. CMH18 is 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.
Similarity:
Belongs to the phospholamban family.
SWISS:
P26678
Gene ID:
5350
Database links:
Entrez Gene: 5350 Human
Entrez Gene: 18821 Mouse
Entrez Gene: 64672 Rat
Omim: 17485 Human
SwissProt: P26677 Chicken
SwissProt: A4IFH6 Cow
SwissProt: P61012 Dog
SwissProt: P26678 Human
SwissProt: P61014 Mouse
SwissProt: P61013 Pig
SwissProt: P61015 Rabbit
SwissProt: P61016 Rat
Unigene: 170839 Human
Unigene: 34145 Mouse
Unigene: 9740 Rat
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