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Phospholamban: Wikis


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1zll opm.gif
Phospholamban pentamer
Symbol Phospholamban
Pfam PF04272
InterPro IPR005984
SCOP 1fjk
TCDB 8.A.11
OPM family 70
OPM protein 1zll
Human phospholamban
Symbol PLN
Alt. symbols PLB
Entrez 5350
HUGO 9080
OMIM 172405
RefSeq NM_002667
UniProt P26678
Other data
Locus Chr. 6 q22.1

Phospholamban is a 52 amino acid integral membrane protein that regulates the Ca2+ pump in cardiac muscle and skeletal muscle cells.[1]



When phospholamban is phosphorylated by protein kinase A (PKA) its ability to inhibit the sarcoplasmic reticulum calcium pump (SERCA) is lost.[2] Thus, activators of PKA, such as the beta-adrenergic agonist epinephrine (released by sympathetic stimulation) may enhance the rate of cardiac myocyte relaxation. Additionally, since SERCA is more active, the next action potential will cause an increased release of calcium resulting in increased contraction (positive inotropic effect). When phospholamban is not phosphorylated, such as when PKA is inactive, it can interact with and inhibit SERCA. The overall effect of phospholamban is to increase the rate of muscle relaxation and contractility thereby decreasing heart rate and stroke volume respectively.[3]

Clinical significance

Gene knockout of phospholamban results in animals with hyperdynamic hearts, with little apparent negative consequence.[4]

Mutations in this gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure.[5]


Phospholamban was discovered by Arnold Katz and coworkers in 1974.[6]


  1. ^ Rodriguez P, Kranias EG (December 2005). "Phospholamban: a key determinant of cardiac function and dysfunction". Arch Mal Coeur Vaiss 98 (12): 1239–43. PMID 16435604. 
  2. ^ Medical Physiology. Philadelphia: Saunders. 2004. ISBN 0-8089-2333-1. 
  3. ^ Brittsan AG, Kranias EG (December 2000). "Phospholamban and cardiac contractile function". J. Mol. Cell. Cardiol. 32 (12): 2131–9. doi:10.1006/jmcc.2000.1270. PMID 11112989. 
  4. ^ Luo W, Grupp IL, Harrer J, Ponniah S, Grupp G, Duffy JJ, Doetschman T, Kranias EG (September 1994). "Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation". Circ. Res. 75 (3): 401–9. PMID 8062415. 
  5. ^ Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG, MacLennan DH, Seidman JG, Seidman CE (February 2003). "Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban". Science (journal) 299 (5611): 1410–3. doi:10.1126/science.1081578. PMID 12610310. 
  6. ^ Tada M, Kirchberger MA, Repke DI, Katz AM (October 1974). "The stimulation of calcium transport in cardiac sarcoplasmic reticulum by adenosine 3':5'-monophosphate-dependent protein kinase". J Biol Chem 10 (249(19)): 6174-80. PMID 4371608. 

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