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FLASH GENE
Symbol PLN contributors: mct/npt - updated : 17-04-2016
HGNC name phospholamban
HGNC id 9080
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal di-arginine motif that may act as a general ER retrieval sequence
    • secondary structure
  • in lipid bilayers, PLN adopts a helix-turn-helix structure arranged in an L-shaped configuration
    • conjugated PhosphoP
    mono polymer homomer , pentamer
    HOMOLOGY
    Homologene
    FAMILY
  • phospholamban family
    • CATEGORY motor/contractile , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,vesicle
    text highly expressed in the sarcoplasmic reticulum (SR) where it colocalizes with the ryanodine receptor and DMPK
    basic FUNCTION
  • regulating the activity of the sarcoplasmic Ca++ ATPase (ATP2A2) isoform a, regulator of the kinetics of cardiac contraction (diastolic function)
  • phosphorylation of PLN acts to release constraints involving interdomain subunit interactions that enhance catalytically important N-domain motions
  • enriched in the ER due to COP I-mediated transport that is dependent on its intact di-arginine motif and the N-terminal di-arginine motif may act as a general ER retrieval sequence
  • unphosphorylated PLN reduces ATP2A1 affinity for Ca(2+) and affects the enzymatic turnover
  • crucial Ca(2+) cycling protein and a primary mediator of the beta-adrenergic effects resulting in enhanced cardiac output
  • inhibitor of cardiac sarco(endo)plasmic reticulum Ca²&
    • 8314; ATPase
  • effect of PLN and SLN, which becomes synergic when they are both present in the SR membrane, is expected to favor a rapid equilibration of ions on both sides of the membrane
  • PLN does not function as a simple on/off switch for Ca2+ translocation; rather, its conformational equilibrium exerts a gradual control (“physiological rheostat”) on ATP2A1 activity
  • SLN and its close analog phospholamban (PLN) are membrane proteins that regulate SERCA by inhibiting Ca(2+) transport in skeletal and cardiac muscl
  • SLN, not PLN, is required for muscle-based thermogenesis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cardiovascular
    PATHWAY
    metabolism
    signaling
    a component ATP2A1/ PLN complex regulates Ca2+ translocation into the sarcoplasmic reticulum (SR) of cardiomyocytes and constitutes the main mechanism of cardiac relaxation (diastole)
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to S100A1, SLN
  • associated with the fast-twitch skeletal muscle sarcoplasmic reticulum Ca++ ATPase (ATP2A1)
  • inhibiting ATP2A2a (a weak inhibitor of ATP2A2, PLN(R9C), which is diminished in its ability to modify the level of ATP2A2a activity, leads to heart failure despite fast sarcoplasmic reticulum Ca(2+) reuptake) (Schmitt 2009)
  • binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (ATP2A1) in the sarcoplasmic reticulum
  • allosteric regulation of ATP2A1 depends on the conformational equilibrium of PLN
  • SLN and PLN inhibit ATP2A1 by using a similar mechanism
  • HAX1 is likely a major mediator of PLN inhibitory activity and a critical gatekeeper of sarcoplasmic reticulum calcium cycling and contractility in the heart
    • cell & other
    REGULATION
    inhibited by SLN, via inhibition of polymerization of the pentamer
    Other phosphoregulated by cAMP-dependent and other protein kinases
    ASSOCIATED DISORDERS
    corresponding disease(s) CMD1P
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in tetralogy of Fallot (Vittorini 2007)
    constitutional germinal mutation      
    cause of inherited dilated cardiomyopathy with refractory congestive heart failure
    constitutional     --low  
    results in cardiac hypertrophy and decreased cardiac contractility
    Susceptibility to familial hypertrophic cardiomyopathy
    Variant & Polymorphism truncation mutation in the PLN gene (Leu39Ter) associated to familial hypertrophic cardiomyopathy (Chiu 2007)
    Candidate gene may be responsible for cardiomyopathy
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Pln-KO protected RyR2-R4496C mutant mice from stress-induced ventricular tachyarrhythmias