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FLASH GENE
Symbol PLN contributors: mct/npt - updated : 17-04-2016
HGNC name phospholamban
HGNC id 9080
Corresponding disease
CMD1P cardiomyopathy dilated or hypertrophic, 1P
Location 6q22.31      Physical location : 118.869.441 - 118.881.586
Synonym name cardiac phospholamban
Synonym symbol(s) PLB
DNA
TYPE functioning gene
STRUCTURE 12.15 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
2 - 1742 5.98 52 - 2009 19139388
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   predominantly Homo sapiens
Digestivemouth   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularsmooth   
Muscularstriatumcardiac predominantly Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
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