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FLASH GENE

Symbol

PLN

contributors: mct/npt - updated : 17-04-2016

HGNC name	phospholamban
HGNC id	9080

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002667 2 - 1742 NP_002658 5.98 52 - 2009 19139388

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       predominantly Homo sapiens Digestive mouth       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular smooth       Muscular striatum cardiac   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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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