Phospholamban

Phospholamban pentamer
Identifiers
Symbol	Phospholamban
Pfam	PF04272
InterPro	IPR005984
SCOP2	1fjk / SCOPe / SUPFAM
TCDB	1.A.50
OPM superfamily	62
OPM protein	1zll
Membranome	383
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

PLN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1PLP, 1ZLL, 2HYN
Identifiers
Aliases	PLN, CMD1P, CMH18, PLB, phospholamban
External IDs	OMIM: 172405; MGI: 97622; HomoloGene: 136758; GeneCards: PLN; OMA:PLN - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q22.31 Start 118,548,296 bp[1] End 118,561,716 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10|10 B3 Start 53,213,763 bp[2] End 53,222,083 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ventricle myocardium myocardium of left ventricle cardiac muscle tissue of right atrium vena cava Skeletal muscle tissue of rectus abdominis biceps brachii Skeletal muscle tissue of biceps brachii tail of epididymis triceps brachii muscle Top expressed in interventricular septum right ventricle cardiac muscles myocardium of ventricle atrioventricular valve left ventricle aortic valve endocardial cushion atrium extraocular muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function enzyme inhibitor activity ATPase binding calcium channel regulator activity protein binding ATPase inhibitor activity identical protein binding protein homodimerization activity Cellular component integral component of membrane vesicle endoplasmic reticulum membrane membrane mitochondrial membranes sarcoplasmic reticulum endoplasmic reticulum mitochondrion sarcoplasmic reticulum membrane perinuclear region of cytoplasm calcium ion-transporting ATPase complex protein-containing complex Biological process Notch signaling pathway regulation of ryanodine-sensitive calcium-release channel activity negative regulation of calcium ion binding regulation of cardiac conduction regulation of calcium ion transport negative regulation of catalytic activity regulation of heart contraction regulation of cytosolic calcium ion concentration cardiac muscle tissue development negative regulation of heart contraction response to testosterone regulation of the force of heart contraction regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion negative regulation of ATP-dependent activity regulation of ATPase-coupled calcium transmembrane transporter activity regulation of calcium ion import response to zinc ion cellular calcium ion homeostasis regulation of relaxation of cardiac muscle negative regulation of calcium ion transmembrane transporter activity blood circulation negative regulation of heart rate negative regulation of calcium ion import response to insulin regulation of cardiac muscle cell contraction negative regulation of ATPase-coupled calcium transmembrane transporter activity negative regulation of calcium ion transport adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process regulation of cardiac muscle cell membrane potential regulation of the force of heart contraction by cardiac conduction regulation of relaxation of muscle negative regulation of calcium ion import into sarcoplasmic reticulum protein homooligomerization regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum relaxation of cardiac muscle calcium ion transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5350 18821 Ensembl ENSG00000198523 ENSMUSG00000038583 UniProt P26678 P61014 RefSeq (mRNA) NM_002667 NM_001141927 NM_023129 RefSeq (protein) NP_002658 NP_001135399 NP_075618 Location (UCSC) Chr 6: 118.55 – 118.56 Mb Chr 10: 53.21 – 53.22 Mb PubMed search [3] [4]
Wikidata
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Phospholamban, also known as PLN or PLB, is a micropeptide protein that in humans is encoded by the PLN gene.^[5] Phospholamban is a 52-amino acid integral membrane protein that regulates the calcium (Ca²⁺) pump in cardiac muscle cells.^[6]

This protein is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase (PKA) in cardiac muscle. In the unphosphorylated state, phospholamban is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2)^[7] which transports calcium from cytosol into the sarcoplasmic reticulum. When phosphorylated (by PKA) - disinhibition of Ca²⁺-ATPase of SR leads to faster Ca²⁺ uptake into the sarcoplasmic reticulum, thereby contributing to the lusitropic response elicited in heart by beta-agonists.^[8] The 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.^[9]

When phospholamban is phosphorylated by PKA, its ability to inhibit SERCA2 is lost.^[10] Thus, activators of PKA, such as the beta-adrenergic agonist epinephrine (released by sympathetic stimulation), may enhance the rate of cardiac myocyte relaxation. In addition, since SERCA2 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. Thus, the overall effect of unphosphorylated phospholamban is to decrease contractility and the rate of muscle relaxation, thereby decreasing stroke volume and heart rate, respectively.^[11]

Gene knockout of phospholamban results in animals with hyperdynamic hearts, with little apparent negative consequence.^[12]

Mutations in this gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure.^[13][14]

Phospholamban was discovered by Arnold Martin Katz and coworkers in 1974.^[15]

PLN has been shown to interact with SLN^[16][17] and SERCA1.^[17][18][19]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Cardiac phospholamban