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Protein

Cardiac phospholamban

Gene

PLN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Reversibly inhibits the activity of ATP2A2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca2+. Modulates the contractility of the heart muscle in response to physiological stimuli via its effects on ATP2A2. Modulates calcium re-uptake during muscle relaxation and plays an important role in calcium homeostasis in the heart muscle. The degree of ATP2A2 inhibition depends on the oligomeric state of PLN. ATP2A2 inhibition is alleviated by PLN phosphorylation.2 Publications

Miscellaneous

For practical reasons, PLN activity is most often studied with ATP2A1 instead of ATP2A2.

GO - Molecular functioni

  • ATPase binding Source: BHF-UCL
  • ATPase inhibitor activity Source: BHF-UCL
  • calcium channel regulator activity Source: InterPro
  • enzyme inhibitor activity Source: BHF-UCL
  • identical protein binding Source: BHF-UCL

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-5578775 Ion homeostasis
R-HSA-936837 Ion transport by P-type ATPases
SIGNORiP26678

Protein family/group databases

TCDBi1.A.50.1.1 the phospholamban (ca(2+)-channel and ca(2+)-atpase regulator) (plb) family

Names & Taxonomyi

Protein namesi
Recommended name:
Cardiac phospholamban
Short name:
PLB
Gene namesi
Name:PLN
Synonyms:PLB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000198523.5
HGNCiHGNC:9080 PLN
MIMi172405 gene
neXtProtiNX_P26678

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 31CytoplasmicCuratedAdd BLAST31
Transmembranei32 – 52HelicalCuratedAdd BLAST21

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Sarcoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, dilated 1P (CMD1P)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
See also OMIM:609909
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0259899R → C in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 3 PublicationsCorresponds to variant dbSNP:rs111033559EnsemblClinVar.1
Natural variantiVAR_0729259R → H in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 2 PublicationsCorresponds to variant dbSNP:rs754782171EnsemblClinVar.1
Natural variantiVAR_0729269R → L in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 2 Publications1
Natural variantiVAR_02599014Missing in CMD1P; impairs phosphorylation by PKA, destabilizes the homopentamer and mildly reduces inhibition of ATP2A1-mediated calcium uptake. 3 Publications1
Cardiomyopathy, familial hypertrophic 18 (CMH18)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
See also OMIM:613874

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi13R → A: Abolishes phosphorylation by PKA. 1 Publication1
Mutagenesisi14R → A: Abolishes phosphorylation by PKA. 1 Publication1
Mutagenesisi16S → A: Abolishes phosphorylation by PKA. 1 Publication1
Mutagenesisi17T → A: No effect on phosphorylation by PKA. 1 Publication1

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

DisGeNETi5350
GeneReviewsiPLN
MalaCardsiPLN
MIMi609909 phenotype
613874 phenotype
OpenTargetsiENSG00000198523
Orphaneti154 Familial isolated dilated cardiomyopathy
155 NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy
PharmGKBiPA272

Polymorphism and mutation databases

BioMutaiPLN
DMDMi130774

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001912441 – 52Cardiac phospholambanAdd BLAST52

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei16Phosphoserine; by PKA and DMPK2 Publications1
Modified residuei17Phosphothreonine; by CaMK21 Publication1
Lipidationi36S-palmitoyl cysteineBy similarity1

Post-translational modificationi

Phosphorylation by PKA abolishes the inhibition of ATP2A2-mediated calcium uptake. Phosphorylated at Thr-17 by CaMK2, and in response to beta-adrenergic stimulation. Phosphorylation by DMPK may stimulate sarcoplasmic reticulum calcium uptake in cardiomyocytes.3 Publications
Palmitoylated by ZDHHC16, promoting formation of the homopentamer.By similarity

Keywords - PTMi

Acetylation, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP26678
PeptideAtlasiP26678
PRIDEiP26678
ProteomicsDBi54361
TopDownProteomicsiP26678

PTM databases

iPTMnetiP26678
PhosphoSitePlusiP26678

Expressioni

Tissue specificityi

Heart muscle (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000198523 Expressed in 192 organ(s), highest expression level in heart
CleanExiHS_PLN
ExpressionAtlasiP26678 baseline and differential
GenevisibleiP26678 HS

Organism-specific databases

HPAiCAB005597
HPA026900

Interactioni

Subunit structurei

Homopentamer (PubMed:16043693, PubMed:16897780). Interacts with HAX1 and ATP2A2 (PubMed:17241641).3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111365, 9 interactors
ComplexPortaliCPX-51 Cardiac phospholamban complex
CORUMiP26678
DIPiDIP-33582N
ELMiP26678
IntActiP26678, 50 interactors
STRINGi9606.ENSP00000350132

Structurei

Secondary structure

152
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP26678
SMRiP26678
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26678

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni16 – 22Involved in HAX1 binding7

Sequence similaritiesi

Belongs to the phospholamban family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J7H0 Eukaryota
ENOG4111BFT LUCA
GeneTreeiENSGT00390000002403
HOGENOMiHOG000115660
HOVERGENiHBG108280
InParanoidiP26678
KOiK05852
OMAiMERVQHM
PhylomeDBiP26678
TreeFamiTF330750

Family and domain databases

InterProiView protein in InterPro
IPR005984 PLB
PANTHERiPTHR21194 PTHR21194, 1 hit
PfamiView protein in Pfam
PF04272 Phospholamban, 1 hit
PIRSFiPIRSF001665 PLB, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD014689 P_lamban, 1 hit
TIGRFAMsiTIGR01294 P_lamban, 1 hit

Sequencei

Sequence statusi: Complete.

P26678-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEKVQYLTRS AIRRASTIEM PQQARQKLQN LFINFCLILI CLLLICIIVM

LL
Length:52
Mass (Da):6,109
Last modified:August 1, 1992 - v1
Checksum:i0766304A76A854D3
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0259899R → C in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 3 PublicationsCorresponds to variant dbSNP:rs111033559EnsemblClinVar.1
Natural variantiVAR_0729259R → H in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 2 PublicationsCorresponds to variant dbSNP:rs754782171EnsemblClinVar.1
Natural variantiVAR_0729269R → L in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 2 Publications1
Natural variantiVAR_02599014Missing in CMD1P; impairs phosphorylation by PKA, destabilizes the homopentamer and mildly reduces inhibition of ATP2A1-mediated calcium uptake. 3 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63603 mRNA Translation: AAA60083.1
M60411 mRNA Translation: AAA60109.1
AF177764 Genomic DNA Translation: AAD55950.1
BC005269 mRNA Translation: AAH05269.1
CCDSiCCDS5120.1
PIRiA40424
RefSeqiNP_002658.1, NM_002667.4
UniGeneiHs.170839
Hs.745010

Genome annotation databases

EnsembliENST00000357525; ENSP00000350132; ENSG00000198523
GeneIDi5350
KEGGihsa:5350

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63603 mRNA Translation: AAA60083.1
M60411 mRNA Translation: AAA60109.1
AF177764 Genomic DNA Translation: AAD55950.1
BC005269 mRNA Translation: AAH05269.1
CCDSiCCDS5120.1
PIRiA40424
RefSeqiNP_002658.1, NM_002667.4
UniGeneiHs.170839
Hs.745010

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K9Nmodel-A/B/C/D/E35-52[»]
1KCHmodel-A/B/C/D/E35-52[»]
1PLNmodel-A/B/C/D/E35-52[»]
1PLPNMR-A1-24[»]
1PSLmodel-A/B/C/D/E1-52[»]
1ZLLNMR-A/B/C/D/E1-52[»]
2HYNNMR-A/B/C/D/E1-52[»]
ProteinModelPortaliP26678
SMRiP26678
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111365, 9 interactors
ComplexPortaliCPX-51 Cardiac phospholamban complex
CORUMiP26678
DIPiDIP-33582N
ELMiP26678
IntActiP26678, 50 interactors
STRINGi9606.ENSP00000350132

Protein family/group databases

TCDBi1.A.50.1.1 the phospholamban (ca(2+)-channel and ca(2+)-atpase regulator) (plb) family

PTM databases

iPTMnetiP26678
PhosphoSitePlusiP26678

Polymorphism and mutation databases

BioMutaiPLN
DMDMi130774

Proteomic databases

PaxDbiP26678
PeptideAtlasiP26678
PRIDEiP26678
ProteomicsDBi54361
TopDownProteomicsiP26678

Protocols and materials databases

DNASUi5350
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357525; ENSP00000350132; ENSG00000198523
GeneIDi5350
KEGGihsa:5350

Organism-specific databases

CTDi5350
DisGeNETi5350
EuPathDBiHostDB:ENSG00000198523.5
GeneCardsiPLN
GeneReviewsiPLN
HGNCiHGNC:9080 PLN
HPAiCAB005597
HPA026900
MalaCardsiPLN
MIMi172405 gene
609909 phenotype
613874 phenotype
neXtProtiNX_P26678
OpenTargetsiENSG00000198523
Orphaneti154 Familial isolated dilated cardiomyopathy
155 NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy
PharmGKBiPA272
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J7H0 Eukaryota
ENOG4111BFT LUCA
GeneTreeiENSGT00390000002403
HOGENOMiHOG000115660
HOVERGENiHBG108280
InParanoidiP26678
KOiK05852
OMAiMERVQHM
PhylomeDBiP26678
TreeFamiTF330750

Enzyme and pathway databases

ReactomeiR-HSA-5578775 Ion homeostasis
R-HSA-936837 Ion transport by P-type ATPases
SIGNORiP26678

Miscellaneous databases

EvolutionaryTraceiP26678
GeneWikiiPhospholamban
GenomeRNAii5350
PROiPR:P26678
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198523 Expressed in 192 organ(s), highest expression level in heart
CleanExiHS_PLN
ExpressionAtlasiP26678 baseline and differential
GenevisibleiP26678 HS

Family and domain databases

InterProiView protein in InterPro
IPR005984 PLB
PANTHERiPTHR21194 PTHR21194, 1 hit
PfamiView protein in Pfam
PF04272 Phospholamban, 1 hit
PIRSFiPIRSF001665 PLB, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD014689 P_lamban, 1 hit
TIGRFAMsiTIGR01294 P_lamban, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPPLA_HUMAN
AccessioniPrimary (citable) accession number: P26678
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: November 7, 2018
This is version 182 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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