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P26678

- PPLA_HUMAN

UniProt

P26678 - PPLA_HUMAN

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Protein
Cardiac phospholamban
Gene
PLN, PLB
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - 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

GO - Molecular functioni

  1. ATPase binding Source: BHF-UCL
  2. ATPase inhibitor activity Source: BHF-UCL
  3. calcium channel regulator activity Source: InterPro
  4. enzyme inhibitor activity Source: BHF-UCL
  5. identical protein binding Source: BHF-UCL
  6. protein binding Source: IntAct

GO - Biological processi

  1. adrenergic receptor signaling pathway involved in heart process Source: Ensembl
  2. blood circulation Source: ProtInc
  3. calcium ion transport Source: Ensembl
  4. cardiac muscle tissue development Source: Ensembl
  5. cytosolic calcium ion homeostasis Source: BHF-UCL
  6. negative regulation of ATPase activity Source: BHF-UCL
  7. negative regulation of calcium ion binding Source: BHF-UCL
  8. negative regulation of calcium ion import Source: BHF-UCL
  9. negative regulation of calcium ion import into sarcoplasmic reticulum Source: BHF-UCL
  10. negative regulation of calcium ion transmembrane transporter activity Source: BHF-UCL
  11. negative regulation of calcium ion transport Source: BHF-UCL
  12. negative regulation of calcium-transporting ATPase activity Source: BHF-UCL
  13. negative regulation of catalytic activity Source: BHF-UCL
  14. negative regulation of heart rate Source: BHF-UCL
  15. protein homooligomerization Source: Ensembl
  16. regulation of calcium ion transport Source: UniProtKB
  17. regulation of calcium-transporting ATPase activity Source: UniProtKB
  18. regulation of cardiac muscle cell contraction Source: BHF-UCL
  19. regulation of cardiac muscle cell membrane potential Source: BHF-UCL
  20. regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: Ensembl
  21. regulation of heart contraction Source: BHF-UCL
  22. regulation of relaxation of cardiac muscle Source: BHF-UCL
  23. regulation of ryanodine-sensitive calcium-release channel activity Source: Ensembl
  24. regulation of the force of heart contraction Source: BHF-UCL
  25. regulation of the force of heart contraction by cardiac conduction Source: Ensembl
  26. relaxation of cardiac muscle Source: BHF-UCL
  27. response to testosterone Source: Ensembl
  28. response to zinc ion Source: Ensembl
Complete GO annotation...

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
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:9080. PLN.

Subcellular locationi

Sarcoplasmic reticulum membrane; Single-pass membrane protein. Mitochondrion membrane; Single-pass membrane protein By similarity. Endoplasmic reticulum membrane; Single-pass membrane protein 4 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3131Cytoplasmic Inferred
Add
BLAST
Transmembranei32 – 5221Helical; Inferred
Add
BLAST

GO - Cellular componenti

  1. calcium ion-transporting ATPase complex Source: BHF-UCL
  2. endoplasmic reticulum Source: BHF-UCL
  3. membrane Source: BHF-UCL
  4. mitochondrial membrane Source: UniProtKB-SubCell
  5. mitochondrion Source: UniProt
  6. perinuclear region of cytoplasm Source: BHF-UCL
  7. sarcoplasmic reticulum membrane Source: UniProtKB-SubCell
  8. vesicle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Sarcoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, dilated 1P (CMD1P) [MIM:609909]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Note: The disease is caused by mutations affecting the gene represented in this entry.4 Publications
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti9 – 91R → C in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 3 Publications
VAR_025989
Natural varianti14 – 141Missing in CMD1P; impairs phosphorylation by PKA, destabilizes the homopentamer and mildly reduces inhibition of ATP2A1-mediated calcium uptake. 3 Publications
VAR_025990
Cardiomyopathy, familial hypertrophic 18 (CMH18) [MIM:613874]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi9 – 91R → H or L: Impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 1 Publication
Mutagenesisi13 – 131R → A: Abolishes phosphorylation by PKA. 1 Publication
Mutagenesisi14 – 141R → A: Abolishes phosphorylation by PKA. 1 Publication
Mutagenesisi16 – 161S → A: Abolishes phosphorylation by PKA. 1 Publication
Mutagenesisi17 – 171T → A: No effect on phosphorylation by PKA. 1 Publication

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

MIMi609909. phenotype.
613874. phenotype.
Orphaneti154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA272.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 5252Cardiac phospholamban
PRO_0000191244Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine By similarity
Modified residuei16 – 161Phosphoserine; by PKA and DMPK2 Publications
Modified residuei17 – 171Phosphothreonine; by CaMK21 Publication

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP26678.
PaxDbiP26678.
PRIDEiP26678.

PTM databases

PhosphoSiteiP26678.

Expressioni

Tissue specificityi

Heart muscle (at protein level).1 Publication

Gene expression databases

ArrayExpressiP26678.
BgeeiP26678.
CleanExiHS_PLN.
GenevestigatoriP26678.

Organism-specific databases

HPAiCAB005597.
HPA026900.

Interactioni

Subunit structurei

Homopentamer. Interacts with HAX1 and ATP2A2.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DMPKQ090134EBI-692836,EBI-692774

Protein-protein interaction databases

BioGridi111365. 5 interactions.
IntActiP26678. 2 interactions.
STRINGi9606.ENSP00000350132.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 1411
Beta strandi18 – 203
Helixi23 – 5028

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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. Positions 1-35.

Miscellaneous databases

EvolutionaryTraceiP26678.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni16 – 227Involved in HAX1 binding

Sequence similaritiesi

Belongs to the phospholamban family.

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG44917.
HOGENOMiHOG000115660.
HOVERGENiHBG108280.
InParanoidiP26678.
KOiK05852.
OMAiQHARQNL.
PhylomeDBiP26678.
TreeFamiTF330750.

Family and domain databases

InterProiIPR005984. P_lamban.
[Graphical view]
PANTHERiPTHR21194. PTHR21194. 1 hit.
PfamiPF04272. Phospholamban. 1 hit.
[Graphical view]
PIRSFiPIRSF001665. PLB. 1 hit.
ProDomiPD014689. P_lamban. 1 hit.
[Graphical view] [Entries sharing at least one domain]
TIGRFAMsiTIGR01294. P_lamban. 1 hit.

Sequencei

Sequence statusi: Complete.

P26678-1 [UniParc]FASTAAdd to Basket

« Hide

MEKVQYLTRS AIRRASTIEM PQQARQKLQN LFINFCLILI CLLLICIIVM   50
LL 52
Length:52
Mass (Da):6,109
Last modified:August 1, 1992 - v1
Checksum:i0766304A76A854D3
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti9 – 91R → C in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 3 Publications
VAR_025989
Natural varianti14 – 141Missing in CMD1P; impairs phosphorylation by PKA, destabilizes the homopentamer and mildly reduces inhibition of ATP2A1-mediated calcium uptake. 3 Publications
VAR_025990

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_002667.3.
UniGeneiHs.170839.

Genome annotation databases

EnsembliENST00000357525; ENSP00000350132; ENSG00000198523.
GeneIDi5350.
KEGGihsa:5350.
UCSCiuc003pye.3. human.

Polymorphism databases

DMDMi130774.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M63603 mRNA. Translation: AAA60083.1 .
M60411 mRNA. Translation: AAA60109.1 .
AF177764 Genomic DNA. Translation: AAD55950.1 .
BC005269 mRNA. Translation: AAH05269.1 .
CCDSi CCDS5120.1.
PIRi A40424.
RefSeqi NP_002658.1. NM_002667.3.
UniGenei Hs.170839.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1K9N model - A/B/C/D/E 35-52 [» ]
1KCH model - A/B/C/D/E 35-52 [» ]
1PLN model - A/B/C/D/E 35-52 [» ]
1PLP NMR - A 1-24 [» ]
1PSL model - A/B/C/D/E 1-52 [» ]
1ZLL NMR - A/B/C/D/E 1-52 [» ]
2HYN NMR - A/B/C/D/E 1-52 [» ]
ProteinModelPortali P26678.
SMRi P26678. Positions 1-35.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111365. 5 interactions.
IntActi P26678. 2 interactions.
STRINGi 9606.ENSP00000350132.

Protein family/group databases

TCDBi 1.A.50.1.1. the phospholamban (ca(2+)-channel and ca(2+)-atpase regulator) (plb) family.

PTM databases

PhosphoSitei P26678.

Polymorphism databases

DMDMi 130774.

Proteomic databases

MaxQBi P26678.
PaxDbi P26678.
PRIDEi P26678.

Protocols and materials databases

DNASUi 5350.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000357525 ; ENSP00000350132 ; ENSG00000198523 .
GeneIDi 5350.
KEGGi hsa:5350.
UCSCi uc003pye.3. human.

Organism-specific databases

CTDi 5350.
GeneCardsi GC06P118869.
GeneReviewsi PLN.
HGNCi HGNC:9080. PLN.
HPAi CAB005597.
HPA026900.
MIMi 172405. gene.
609909. phenotype.
613874. phenotype.
neXtProti NX_P26678.
Orphaneti 154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBi PA272.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG44917.
HOGENOMi HOG000115660.
HOVERGENi HBG108280.
InParanoidi P26678.
KOi K05852.
OMAi QHARQNL.
PhylomeDBi P26678.
TreeFami TF330750.

Miscellaneous databases

EvolutionaryTracei P26678.
GeneWikii Phospholamban.
GenomeRNAii 5350.
NextBioi 20738.
PROi P26678.
SOURCEi Search...

Gene expression databases

ArrayExpressi P26678.
Bgeei P26678.
CleanExi HS_PLN.
Genevestigatori P26678.

Family and domain databases

InterProi IPR005984. P_lamban.
[Graphical view ]
PANTHERi PTHR21194. PTHR21194. 1 hit.
Pfami PF04272. Phospholamban. 1 hit.
[Graphical view ]
PIRSFi PIRSF001665. PLB. 1 hit.
ProDomi PD014689. P_lamban. 1 hit.
[Graphical view ] [Entries sharing at least one domain ]
TIGRFAMsi TIGR01294. P_lamban. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6."
    Fujii J., Zarain-Herzberg A., Willard H.F., Tada M., Maclennan D.H.
    J. Biol. Chem. 266:11669-11675(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Cloning of human cardiac phospholamban."
    Salvatore C.A., Jacobson M.A.
    Submitted (MAR-1991) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Liver.
  5. "Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy."
    Minamisawa S., Sato Y., Tatsuguchi Y., Fujino T., Imamura S., Uetsuka Y., Nakazawa M., Matsuoka R.
    Biochem. Biophys. Res. Commun. 304:1-4(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CMH18.
  6. "Myotonic dystrophy protein kinase phosphorylates phospholamban and regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum."
    Kaliman P., Catalucci D., Lam J.T., Kondo R., Gutierrez J.C., Reddy S., Palacin M., Zorzano A., Chien K.R., Ruiz-Lozano P.
    J. Biol. Chem. 280:8016-8021(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-16 BY DMPK.
  7. "Ca2+-calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise."
    Rose A.J., Kiens B., Richter E.A.
    J. Physiol. (Lond.) 574:889-903(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-17 BY CAMK2.
  8. "Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function."
    Vafiadaki E., Sanoudou D., Arvanitis D.A., Catino D.H., Kranias E.G., Kontrogianni-Konstantopoulos A.
    J. Mol. Biol. 367:65-79(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HAX1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  9. "Lethal, hereditary mutants of phospholamban elude phosphorylation by protein kinase A."
    Ceholski D.K., Trieber C.A., Holmes C.F., Young H.S.
    J. Biol. Chem. 287:26596-26605(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS CMD1P CYS-9 AND ARG-14 DEL, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-16, MUTAGENESIS OF ARG-9; ARG-13; ARG-14; SER-16 AND THR-17.
  10. "Solution structure of the cytoplasmic domain of phospholamban: phosphorylation leads to a local perturbation in secondary structure."
    Mortishire-Smith R.J., Pitzenberger S.M., Burke C.J., Middaugh C.R., Garsky V.M., Johnson R.G.
    Biochemistry 34:7603-7613(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 1-25.
  11. "Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban."
    Adams P.D., Arkin I.T., Engelman D.M., Bruenger A.T.
    Nat. Struct. Biol. 2:154-162(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING.
  12. "Using experimental information to produce a model of the transmembrane domain of the ion channel phospholamban."
    Herzyk P., Hubbard R.E.
    Biophys. J. 74:1203-1214(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING.
  13. "The structure of phospholamban pentamer reveals a channel-like architecture in membranes."
    Oxenoid K., Chou J.J.
    Proc. Natl. Acad. Sci. U.S.A. 102:10870-10875(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR, SUBCELLULAR LOCATION, SUBUNIT.
  14. "Structure determination of symmetric homo-oligomers by a complete search of symmetry configuration space, using NMR restraints and van der Waals packing."
    Potluri S., Yan A.K., Chou J.J., Donald B.R., Bailey-Kellogg C.
    Proteins 65:203-219(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR, SUBUNIT.
  15. "Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban."
    Schmitt J.P., Kamisago M., Asahi M., Li G.H., Ahmad F., Mende U., Kranias E.G., MacLennan D.H., Seidman J.G., Seidman C.E.
    Science 299:1410-1413(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CMD1P CYS-9, CHARACTERIZATION OF VARIANT CMD1P CYS-9.
  16. Cited for: VARIANT CMD1P ARG-14 DEL, CHARACTERIZATION OF VARIANT CMD1P ARG-14 DEL.
  17. "Hydrophobic imbalance in the cytoplasmic domain of phospholamban is a determinant for lethal dilated cardiomyopathy."
    Ceholski D.K., Trieber C.A., Young H.S.
    J. Biol. Chem. 287:16521-16529(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANTS CMD1P CYS-9 AND ARG-14 DEL, FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiPPLA_HUMAN
AccessioniPrimary (citable) accession number: P26678
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: July 9, 2014
This is version 143 of the entry and version 1 of the sequence. [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

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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