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P26678 (PPLA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cardiac phospholamban

Short name=PLB
Gene names
Name:PLN
Synonyms:PLB
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length52 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9 Ref.17

Subunit structure

Homopentamer. Interacts with HAX1 and ATP2A2. Ref.8 Ref.13 Ref.14

Subcellular location

Sarcoplasmic reticulum membrane; Single-pass membrane protein. Mitochondrion membrane; Single-pass membrane protein By similarity. Endoplasmic reticulum membrane; Single-pass membrane protein Ref.8 Ref.9 Ref.13 Ref.17.

Tissue specificity

Heart muscle (at protein level). Ref.8

Post-translational modification

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. Ref.6 Ref.7 Ref.9

Involvement in disease

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. Ref.9 Ref.15 Ref.16 Ref.17

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. Ref.5

Miscellaneous

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

Sequence similarities

Belongs to the phospholamban family.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Mitochondrion
Sarcoplasmic reticulum
   DiseaseCardiomyopathy
Disease mutation
   DomainTransmembrane
Transmembrane helix
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadrenergic receptor signaling pathway involved in heart process

Inferred from electronic annotation. Source: Ensembl

blood circulation

Non-traceable author statement PubMed 8406504. Source: ProtInc

calcium ion transport

Inferred from electronic annotation. Source: Ensembl

cardiac muscle tissue development

Inferred from electronic annotation. Source: Ensembl

cytosolic calcium ion homeostasis

Inferred by curator PubMed 19708671. Source: BHF-UCL

negative regulation of ATPase activity

Inferred from direct assay PubMed 19708671. Source: BHF-UCL

negative regulation of calcium ion binding

Inferred from direct assay PubMed 19708671. Source: BHF-UCL

negative regulation of calcium ion import

Inferred from sequence or structural similarity PubMed 12032137. Source: BHF-UCL

negative regulation of calcium ion import into sarcoplasmic reticulum

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of calcium ion transmembrane transporter activity

Inferred from direct assay PubMed 19708671. Source: BHF-UCL

negative regulation of calcium ion transport

Inferred from direct assay PubMed 19708671. Source: BHF-UCL

negative regulation of calcium-transporting ATPase activity

Inferred from direct assay PubMed 19708671. Source: BHF-UCL

negative regulation of catalytic activity

Inferred from sequence or structural similarity PubMed 12032137. Source: BHF-UCL

negative regulation of heart rate

Inferred from mutant phenotype Ref.16. Source: BHF-UCL

protein homooligomerization

Inferred from electronic annotation. Source: Ensembl

regulation of calcium ion transport

Inferred from direct assay Ref.17. Source: UniProtKB

regulation of calcium-transporting ATPase activity

Inferred from direct assay Ref.17. Source: UniProtKB

regulation of cardiac muscle cell contraction

Inferred by curator PubMed 19708671. Source: BHF-UCL

regulation of cardiac muscle cell membrane potential

Inferred by curator PubMed 19708671. Source: BHF-UCL

regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion

Inferred from electronic annotation. Source: Ensembl

regulation of heart contraction

Inferred from mutant phenotype Ref.16. Source: BHF-UCL

regulation of relaxation of cardiac muscle

Inferred by curator PubMed 19708671. Source: BHF-UCL

regulation of ryanodine-sensitive calcium-release channel activity

Inferred from electronic annotation. Source: Ensembl

regulation of the force of heart contraction

Inferred by curator PubMed 19708671. Source: BHF-UCL

regulation of the force of heart contraction by cardiac conduction

Inferred from electronic annotation. Source: Ensembl

relaxation of cardiac muscle

Traceable author statement PubMed 22679139. Source: BHF-UCL

response to testosterone

Inferred from electronic annotation. Source: Ensembl

response to zinc ion

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcalcium ion-transporting ATPase complex

Inferred from direct assay PubMed 19708671. Source: BHF-UCL

endoplasmic reticulum

Inferred from sequence or structural similarity. Source: BHF-UCL

membrane

Inferred from direct assay PubMed 19708671. Source: BHF-UCL

mitochondrial membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay PubMed 20833797. Source: UniProt

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: BHF-UCL

sarcoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

vesicle

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATPase binding

Inferred from sequence or structural similarity PubMed 12032137. Source: BHF-UCL

ATPase inhibitor activity

Inferred from direct assay PubMed 19708671. Source: BHF-UCL

calcium channel regulator activity

Inferred from electronic annotation. Source: InterPro

enzyme inhibitor activity

Inferred from sequence or structural similarity PubMed 12032137. Source: BHF-UCL

identical protein binding

Inferred from sequence or structural similarity. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.6. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DMPKQ090134EBI-692836,EBI-692774

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 5252Cardiac phospholamban
PRO_0000191244

Regions

Topological domain1 – 3131Cytoplasmic Probable
Transmembrane32 – 5221Helical; Probable
Region16 – 227Involved in HAX1 binding

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue161Phosphoserine; by PKA and DMPK Ref.6 Ref.9
Modified residue171Phosphothreonine; by CaMK2 Ref.7

Natural variations

Natural variant91R → C in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. Ref.9 Ref.15 Ref.17
VAR_025989
Natural variant141Missing in CMD1P; impairs phosphorylation by PKA, destabilizes the homopentamer and mildly reduces inhibition of ATP2A1-mediated calcium uptake. Ref.9 Ref.16 Ref.17
VAR_025990

Experimental info

Mutagenesis91R → H or L: Impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. Ref.9
Mutagenesis131R → A: Abolishes phosphorylation by PKA. Ref.9
Mutagenesis141R → A: Abolishes phosphorylation by PKA. Ref.9
Mutagenesis161S → A: Abolishes phosphorylation by PKA. Ref.9
Mutagenesis171T → A: No effect on phosphorylation by PKA. Ref.9

Secondary structure

....... 52
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P26678 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: 0766304A76A854D3

FASTA526,109
        10         20         30         40         50 
MEKVQYLTRS AIRRASTIEM PQQARQKLQN LFINFCLILI CLLLICIIVM LL 

« Hide

References

« Hide 'large scale' references
[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]"The human phospholamban gene: structure and expression."
McTiernan C.F., Frye C.S., Lemster B.H., Kinder E.A., Ogletree-Hughes M.L., Moravec C.S., Feldman A.M.
J. Mol. Cell. Cardiol. 31:679-692(1999) [PubMed] [Europe PMC] [Abstract]
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]"A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy."
Haghighi K., Kolokathis F., Gramolini A.O., Waggoner J.R., Pater L., Lynch R.A., Fan G.C., Tsiapras D., Parekh R.R., Dorn G.W. II, MacLennan D.H., Kremastinos D.T., Kranias E.G.
Proc. Natl. Acad. Sci. U.S.A. 103:1388-1393(2006) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M63603 mRNA. Translation: AAA60083.1.
M60411 mRNA. Translation: AAA60109.1.
AF177764 Genomic DNA. Translation: AAD55950.1.
BC005269 mRNA. Translation: AAH05269.1.
CCDSCCDS5120.1.
PIRA40424.
RefSeqNP_002658.1. NM_002667.3.
UniGeneHs.170839.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP26678.
SMRP26678. Positions 1-35.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111365. 5 interactions.
IntActP26678. 2 interactions.
STRING9606.ENSP00000350132.

Protein family/group databases

TCDB1.A.50.1.1. the phospholamban (ca(2+)-channel and ca(2+)-atpase regulator) (plb) family.

PTM databases

PhosphoSiteP26678.

Polymorphism databases

DMDM130774.

Proteomic databases

MaxQBP26678.
PaxDbP26678.
PRIDEP26678.

Protocols and materials databases

DNASU5350.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000357525; ENSP00000350132; ENSG00000198523.
GeneID5350.
KEGGhsa:5350.
UCSCuc003pye.3. human.

Organism-specific databases

CTD5350.
GeneCardsGC06P118869.
GeneReviewsPLN.
HGNCHGNC:9080. PLN.
HPACAB005597.
HPA026900.
MIM172405. gene.
609909. phenotype.
613874. phenotype.
neXtProtNX_P26678.
Orphanet154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBPA272.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG44917.
HOGENOMHOG000115660.
HOVERGENHBG108280.
InParanoidP26678.
KOK05852.
OMAQHARQNL.
PhylomeDBP26678.
TreeFamTF330750.

Gene expression databases

ArrayExpressP26678.
BgeeP26678.
CleanExHS_PLN.
GenevestigatorP26678.

Family and domain databases

InterProIPR005984. P_lamban.
[Graphical view]
PANTHERPTHR21194. PTHR21194. 1 hit.
PfamPF04272. Phospholamban. 1 hit.
[Graphical view]
PIRSFPIRSF001665. PLB. 1 hit.
ProDomPD014689. P_lamban. 1 hit.
[Graphical view] [Entries sharing at least one domain]
TIGRFAMsTIGR01294. P_lamban. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP26678.
GeneWikiPhospholamban.
GenomeRNAi5350.
NextBio20738.
PROP26678.
SOURCESearch...

Entry information

Entry namePPLA_HUMAN
AccessionPrimary (citable) accession number: P26678
Entry history
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 statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM