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P26678

- PPLA_HUMAN

UniProt

P26678 - PPLA_HUMAN

Protein

Cardiac phospholamban

Gene

PLN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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

    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

    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

    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti9 – 91R → C in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 1 Publication
    VAR_025989
    Natural varianti14 – 141Missing in CMD1P; impairs phosphorylation by PKA, destabilizes the homopentamer and mildly reduces inhibition of ATP2A1-mediated calcium uptake. 1 Publication
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    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 phospholambanPRO_0000191244Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy 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

    1
    52
    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP26678.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3131CytoplasmicCuratedAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei32 – 5221HelicalCuratedAdd
    BLAST

    Family & Domainsi

    Region

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

    Sequence similaritiesi

    Belongs to the phospholamban family.Curated

    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. 1 Publication
    VAR_025989
    Natural varianti14 – 141Missing in CMD1P; impairs phosphorylation by PKA, destabilizes the homopentamer and mildly reduces inhibition of ATP2A1-mediated calcium uptake. 1 Publication
    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

    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: October 1, 2014
    This is version 144 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