PPLA_HUMAN
ID PPLA_HUMAN Reviewed; 52 AA.
AC P26678;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Cardiac phospholamban {ECO:0000305};
DE Short=PLB;
GN Name=PLN {ECO:0000312|HGNC:HGNC:9080}; Synonyms=PLB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1828805; DOI=10.1016/s0021-9258(18)99009-5;
RA Fujii J., Zarain-Herzberg A., Willard H.F., Tada M., Maclennan D.H.;
RT "Structure of the rabbit phospholamban gene, cloning of the human cDNA, and
RT assignment of the gene to human chromosome 6.";
RL J. Biol. Chem. 266:11669-11675(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Salvatore C.A., Jacobson M.A.;
RT "Cloning of human cardiac phospholamban.";
RL Submitted (MAR-1991) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10198197; DOI=10.1006/jmcc.1998.0904;
RA McTiernan C.F., Frye C.S., Lemster B.H., Kinder E.A., Ogletree-Hughes M.L.,
RA Moravec C.S., Feldman A.M.;
RT "The human phospholamban gene: structure and expression.";
RL J. Mol. Cell. Cardiol. 31:679-692(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INVOLVEMENT IN CMH18.
RX PubMed=12705874; DOI=10.1016/s0006-291x(03)00526-6;
RA Minamisawa S., Sato Y., Tatsuguchi Y., Fujino T., Imamura S., Uetsuka Y.,
RA Nakazawa M., Matsuoka R.;
RT "Mutation of the phospholamban promoter associated with hypertrophic
RT cardiomyopathy.";
RL Biochem. Biophys. Res. Commun. 304:1-4(2003).
RN [6]
RP INTERACTION WITH S100A1, AND SUBCELLULAR LOCATION.
RX PubMed=12804600; DOI=10.1016/s0006-291x(03)00987-2;
RA Kiewitz R., Acklin C., Schaefer B.W., Maco B., Uhrik B., Wuytack F.,
RA Erne P., Heizmann C.W.;
RT "Ca2+ -dependent interaction of S100A1 with the sarcoplasmic reticulum Ca2+
RT -ATPase2a and phospholamban in the human heart.";
RL Biochem. Biophys. Res. Commun. 306:550-557(2003).
RN [7]
RP PHOSPHORYLATION AT SER-16 BY DMPK, AND SUBCELLULAR LOCATION.
RX PubMed=15598648; DOI=10.1074/jbc.m412845200;
RA Kaliman P., Catalucci D., Lam J.T., Kondo R., Gutierrez J.C., Reddy S.,
RA Palacin M., Zorzano A., Chien K.R., Ruiz-Lozano P.;
RT "Myotonic dystrophy protein kinase phosphorylates phospholamban and
RT regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum.";
RL J. Biol. Chem. 280:8016-8021(2005).
RN [8]
RP PHOSPHORYLATION AT THR-17 BY CAMK2.
RX PubMed=16690701; DOI=10.1113/jphysiol.2006.111757;
RA Rose A.J., Kiens B., Richter E.A.;
RT "Ca2+-calmodulin-dependent protein kinase expression and signalling in
RT skeletal muscle during exercise.";
RL J. Physiol. (Lond.) 574:889-903(2006).
RN [9]
RP INTERACTION WITH HAX1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17241641; DOI=10.1016/j.jmb.2006.10.057;
RA Vafiadaki E., Sanoudou D., Arvanitis D.A., Catino D.H., Kranias E.G.,
RA Kontrogianni-Konstantopoulos A.;
RT "Phospholamban interacts with HAX-1, a mitochondrial protein with anti-
RT apoptotic function.";
RL J. Mol. Biol. 367:65-79(2007).
RN [10]
RP FUNCTION, CHARACTERIZATION OF VARIANTS CMD1P HIS-9; LEU-9; CYS-9 AND ARG-14
RP DEL, PHOSPHORYLATION AT SER-16, AND MUTAGENESIS OF ARG-13; ARG-14; SER-16
RP AND THR-17.
RX PubMed=22707725; DOI=10.1074/jbc.m112.382713;
RA Ceholski D.K., Trieber C.A., Holmes C.F., Young H.S.;
RT "Lethal, hereditary mutants of phospholamban elude phosphorylation by
RT protein kinase A.";
RL J. Biol. Chem. 287:26596-26605(2012).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP FUNCTION, AND INTERACTION WITH ATP2A2 AND VMP1.
RX PubMed=28890335; DOI=10.1016/j.molcel.2017.08.005;
RA Zhao Y.G., Chen Y., Miao G., Zhao H., Qu W., Li D., Wang Z., Liu N., Li L.,
RA Chen S., Liu P., Feng D., Zhang H.;
RT "The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity
RT to Control ER-Isolation Membrane Contacts for Autophagosome Formation.";
RL Mol. Cell 67:974.e6-989.e6(2017).
RN [13]
RP STRUCTURE BY NMR OF 1-25.
RX PubMed=7779806; DOI=10.1021/bi00023a006;
RA Mortishire-Smith R.J., Pitzenberger S.M., Burke C.J., Middaugh C.R.,
RA Garsky V.M., Johnson R.G.;
RT "Solution structure of the cytoplasmic domain of phospholamban:
RT phosphorylation leads to a local perturbation in secondary structure.";
RL Biochemistry 34:7603-7613(1995).
RN [14]
RP 3D-STRUCTURE MODELING.
RX PubMed=7749920; DOI=10.1038/nsb0295-154;
RA Adams P.D., Arkin I.T., Engelman D.M., Bruenger A.T.;
RT "Computational searching and mutagenesis suggest a structure for the
RT pentameric transmembrane domain of phospholamban.";
RL Nat. Struct. Biol. 2:154-162(1995).
RN [15]
RP 3D-STRUCTURE MODELING.
RX PubMed=9512019; DOI=10.1016/s0006-3495(98)77835-x;
RA Herzyk P., Hubbard R.E.;
RT "Using experimental information to produce a model of the transmembrane
RT domain of the ion channel phospholamban.";
RL Biophys. J. 74:1203-1214(1998).
RN [16]
RP STRUCTURE BY NMR, AND SUBUNIT.
RX PubMed=16043693; DOI=10.1073/pnas.0504920102;
RA Oxenoid K., Chou J.J.;
RT "The structure of phospholamban pentamer reveals a channel-like
RT architecture in membranes.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:10870-10875(2005).
RN [17]
RP STRUCTURE BY NMR, AND SUBUNIT.
RX PubMed=16897780; DOI=10.1002/prot.21091;
RA Potluri S., Yan A.K., Chou J.J., Donald B.R., Bailey-Kellogg C.;
RT "Structure determination of symmetric homo-oligomers by a complete search
RT of symmetry configuration space, using NMR restraints and van der Waals
RT packing.";
RL Proteins 65:203-219(2006).
RN [18]
RP VARIANT CMD1P CYS-9, AND CHARACTERIZATION OF VARIANT CMD1P CYS-9.
RX PubMed=12610310; DOI=10.1126/science.1081578;
RA Schmitt J.P., Kamisago M., Asahi M., Li G.H., Ahmad F., Mende U.,
RA Kranias E.G., MacLennan D.H., Seidman J.G., Seidman C.E.;
RT "Dilated cardiomyopathy and heart failure caused by a mutation in
RT phospholamban.";
RL Science 299:1410-1413(2003).
RN [19]
RP VARIANT CMD1P ARG-14 DEL, AND CHARACTERIZATION OF VARIANT CMD1P ARG-14 DEL.
RX PubMed=16432188; DOI=10.1073/pnas.0510519103;
RA Haghighi K., Kolokathis F., Gramolini A.O., Waggoner J.R., Pater L.,
RA Lynch R.A., Fan G.C., Tsiapras D., Parekh R.R., Dorn G.W. II,
RA MacLennan D.H., Kremastinos D.T., Kranias E.G.;
RT "A mutation in the human phospholamban gene, deleting arginine 14, results
RT in lethal, hereditary cardiomyopathy.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:1388-1393(2006).
RN [20]
RP VARIANTS CMD1P HIS-9 AND LEU-9.
RX PubMed=22137083; DOI=10.1016/j.ahj.2011.07.028;
RA Medeiros A., Biagi D.G., Sobreira T.J., de Oliveira P.S., Negrao C.E.,
RA Mansur A.J., Krieger J.E., Brum P.C., Pereira A.C.;
RT "Mutations in the human phospholamban gene in patients with heart
RT failure.";
RL Am. Heart J. 162:1088-1095(2011).
RN [21]
RP CHARACTERIZATION OF VARIANTS CMD1P CYS-9 AND ARG-14 DEL, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=22427649; DOI=10.1074/jbc.m112.360859;
RA Ceholski D.K., Trieber C.A., Young H.S.;
RT "Hydrophobic imbalance in the cytoplasmic domain of phospholamban is a
RT determinant for lethal dilated cardiomyopathy.";
RL J. Biol. Chem. 287:16521-16529(2012).
CC -!- FUNCTION: Reversibly inhibits the activity of ATP2A2 in cardiac
CC sarcoplasmic reticulum by decreasing the apparent affinity of the
CC ATPase for Ca(2+) (PubMed:28890335). Modulates the contractility of the
CC heart muscle in response to physiological stimuli via its effects on
CC ATP2A2. Modulates calcium re-uptake during muscle relaxation and plays
CC an important role in calcium homeostasis in the heart muscle. The
CC degree of ATP2A2 inhibition depends on the oligomeric state of PLN.
CC ATP2A2 inhibition is alleviated by PLN phosphorylation.
CC {ECO:0000269|PubMed:22427649, ECO:0000269|PubMed:22707725,
CC ECO:0000269|PubMed:28890335}.
CC -!- SUBUNIT: Homopentamer (PubMed:16043693, PubMed:16897780). Interacts
CC with HAX1 (PubMed:17241641). Interact with ATP2A2; the inhibition
CC decreases ATP2A2 Ca(2+) affinity (PubMed:28890335). Interacts with
CC VMP1; VMP1 competes with PLN and SLN to prevent them from forming an
CC inhibitory complex with ATP2A2 (PubMed:28890335). Interacts with S100A1
CC in a Ca(2+)-dependent manner (PubMed:12804600).
CC {ECO:0000269|PubMed:12804600, ECO:0000269|PubMed:16043693,
CC ECO:0000269|PubMed:16897780, ECO:0000269|PubMed:17241641,
CC ECO:0000269|PubMed:28890335}.
CC -!- INTERACTION:
CC P26678; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-692836, EBI-11343438;
CC P26678; P07307-3: ASGR2; NbExp=3; IntAct=EBI-692836, EBI-12808270;
CC P26678; O15342: ATP6V0E1; NbExp=3; IntAct=EBI-692836, EBI-12935759;
CC P26678; Q9BXK5: BCL2L13; NbExp=8; IntAct=EBI-692836, EBI-747430;
CC P26678; Q13323: BIK; NbExp=3; IntAct=EBI-692836, EBI-700794;
CC P26678; P19397: CD53; NbExp=3; IntAct=EBI-692836, EBI-6657396;
CC P26678; O95471: CLDN7; NbExp=3; IntAct=EBI-692836, EBI-740744;
CC P26678; Q9UHP7-3: CLEC2D; NbExp=3; IntAct=EBI-692836, EBI-11749983;
CC P26678; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-692836, EBI-18013275;
CC P26678; O43889-2: CREB3; NbExp=3; IntAct=EBI-692836, EBI-625022;
CC P26678; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-692836, EBI-6942903;
CC P26678; Q09013: DMPK; NbExp=4; IntAct=EBI-692836, EBI-692774;
CC P26678; Q92838: EDA; NbExp=11; IntAct=EBI-692836, EBI-529425;
CC P26678; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-692836, EBI-18535450;
CC P26678; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-692836, EBI-18304435;
CC P26678; Q14318: FKBP8; NbExp=3; IntAct=EBI-692836, EBI-724839;
CC P26678; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-692836, EBI-12142257;
CC P26678; P48165: GJA8; NbExp=3; IntAct=EBI-692836, EBI-17458373;
CC P26678; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-692836, EBI-13345167;
CC P26678; O60883: GPR37L1; NbExp=3; IntAct=EBI-692836, EBI-2927498;
CC P26678; Q8TED1: GPX8; NbExp=3; IntAct=EBI-692836, EBI-11721746;
CC P26678; P31937: HIBADH; NbExp=3; IntAct=EBI-692836, EBI-11427100;
CC P26678; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-692836, EBI-18053395;
CC P26678; P43628: KIR2DL3; NbExp=3; IntAct=EBI-692836, EBI-8632435;
CC P26678; Q5T700: LDLRAD1; NbExp=4; IntAct=EBI-692836, EBI-10173166;
CC P26678; Q8N112: LSMEM2; NbExp=3; IntAct=EBI-692836, EBI-10264855;
CC P26678; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-692836, EBI-11956541;
CC P26678; Q6N075: MFSD5; NbExp=3; IntAct=EBI-692836, EBI-3920969;
CC P26678; Q99735: MGST2; NbExp=3; IntAct=EBI-692836, EBI-11324706;
CC P26678; O14880: MGST3; NbExp=3; IntAct=EBI-692836, EBI-724754;
CC P26678; Q9GZW8: MS4A7; NbExp=3; IntAct=EBI-692836, EBI-721391;
CC P26678; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-692836, EBI-3923617;
CC P26678; P15941-11: MUC1; NbExp=3; IntAct=EBI-692836, EBI-17263240;
CC P26678; Q8TBJ4: PLPPR1; NbExp=3; IntAct=EBI-692836, EBI-18063495;
CC P26678; O95197-3: RTN3; NbExp=3; IntAct=EBI-692836, EBI-11525735;
CC P26678; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-692836, EBI-3920694;
CC P26678; A0A0S2Z4U3: SDC3; NbExp=3; IntAct=EBI-692836, EBI-10204280;
CC P26678; Q9Y3P8: SIT1; NbExp=3; IntAct=EBI-692836, EBI-6977215;
CC P26678; Q15849: SLC14A2; NbExp=3; IntAct=EBI-692836, EBI-1573290;
CC P26678; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-692836, EBI-10262251;
CC P26678; O95436-2: SLC34A2; NbExp=3; IntAct=EBI-692836, EBI-12811757;
CC P26678; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-692836, EBI-17295964;
CC P26678; Q9NP94: SLC39A2; NbExp=3; IntAct=EBI-692836, EBI-12898013;
CC P26678; Q9HBV2: SPACA1; NbExp=3; IntAct=EBI-692836, EBI-17498703;
CC P26678; Q9NPE6: SPAG4; NbExp=3; IntAct=EBI-692836, EBI-10819434;
CC P26678; Q16623: STX1A; NbExp=3; IntAct=EBI-692836, EBI-712466;
CC P26678; P32856-2: STX2; NbExp=3; IntAct=EBI-692836, EBI-11956649;
CC P26678; Q9BVX2: TMEM106C; NbExp=3; IntAct=EBI-692836, EBI-2821497;
CC P26678; Q7Z7N9: TMEM179B; NbExp=3; IntAct=EBI-692836, EBI-11724423;
CC P26678; Q6UW68: TMEM205; NbExp=3; IntAct=EBI-692836, EBI-6269551;
CC P26678; Q9NWC5: TMEM45A; NbExp=3; IntAct=EBI-692836, EBI-10823938;
CC P26678; Q96B21: TMEM45B; NbExp=3; IntAct=EBI-692836, EBI-3923061;
CC P26678; Q4KMG9: TMEM52B; NbExp=3; IntAct=EBI-692836, EBI-18178701;
CC P26678; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-692836, EBI-2548832;
CC P26678; O15393-2: TMPRSS2; NbExp=3; IntAct=EBI-692836, EBI-12345267;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:17241641}; Single-pass membrane protein
CC {ECO:0000255}. Sarcoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12804600, ECO:0000269|PubMed:15598648,
CC ECO:0000269|PubMed:22427649}; Single-pass membrane protein
CC {ECO:0000255}. Mitochondrion membrane {ECO:0000250|UniProtKB:A4IFH6};
CC Single-pass membrane protein {ECO:0000255}. Membrane
CC {ECO:0000250|UniProtKB:P61014}; Single-pass membrane protein
CC {ECO:0000255}. Note=Colocalizes with HAX1 at the endoplasmic reticulum
CC (PubMed:17241641). Colocalizes with DMPK a the sarcoplasmic reticulum
CC (PubMed:15598648). {ECO:0000269|PubMed:15598648,
CC ECO:0000269|PubMed:17241641}.
CC -!- TISSUE SPECIFICITY: Heart muscle (at protein level).
CC {ECO:0000269|PubMed:17241641}.
CC -!- PTM: Phosphorylation by PKA abolishes the inhibition of ATP2A2-mediated
CC calcium uptake. Phosphorylated at Thr-17 by CaMK2, and in response to
CC beta-adrenergic stimulation. Phosphorylation by DMPK may stimulate
CC sarcoplasmic reticulum calcium uptake in cardiomyocytes.
CC {ECO:0000269|PubMed:15598648, ECO:0000269|PubMed:16690701,
CC ECO:0000269|PubMed:22707725}.
CC -!- PTM: Palmitoylated by ZDHHC16, promoting formation of the homopentamer.
CC {ECO:0000250|UniProtKB:P61014}.
CC -!- DISEASE: Cardiomyopathy, dilated 1P (CMD1P) [MIM:609909]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. {ECO:0000269|PubMed:12610310,
CC ECO:0000269|PubMed:16432188, ECO:0000269|PubMed:22137083,
CC ECO:0000269|PubMed:22427649, ECO:0000269|PubMed:22707725}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 18 (CMH18) [MIM:613874]:
CC A hereditary heart disorder characterized by ventricular hypertrophy,
CC which is usually asymmetric and often involves the interventricular
CC septum. The symptoms include dyspnea, syncope, collapse, palpitations,
CC and chest pain. They can be readily provoked by exercise. The disorder
CC has inter- and intrafamilial variability ranging from benign to
CC malignant forms with high risk of cardiac failure and sudden cardiac
CC death. {ECO:0000269|PubMed:12705874}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: For practical reasons, PLN activity is most often
CC studied with ATP2A1 instead of ATP2A2.
CC -!- SIMILARITY: Belongs to the phospholamban family. {ECO:0000305}.
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DR EMBL; M63603; AAA60083.1; -; mRNA.
DR EMBL; M60411; AAA60109.1; -; mRNA.
DR EMBL; AF177764; AAD55950.1; -; Genomic_DNA.
DR EMBL; BC005269; AAH05269.1; -; mRNA.
DR CCDS; CCDS5120.1; -.
DR PIR; A40424; A40424.
DR RefSeq; NP_002658.1; NM_002667.4.
DR PDB; 1PLP; NMR; -; A=1-24.
DR PDB; 1ZLL; NMR; -; A/B/C/D/E=1-52.
DR PDB; 2HYN; NMR; -; A/B/C/D/E=1-52.
DR PDB; 6Y40; X-ray; 1.75 A; P=6-21.
DR PDBsum; 1PLP; -.
DR PDBsum; 1ZLL; -.
DR PDBsum; 2HYN; -.
DR PDBsum; 6Y40; -.
DR AlphaFoldDB; P26678; -.
DR SMR; P26678; -.
DR BioGRID; 111365; 66.
DR ComplexPortal; CPX-51; Cardiac phospholamban complex.
DR CORUM; P26678; -.
DR DIP; DIP-33582N; -.
DR ELM; P26678; -.
DR IntAct; P26678; 59.
DR MINT; P26678; -.
DR STRING; 9606.ENSP00000350132; -.
DR TCDB; 1.A.50.1.1; the phospholamban (ca(2+)-channel and ca(2+)-atpase regulator) (plb) family.
DR iPTMnet; P26678; -.
DR PhosphoSitePlus; P26678; -.
DR BioMuta; PLN; -.
DR DMDM; 130774; -.
DR jPOST; P26678; -.
DR MassIVE; P26678; -.
DR PaxDb; P26678; -.
DR PeptideAtlas; P26678; -.
DR PRIDE; P26678; -.
DR ProteomicsDB; 54361; -.
DR TopDownProteomics; P26678; -.
DR Antibodypedia; 3353; 514 antibodies from 39 providers.
DR DNASU; 5350; -.
DR Ensembl; ENST00000357525.6; ENSP00000350132.5; ENSG00000198523.6.
DR GeneID; 5350; -.
DR KEGG; hsa:5350; -.
DR MANE-Select; ENST00000357525.6; ENSP00000350132.5; NM_002667.5; NP_002658.1.
DR CTD; 5350; -.
DR DisGeNET; 5350; -.
DR GeneCards; PLN; -.
DR GeneReviews; PLN; -.
DR HGNC; HGNC:9080; PLN.
DR HPA; ENSG00000198523; Group enriched (heart muscle, skeletal muscle).
DR MalaCards; PLN; -.
DR MIM; 172405; gene.
DR MIM; 609909; phenotype.
DR MIM; 613874; phenotype.
DR neXtProt; NX_P26678; -.
DR OpenTargets; ENSG00000198523; -.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA272; -.
DR VEuPathDB; HostDB:ENSG00000198523; -.
DR eggNOG; ENOG502S97F; Eukaryota.
DR GeneTree; ENSGT00390000002403; -.
DR HOGENOM; CLU_214576_0_0_1; -.
DR InParanoid; P26678; -.
DR OMA; FTNFCLI; -.
DR PhylomeDB; P26678; -.
DR TreeFam; TF330750; -.
DR PathwayCommons; P26678; -.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR Reactome; R-HSA-936837; Ion transport by P-type ATPases.
DR SignaLink; P26678; -.
DR SIGNOR; P26678; -.
DR BioGRID-ORCS; 5350; 11 hits in 584 CRISPR screens.
DR ChiTaRS; PLN; human.
DR EvolutionaryTrace; P26678; -.
DR GeneWiki; Phospholamban; -.
DR GenomeRNAi; 5350; -.
DR Pharos; P26678; Tbio.
DR PRO; PR:P26678; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P26678; protein.
DR Bgee; ENSG00000198523; Expressed in heart right ventricle and 175 other tissues.
DR ExpressionAtlas; P26678; baseline and differential.
DR Genevisible; P26678; HS.
DR GO; GO:0090534; C:calcium ion-transporting ATPase complex; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0016020; C:membrane; IDA:BHF-UCL.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; ISS:BHF-UCL.
DR GO; GO:0042030; F:ATPase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0004857; F:enzyme inhibitor activity; ISS:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; ISS:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0086023; P:adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process; IEA:Ensembl.
DR GO; GO:0008015; P:blood circulation; NAS:ProtInc.
DR GO; GO:0048738; P:cardiac muscle tissue development; IEA:Ensembl.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:Ensembl.
DR GO; GO:0032780; P:negative regulation of ATP-dependent activity; IDA:BHF-UCL.
DR GO; GO:1901895; P:negative regulation of ATPase-coupled calcium transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:1901877; P:negative regulation of calcium ion binding; IDA:BHF-UCL.
DR GO; GO:0090281; P:negative regulation of calcium ion import; ISS:BHF-UCL.
DR GO; GO:1902081; P:negative regulation of calcium ion import into sarcoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:1901020; P:negative regulation of calcium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0051926; P:negative regulation of calcium ion transport; IDA:BHF-UCL.
DR GO; GO:0043086; P:negative regulation of catalytic activity; ISS:BHF-UCL.
DR GO; GO:0010459; P:negative regulation of heart rate; IMP:BHF-UCL.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:1901894; P:regulation of ATPase-coupled calcium transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0051924; P:regulation of calcium ion transport; IDA:UniProtKB.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IC:BHF-UCL.
DR GO; GO:0086036; P:regulation of cardiac muscle cell membrane potential; IC:BHF-UCL.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IEA:Ensembl.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IC:BHF-UCL.
DR GO; GO:0008016; P:regulation of heart contraction; IMP:BHF-UCL.
DR GO; GO:1901897; P:regulation of relaxation of cardiac muscle; IC:BHF-UCL.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; IEA:Ensembl.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IC:BHF-UCL.
DR GO; GO:0086092; P:regulation of the force of heart contraction by cardiac conduction; IEA:Ensembl.
DR GO; GO:0055119; P:relaxation of cardiac muscle; TAS:BHF-UCL.
DR CDD; cd20250; Phospholamban; 1.
DR InterPro; IPR005984; PLB.
DR PANTHER; PTHR21194; PTHR21194; 1.
DR Pfam; PF04272; Phospholamban; 1.
DR PIRSF; PIRSF001665; PLB; 1.
DR TIGRFAMs; TIGR01294; P_lamban; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cardiomyopathy; Disease variant;
KW Endoplasmic reticulum; Lipoprotein; Membrane; Mitochondrion; Palmitate;
KW Phosphoprotein; Reference proteome; Sarcoplasmic reticulum; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..52
FT /note="Cardiac phospholamban"
FT /id="PRO_0000191244"
FT TOPO_DOM 1..31
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000305"
FT REGION 16..22
FT /note="Involved in HAX1 binding"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:A4IFH6"
FT MOD_RES 16
FT /note="Phosphoserine; by PKA and DMPK"
FT /evidence="ECO:0000269|PubMed:15598648,
FT ECO:0000269|PubMed:22707725"
FT MOD_RES 17
FT /note="Phosphothreonine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:16690701"
FT LIPID 36
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P61014"
FT VARIANT 9
FT /note="R -> C (in CMD1P; impairs phosphorylation by PKA and
FT inhibition of ATP2A1-mediated calcium uptake;
FT dbSNP:rs111033559)"
FT /evidence="ECO:0000269|PubMed:12610310,
FT ECO:0000269|PubMed:22427649, ECO:0000269|PubMed:22707725"
FT /id="VAR_025989"
FT VARIANT 9
FT /note="R -> H (in CMD1P; impairs phosphorylation by PKA and
FT inhibition of ATP2A1-mediated calcium uptake;
FT dbSNP:rs754782171)"
FT /evidence="ECO:0000269|PubMed:22137083,
FT ECO:0000269|PubMed:22707725"
FT /id="VAR_072925"
FT VARIANT 9
FT /note="R -> L (in CMD1P; impairs phosphorylation by PKA and
FT inhibition of ATP2A1-mediated calcium uptake)"
FT /evidence="ECO:0000269|PubMed:22137083,
FT ECO:0000269|PubMed:22707725"
FT /id="VAR_072926"
FT VARIANT 14
FT /note="Missing (in CMD1P; impairs phosphorylation by PKA,
FT destabilizes the homopentamer and mildly reduces inhibition
FT of ATP2A1-mediated calcium uptake; dbSNP:rs397516784)"
FT /evidence="ECO:0000269|PubMed:16432188,
FT ECO:0000269|PubMed:22427649, ECO:0000269|PubMed:22707725"
FT /id="VAR_025990"
FT MUTAGEN 13
FT /note="R->A: Abolishes phosphorylation by PKA."
FT /evidence="ECO:0000269|PubMed:22707725"
FT MUTAGEN 14
FT /note="R->A: Abolishes phosphorylation by PKA."
FT /evidence="ECO:0000269|PubMed:22707725"
FT MUTAGEN 16
FT /note="S->A: Abolishes phosphorylation by PKA."
FT /evidence="ECO:0000269|PubMed:22707725"
FT MUTAGEN 17
FT /note="T->A: No effect on phosphorylation by PKA."
FT /evidence="ECO:0000269|PubMed:22707725"
FT HELIX 4..14
FT /evidence="ECO:0007829|PDB:1PLP"
FT STRAND 18..20
FT /evidence="ECO:0007829|PDB:1PLP"
FT HELIX 23..50
FT /evidence="ECO:0007829|PDB:1ZLL"
SQ SEQUENCE 52 AA; 6109 MW; 0766304A76A854D3 CRC64;
MEKVQYLTRS AIRRASTIEM PQQARQKLQN LFINFCLILI CLLLICIIVM LL
