PPLA_RABIT
ID PPLA_RABIT Reviewed; 52 AA.
AC P61015; P20006;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Cardiac phospholamban;
DE Short=PLB;
GN Name=PLN;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
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].
RX PubMed=2962883; DOI=10.1016/0014-5793(88)81412-1;
RA Fujii J., Lytton J., Tada M., Maclennan D.H.;
RT "Rabbit cardiac and slow-twitch muscle express the same phospholamban
RT gene.";
RL FEBS Lett. 227:51-55(1988).
RN [3]
RP STRUCTURE BY NMR.
RX PubMed=14507721; DOI=10.1016/s0006-3495(03)74681-5;
RA Zamoon J., Mascioni A., Thomas D.D., Veglia G.;
RT "NMR solution structure and topological orientation of monomeric
RT phospholamban in dodecylphosphocholine micelles.";
RL Biophys. J. 85:2589-2598(2003).
RN [4]
RP 3D-STRUCTURE MODELING.
RX PubMed=15766259; DOI=10.1021/bi0478446;
RA Robia S.L., Flohr N.C., Thomas D.D.;
RT "Phospholamban pentamer quaternary conformation determined by in-gel
RT fluorescence anisotropy.";
RL Biochemistry 44:4302-4311(2005).
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+). Modulates the contractility of the heart muscle in
CC response to physiological stimuli via its effects on ATP2A2. Modulates
CC calcium re-uptake during muscle relaxation and plays an important role
CC in calcium homeostasis in the heart muscle. The degree of ATP2A2
CC inhibition depends on the oligomeric state of PLN. ATP2A2 inhibition is
CC alleviated by PLN phosphorylation (By similarity).
CC {ECO:0000250|UniProtKB:P26678}.
CC -!- SUBUNIT: Homopentamer. Interacts with HAX1. Interact with ATP2A2; the
CC inhibition decreases ATP2A2 Ca(2+) affinity. Interacts with VMP1; VMP1
CC competes with PLN and SLN to prevent them from forming an inhibitory
CC complex with ATP2A2. Interacts with S100A1 in a Ca(2+)-dependent
CC manner. {ECO:0000250|UniProtKB:P26678}.
CC -!- INTERACTION:
CC P61015; P61015: PLN; NbExp=8; IntAct=EBI-79236, EBI-79236;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P26678}; Single-pass membrane protein
CC {ECO:0000255}. Sarcoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P26678}; 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 Colocalizes with DMPK a the sarcoplasmic reticulum.
CC {ECO:0000250|UniProtKB:P26678}.
CC -!- TISSUE SPECIFICITY: Heart. {ECO:0000269|PubMed:1828805}.
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 (By
CC similarity). {ECO:0000250|UniProtKB:P26678}.
CC -!- PTM: Palmitoylated by ZDHHC16, promoting formation of the homopentamer.
CC {ECO:0000250|UniProtKB:P61014}.
CC -!- SIMILARITY: Belongs to the phospholamban family. {ECO:0000305}.
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DR EMBL; M63600; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M63601; AAA31445.1; -; Genomic_DNA.
DR EMBL; Y00761; CAA68730.1; -; mRNA.
DR PIR; B40424; B40424.
DR RefSeq; NP_001076090.1; NM_001082621.2.
DR PDB; 1N7L; NMR; -; A=1-52.
DR PDB; 2KB7; Other; -; P=1-52.
DR PDB; 2KYV; Other; -; A/B/C/D/E=1-52.
DR PDB; 2LPF; NMR; -; A=1-52.
DR PDB; 2M3B; Other; -; A/B/C/D/E=1-52.
DR PDBsum; 1N7L; -.
DR PDBsum; 2KB7; -.
DR PDBsum; 2KYV; -.
DR PDBsum; 2LPF; -.
DR PDBsum; 2M3B; -.
DR AlphaFoldDB; P61015; -.
DR BMRB; P61015; -.
DR SMR; P61015; -.
DR DIP; DIP-31022N; -.
DR IntAct; P61015; 6.
DR STRING; 9986.ENSOCUP00000011917; -.
DR iPTMnet; P61015; -.
DR Ensembl; ENSOCUT00000013855; ENSOCUP00000011917; ENSOCUG00000013865.
DR GeneID; 100009299; -.
DR KEGG; ocu:100009299; -.
DR CTD; 5350; -.
DR eggNOG; ENOG502S97F; Eukaryota.
DR GeneTree; ENSGT00390000002403; -.
DR InParanoid; P61015; -.
DR OMA; FTNFCLI; -.
DR EvolutionaryTrace; P61015; -.
DR Proteomes; UP000001811; Chromosome 12.
DR Bgee; ENSOCUG00000013865; Expressed in heart and 17 other tissues.
DR ExpressionAtlas; P61015; baseline.
DR GO; GO:0090534; C:calcium ion-transporting ATPase complex; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; IDA:BHF-UCL.
DR GO; GO:0042030; F:ATPase inhibitor activity; IC:BHF-UCL.
DR GO; GO:0004857; F:enzyme inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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:0048738; P:cardiac muscle tissue development; IEA:Ensembl.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:Ensembl.
DR GO; GO:1901895; P:negative regulation of ATPase-coupled calcium transmembrane transporter activity; ISS: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; IDA: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:0043086; P:negative regulation of catalytic activity; IDA:BHF-UCL.
DR GO; GO:0010459; P:negative regulation of heart rate; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0051924; P:regulation of calcium ion transport; IDA:UniProtKB.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IEA:Ensembl.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IEA:Ensembl.
DR GO; GO:1901077; P:regulation of relaxation of muscle; IEA:Ensembl.
DR GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; IEA:Ensembl.
DR GO; GO:0086092; P:regulation of the force of heart contraction by cardiac conduction; IEA:Ensembl.
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; Endoplasmic reticulum; Lipoprotein; Membrane;
KW Mitochondrion; Palmitate; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum; Transmembrane; Transmembrane helix.
FT CHAIN 1..52
FT /note="Cardiac phospholamban"
FT /id="PRO_0000191247"
FT TOPO_DOM 1..31
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
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:0000250|UniProtKB:P61012"
FT MOD_RES 17
FT /note="Phosphothreonine; by CaMK2"
FT /evidence="ECO:0000250|UniProtKB:P61012"
FT LIPID 36
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P61014"
FT HELIX 2..16
FT /evidence="ECO:0007829|PDB:1N7L"
FT HELIX 22..50
FT /evidence="ECO:0007829|PDB:1N7L"
SQ SEQUENCE 52 AA; 6095 MW; 0763601F76A854D3 CRC64;
MEKVQYLTRS AIRRASTIEM PQQARQNLQN LFINFCLILI CLLLICIIVM LL
