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   24-JAN-2024, entry version 125.
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. Controls intracellular Ca(2+) levels
CC       in elongated spermatids. May play a role in germ cell differentiation.
CC       {ECO:0000250|UniProtKB:P61014}.
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   -!- PTM: In elongated spermatids, proteolytically cleaved by SPPL2C which
CC       modulates intracellular Ca(2+) homeostasis.
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   PaxDb; 9986-ENSOCUP00000011917; -.
DR   Ensembl; ENSOCUT00000013855.3; ENSOCUP00000011917.3; ENSOCUG00000013865.3.
DR   GeneID; 100009299; -.
DR   KEGG; ocu:100009299; -.
DR   CTD; 5350; -.
DR   eggNOG; ENOG502S97F; Eukaryota.
DR   GeneTree; ENSGT00390000002403; -.
DR   InParanoid; P61015; -.
DR   OMA; YITRSAM; -.
DR   EvolutionaryTrace; P61015; -.
DR   Proteomes; UP000001811; Chromosome 12.
DR   Bgee; ENSOCUG00000013865; Expressed in heart and 17 other cell types or 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:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
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:0001675; P:acrosome assembly; 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:intracellular calcium ion homeostasis; ISS:UniProtKB.
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:0086092; P:regulation of the force of heart contraction by cardiac conduction; IEA:Ensembl.
DR   CDD; cd20250; Phospholamban; 1.
DR   Gene3D; 1.20.5.290; Phospholamban; 1.
DR   InterPro; IPR005984; PLB.
DR   NCBIfam; TIGR01294; P_lamban; 1.
DR   PANTHER; PTHR21194; CARDIAC PHOSPHOLAMBAN; 1.
DR   PANTHER; PTHR21194:SF1; CARDIAC PHOSPHOLAMBAN; 1.
DR   Pfam; PF04272; Phospholamban; 1.
DR   PIRSF; PIRSF001665; PLB; 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
//