PPLA_CANLF
ID PPLA_CANLF Reviewed; 52 AA.
AC P61012; P07473; Q56UH4;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1988, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Cardiac phospholamban;
DE Short=PLB;
GN Name=PLN;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=3793929; DOI=10.1172/jci112799;
RA Fujii J., Ueno A., Kitano K., Tanaka S., Kadoma M., Tada M.;
RT "Complete complementary DNA-derived amino acid sequence of canine cardiac
RT phospholamban.";
RL J. Clin. Invest. 79:301-304(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart ventricle;
RX PubMed=3628007; DOI=10.1093/nar/15.16.6738;
RA Uyeda A., Kitano K., Fujii J., Kadoma M., Tada M., Tanaka S.;
RT "The cDNA sequence of the major phospholamban mRNA in canine cardiac
RT ventricular muscle.";
RL Nucleic Acids Res. 15:6738-6738(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15233990; DOI=10.1016/j.ygeno.2004.04.001;
RA Housley D.J.E., Ritzert E., Venta P.J.;
RT "Comparative radiation hybrid map of canine chromosome 1 (CFA1)
RT incorporating SNP and indel polymorphisms.";
RL Genomics 84:248-264(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15822587; DOI=10.2460/ajvr.2005.66.432;
RA Stabej P., Leegwater P.A., Stokhof A.A., Domanjko-Petric A., van Oost B.A.;
RT "Evaluation of the phospholamban gene in purebred large-breed dogs with
RT dilated cardiomyopathy.";
RL Am. J. Vet. Res. 66:432-436(2005).
RN [5]
RP PROTEIN SEQUENCE OF 1-45, ACETYLATION AT MET-1, AND SUBUNIT.
RX PubMed=3753485; DOI=10.1016/s0006-291x(86)80387-4;
RA Fujii J., Kadoma M., Tada M., Toda H., Sakiyama F.;
RT "Characterization of structural unit of phospholamban by amino acid
RT sequencing and electrophoretic analysis.";
RL Biochem. Biophys. Res. Commun. 138:1044-1050(1986).
RN [6]
RP PROTEIN SEQUENCE OF 10-45, AND PHOSPHORYLATION AT SER-16 AND THR-17.
RX PubMed=3759968; DOI=10.1016/s0021-9258(18)69309-3;
RA Simmerman H.K.B., Collins J.H., Theibert J.L., Wegener A.D., Jones L.R.;
RT "Sequence analysis of phospholamban. Identification of phosphorylation
RT sites and two major structural domains.";
RL J. Biol. Chem. 261:13333-13341(1986).
RN [7]
RP PHOSPHORYLATION AT SER-16 AND THR-17.
RX PubMed=2544595; DOI=10.1016/s0021-9258(18)60487-9;
RA Wegener A.D., Simmerman H.K.B., Lindemann J.P., Jones L.R.;
RT "Phospholamban phosphorylation in intact ventricles. Phosphorylation of
RT serine 16 and threonine 17 in response to beta-adrenergic stimulation.";
RL J. Biol. Chem. 264:11468-11474(1989).
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 (PubMed:3753485). Interacts with HAX1. Interact
CC with ATP2A2; the inhibition decreases ATP2A2 Ca(2+) affinity. Interacts
CC with VMP1; VMP1 competes with PLN and SLN to prevent them from forming
CC an inhibitory complex with ATP2A2. Interacts with S100A1 in a Ca(2+)-
CC dependent manner. {ECO:0000250|UniProtKB:P26678,
CC ECO:0000269|PubMed:3753485}.
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:3793929}.
CC -!- PTM: Phosphorylation by DMPK may stimulate sarcoplasmic reticulum
CC calcium uptake in cardiomyocytes (By similarity). Phosphorylation by
CC PKA abolishes the inhibition of ATP2A2-mediated calcium uptake.
CC Phosphorylated at Thr-17 by CaMK2, and in response to beta-adrenergic
CC stimulation. {ECO:0000250|UniProtKB:P26678, ECO:0000269|PubMed:2544595,
CC ECO:0000269|PubMed:3759968}.
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; M16012; AAA30884.1; -; mRNA.
DR EMBL; Y00399; CAA68461.1; -; mRNA.
DR EMBL; M35393; AAC41618.1; -; mRNA.
DR EMBL; AY514751; AAT44582.1; -; Genomic_DNA.
DR EMBL; AY576872; AAT48602.1; -; Genomic_DNA.
DR PIR; A29002; A29002.
DR RefSeq; NP_001003332.1; NM_001003332.1.
DR RefSeq; XP_013972393.1; XM_014116918.1.
DR PDB; 4KYT; X-ray; 2.83 A; B/C=1-52.
DR PDB; 4Y3U; X-ray; 3.51 A; B=1-50.
DR PDBsum; 4KYT; -.
DR PDBsum; 4Y3U; -.
DR AlphaFoldDB; P61012; -.
DR BMRB; P61012; -.
DR SMR; P61012; -.
DR STRING; 9615.ENSCAFP00000055407; -.
DR iPTMnet; P61012; -.
DR PaxDb; P61012; -.
DR Ensembl; ENSCAFT00030023576; ENSCAFP00030020549; ENSCAFG00030012743.
DR Ensembl; ENSCAFT00040007630; ENSCAFP00040006659; ENSCAFG00040003994.
DR Ensembl; ENSCAFT00845012486; ENSCAFP00845009755; ENSCAFG00845007035.
DR Ensembl; ENSCAFT00845012506; ENSCAFP00845009770; ENSCAFG00845007035.
DR GeneID; 414755; -.
DR KEGG; cfa:414755; -.
DR CTD; 5350; -.
DR VEuPathDB; HostDB:ENSCAFG00845007035; -.
DR eggNOG; ENOG502S97F; Eukaryota.
DR GeneTree; ENSGT00390000002403; -.
DR HOGENOM; CLU_214576_0_0_1; -.
DR InParanoid; P61012; -.
DR OMA; FTNFCLI; -.
DR TreeFam; TF330750; -.
DR Reactome; R-CFA-5578775; Ion homeostasis.
DR Reactome; R-CFA-936837; Ion transport by P-type ATPases.
DR Proteomes; UP000002254; Chromosome 1.
DR Bgee; ENSCAFG00000049711; Expressed in cardiac muscle of left ventricle and 44 other tissues.
DR GO; GO:0090534; C:calcium ion-transporting ATPase complex; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0042030; F:ATPase inhibitor activity; IDA: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: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: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; ISS:UniProtKB.
DR GO; GO:1901877; P:negative regulation of calcium ion binding; IEA:Ensembl.
DR GO; GO:1902081; P:negative regulation of calcium ion import into sarcoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:1901020; P:negative regulation of calcium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0010459; P:negative regulation of heart rate; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0090279; P:regulation of calcium ion import; IEA:Ensembl.
DR GO; GO:0051924; P:regulation of calcium ion transport; ISS: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 DisProt; DP00801; -.
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; Direct protein sequencing;
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_0000191243"
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:0000269|PubMed:3753485"
FT MOD_RES 16
FT /note="Phosphoserine; by PKA and DMPK"
FT /evidence="ECO:0000269|PubMed:2544595,
FT ECO:0000269|PubMed:3759968"
FT MOD_RES 17
FT /note="Phosphothreonine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:2544595,
FT ECO:0000269|PubMed:3759968"
FT LIPID 36
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P61014"
FT HELIX 25..47
FT /evidence="ECO:0007829|PDB:4KYT"
SQ SEQUENCE 52 AA; 6080 MW; 076361D9ADC424D3 CRC64;
MDKVQYLTRS AIRRASTIEM PQQARQNLQN LFINFCLILI CLLLICIIVM LL
