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1.A.50.1.1
Phospholamban (PLB) pentameric Ca2+/K+ channel (Kovacs et al., 1988; Smeazzetto et al. 2013; Smeazzetto et al. 2014).  In spite of extensive experimental evidence, suggesting a pore size of 2.2 Å, the conclusion of ion channel activity for phospholamban has been questioned (Maffeo and Aksimentiev 2009).  Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca2+ ATPase (SERCA). This cyclic mechanism constitutes the driving force for calcium reuptake from the cytoplasm into the myocite lumen, regulating cardiac contractility. PLN undergoes a conformational transition between a relaxed (R) and tense (T) state, an equilibrium perturbed by the addition of SERCA. Phosphoryl transfer to Ser16 induces a conformational switch to the R state. The binding affinity of PLN to SERCA is not affected ((Kd ~ 60 microM). However, the binding surface and dynamics in domain Ib (residues 22-31) change substantially upon phosphorylation. Since PLN can be singly or doubly phosphorylated at Ser16 and Thr17, these sites may remotely control the conformation of domain Ib (Traaseth et al. 2006).

Accession Number:P26678
Protein Name:PPLA aka PLB aka PLN
Length:52
Molecular Weight:6109.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Mitochondrion membrane1 / Single-pass membrane protein2
Substrate Ca2+, K+

Cross database links:

Genevestigator: P26678
eggNOG: maNOG21649
HEGENOM: HBG125007
RefSeq: NP_002658.1   
Entrez Gene ID: 5350   
Pfam: PF04272   
OMIM: 172405  gene
609909  phenotype
KEGG: hsa:5350   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0031966 C:mitochondrial membrane
GO:0016529 C:sarcoplasmic reticulum
GO:0042030 F:ATPase inhibitor activity
GO:0005246 F:calcium channel regulator activity
GO:0005515 F:protein binding
GO:0008015 P:blood circulation
GO:0006816 P:calcium ion transport
GO:0051924 P:regulation of calcium ion transport

References (9)

[1] “Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6.”  Fujii J.et.al.   1828805
[2] “The human phospholamban gene: structure and expression.”  McTiernan C.F.et.al.   10198197
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function.”  Vafiadaki E.et.al.   17241641
[5] “Solution structure of the cytoplasmic domain of phospholamban: phosphorylation leads to a local perturbation in secondary structure.”  Mortishire-Smith R.J.et.al.   7779806
[6] “Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban.”  Adams P.D.et.al.   7749920
[7] “Using experimental information to produce a model of the transmembrane domain of the ion channel phospholamban.”  Herzyk P.et.al.   9512019
[8] “Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban.”  Schmitt J.P.et.al.   12610310
[9] “A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy.”  Haghighi K.et.al.   16432188
Structure:
1K9N   1KCH   1PLN   1PLP   1PSL   1ZLL   2HYN     

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FASTA formatted sequence
1:	MEKVQYLTRS AIRRASTIEM PQQARQKLQN LFINFCLILI CLLLICIIVM LL