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FB2026_01
,
released March 12, 2026
This report includes information relevant to potential models of the cardiomyopathies caused by the human gene PLN, which encodes phospholamban. This protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca(2+)-ATPase and is a regulator of cardiac diastolic function. PLN is implicated in dilated cardiomyopathy 1P (CMD1P; MIM:609909; FBhh0000161) and hypertrophic cardiomyopathy 18 (CMH18; MIM:613874; FBhh0000416). Involvement of PLN with dilated cardiomyopathy is strongly supported by a large-scale WES analysis; truncated forms of the gene show significant correlation with hypertrophic cardiomyopathy (Walsh, et al., 2016; pubmed:27532257).
There is no identified fly ortholog of PLN, however, Dmel\SclA, which encodes a small cardiac peptide, exhibits a comparable three-dimensional structure to the C-terminal domain of PLN. RNAi targeting constructs and alleles caused by insertional mutagenesis for SclA have been generated. Muscle-specific overexpression of a UAS-SclA construct results in a significant increase in observed cardiac arrhythmicity. A single physical interaction has been described for Dmel\SclA; see below and in the SclA gene report.
Multiple UAS constructs of the human Hsap\PLN gene have been introduced into flies, including wild-type PLN, and a construct in which part of the PLN coding sequence substitutes for the fly gene SclA (Sarcolamban A). Muscle-specific expression of a wild-type UAS-Hsap\PLN construct also results in a significant increase in observed cardiac arrhythmicity.
[updated Oct. 2016 by FlyBase; FBrf0222196]
The protein encoded by this gene is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase in cardiac muscle. The encoded protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca(2+)-ATPase in the unphosphorylated state, but inhibition is relieved upon phosphorylation of the protein. The subsequent activation of the Ca(2+) pump leads to enhanced muscle relaxation rates, thereby contributing to the inotropic response elicited in heart by beta-agonists. The encoded protein is a key regulator of cardiac diastolic function. [from Gene Cards, PLN; 2016.10.24]
Based in part on conserved secondary structure, the human genes PLN and SLN appear to be homologous to fly genes SclA and SclB; postulated that all evolved from an ancestral peptide of ~30 amino acids (FBrf0222626).
SclA has been proposed as a homolog of human PLN and of human sarcolipin (SLN). Dmel\SclA has a three-dimensional structure similar to human SLN and to the C-terminus of the longer human PLN (FBrf0222626). All three genes encode very small polypeptides: PLN is 53aa, SLN is 31aa, Dmel\SclA is 31aa.