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8.A.199.  The Sarcolamban (Sarcolamban) Family

Short peptides (sarcolambans) of less than 30 amino acids regulate calcium transport via SARCA, and hence, they influence muscle contraction in the Drosophila heart. These peptides seem conserved for more than 550 million years in a range of species from flies to humans, in which they have been implicated in cardiac pathologies (Magny et al. 2013). Sarcolamban peptides are superinhibitors of mammalian SERCA, exhibiting either phospholamban-like or sarcolipin-like characteristics (Bak et al. 2022). The Drosophila endopeptidase Neprilysin 4 hydrolyzes SERCA-inhibitory sarcolamban peptides in membranes of the sarcoplasmic reticulum, thereby ensuring proper regulation of SERCA. Cleavage is necessary and sufficient to maintain homeostasis and function of the micropeptides. Analyses on human Neprilysin, sarcolipin, and ventricular cardiomyocytes indicates that the regulatory mechanism is evolutionarily conserved (Schiemann et al. 2022).

References associated with 8.A.199 family:

Bak, J.J., R. Aguayo-Ortiz, N. Rathod, J.O. Primeau, M.B. Khan, S.L. Robia, M.J. Lemieux, L.M. Espinoza-Fonseca, and H.S. Young. (2022). Primitive Phospholamban- and Sarcolipin-like Peptides Inhibit the Sarcoplasmic Reticulum Calcium Pump SERCA. Biochemistry 61: 1419-1430. 35771007
Magny, E.G., J.I. Pueyo, F.M. Pearl, M.A. Cespedes, J.E. Niven, S.A. Bishop, and J.P. Couso. (2013). Conserved regulation of cardiac calcium uptake by peptides encoded in small open reading frames. Science 341: 1116-1120. 23970561
Schiemann, R., A. Buhr, E. Cordes, S. Walter, J.J. Heinisch, P. Ferrero, H. Milting, A. Paululat, and H. Meyer. (2022). Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides. Nat Commun 13: 4420. 35906206