Molecular cloning of human calmitine, a mitochondrial calcium binding protein, reveals identity with calsequestrine.

The cDNA of a mitochondrial calcium binding protein, "calmitine", has been cloned from a human skeletal muscle cDNA library. One cDNA of 1.8 kb has been isolated and sequenced. It encodes for a protein of 390 amino acid residues of 41,746 KDa and contains a leading peptide of 28 amino acids. The sequencing showed the possibility for 21 phosphorylation sites, 4 myristylation sites, and one N glycosylation site. Sequence comparison with other proteins revealed the identity of calmitine with calsequestrine, the sarcoplasmic reticulum low affinity, but high Ca2+ binding capacity, protein isolated in 1971. Subcellular fractionation showed a marked increase in these Ca2+ binding proteins in mitochondria as compared with the sarcoplasmic reticulum; furthermore the mitochondrial matrix is highly enriched with that protein. Therefore, our data either suggest a bicompartimentation of calmitine or indicate that the localization of calsequestrine should be reconsidered in the light of our data. Calmitine represents the Ca2+ reservoir of mitochondria, the function of which could be similar to what has been reported for calsequestrine in the sarcoplasmic reticulum.