Structural organization and developmental expression of the protein isoaspartyl methyltransferase gene from Drosophila melanogaster.

A protein carboxyl methyltransferase activity (PCMT) with a specificity for age-damaged protein D-aspartyl and L-isoaspartyl residues (E.C. 2.1.1.77) has been identified and cloned in Drosophila. The Drosophila gene was localized by chromosome in-situ hybridization to region 83AB of the third chromosome. The methyltransferase coding sequence is distributed among four exons within a 1.4-kb segment of the genome; it predicts a polypeptide of 226 amino acids that is 55% identical to the mouse enzyme. When expressed in bacteria, the Drosophila protein exhibits PCMT activity. A single 1.4-kb Pcmt transcript is detected in RNA preparations from embryos, larvae, pupae and adults. The abundance of the transcript, which is lowest in larvae and highest in adults, parallels the specific activity of the enzyme measured in extracts from the same developmental stages. It has been proposed that the PCMT initiates the repair of structurally damaged cellular proteins. The constitutive expression of PCMT and the relatively high level of expression in postmitotic adult cells suggest that PCMT activity is required through development, but acquires additional significance in aging tissues.