APOBEC-2, a cardiac- and skeletal muscle-specific member of the cytidine deaminase supergene family

APOBEC-1, which mediates the editing of apolipoprotein (apo) B mRNA, is the only known member of the C (cytidine)--> U (uridine) editing enzyme subfam ily of the cytidine deaminase supergene family. Here we report the cloning of APOBEC-2, another member of the subfamily. Human and mouse APOBEC-2 both contain 224 amino acid residues, and their genes are mapped to syntenic re gions of human chromosome 6 (6p21) and mouse chromosome 17. By phylogenetic analysis, APOBEC-2 is shown to be evolutionarily related to APOBEC-1, and analysis of substitution rates indicates that APOBEC-2 is a much better con served gene than APOBEC-1. APOBEC-2 mRNA and protein are expressed exclusiv ely in heart and skeletal muscle, APOBEC-2 does not display detectable apoB mRNA editing activity. Like other editing enzymes of the cytidine deaminas e superfamily, APOBEC-2 has low, but definite, intrinsic cytidine deaminase activity. The identification of APOBEC-2: indicates that APOBEC-1 is not t he only member of the C-->U editing enzyme subfamily, which, Like the A (ad enosine)-->I (inosine) subfamily of editing enzymes, must encompass at leas t two and possibly more different deaminase enzymes. It suggests that the C -->U editing affecting apoB mRNA and other RNAs is not an isolated event me diated by a single enzyme but involves multiple related proteins that have evolved from a primordial gene closely related to the housekeeping enzyme c ytidine deaminase. (C) 1999 Academic Press.