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 subfamily 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 regions 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 conserved gene than APOBEC-1. APOBEC-2 mRNA and protein are expressed exclusively in heart and skeletal muscle. APOBEC-2 does not display detectable apoB mRNA editing activity. Like other editing enzymes of the cytidine deaminase superfamily, APOBEC-2 has low, but definite, intrinsic cytidine deaminase activity. The identification of APOBEC-2 indicates that APOBEC-1 is not the only member of the C-->U editing enzyme subfamily, which, like the A (adenosine)-->I (inosine) subfamily of editing enzymes, must encompass at least 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 mediated by a single enzyme but involves multiple related proteins that have evolved from a primordial gene closely related to the housekeeping enzyme cytidine deaminase.
Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, Texas, 77030-3498, USA.
W
W
Liao
S H
SH
Hong
B H
BH
Chan
F B
FB
Rudolph
S C
SC
Clark
L
L
Chan
D000071478:APOBEC Deaminases; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D009124:Muscle Proteins; D012333:RNA, Messenger; D000071478:APOBEC Deaminases; C120388:APOBEC2 protein, human; C485629:Apobec2 protein, mouse; D003564:Cytidine Deaminase