An overview of cytidine deaminases.
Enzymes that deaminate cytidine to uridine play an important role in a variety of pathways from bacteria to man. Ancestral members of this family were able to deaminate cytidine only in a mononucleotide or nucleoside context. Recently, a family of enzymes has been discovered with the ability to deaminate cytidines on RNA or DNA. The first member of this new family is APOBEC1, which deaminates apolipoprotein B messenger RNA to generate a premature stop codon. APOBEC1 has the conserved active site motif found in Escherichia coli cytidine deaminase. In addition, APOBEC1 has a unique motif containing 2 phenylalanine residues and an insert of 4 amino acid residues across the active site motif. This motif is present in APOBEC family members including activation-induced cytidine deaminase (AID), APOBEC2, and APOBEC3A through APOBEC3G. AID is essential for initiating class-switch recombination, somatic hypermutation, and gene conversion. The APOBEC3 family is unique to primates. APOBEC3G is able to protect cells from human immunodeficiency virus and other viral infections. This function is not unique to APOBEC3G; other APOBEC3 family members also have this ability. Overexpression of enzymes in this family can cause cancer, suggesting that the genes for the APOBEC family of proteins are proto-oncogenes. Recent advances in the understanding of the mechanism of action of this family are summarized in this review.
Navaratnam
Naveenan
N
MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom. naveenan.navaratnam@csc.mrc.ac.uk
Sarwar
Rizwan
R
D000071478:APOBEC Deaminases; D000071479:APOBEC-1 Deaminase; D000818:Animals; D001665:Binding Sites; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D017393:RNA Editing / Q000235:genetics; D014777:Virus Diseases / Q000201:enzymology* / Q000235:genetics
D015513:Oncogene Proteins; D043525:Cytosine Deaminase; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase