APOBEC

APOBEC refers to a family of zinc-dependent cytidine deaminases that catalyze the deamination of cytidine to uridine in RNA or single-stranded DNA. The name originates from apolipoprotein B mRNA editing enzyme catalytic polypeptide-like, reflecting one of its first described functions, but the family now includes multiple members with diverse roles in RNA and DNA editing.

In RNA editing, APOBEC1 edits apolipoprotein B mRNA in vertebrate small intestine, creating a premature stop codon and producing the truncated ApoB-48 protein. Many other APOBEC enzymes act on DNA or RNA in a context-dependent manner. All APOBEC enzymes share a catalytic zinc-binding motif and the ability to deaminate cytidine, with the reaction often generating uracil that can lead to mutations after replication. The catalytic motif is typically described as HxE followed by a PCX2-4C sequence.

Biological roles include antiviral defense and restriction of retroelements. The APOBEC3 subfamily (A3A, A3B, A3C, A3D, A3F, A3G, A3H) can raise G-to-A mutations in viral cDNA during reverse transcription, inhibiting replication. Viruses such as HIV-1 have evolved countermeasures, notably the Vif protein, which targets certain APOBEC3 enzymes for degradation. APOBEC2 and other family members have less clearly defined functions, with APOBEC2 linked to muscle tissue and APOBEC4 having unclear activity in humans.

Clinical relevance includes the contribution of APOBEC activity to mutational signatures in cancer. Tumor genomes often show C to T and C to G mutations in TCW motifs, attributed to APOBEC mutagenesis, which can drive clonal evolution and impact prognosis and therapy.