Guidelines for Naming Nonprimate APOBEC3 Genes and Proteins

Abstract

15 APOBEC3 GENES ARE UNIQUE TO MAMMALS, BUT COPY NUMBERS VARY SIGNIFICANTLYAPOBEC3 (A3) proteins are of considerable interest because most are potent DNA cytidine deaminases that have the capacity to restrict the replication and/or edit the sequences of a wide variety of parasitic elements, including many retroviruses and retrotransposons (reviewed in references 5, 8-10, and 14). Likely substrates include (i) lentiviruses, such as human immunodeficiency virus type 1, human immunodeficiency virus type 2, simian immunodeficiency virus, maedi-visna virus, feline immunodeficiency virus, and equine infectious anemia virus; (ii) alpha-, beta-, gamma-, and deltaretroviruses, such as Rous sarcoma virus, MasonPfizer monkey virus or mouse mammary tumor virus, murine leukemia virus or feline leukemia virus, and human T-cell leukemia virus or bovine leukemia virus, respectively; (iii) spumaviruses, such as primate foamy virus and feline foamy virus; (iv) hepadnaviruses, such as hepatitis B virus; (v) endogenous retroviruses and long terminal repeat retrotransposons, such as human endogenous retrovirus K, murine intracisternal A particle, murine MusD, and porcine endogenous retrovirus; (vi) non-long terminal repeat retroposons, such as L1 and Alu; and (vii) DNA viruses, such as adenoassociated virus and human papillomavirus. Over the past few years, there has also been an increasing appreciation for the multiple, distinct mechanisms that parasitic elements use to coexist with the A3 proteins of their hosts. Together, these observations indicate that the evolution of the A3 proteins has been driven by a requirement to minimize the spread of exogenous and endogenous genetic threats. The likelihood that the A3 proteins might exist solely for this purpose has been supported recently by studies indicating that A3-deficient mice have no obvious phenotypes apart from a notable increase in susceptibility to retrovirus infection (16,19,21,23).A3 genes are specific to mammals and are organized in a tandem array between two vertebrate-conserved flanking genes, CBX6 and CBX7 (Fig. 1A) (e.g., see reference 13). Based on a limited number of genomic sequences, it is already clear that the A3 copy number can vary greatly from mammal to mammal. For instance, mice have one A3 gene (10, 16), pigs have two (13), cattle and sheep have three (13), cats have four (17), horses have six (2), and humans and chimpanzees have seven (4, 10, 11). Other mammals are likely to have copy numbers within this range, but the cat and horse loci, in particular, highlight the difficulty in making such predictions (2, 17).

Biochemical and Biological Studies of Mouse APOBEC3

“…mA3, like hA3G and many other APOBEC3 family members, has two catalytic domains, each with the hallmark H-X-E active site, followed 23 to 28 residues later by the zinc finger motif P-C-X 2-4--C (18,19). In the case of hA3G, only the C-terminal catalytic domain actually possesses catalytic activity; it is not known why the N-terminal domain is not an active deaminase (14).…”

Genetic Editing of Herpes Simplex Virus 1 and Epstein-Barr Herpesvirus Genomes by Human APOBEC3 Cytidine Deaminases in Culture and In Vivo

“…The A3 gene locus appears with the emergence of placental mammals, and while it is generally bounded by the cbx6 and cbx7 genes, there is considerable variation (24). For example, the rat and mouse genomes encode a single A3 gene, the cow genome two, cats three/four, and horses five/six, while the primate lineage encodes seven A3 genes, six of which are functional (24,25).…”

APOBEC3B: Pathological consequences of an innate immune DNA mutator

“…However, this nomenclature is misnomeric as APOBEC1 is the only family member whose gene product carries out apolipoprotein B mRNA editing. [16][17][18] In fact, many of these proteins have independent physiological functions. For example, AID is essential for both somatic hypermutation and class-switch recombination through deamination of variable and switch region DNA segments within rearranged immunoglobulin heavy and light chain genes.…”