Alternative titles; symbols
HGNC Approved Gene Symbol: APOBEC3C
Cytogenetic location: 22q13.1 Genomic coordinates (GRCh38): 22:39,014,257-39,020,352 (from NCBI)
APOBEC3C is related to APOBEC1 (600130), a cytidine deaminase responsible for cytidine-to-uridine editing of apolipoprotein B (APOB; 107730) mRNA (Jarmuz et al., 2002).
By searching an EST database using the signature sequence for RNA-editing cytidine deaminases as probe, followed by RACE using RNA from HeLa cells, Jarmuz et al. (2002) cloned APOBEC3C. The deduced 190-amino acid protein shares the overall domain structure of APOBEC1, including an active site, a linker region, and a pseudoactive site, but it lacks the N-terminal alpha helix. Northern blot analysis detected moderate to high expression in spleen, testis, peripheral blood leukocytes, heart, thymus, prostate, and ovary. Moderate to low expression was found in other tissues, including colon. APOBEC3C was expressed at high levels in colorectal adenocarcinoma and chronic myelogenous leukemia cells, and to a lesser extent in several other lymphoma and leukemia cell lines.
Harris et al. (2002) showed that APOBEC1 and its homologs APOBEC3C and APOBEC3G (607113) exhibited potent DNA mutator activity in an E. coli assay. These proteins appeared to trigger DNA mutation through dC deamination, and each protein exhibited a distinct local target sequence specificity. The results revealed the existence of a family of potential active dC/dG mutators, with possible implications for cancer.
Three human APOBEC3 genes, APOBEC3A (607109), APOBEC3B, and APOBEC3H (610976), are expressed in keratinocytes and skin, leading Vartanian et al. (2008) to investigate whether genetic editing of human papillomavirus DNA occurred. In a study of HPV1a plantar warts and HPV16 precancerous cervical biopsies, hyperedited HPV1a and HPV16 genomes were found. Strictly analogous results were obtained from transfection experiments with HPV plasmid DNA and the 3 nuclear-localized enzymes APOBEC3A, APOBEC3B, and APOBEC3H. Thus, Vartanian et al. (2008) suggested that stochastic or transient overexpression of APOBEC3 genes may expose the genome to a broad spectrum of mutations that could influence the development of tumors.
By modeling and probing the structure of A3C, Stauch et al. (2009) showed that A3C dimerization was critical for antiviral activity in an African green monkey simian immunodeficiency virus system using embryonic kidney and osteosarcoma cell lines. They identified a cavity in A3C similar to nucleic acid-binding pockets of known enzymes and found that the cavity was important for A3C encapsidation and 5.8S RNA binding. Stauch et al. (2009) proposed that the binding pocket of A3C interacts with RNA and that the interaction is required for encapsidation mediated by binding of nucleocapsid, but that antiviral activity requires A3C dimerization.
Jarmuz et al. (2002) determined that the APOBEC3C gene contains 4 exons and that the 5-prime untranslated region contains long repeat sequences. The promoter region does not have a TATA or CATT box.
By FISH, Jarmuz et al. (2002) mapped the APOBEC3C gene to a cluster of APOBEC3 genes and pseudogenes on chromosome 22q13.1-q13.2. They determined that these APOBEC3 genes are all transcribed in the centromere to telomere direction.
Harris, R. S., Petersen-Mahrt, S. K., Neuberger, M. S. RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Molec. Cell 10: 1247-1253, 2002. [PubMed: 12453430] [Full Text: https://doi.org/10.1016/s1097-2765(02)00742-6]
Jarmuz, A., Chester, A., Bayliss, J., Gisbourne, J., Dunham, I., Scott, J., Navaratnam, N. An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22. Genomics 79: 285-296, 2002. [PubMed: 11863358] [Full Text: https://doi.org/10.1006/geno.2002.6718]
Stauch, B., Hofmann, H., Perkovic, M., Weisel, M., Kopietz, F., Cichutek, K., Munk, C., Schneider, G. Model structure of APOBEC3C reveals a binding pocket modulating ribonucleic acid interaction required for encapsidation. Proc. Nat. Acad. Sci. 106: 12079-12084, 2009. [PubMed: 19581596] [Full Text: https://doi.org/10.1073/pnas.0900979106]
Vartanian, J.-P., Guetard, D., Henry, M., Wain-Hobson, S. Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions. Science 320: 230-233, 2008. [PubMed: 18403710] [Full Text: https://doi.org/10.1126/science.1153201]