Adenosine Kinase - Characteristics of The AdK Gene and Its Isoforms

Characteristics of The AdK Gene and Its Isoforms

The AdK gene in humans is located on chromosome 10 in the 10q11-10q24 region. In contrast to its coding sequence (about 1 Kb), the AdK gene in mammalian species is unusually large (~546 Kb in humans) and it consists of 11 exons (36 to 173 bp in length) and 10 introns whose lengths vary from 4.2 Kb to 128.6 Kb (average ~50Kb). The ratio of the non-coding to coding sequence for human ADK (>550) is the highest known for any gene. The AdK gene in mammalian organisms is also linked in a head to head manner to the gene for the long isoform of AdK to the gene for μ3A adaptor protein, and both these genes are transcribed from a single bi-directional promoter. The large size of the AdK gene and its linkage to the gene for μ3A adaptor protein are apparently unique characteristic of the amniotes (e.g. various mammals, birds, and reptiles). In contrast, the AdK genes in other eukaryotic organisms are much smaller in lengths (1.3 – 20 Kb long). In mammals, two isoforms of Adk are present. These two isoforms show no difference in their biological activity and they differ only at the N-terminus where the long isoform (AdK-long) contains extra 21 amino acids that replace the first 4 amino acids of the short isoform (AdK-short). These two isoforms are independently regulated at the transcriptional level and the promoter for the short isoform is located within the first large AdK intron. It was recently shown that of the two AdK isoforms, the AdK-long isoform is localized in the nucleus, whereas AdK-short is found in the cytoplasm.