Identification of a novel adenylate kinase system in the brain: cloning of the fourth adenylate kinase.

We identify a novel subtype of adenylate kinase, which is the 4th adenylate kinase (AK4), in the vertebrate. AK4 mRNA is expressed in the mammalian central nervous system in a region-specific manner from the middle stage of embryogenesis to the adulthood in the rodent. The presence of three isozymes of adenylate kinase (AK1, AK2 and AK3) that maintains the homeostasis of adenine and guanine nucleotide composition has been reported in the vertebrate. Obtained mouse AK4 cDNA is 3667 bp in size. The predicted open reading frame consists of 223 amino acid residues. Rat AK4 cDNA is also obtained, and the predicted open reading frame is the same length as that of the mouse. The predicted rat AK4 molecule shows 97.8% homology with mouse AK4. Rat AK4 protein is distinct from rat AK3, 53.8% homologous with rat AK3, although the adenylate kinase signature and the mitochondrial energy transfer protein signature are found in both sequences. Interestingly, rat AK4 is 89.2% homologous with the human AK3 over 223 amino acid residues and rat AK3 is 53.7% homologous with the human AK3 indicating that the reported human AK3 actually belongs to the AK4 group (therefore, it should be referred to as human AK4). Although the sequence of AK4 is most similar to that of AK3 among the AK isozymes, its in vivo expression is completely different from AK3; AK4 mRNA is expressed in the pyramidal cells in the hippocampus (mainly in the subfield CA3), the granular cells in the cerebellum, nasal neuroepithelium and the liver while AK3 mRNA is expressed ubiquitously in the body. It is probable that AK4 acts on the specific mechanism of energy metabolism rather than control of the homeostasis of the ADP pool ubiquitously. Copyright 1998 Elsevier Science B.V.