IDENTIFICATION OF A NOVEL ADENYLATE KINASE SYSTEM IN THE BRAIN - CLONING OF THE 4TH ADENYLATE KINASE

We identify a novel subtype of adenylate kinase, which is the 4th aden ylate kinase (AK4), in the vertebrate. AK4 mRNA is expressed in the ma mmalian central nervous system in a region-specific manner from the mi ddle stage of embryogenesis to the adulthood in the rodent. The presen ce of three isozymes of adenylate kinase (AK1, AK2 and AK3) that maint ains the homeostasis of adenine and guanine nucleotide composition has been reported in the vertebrate. Obtained mouse AK4 cDNA is 3667 bp i n size. The predicted open reading frame consists of 223 amino acid re sidues. 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 m olecule shows 97.8% homology with mouse AK4. Rat AK4 protein is distin ct from rat AK3, 53.8% homologous with rat AK3, although the adenylate kinase signature and the mitochondrial energy transfer protein signat ure are found in both sequences. Interestingly, rat AK4 is 89.2% homol ogous with the human AK3 over 223 amino acid residues and rat AK3 is 5 3.7% homologous with the human AK3 indicating that the reported human AK3 actually belongs to the AK4 group (therefore, it should be referre d to as human AK4). Although the sequence of AK4 is most similar to th at of AK3 among the AK isozymes, its in vivo expression is completely different from AK3; AK4 mRNA is expressed in the pyramidal cells in th e hippocampus (mainly in the subfield CA3), the granular cells in the cerebellum, nasal neuroepithelium and the liver while AK3 mRNA is expr essed ubiquitously in the body. It is probable that AK4 acts on the sp ecific mechanism of energy metabolism rather than control of the homeo stasis of the ADP pool ubiquitously. (C) 1998 Elsevier Science B.V. Al l rights reserved.