Ancient divergence of long and short isoforms of adenylate kinase: molecular evolution of the nucleoside monophosphate kinase family.

Adenylate kinases (AK) from vertebrates are separated into three isoforms, AK1, AK2 and AK3, based on structure, subcellular localization and substrate specificity. AK1 is the short type with the amino acid sequence being 27 residues shorter than sequences of the long types, AK2 and AK3. A phylogenetic tree prepared for the AK isozymes and other members of the nucleoside monophosphate (NMP) kinase family shows that the divergence of long and short types occurred first and then differentiation in subcellular localization or substrate specificity took place. The first step involved a drastic change in the three-dimensional structure of the LID domain. The second step was caused mainly by smaller changes in amino acid sequences.