Functional Diversity and Emerging Roles of Human NME/NDPK Group II Proteins

NME/NDP kinases are enzymes primarily responsible for maintaining nucleotide balance in the cell. They arose early in evolution, during which they acquired additional biochemical and biological functions such as protein histidine kinase activity, DNA transcription and repair, and the binding and transfer of phospholipids. The human NME/NDPK family comprises 10 proteins divided into two groups. The well-documented Group I (NME1-4) is characterized by high sequence homology and a single active NDPK domain. In contrast, the remaining NME genes/proteins belong to the poorly understood and more heterogeneous Group II. They possess one or more NDPK domains and are divergent in their amino acid sequences. Except for NME6, they have been considered enzymatically inactive. In recent years, NME Group II proteins have attracted more interest from researchers, and new emerging evidence may change the established perspective.