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Functional Diversity and Emerging Roles of Human NME/NDPK Group II Proteins
Bastien Proust1, Helena Ćetković1, Maja Jazvinšćak Jembrek2
1Division of Molecular Biology, Ruđer Bošković Institute, Bijenička Cesta 54, 10002 Zagreb, Croatia.
International Journal of Molecular Sciences
|June 12, 2026
Summary
Nucleotide diphosphate kinases (NME/NDPKs) maintain cellular nucleotide balance and have diverse functions. Emerging research highlights the potential enzymatic activity and significance of the poorly understood NME Group II proteins.
Area of Science:
- Biochemistry
- Molecular Biology
- Evolutionary Biology
Background:
- NME/NDP kinases are crucial enzymes for nucleotide homeostasis.
- They evolved early and acquired diverse functions, including DNA repair and phospholipid transfer.
- The human NME/NDPK family has 10 proteins in two groups: Group I (NME1-4) and the heterogeneous Group II.
Purpose of the Study:
- To review the current understanding of NME/NDP kinases, focusing on the understudied Group II.
- To highlight emerging evidence that may alter the perception of Group II protein enzymatic activity.
- To explore the evolutionary context and diverse functions of the NME/NDPK family.
Main Methods:
- Literature review of NME/NDP kinase research.
- Comparative analysis of NME Group I and Group II protein structures and functions.
- Synthesis of recent findings on NME Group II protein activities.
Main Results:
- Group I NME/NDP kinases are well-characterized with conserved NDPK domains.
- Group II proteins are diverse, possess varied NDPK domains, and were largely considered inactive, except for NME6.
- Recent studies suggest potential enzymatic roles and biological significance for NME Group II proteins.
Conclusions:
- The NME/NDP kinase family exhibits significant functional and structural diversity.
- NME Group II proteins, previously overlooked, are gaining attention for their potential enzymatic activities.
- Further research into NME Group II is essential to fully understand nucleotide metabolism and cellular regulation.
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