Nucleoside diphosphate kinase 2 (NME2)

Nucleoside diphosphate kinase 2 (NME2), also known as NDPK-B, is a multifunctional enzyme that maintains the intracellular balance of nucleoside triphosphates by catalyzing the reversible transfer of terminal phosphate groups via a ping-pong mechanism [4, 16]. Beyond its core metabolic role, NME2 acts as a transcriptional activator for the c-myc oncogene and a histidine protein kinase that regulates G-protein signaling and potassium channel activity [5, 9]. In oncology, NME2 is primarily recognized as a metastasis suppressor, although its role is context-dependent and it may act as an oncogene in certain cancers like osteosarcoma or lung cancer [11, 13, 18]. It also plays a significant role in cardiovascular health, particularly in vascular integrity and the regulation of hypertension [6, 9]. While various inhibitors such as ellagic acid and polyphenols have been identified in research, the essential nature of NME2 in general nucleotide metabolism makes it a challenging therapeutic target due to the risk of systemic toxicity [1, 2, 12].

Other names

NDPK-BNM23-H2NME2NDPKBNDK BNucleoside diphosphate kinase BC-myc purine-binding transcription factor PUFHistidine protein kinase NDKBNM23B

NME2 facilitates phosphoryl transfer between nucleoside triphosphates (NTPs) and nucleoside diphosphates (NDPs) through a transiently phosphorylated histidine intermediate (His-118 in humans), maintaining balanced pools of non-adenine nucleotides like GTP, UTP, and CTP [4, 16, 19].