Catalyzes the transfer of a gamma-phosphoryl group from a nucleoside triphosphate, mainly ATP, to a nucleoside diphosphate via a ping-pong mechanism involving a phosphohistidine intermediate, therefore contributing to the nucleoside triphosphate homeostasis (PubMed:11121025, PubMed:16313181, PubMed:1851158, PubMed:25679041). Also functions as a histidine protein kinase by transferring the phosphoryl group from the phosphohistidine intermediate to a histidine residue in target proteins (PubMed:17157250, PubMed:20946858). Phosphorylates the GNB1 subunit of heterotrimeric G proteins at 'His- 266', generating a high-energy phosphate group that promotes GTP formation and enables receptor-independent activation of heterotrimeric G proteins (By similarity). Also phosphorylates KCNN4 at 'His-358', leading to activation of its intermediate conductance calcium-activated potassium channel activity, Ca(2+) influx, and subsequent activation of B and T cells (PubMed:17157250). Additionally involved in transcriptional regulation through direct DNA binding and chromatin remodeling (PubMed:11121025, PubMed:11694515, PubMed:19033359, PubMed:19435876, PubMed:25679041, PubMed:8392752). In this context, functions as a single-stranded DNA binding protein that binds and stabilizes the G-quadruplex (G4) structures within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter, facilitating recruitment of additional single-strand DNA binding proteins and activation of MYC transcription (PubMed:19033359, PubMed:19435876, PubMed:25679041, PubMed:8392752). G4 DNA-binding activity is independent of its nucleoside diphosphate kinase function and recognizes both folded and unfolded G4 structures (PubMed:25679041). With NME1, may regulate acetyl-CoA (AcCoA) usage between histone acetylation and fatty acid synthesis by targeting AcCoA release at ATP-rich, HAT-associated chromatin regions (By similarity). Also negatively regulates Rho activity by interacting with AKAP13/LBC (PubMed:15249197). {ECO:0000250|UniProtKB:Q01768, ECO:0000250|UniProtKB:Q3T0Q4, ECO:0000269|PubMed:11121025, ECO:0000269|PubMed:11694515, ECO:0000269|PubMed:15249197, ECO:0000269|PubMed:16313181, ECO:0000269|PubMed:17157250, ECO:0000269|PubMed:1851158, ECO:0000269|PubMed:19033359, ECO:0000269|PubMed:19435876, ECO:0000269|PubMed:20946858, ECO:0000269|PubMed:25679041, ECO:0000269|PubMed:8392752}. This is the function of ENSG00000243678 (NME2, NME/NM23 nucleoside diphosphate kinase 2).