Recombinant Human Nucleoside diphosphate kinase B (NME2), partial

Function

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)

Subcellular Location

Cytoplasm; Cytoplasm, perinuclear region; Nucleus

Tissue Specificity

Ubiquitously expressed

Subunit

Homohexamer (PubMed:1851158, PubMed:19435876, PubMed:7658474, PubMed:8747457). Heterohexamer of two different chains: A/NME1 and B/NME2 (A5B or A4B2 or A3B3 or A2B4 or AB5) (PubMed:1851158). Interacts with CAPN8 (By similarity). Interacts with AKAP13 (PubMed:15249197). Interacts with ITGB1BP1 (via C-terminal domain region); this interaction leads to their recruitment to ITGB1-rich cell adhesion sites in cell spreading on FN1 (PubMed:11919189). Interacts with BCL2L10 (PubMed:17532299)

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• Gilles A.-M. et al. Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. — J. Biol. Chem. (1991)
• Postel E.H. et al. Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. — Science (1993)
• Valentijn L.J. et al. Read-through transcript from NM23-H1 into the neighboring NM23-H2 gene encodes a novel protein, NM23-LV. — Genomics (2006)
• Zody M.C. et al. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Seifert M. et al. Characterization of the human nm23-H2 promoter region and localization of the microsatellite D17S396. — Biochem. Biophys. Res. Commun. (1995)
• Schaertl S. et al. Substrate specificity of human nucleoside-diphosphate kinase revealed by transient kinetic analysis. — J. Biol. Chem. (1998)