Search Results
Overview
| Uniprot ID | P22392 |
|---|---|
| Protein Name | Nucleoside diphosphate kinase B |
| Gene Name | NME2 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 100 | ETNPADSKPGTIRGD |
| 12 | ERTFIAIKPDGVQRG |
| 124 | IHGSDSVKSAEKEIS |
| 143 | PEELVDYKSCAHDWV |
| 26 | GLVGEIIKRFEQKGF |
| 31 | IIKRFEQKGFRLVAM |
| 39 | GFRLVAMKFLRASEE |
| 49 | RASEEHLKQHYIDLK |
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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Biological Process | GO:0045893 | positive regulation of DNA-templated transcription |
| Cellular Component | GO:0071944 | cell periphery |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0005576 | extracellular region |
| Cellular Component | GO:1904813 | ficolin-1-rich granule lumen |
| Cellular Component | GO:0030027 | lamellipodium |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0048471 | perinuclear region of cytoplasm |
| Cellular Component | GO:0001726 | ruffle |
| Cellular Component | GO:0034774 | secretory granule lumen |
| Molecular Function | GO:0120225 | coenzyme A binding |
| Molecular Function | GO:0003677 | DNA binding |
| Molecular Function | GO:0001216 | DNA-binding transcription activator activity |
| Molecular Function | GO:0051880 | G-quadruplex DNA binding |
| Molecular Function | GO:0019003 | GDP binding |
| Molecular Function | GO:0042802 | identical protein binding |
| Molecular Function | GO:0016301 | kinase activity |
| Molecular Function | GO:0046872 | metal ion binding |
| Molecular Function | GO:0004550 | nucleoside diphosphate kinase activity |
| Molecular Function | GO:0004673 | protein histidine kinase activity |
| Biological Process | GO:0007155 | cell adhesion |
| Biological Process | GO:0006241 | CTP biosynthetic process |
| Biological Process | GO:0006351 | DNA-templated transcription |
| Biological Process | GO:0006183 | GTP biosynthetic process |
| Biological Process | GO:0007229 | integrin-mediated signaling pathway |
| Biological Process | GO:0046042 | ITP biosynthetic process |
| Biological Process | GO:0043066 | negative regulation of apoptotic process |
| Biological Process | GO:0009142 | nucleoside triphosphate biosynthetic process |
| Biological Process | GO:2000144 | positive regulation of DNA-templated transcription initiation |
| Biological Process | GO:0050679 | positive regulation of epithelial cell proliferation |
| Biological Process | GO:0045618 | positive regulation of keratinocyte differentiation |
| Biological Process | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| Biological Process | GO:0042981 | regulation of apoptotic process |
| Biological Process | GO:0045682 | regulation of epidermis development |
| Biological Process | GO:0042304 | regulation of fatty acid biosynthetic process |
| Biological Process | GO:0006228 | UTP biosynthetic process |
Reference
[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.
[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.
[4] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.
[5] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.
[6] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[7] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.