The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

NME2  -  NME/NM23 nucleoside diphosphate kinase 2

Homo sapiens

Synonyms: C-myc purine-binding transcription factor PUF, Histidine protein kinase NDKB, NDK B, NDKB, NDP kinase B, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of NME2


High impact information on NME2


Chemical compound and disease context of NME2


Biological context of NME2

  • The human NME2 gene lies within 18kb of NME1 in chromosome 17 [12].
  • We have isolated and characterized five yeast artificial chromosome (YAC) clones and three cosmid clones that contain both genes, demonstrating that the NME2 gene is also located on chromosome 17 and is separated by not more than 18 kb from the NME1 gene [12].
  • NM23-H2/NDP kinase B has been identified as a sequence-specific DNA-binding protein with affinity for a nuclease-hypersensitive element of the c-MYC gene promoter (Postel et al., 1993) [13].
  • We obtained a hen antibody that specifically reacts with Nme1 without any cross-reaction with Nme2 [14].
  • Furthermore the identification of possible binding sites for MYC proteins and additionally the NM23-H2 protein itself (the transcription factor PuF for c-myc gene activation) is of importance with respect to possible para- and autoregulatory interactions [15].

Anatomical context of NME2

  • To determine the human chromosomal location of the NME2 gene, we have analyzed DNA from rodent-human cell lines and hybrid cell lines containing portions of chromosome 17 by a combination of PCR amplification and Southern hybridization [16].
  • Surface NM23-H1 and NM23-H2 proteins were decreased during in vitro erythroid and granulocyte differentiation [2].
  • To examine what types of tumor cell line express the cell surface NM23 protein, we measured the cell surface NM23-H1 and NM23-H2 proteins of leukemia line cells on various cellular lineage and differentiation stages [2].
  • These adhesion sites are enriched in occupied beta(1) integrins and precede the formation of focal adhesions devoid of ICAP-1alpha and nm23-H2, indicating the dynamic segregation of components of matrix adhesions [17].
  • The physiological relevance of this interaction is provided by confocal fluorescence microscopy, which shows that ICAP-1alpha and nm23-H2 are co-localized in lamellipodia during the early stages of cell spreading [17].

Associations of NME2 with chemical compounds


Physical interactions of NME2

  • In vitro-binding assays using different recombinant nucleoside diphosphate kinases showed that TRF1 predominantly binds the nm23-H2 isoform rather than nm23-H1 [22].
  • Nm23-H2 interacts with TPb (Thromboxane receptor isoform b) and through this association regulates TP endocytosis through a Rac1 dependent mechanism [23]

Enzymatic interactions of NME2


Regulatory relationships of NME2

  • NM23-H1 and NM23-H2 repress transcriptional activities of nuclease-hypersensitive elements in the platelet-derived growth factor-A promoter [24].
  • Nm23-H1 and nm23-H2 are strongly up-regulated downstream targets of N-myc [25].

Other interactions of NME2

  • Subsequently, two related human nm23 genes, nm23-H1 and nm23-H2, were identified [1].
  • Compared to typical proteins of this family such as NME1 and NME2, NME6 has three additional residues located in the Kpn loop, and a 22-residue extension at the COOH-terminal [26].
  • Human metastasis-suppressor genes nm23-1 (NME1) and nm23-2 (NME2) are implicated in control of the metastatic potential of malignant cells [27].
  • The relationship between expression of nm23-H1 and nm23-H2 in hepatocellular carcinoma specimens from 30 patients and metastatic potential was investigated with the use of a quantitative reverse transcription-PCR procedure [1].
  • This finding represents the first evidence that the tumor suppressor nm23-H2 could act on beta(1) integrin-mediated cell adhesion by interacting with one of the integrin partners, ICAP-1alpha [17].

Analytical, diagnostic and therapeutic context of NME2


  1. NM23-H1 and NM23-H2 messenger RNA abundance in human hepatocellular carcinoma. Iizuka, N., Oka, M., Noma, T., Nakazawa, A., Hirose, K., Suzuki, T. Cancer Res. (1995) [Pubmed]
  2. Expression of cell surface NM23 proteins of human leukemia cell lines of various cellular lineage and differentiation stages. Okabe-Kado, J., Kasukabe, T., Honma, Y. Leuk. Res. (2002) [Pubmed]
  3. Human nucleoside diphosphate kinase B (Nm23-H2) from melanoma cells shows altered phosphoryl transfer activity due to the S122P mutation. Schaertl, S., Geeves, M.A., Konrad, M. J. Biol. Chem. (1999) [Pubmed]
  4. The N-myc and c-myc downstream pathways include the chromosome 17q genes nm23-H1 and nm23-H2. Godfried, M.B., Veenstra, M., v Sluis, P., Boon, K., v Asperen, R., Hermus, M.C., v Schaik, B.D., Voûte, T.P., Schwab, M., Versteeg, R., Caron, H.N. Oncogene (2002) [Pubmed]
  5. The crystal structure of a human nucleoside diphosphate kinase, NM23-H2. Webb, P.A., Perisic, O., Mendola, C.E., Backer, J.M., Williams, R.L. J. Mol. Biol. (1995) [Pubmed]
  6. An intercistronic stem-loop structure functions as an mRNA decay terminator necessary but insufficient for puf mRNA stability. Chen, C.Y., Beatty, J.T., Cohen, S.N., Belasco, J.G. Cell (1988) [Pubmed]
  7. Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. Postel, E.H., Berberich, S.J., Flint, S.J., Ferrone, C.A. Science (1993) [Pubmed]
  8. Histidine Phosphorylation of the Potassium Channel KCa3.1 by Nucleoside Diphosphate Kinase B Is Required for Activation of KCa3.1 and CD4 T Cells. Srivastava, S., Li, Z., Ko, K., Choudhury, P., Albaqumi, M., Johnson, A.K., Yan, Y., Backer, J.M., Unutmaz, D., Coetzee, W.A., Skolnik, E.Y. Mol. Cell (2006) [Pubmed]
  9. Cell cycle effects and control of gene expression by resveratrol in human breast carcinoma cell lines with different metastatic potentials. Hsieh, T.C., Burfeind, P., Laud, K., Backer, J.M., Traganos, F., Darzynkiewicz, Z., Wu, J.M. Int. J. Oncol. (1999) [Pubmed]
  10. Pleiotropic effects of puf interposon mutagenesis on carotenoid biosynthesis in Rubrivivax gelatinosus. A new gene organization in purple bacteria. Ouchane, S., Picaud, M., Vernotte, C., Reiss-Husson, F., Astier, C. J. Biol. Chem. (1997) [Pubmed]
  11. Nucleotide sequences of genes coding for photosynthetic reaction centers and light-harvesting proteins of Acidiphilium rubrum and related aerobic acidophilic bacteria. Nagashima, K.V., Matsuura, K., Wakao, N., Hiraishi, A., Shimada, K. Plant Cell Physiol. (1997) [Pubmed]
  12. The human NME2 gene lies within 18kb of NME1 in chromosome 17. Chandrasekharappa, S.C., Gross, L.A., King, S.E., Collins, F.S. Genes Chromosomes Cancer (1993) [Pubmed]
  13. Human NM23/nucleoside diphosphate kinase regulates gene expression through DNA binding to nuclease-hypersensitive transcriptional elements. Postel, E.H., Berberich, S.J., Rooney, J.W., Kaetzel, D.M. J. Bioenerg. Biomembr. (2000) [Pubmed]
  14. Potential prognostic value in human breast cancer of cytosolic Nme1 protein detection using an original hen specific antibody. Toulas, C., Mihura, J., de Balincourt, C., Marques, B., Marek, E., Soula, G., Roche, H., Favre, G. Br. J. Cancer (1996) [Pubmed]
  15. Characterization of the human nm23-H2 promoter region and localization of the microsatellite D17S396. Seifert, M., Seib, T., Engel, M., Dooley, S., Welter, C. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  16. Localization of a second NM23 gene, NME2, to chromosome 17q21-q22. Kelsell, D.P., Black, D.M., Solomon, E., Spurr, N.K. Genomics (1993) [Pubmed]
  17. Integrin cytoplasmic domain-associated protein 1alpha (ICAP-1alpha ) interacts directly with the metastasis suppressor nm23-H2, and both proteins are targeted to newly formed cell adhesion sites upon integrin engagement. Fournier, H.N., Dupé-Manet, S., Bouvard, D., Lacombe, M.L., Marie, C., Block, M.R., Albiges-Rizo, C. J. Biol. Chem. (2002) [Pubmed]
  18. Identification of a second human nm23 gene, nm23-H2. Stahl, J.A., Leone, A., Rosengard, A.M., Porter, L., King, C.R., Steeg, P.S. Cancer Res. (1991) [Pubmed]
  19. The nucleoside diphosphate kinase of human neutrophils. Guignard, F., Markert, M. Biochem. J. (1996) [Pubmed]
  20. Catalysis of DNA cleavage and nucleoside triphosphate synthesis by NM23-H2/NDP kinase share an active site that implies a DNA repair function. Postel, E.H., Abramczyk, B.M., Levit, M.N., Kyin, S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  21. Evidence for nm23 RNA overexpression, DNA amplification and mutation in aggressive childhood neuroblastomas. Leone, A., Seeger, R.C., Hong, C.M., Hu, Y.Y., Arboleda, M.J., Brodeur, G.M., Stram, D., Slamon, D.J., Steeg, P.S. Oncogene (1993) [Pubmed]
  22. Association of nucleoside diphosphate kinase nm23-H2 with human telomeres. Nosaka, K., Kawahara, M., Masuda, M., Satomi, Y., Nishino, H. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  23. Nm23-H2 interacts with a G protein-coupled receptor to regulate its endocytosis through an Rac1-dependent mechanism. Rochdi, M.D., Laroche, G., Dupré, E., Giguère, P., Lebel, A., Watier, V., Hamelin, E., Lépine, M.C., Dupuis, G., Parent, J.L. J. Biol. Chem. (2004) [Pubmed]
  24. NM23-H1 and NM23-H2 repress transcriptional activities of nuclease-hypersensitive elements in the platelet-derived growth factor-A promoter. Ma, D., Xing, Z., Liu, B., Pedigo, N.G., Zimmer, S.G., Bai, Z., Postel, E.H., Kaetzel, D.M. J. Biol. Chem. (2002) [Pubmed]
  25. Inhibition of a new differentiation pathway in neuroblastoma by copy number defects of N-myc, Cdc42, and nm23 genes. Valentijn, L.J., Koppen, A., van Asperen, R., Root, H.A., Haneveld, F., Versteeg, R. Cancer Res. (2005) [Pubmed]
  26. NME6: a new member of the nm23/nucleoside diphosphate kinase gene family located on human chromosome 3p21.3. Mehus, J.G., Deloukas, P., Lambeth, D.O. Hum. Genet. (1999) [Pubmed]
  27. Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2. Backer, J.M., Mendola, C.E., Kovesdi, I., Fairhurst, J.L., O'Hara, B., Eddy, R.L., Shows, T.B., Mathew, S., Murty, V.V., Chaganti, R.S. Oncogene (1993) [Pubmed]
  28. Cytoskeletal association of the A and B nucleoside diphosphate kinases of interphasic but not mitotic human carcinoma cell lines: specific nuclear localization of the B subunit. Pinon, V.P., Millot, G., Munier, A., Vassy, J., Linares-Cruz, G., Capeau, J., Calvo, F., Lacombe, M.L. Exp. Cell Res. (1999) [Pubmed]
  29. NM23-H1 and NM23-H2 gene expression in human renal tumors. Theisinger, B., Engel, M., Seifert, M., Seitz, G., Welter, C. Anticancer Res. (1998) [Pubmed]
  30. The NM23 gene and its expression in oral squamous cell carcinoma. Lo Muzio, L., Mignogna, M.D., Pannone, G., Staibano, S., Procaccini, M., Serpico, R., De Rosa, G., Scully, C. Oncol. Rep. (1999) [Pubmed]
  31. Differential gene expression in stromal cells of human giant cell tumor of bone. Wuelling, M., Delling, G., Kaiser, E. Virchows Arch. (2004) [Pubmed]
WikiGenes - Universities