NME1

NME/NM23 nucleoside diphosphate kinase 1
PDB rendering based on 1be4.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1JXV​, 1UCN​, 2HVD​, 2HVE​, 3L7U​, 4ENO​
Identifiers
Symbols	NME1 ; AWD; GAAD; NB; NBS; NDKA; NDPK-A; NDPKA; NM23; NM23-H1
External IDs	OMIM: 156490 MGI: 97355 HomoloGene: 128514 ChEMBL: 2159 GeneCards: NME1 Gene
EC number	2.7.4.6
Gene ontology Molecular function • magnesium ion binding • deoxyribonuclease activity • nucleoside diphosphate kinase activity • protein binding • ATP binding • GTP binding • identical protein binding • ribosomal small subunit binding • poly(A) RNA binding Cellular component • intracellular • nucleus • cytoplasm • cytosol • membrane • ruffle membrane • extracellular exosome Biological process • purine nucleotide metabolic process • nucleoside diphosphate phosphorylation • GTP biosynthetic process • pyrimidine nucleotide metabolic process • UTP biosynthetic process • CTP biosynthetic process • DNA metabolic process • endocytosis • nervous system development • negative regulation of cell proliferation • nucleoside triphosphate biosynthetic process • nucleobase-containing small molecule interconversion • cell differentiation • regulation of apoptotic process • positive regulation of DNA binding • small molecule metabolic process • positive regulation of epithelial cell proliferation • nucleobase-containing small molecule metabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4830	18102
Ensembl	ENSG00000239672	ENSMUSG00000037601
UniProt	P15531	P15532
RefSeq (mRNA)	NM_000269	NM_008704
RefSeq (protein)	NP_000260	NP_032730
Location (UCSC)	Chr 17: 51.15 – 51.16 Mb	Chr 11: 93.96 – 93.97 Mb
PubMed search

Nucleoside diphosphate kinase A is an enzyme that in humans is encoded by the NME1 gene.^[1] It is thought to be a metastasis suppressor.

Function

This gene (NME1) was identified because of its reduced mRNA transcript levels in highly metastatic cells. Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by this gene) and 'B' (encoded by NME2) isoforms. Mutations in this gene have been identified in aggressive neuroblastomas. Two transcript variants encoding different isoforms have been found for this gene. Co-transcription of this gene and the neighboring downstream gene (NME2) generates naturally-occurring transcripts (NME1-NME2), which encodes a fusion protein consisting of sequence sharing identity with each individual gene product.^[2]

Interactions

NME1 has been shown to interact with:

• Aurora A kinase,^[3]
• CD29^[4]
• NME3,^[5][6]
• Protein SET,^[7]
• RAR-related orphan receptor alpha,^[8]
• RAR-related orphan receptor beta,^[8] and
• TERF1.^[9]

See also

• Nucleoside-diphosphate kinase

References

1. Dooley S, Seib T, Engel M, Theisinger B, Janz H, Piontek K, Zang KD, Welter C (February 1994). "Isolation and characterization of the human genomic locus coding for the putative metastasis control gene nm23-H1". Hum. Genet. 93 (1): 63–6. doi:10.1007/bf00218915. PMID 8270257.
2. "Entrez Gene: NME1 non-metastatic cells 1, protein (NM23A) expressed in".
3. Du J, Hannon GJ (December 2002). "The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1". Nucleic Acids Res. 30 (24): 5465–75. doi:10.1093/nar/gkf678. PMC 140054. PMID 12490715.
4. Fournier HN, Dupé-Manet S, Bouvard D, Lacombe ML, Marie C, Block MR, Albiges-Rizo C (June 2002). "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". J. Biol. Chem. 277 (23): 20895–902. doi:10.1074/jbc.M200200200. PMID 11919189.
5. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
6. Negroni A, Venturelli D, Tanno B, Amendola R, Ransac S, Cesi V, Calabretta B, Raschellà G (September 2000). "Neuroblastoma specific effects of DR-nm23 and its mutant forms on differentiation and apoptosis". Cell Death Differ. 7 (9): 843–50. doi:10.1038/sj.cdd.4400720. PMID 11042679.
7. Chakravarti D, Hong R (March 2003). "SET-ting the stage for life and death". Cell 112 (5): 589–91. doi:10.1016/s0092-8674(03)00151-x. PMID 12628178.
8. Paravicini G, Steinmayr M, André E, Becker-André M (October 1996). "The metastasis suppressor candidate nucleotide diphosphate kinase NM23 specifically interacts with members of the ROR/RZR nuclear orphan receptor subfamily". Biochem. Biophys. Res. Commun. 227 (1): 82–7. doi:10.1006/bbrc.1996.1471. PMID 8858107.
9. Nosaka K, Kawahara M, Masuda M, Satomi Y, Nishino H (February 1998). "Association of nucleoside diphosphate kinase nm23-H2 with human telomeres". Biochem. Biophys. Res. Commun. 243 (2): 342–8. doi:10.1006/bbrc.1997.8097. PMID 9480811.

Further reading

• Freije JM, MacDonald NJ, Steeg PS (1998). "Nm23 and tumour metastasis: basic and translational advances". Biochem. Soc. Symp. 63: 261–71. PMID 9513729.
• Roymans D, Willems R, Van Blockstaele DR, Slegers H (2002). "Nucleoside diphosphate kinase (NDPK/NM23) and the waltz with multiple partners: possible consequences in tumor metastasis". Clin. Exp. Metastasis 19 (6): 465–76. doi:10.1023/A:1020396722860. PMID 12405283.
• Tee YT, Chen GD, Lin LY, Ko JL, Wang PH (2006). "Nm23-H1: a metastasis-associated gene". Taiwan J Obstet Gynecol 45 (2): 107–13. doi:10.1016/S1028-4559(09)60206-0. PMID 17197349.
• Gilles AM, Presecan E, Vonica A, Lascu I (1991). "Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme". J. Biol. Chem. 266 (14): 8784–9. PMID 1851158.
• Leone A, McBride OW, Weston A, Wang MG, Anglard P, Cropp CS, Goepel JR, Lidereau R, Callahan R, Linehan WM (1991). "Somatic allelic deletion of nm23 in human cancer". Cancer Res. 51 (9): 2490–3. PMID 2015608.
• Hailat N, Keim DR, Melhem RF, Zhu XX, Eckerskorn C, Brodeur GM, Reynolds CP, Seeger RC, Lottspeich F, Strahler JR (1991). "High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification". J. Clin. Invest. 88 (1): 341–5. doi:10.1172/JCI115299. PMC 296039. PMID 2056128.
• Rosengard AM, Krutzsch HC, Shearn A, Biggs JR, Barker E, Margulies IM, King CR, Liotta LA, Steeg PS (1989). "Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development". Nature 342 (6246): 177–80. doi:10.1038/342177a0. PMID 2509941.
• Wang L, Patel U, Ghosh L, Chen HC, Banerjee S (1993). "Mutation in the nm23 gene is associated with metastasis in colorectal cancer". Cancer Res. 53 (4): 717–20. PMID 7916650.
• Chang CL, Zhu XX, Thoraval DH, Ungar D, Rawwas J, Hora N, Strahler JR, Hanash SM, Radany E (1994). "Nm23-H1 mutation in neuroblastoma". Nature 370 (6488): 335–6. doi:10.1038/370335a0. PMID 8047138.
• MacDonald NJ, De la Rosa A, Benedict MA, Freije JM, Krutsch H, Steeg PS (1993). "A serine phosphorylation of Nm23, and not its nucleoside diphosphate kinase activity, correlates with suppression of tumor metastatic potential". J. Biol. Chem. 268 (34): 25780–9. PMID 8245015.
• Postel EH, Berberich SJ, Flint SJ, Ferrone CA (1993). "Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis". Science 261 (5120): 478–80. doi:10.1126/science.8392752. PMID 8392752.
• Sudbrak R, Golla A, Hogan K, Powers P, Gregg R, Du Chesne I, Lehmann-Horn F, Deufel T (1993). "Exclusion of malignant hyperthermia susceptibility (MHS) from a putative MHS2 locus on chromosome 17q and of the alpha 1, beta 1, and gamma subunits of the dihydropyridine receptor calcium channel as candidates for the molecular defect". Hum. Mol. Genet. 2 (7): 857–62. doi:10.1093/hmg/2.7.857. PMID 8395939.
• MacDonald NJ, Freije JM, Stracke ML, Manrow RE, Steeg PS (1996). "Site-directed mutagenesis of nm23-H1. Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells". J. Biol. Chem. 271 (41): 25107–16. doi:10.1074/jbc.271.41.25107. PMID 8810265.
• Paravicini G, Steinmayr M, André E, Becker-André M (1996). "The metastasis suppressor candidate nucleotide diphosphate kinase NM23 specifically interacts with members of the ROR/RZR nuclear orphan receptor subfamily". Biochem. Biophys. Res. Commun. 227 (1): 82–7. doi:10.1006/bbrc.1996.1471. PMID 8858107.
• Nosaka K, Kawahara M, Masuda M, Satomi Y, Nishino H (1998). "Association of nucleoside diphosphate kinase nm23-H2 with human telomeres". Biochem. Biophys. Res. Commun. 243 (2): 342–8. doi:10.1006/bbrc.1997.8097. PMID 9480811.
• Schaertl S, Konrad M, Geeves MA (1998). "Substrate specificity of human nucleoside-diphosphate kinase revealed by transient kinetic analysis". J. Biol. Chem. 273 (10): 5662–9. doi:10.1074/jbc.273.10.5662. PMID 9488696.
• Willems R, Van Bockstaele DR, Lardon F, Lenjou M, Nijs G, Snoeck HW, Berneman ZN, Slegers H (1998). "Decrease in nucleoside diphosphate kinase (NDPK/nm23) expression during hematopoietic maturation". J. Biol. Chem. 273 (22): 13663–8. doi:10.1074/jbc.273.22.13663. PMID 9593706.
• Manda R, Kohno T, Matsuno Y, Takenoshita S, Kuwano H, Yokota J (1999). "Identification of genes (SPON2 and C20orf2) differentially expressed between cancerous and noncancerous lung cells by mRNA differential display". Genomics 61 (1): 5–14. doi:10.1006/geno.1999.5939. PMID 10512675.