NME1

Nucleoside diphosphate kinase A is an enzyme that in humans is encoded by the NME1 gene.[4] It is thought to be a metastasis suppressor.

NME1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1JXV, 1UCN, 2HVD, 2HVE, 3L7U, 4ENO
Identifiers
Aliases	NME1, AWD, GAAD, NB, NBS, NDKA, NDPK-A, NDPKA, NM23, NM23-H1, NME/NM23 nucleoside diphosphate kinase 1
External IDs	OMIM: 156490 MGI: 97355 HomoloGene: 128514 GeneCards: NME1
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.33 Start 51,153,536 bp[1] End 51,162,428 bp[1]
Gene ontology Molecular function • transferase activity • nucleotide binding • deoxyribonuclease activity • ribosomal small subunit binding • GTP binding • metal ion binding • kinase activity • GO:0001948 protein binding • identical protein binding • ATP binding • magnesium ion binding • nucleoside diphosphate kinase activity • RNA binding • RNA polymerase II regulatory region sequence-specific DNA binding • single-stranded DNA binding • intermediate filament binding • enzyme binding • protein kinase binding • gamma-tubulin binding Cellular component • ruffle membrane • extracellular exosome • cell nucleus • cytoplasm • mitochondrial outer membrane • centrosome • cytosol • intermediate filament • membrane • perinuclear region of cytoplasm • mitochondrion • myelin Biological process • UTP biosynthetic process • regulation of apoptotic process • cell differentiation • nucleobase-containing small molecule interconversion • CTP biosynthetic process • endocytosis • phosphorylation • positive regulation of epithelial cell proliferation • nucleotide metabolic process • nucleoside diphosphate phosphorylation • nervous system development • positive regulation of DNA binding • GTP biosynthetic process • negative regulation of cell proliferation • DNA metabolic process • negative regulation of myeloid leukocyte differentiation • negative regulation of gene expression • positive regulation of neuron projection development • response to amine • hippocampus development • response to testosterone • cellular response to drug • response to drug • response to cAMP • cellular response to glucose stimulus • cellular response to fatty acid • lactation • mammary gland development Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4830	18102
Ensembl	ENSG00000239672	n/a
UniProt	P15531	P15532
RefSeq (mRNA)	NM_198175 NM_000269	NM_008704 NM_001378854
RefSeq (protein)	NP_000260 NP_937818	NP_032730 NP_001365783
Location (UCSC)	Chr 17: 51.15 – 51.16 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

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.[5]

Interactions

NME1 has been shown to interact with:

• Aurora A kinase,[6]
• CD29[7]
• NME3,[8][9]
• Protein SET,[10]
• RAR-related orphan receptor alpha,[11]
• RAR-related orphan receptor beta,[11] and
• TERF1.[12]

See also

• Nucleoside-diphosphate kinase

References

1. GRCh38: Ensembl release 89: ENSG00000239672 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. 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.
5. "Entrez Gene: NME1 non-metastatic cells 1, protein (NM23A) expressed in".
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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" (PDF). 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" (PDF). 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.