NME1

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; OMA:NME1 - orthologs
Gene location (Human)
Chr.	Chromosome 17 (human)
End	51,162,428 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	93,859,347 bp
RNA expression pattern
	Top expressed in
	prefrontal cortex; ; hypothalamus; ; Brodmann area 9; ; superior frontal gyrus; ; islet of Langerhans; ; ganglionic eminence; ; right frontal lobe; ; hippocampus proper; ; primary visual cortex; ; cingulate gyrus;
	Top expressed in
	right kidney; ; epiblast; ; neural tube; ; proximal tubule; ; embryo; ; embryo; ; ganglionic eminence; ; dentate gyrus of hippocampal formation granule cell; ; morula; ; blastocyst;
	More reference expression data
	n/a
Gene ontology
Molecular function	transferase activity; nucleotide binding; deoxyribonuclease activity; ribosomal small subunit binding; GTP binding; metal ion binding; kinase activity; protein binding; identical protein binding; ATP binding; magnesium ion binding; nucleoside diphosphate kinase activity; RNA binding; RNA polymerase II transcription 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; nucleus; cytoplasm; mitochondrial outer membrane; centrosome; cytosol; intermediate filament; membrane; perinuclear region of cytoplasm; mitochondrion; myelin sheath;
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 population 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; response to cAMP; cellular response to glucose stimulus; cellular response to fatty acid; lactation; mammary gland development;
	Sources:Amigo / QuickGO
Orthologs
	4830
	18102
	ENSG00000239672
	ENSMUSG00000037601
	P15531
	P15532
	NM_198175; NM_000269
	NM_008704; NM_001378854
	NP_000260; NP_937818
	NP_032730; NP_001365783
	Wikidata
View/Edit Human	View/Edit Mouse

Nucleoside diphosphate kinase A is an enzyme that in humans is encoded by the NME1 gene.^[5] 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.^[6]

A bioinformatics study published in 2023 suggested that the NME1 gene might have a prognostic role in neuroblastoma.^[7]

Interactions

NME1 has been shown to interact with:

Aurora A kinase,^[8]
CD29^[9]
NME3,^[10]^[11]
Protein SET,^[12]
RAR-related orphan receptor alpha,^[13]
RAR-related orphan receptor beta,^[13] and
TERF1.^[14]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000239672 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000037601 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Dooley S, Seib T, Engel M, Theisinger B, Janz H, Piontek K, et al. (February 1994). "Isolation and characterization of the human genomic locus coding for the putative metastasis control gene nm23-H1". Human Genetics. 93 (1): 63–66. doi:10.1007/bf00218915. PMID 8270257. S2CID 6373221.
^ "Entrez Gene: NME1 non-metastatic cells 1, protein (NM23A) expressed in".
^ Chicco D, Sanavia T, Jurman G (March 2023). "Signature literature review reveals AHCY, DPYSL3, and NME1 as the most recurrent prognostic genes for neuroblastoma". BioData Mining. 16 (1) 7. doi:10.1186/s13040-023-00325-1. eISSN 1756-0381. PMC 9985261. PMID 36870971.
^ Du J, Hannon GJ (December 2002). "The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1". Nucleic Acids Research. 30 (24): 5465–5475. doi:10.1093/nar/gkf678. PMC 140054. PMID 12490715.
^ Fournier HN, Dupé-Manet S, Bouvard D, Lacombe ML, Marie C, Block MR, et al. (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". The Journal of Biological Chemistry. 277 (23): 20895–20902. doi:10.1074/jbc.M200200200. PMID 11919189.
^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
^ Negroni A, Venturelli D, Tanno B, Amendola R, Ransac S, Cesi V, et al. (September 2000). "Neuroblastoma specific effects of DR-nm23 and its mutant forms on differentiation and apoptosis". Cell Death and Differentiation. 7 (9): 843–850. doi:10.1038/sj.cdd.4400720. hdl:11380/695506. PMID 11042679.
^ Chakravarti D, Hong R (March 2003). "SET-ting the stage for life and death". Cell. 112 (5): 589–591. doi:10.1016/s0092-8674(03)00151-x. PMID 12628178. S2CID 16423565.
^ ^a ^b 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". Biochemical and Biophysical Research Communications. 227 (1): 82–87. doi:10.1006/bbrc.1996.1471. PMID 8858107.
^ Nosaka K, Kawahara M, Masuda M, Satomi Y, Nishino H (February 1998). "Association of nucleoside diphosphate kinase nm23-H2 with human telomeres". Biochemical and Biophysical Research Communications. 243 (2): 342–348. doi:10.1006/bbrc.1997.8097. PMID 9480811.

Freije JM, MacDonald NJ, Steeg PS (1998). "Nm23 and tumour metastasis: basic and translational advances". Biochemical Society Symposium. 63: 261–271. 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". Clinical & Experimental Metastasis. 19 (6): 465–476. doi:10.1023/A:1020396722860. PMID 12405283. S2CID 21876557.
Tee YT, Chen GD, Lin LY, Ko JL, Wang PH (2006). "Nm23-H1: a metastasis-associated gene". Taiwanese Journal of Obstetrics & Gynecology. 45 (2): 107–113. 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". The Journal of Biological Chemistry. 266 (14): 8784–8789. doi:10.1016/S0021-9258(18)31515-1. PMID 1851158.
Leone A, McBride OW, Weston A, Wang MG, Anglard P, Cropp CS, et al. (1991). "Somatic allelic deletion of nm23 in human cancer". Cancer Research. 51 (9): 2490–2493. PMID 2015608.
Hailat N, Keim DR, Melhem RF, Zhu XX, Eckerskorn C, Brodeur GM, et al. (1991). "High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification". The Journal of Clinical Investigation. 88 (1): 341–345. doi:10.1172/JCI115299. PMC 296039. PMID 2056128.
Rosengard AM, Krutzsch HC, Shearn A, Biggs JR, Barker E, Margulies IM, et al. (1989). "Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development". Nature. 342 (6246): 177–180. Bibcode:1989Natur.342..177R. doi:10.1038/342177a0. PMID 2509941. S2CID 4340066.
Wang L, Patel U, Ghosh L, Chen HC, Banerjee S (1993). "Mutation in the nm23 gene is associated with metastasis in colorectal cancer". Cancer Research. 53 (4): 717–720. PMID 7916650.
Chang CL, Zhu XX, Thoraval DH, Ungar D, Rawwas J, Hora N, et al. (1994). "Nm23-H1 mutation in neuroblastoma". Nature. 370 (6488): 335–336. Bibcode:1994Natur.370..335C. doi:10.1038/370335a0. hdl:2027.42/62612. PMID 8047138. S2CID 4356706.
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". The Journal of Biological Chemistry. 268 (34): 25780–25789. doi:10.1016/S0021-9258(19)74458-5. 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). New York, N.Y.: 478–480. Bibcode:1993Sci...261..478P. doi:10.1126/science.8392752. PMID 8392752.
Sudbrak R, Golla A, Hogan K, Powers P, Gregg R, Du Chesne I, et al. (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). Human Molecular Genetics. 2 (7): 857–862. doi:10.1093/hmg/2.7.857. PMID 8395939. S2CID 86750140. Archived from the original (PDF) on 2020-02-07.
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". The Journal of Biological Chemistry. 271 (41): 25107–25116. doi:10.1074/jbc.271.41.25107. PMID 8810265.
Schaertl S, Konrad M, Geeves MA (1998). "Substrate specificity of human nucleoside-diphosphate kinase revealed by transient kinetic analysis". The Journal of Biological Chemistry. 273 (10): 5662–5669. doi:10.1074/jbc.273.10.5662. PMID 9488696.
Willems R, Van Bockstaele DR, Lardon F, Lenjou M, Nijs G, Snoeck HW, et al. (1998). "Decrease in nucleoside diphosphate kinase (NDPK/nm23) expression during hematopoietic maturation". The Journal of Biological Chemistry. 273 (22): 13663–13668. 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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000239672 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000037601 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Dooley_1994-5] Dooley S, Seib T, Engel M, Theisinger B, Janz H, Piontek K, et al. (February 1994). "Isolation and characterization of the human genomic locus coding for the putative metastasis control gene nm23-H1". Human Genetics. 93 (1): 63–66. doi:10.1007/bf00218915. PMID 8270257. S2CID 6373221.

[entrez-6] "Entrez Gene: NME1 non-metastatic cells 1, protein (NM23A) expressed in".

[ChiccoSanaviaJurman2023-7] Chicco D, Sanavia T, Jurman G (March 2023). "Signature literature review reveals AHCY, DPYSL3, and NME1 as the most recurrent prognostic genes for neuroblastoma". BioData Mining. 16 (1) 7. doi:10.1186/s13040-023-00325-1. eISSN 1756-0381. PMC 9985261. PMID 36870971.

[Du_2002-8] Du J, Hannon GJ (December 2002). "The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1". Nucleic Acids Research. 30 (24): 5465–5475. doi:10.1093/nar/gkf678. PMC 140054. PMID 12490715.

[Fournier_2002-9] Fournier HN, Dupé-Manet S, Bouvard D, Lacombe ML, Marie C, Block MR, et al. (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". The Journal of Biological Chemistry. 277 (23): 20895–20902. doi:10.1074/jbc.M200200200. PMID 11919189.

[Rual_2005-10] Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

[Negroni_2000-11] Negroni A, Venturelli D, Tanno B, Amendola R, Ransac S, Cesi V, et al. (September 2000). "Neuroblastoma specific effects of DR-nm23 and its mutant forms on differentiation and apoptosis". Cell Death and Differentiation. 7 (9): 843–850. doi:10.1038/sj.cdd.4400720. hdl:11380/695506. PMID 11042679.

[Chakravarti_2003-12] Chakravarti D, Hong R (March 2003). "SET-ting the stage for life and death". Cell. 112 (5): 589–591. doi:10.1016/s0092-8674(03)00151-x. PMID 12628178. S2CID 16423565.

[Paravicini_1996-13] 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". Biochemical and Biophysical Research Communications. 227 (1): 82–87. doi:10.1006/bbrc.1996.1471. PMID 8858107.

[Nosaka_1998-14] Nosaka K, Kawahara M, Masuda M, Satomi Y, Nishino H (February 1998). "Association of nucleoside diphosphate kinase nm23-H2 with human telomeres". Biochemical and Biophysical Research Communications. 243 (2): 342–348. doi:10.1006/bbrc.1997.8097. PMID 9480811.

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NME1

Function

Interactions

See also

References

Further reading