Nucleoside diphosphate kinase A (NME1)
The protein contains 152 amino acids for an estimated molecular weight of 17149 Da.
Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. During GZMA-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| a neuroblastoma sample |
Biological Process
Cell differentiation
Cellular response to drug
Cellular response to fatty acid
Cellular response to glucose stimulus
CTP biosynthetic process
DNA catabolic process
Endocytosis
GTP biosynthetic process
Hippocampus development
Lactation
Negative regulation of cell population proliferation
Negative regulation of gene expression
Negative regulation of myeloid leukocyte differentiation
Nervous system development
Nucleobase-containing small molecule interconversion
Nucleobase-containing small molecule metabolic process
Nucleoside triphosphate biosynthetic process
Positive regulation of DNA binding
Positive regulation of epithelial cell proliferation
Positive regulation of neuron projection development
Purine nucleotide metabolic process
Pyrimidine nucleotide metabolic process
Regulation of apoptotic process
Response to amine
Response to cAMP
Response to testosterone
Small molecule metabolic process
UTP biosynthetic process
Cellular Component
Centrosome
Cytoplasm
Cytosol
Extracellular exosome
Intermediate filament
Membrane
Mitochondrial outer membrane
Mitochondrion
Myelin sheath
Nucleus
Obsolete cell
Perinuclear region of cytoplasm
Ruffle membrane
Molecular Function
ATP binding
Deoxyribonuclease activity
Enzyme binding
Gamma-tubulin binding
GTP binding
Identical protein binding
Intermediate filament binding
Magnesium ion binding
Nucleoside diphosphate kinase activity
Poly(A) RNA binding
Ribosomal small subunit binding
RNA binding
RNA polymerase II transcription regulatory region sequence-specific DNA binding
Single-stranded DNA binding
The reference OMIM entry for this protein is 156490
Nonmetastatic cells 1, protein expressed in; nme1
Metastasis inhibition factor nm23
Nonmetastatic protein 23; nm23
Nonmetastatic protein 23, homolog 1; nm23h1
Nucleoside diphosphate kinase-a; ndpka
Gzma-activated dnase; gaad
Awd, drosophi
CLONING
Steeg et al. (1988) gave the name NM23 to a gene they cloned from a murine melanoma cell line. Expression of the gene correlated inversely with metastatic potential. NM23 RNA levels are highest in cell lines with low metastatic potential. RNA levels did not correlate with cell sensitivity to host immune responses. The authors therefore hypothesized that expression of this gene may be associated with intrinsic aggressiveness of the line. Several observations suggested that NM23 activity may be correlated with inhibition of the tumor metastatic process. Bevilacqua et al. (1989) concluded that NM23 RNA levels are differentially expressed in human breast tumors and that low NM23 RNA levels are associated with histopathologic indications of high metastatic potential. The product of the NM23 gene is a nucleoside diphosphate kinase, which has been designated p19/nm23. Keim et al. (1992) presented evidence that the expression of the gene is related to cell proliferative activity. Rosengard et al. (1989) found that the human NM23 protein has sequence homology over the entire translated region with a developmentally related protein in Drosophila encoded by the 'abnormal wing discs' (awd) gene. Mutations in awd cause abnormal tissue morphology and necrosis and widespread aberrant differentiation in Drosophila, analogous to the changes in malignant progression. Postel et al. (1993) reported evidence suggesting that the protein encoded by 1 of the 2 closely related NM23 genes (see NME2; 156491) may be a transcription factor. The gene that may be turned on is the MYC oncogene (190080). Although a dozen DNA binding proteins had been identified for the MYC gene, only one, called PuF (for purine-binding factor, because the DNA sequence it recognizes has a high content of purine bases), was known to regulate MYC transcription in vitro. PuF was identified by Postel and her colleagues (Postel et al., 1989; Postel, 1992) as a partially purified HeLa cell (human cervical carcinoma) factor that binds to a nuclease-hypersensitive element (NHE) at positions -142 to -115 of the human MYC P1 promoter and is necessary for efficient P1 and P2 transcription initiation in vitro. Postel et al. (1993) identified the human gene encoding PuF by screening a cervical carcinoma cell cDNA library with a DNA fragment containing PuF binding sites. DNA sequence analysis of recombinant PuF demonstrated perfect identity with the NM23 gene. Although no clear correlation has yet been established between overexpression of MYC and tumor metastasis, the inverse relation between MYC expression and cell differentiation is well documented. Furthermore, Okabe-Kado et al. (1992) identified a differentiation inhibiting factor in the mouse myeloid leukemia cells as a murine homolog of NM23. Findings leave the conundrum of how NM23 can be both a tumor suppressor and an activator of MYC. Gilles et al. (1991) showed that nucleoside diphosphate kinases A and B are identical to NM23-H1 and NM23-H2, respectively. The genes NME1 and NME2 encode 2 polypeptide chains that are responsible for heterogeneity of the hexameric enzyme. Using Northern blot analysis of several mouse tissues, Masse et al. (2002) found that mouse Nme1, which they called nm23-M1, was expressed as 2 transcripts due to the use of 2 alternate polyadenylation signals. Expression was highest in the central nervous system, liver, and kidney. In situ hybridization of 15-day postcoitum mouse embryos showed Nme1 expre ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for NME1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 156490 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed