Nucleoside diphosphate kinase 3 (NME3)
The protein contains 169 amino acids for an estimated molecular weight of 19015 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. Probably has a role in normal hematopoiesis by inhibition of granulocyte differentiation and induction of apoptosis. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
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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The reference OMIM entry for this protein is 601817
Nonmetastatic cells 3, protein expressed in; nme3
Dr-nm23
Nonmetastatic protein 23, homolog of; nm23h3
CLONING
Chronic myelogenous leukemia evolves in 2 clinically distinct stages: a chronic phase and a blast crisis phase. Venturelli et al. (1995) identified a cDNA clone, called DR-nm23 by them, which was differentially expressed in a blast-crisis cDNA library. The sequence shares approximately 70% similarity with the putative metastatic suppressor genes, nm23-H1 (NME1; 156490) and nm23-H2 (NME2; 156491). The gene encodes a 168-amino acid polypeptide with a predicted molecular mass of 18 kD. Using Northern blot analysis, Martinez et al. (1997) analyzed the level of NME3 mRNA in several human tumor cell lines. Abundant expression was detected in all solid tumor cell lines and in erythromyeloid cell lines. Lower expression was detected in lymphoid and monocytic cell lines. Fluorescence-tagged NME3 showed a cytoplasmic punctate localization following transfection in osteosarcoma cells. Masse et al. (2002) cloned mouse Nme3, which they called nm23-M3. The deduced 169-amino acid protein shares 88% identity with human NME3. Northern blot analysis of several mouse tissues detected a 0.9-kb transcript expressed at highest levels in liver and kidney, with moderate levels in heart, brain, spleen, and lung. Little to no expression was detected in other mouse tissues examined. In situ hybridization of 15-day postcoitum mouse embryos showed expression in nervous tissue and thymus.GENE FUNCTION
Venturelli et al. (1995) found that DR-nm23 mRNA was preferentially expressed at early stages of myeloid differentiation of highly purified CD34(+) cells. Its constitutive expression in a myeloid precursor line, which is growth-factor dependent for both proliferation and differentiation, resulted in inhibition of granulocytic differentiation induced by granulocyte colony-stimulating factor (138970) and caused apoptotic cell death. Venturelli et al. (1995) considered the results consistent with a role for the NME3 gene in normal hematopoiesis and raised the possibility that its overexpression contributes to differentiation arrest, a feature of blastic transformation in chronic myelogenous leukemia.GENE STRUCTURE
Martinez et al. (1997) determined that the NME3 gene contains 6 exons. The promoter region is GC rich and has a pyrimidine-rich initiator (Inr) element, but no TATA or CAAT boxes. There are putative binding sites for Sp1 (189906), AP2 (107580), MYB (189990), ETS (164720), GATA (see 305371) and HOX1 (see 142950). However, only AP2 was able to transactivate the promoter and to interact with 2 putative AP2 sites. Masse et al. (2002) determined that the mouse and human NME3 genes contain 5 exons and span about 1.0 kb. Their promoters, like those of other NME genes, contain several binding sites for AP2, NF1 (613113), Sp1, LEF1 (153245), and response elements to glucocorticoid receptors (138040). Masse et al. (2002) stated that NME3 has no pyrimidine-rich Inr sequences.MAPPING
By screening human-rodent hybrid cells lines and FISH, Martinez et al. (1997) mapped the NME3 gene to chromosome 16q13. ... More on the omim web site
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 601817 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).