Nucleoside diphosphate kinase B (NME2)
The protein contains 152 amino acids for an estimated molecular weight of 17298 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 (By similarity). Negatively regulates Rho activity by interacting with AKAP13/LBC (PubMed:15249197). Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically (PubMed:8392752, PubMed:19435876). Binds to both single-stranded guanine- and cytosine-rich strands within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter. Does not bind to duplex NHE III(1) (PubMed:19435876). Has G-quadruplex (G4) DNA-binding activity, which is independent of its nucleotide-binding and kinase activity. Binds both folded and unfolded G4 with similar low nanomolar affinities. Stabilizes folded G4s regardless of whether they are prefolded or not (PubMed:25679041). Exhibits histidine protein kinase activity (PubMed:20946858). (updated: Nov. 7, 2018)
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.
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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Biological Process
Adenylate cyclase-activating G protein-coupled receptor signaling pathway
Cell adhesion
Cellular response to drug
Cellular response to fatty acid
Cellular response to glucose stimulus
Cellular response to oxidative stress
CTP biosynthetic process
GTP biosynthetic process
Hippocampus development
Integrin-mediated signaling pathway
Negative regulation of apoptotic process
Negative regulation of gene expression
Negative regulation of myeloid leukocyte differentiation
Neutrophil degranulation
Nucleobase-containing small molecule interconversion
Nucleobase-containing small molecule metabolic process
Nucleoside diphosphate phosphorylation
Nucleoside triphosphate biosynthetic process
Positive regulation of epithelial cell proliferation
Positive regulation of keratinocyte differentiation
Positive regulation of neuron projection development
Positive regulation of transcription by RNA polymerase II
Positive regulation of transcription, DNA-templated
Protein autophosphorylation
Protein complex oligomerization
Purine nucleotide metabolic process
Pyrimidine nucleotide metabolic process
Regulation of apoptotic process
Regulation of epidermis development
Regulation of transcription, DNA-templated
Response to amine
Response to cAMP
Response to growth hormone
Response to testosterone
Small molecule metabolic process
Transcription, DNA-templated
UTP biosynthetic process
Cellular Component
Cell periphery
Centrosome
Cytoplasm
Cytosol
Extracellular exosome
Extracellular region
Ficolin-1-rich granule lumen
Intermediate filament
Lamellipodium
Membrane
Mitochondrial membrane
Mitochondrion
Nucleus
Obsolete cell
Perinuclear region of cytoplasm
Ruffle
Secretory granule lumen
Molecular Function
ATP binding
DNA binding
DNA-binding transcription factor activity
Drug binding
Enzyme binding
Fatty acid binding
G-quadruplex DNA binding
GDP binding
Identical protein binding
Intermediate filament binding
Metal ion binding
Nucleoside diphosphate kinase activity
Protein histidine kinase activity
Protein serine/threonine kinase activity
RNA polymerase II transcription regulatory region sequence-specific DNA binding
Single-stranded DNA binding
Transcription coactivator activity
The reference OMIM entry for this protein is 156491
Nonmetastatic cells 2, protein expressed in; nme2
Metastasis inhibition factor nm23b
Nonmetastatic protein 23b; nm23b
Nonmetastatic protein 23, homolog 2; nm23h2
Nucleoside diphosphate kinase-b; ndpkb
CLONING
NM23 is a heterodimeric protein that acts as a nucleoside diphosphate (NDP) kinase. Gilles et al. (1991) identified NME1 (156490) and NME2 as the A and B polypeptide chains of the NM23 enzyme. Each chain consists of 152 amino acids. NME2 is identical to the beta subunit of human erythrocyte NDP kinase. NDP kinases are involved in the synthesis of nucleoside triphosphates, and the NM23 protein may act in the regulation of signal transduction by complexing with G proteins, causing activation/inactivation of developmental pathways (Gilles et al., 1991). Stahl et al. (1991) identified the NME2 gene, which they referred to as nm23-H2. Its cDNA predicts a 17-kD protein with 88% identity to nm23-H1. The nm23-H1 gene also shares a significant homology with nucleoside diphosphate kinases and the Drosophila developmental gene awd. Northern blot hybridization indicated that the expression of the nm23-H1 gene is reduced to a lesser extent in tumor cells of high metastatic potential than is nm23-H1. Both proteins are independently active nucleoside diphosphate kinases and readily form intra- and intermolecular disulfide bonds. Using Northern blot analysis, Masse et al. (2002) detected high expression of mouse Nme2, which they called nm23-M2, in heart, liver, and kidney, with intermediate expression in skeletal muscle. Little to no expression was detected in other mouse tissues examined. In situ hybridization of 15-day postcoitum mouse embryos showed ubiquitous Nme2 expression. By EST database analysis, Valentijn et al. (2006) identified a transcript that starts from the NM23H1 promoter and reads through the neighboring NM23H2 gene. This transcript, which they called NM23LV (NM23 long variant), is ubiquitously expressed and encodes a protein with most of the NM23H1 amino acids and all of the NM23H2 amino acids. See 156490 for further information on the NM23LV read-through transcript.GENE FUNCTION
Srivastava et al. (2006) demonstrated that the 14 C-terminal amino acids of KCa3.1 (KCNN4; 602754) that mediate the regulation of KCa3.1 by phosphatidylinositol 3-phosphate (PI(3)P) recruit NDPKB to KCa3.1. NDPKB then activates KCa3.1 by phosphorylating residue H358, which is present in the same C-terminal 14-amino acid region. SiRNA treatment of NDPBK in CD4+ T cells resulted in a marked reduction of KCa3.1 channel activity. Srivastava et al. (2006) concluded that histidine phosphorylation regulates KCa3.1 channel activity and that NDPBK is critical to the channel activity and the activation of CD4 T cells. Boissan et al. (2014) found that knockdown of nucleoside diphosphate kinases (NDPKs) NM23H1/H2 (NME1; 156490/NME2), which produce GTP through ATP-driven conversion of GDP, inhibited dynamin-mediated endocytosis. NM23H1/H2 localized at clathrin-coated pits and interacted with the proline-rich domain of dynamin. In vitro, NM23H1/H2 were recruited to dynamin-induced tubules, stimulated GTP-loading on dynamin, and triggered fission in the presence of ATP and GDP. NM23H4 (NME4; 601818), a mitochondria-specific NDPK, colocalized with mitochondrial dynamin-like OPA1 (605290), which is involved in mitochondria inner membrane fusion, and increased GTP-loading on OPA1. Like OPA1 loss of function, silencing of NM23H4 but not NM23H1/H2 resulted in mitochondrial fragmentation, reflecting fusion defects. Boissan et al. (2014) concluded that NDPKs interact with and provide GTP to dynamins, allowing these motor proteins to work with high t ... More on the omim web site
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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 NME2
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 156491 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed