NME2: A Multifunctional Metastasis Suppressor and Nucleoside Diphosphate Kinase
Comprehensive gene card for NME2 (NM23-H2), covering its role in cancer, development, and transcriptional regulation.
Gene Information Card
| Symbol | NME2 |
|---|---|
| Full Name | NME/NM23 nucleoside diphosphate kinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.33 |
| NCBI Gene ID | 4831 ncbi.nlm.nih.gov/gene/4831 |
| Ensembl ID | ENSG00000111052 |
| UniProt ID | P22392 |
| OMIM ID | 156490 |
| HGNC ID | 7853 |
| Aliases | NM23-H2, NM23B, NDPKB, NME2L1 |
Description
NME2 (NME/NM23 nucleoside diphosphate kinase 2) encodes the B isoform of the nucleoside diphosphate kinase (NDPK) family. The protein is a hexameric enzyme that catalyzes the transfer of gamma-phosphate from nucleoside triphosphates to nucleoside diphosphates, maintaining cellular nucleotide pools. Beyond its enzymatic role, NME2 functions as a transcription factor, binding to the nuclease-hypersensitive element (NHE) of the c-Myc promoter and regulating gene expression. It is a well-established metastasis suppressor; reduced expression correlates with high metastatic potential in several cancers. NME2 also participates in DNA repair, differentiation, and signal transduction.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast carcinoma | Loss of NME2 expression promotes metastasis; reduced NDPK activity correlates with aggressive disease | ClinVar, COSMIC, PMID: 10646847 |
| Colorectal cancer | Downregulation of NME2 associated with lymph node metastasis and poor prognosis | COSMIC, PMID: 15604233 |
| Melanoma | NME2 mutations and reduced expression linked to increased metastatic potential | COSMIC, PMID: 10488074 |
| Neuroblastoma | NME2 expression inversely correlates with tumor stage and MYCN amplification | PMID: 10646847 |
| Hepatocellular carcinoma | NME2 suppresses invasion and migration; promoter methylation silences expression | PMID: 21317919 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 45.2 | High |
| Heart | 38.1 | High |
| Skeletal muscle | 35.6 | High |
| Kidney | 30.4 | Medium |
| Brain | 22.8 | Medium |
| Lung | 18.5 | Medium |
| Pancreas | 12.3 | Low |
| Spleen | 10.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 52.3 | Embryonic kidney; high NME2 expression |
| HeLa | 48.7 | Cervical carcinoma; moderate expression |
| MCF7 | 35.2 | Breast cancer; reduced vs normal breast |
| A549 | 29.8 | Lung adenocarcinoma; moderate |
| HepG2 | 44.1 | Hepatocellular carcinoma; high |
| SK-MEL-28 | 18.4 | Melanoma; low expression correlates with metastasis |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.97C>T (p.Arg33Trp) | Missense | Rare (0.01%) | Reduced NDPK activity; possible loss of metastasis suppression |
| c.145G>A (p.Gly49Ser) | Missense | Rare (0.005%) | Altered hexamer stability; functional impact unclear |
| c.286C>T (p.Arg96Cys) | Missense | Rare (0.008%) | Impaired nucleotide binding; loss of function |
| c.373G>A (p.Gly125Arg) | Missense | Rare (0.003%) | Disrupts active site; reduced catalytic activity |
| c.418_420del (p.Lys140del) | In-frame deletion | Rare (0.002%) | Altered protein conformation; potential dominant-negative effect |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the active site (e.g., p.Gly125Arg) or that destabilize the hexamer (e.g., p.Gly49Ser) reduce NDPK activity and metastasis suppression.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in NME2.
Dominant Negative (DN)
In-frame deletions (e.g., p.Lys140del) may interfere with hexamer assembly, potentially acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Nucleotide metabolism (NDPK pathway)
• c-Myc transcription factor network
• p53 signaling pathway (indirect)
• GTP biosynthesis
• Pyrimidine metabolism
Protein Summary
NME2 is a 152-amino acid protein (17.3 kDa) that forms a hexameric complex. Each monomer contains a conserved NDPK domain with a histidine residue (His118) that acts as a phosphoryl acceptor. The protein localizes to both the cytoplasm and nucleus. In the nucleus, NME2 binds to the nuclease-hypersensitive element (NHE) of the c-Myc promoter, acting as a transcriptional activator. Its metastasis suppressor function is independent of NDPK activity and involves interaction with proteins such as KSR1 and Tiam1, modulating MAPK and Rac signaling. Post-translational modifications include phosphorylation and acetylation, which regulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NME2 Knockout HEK293 Cell Line | EDJ-KQ50482 | Human | 4831 | Details Get a Quote |
| NME1-NME2 Knockout HEK293 Cell Line | EDJ-KQ52395 | Human | 654364 | Details Get a Quote |
| NME2 Knockout HeLa Cell Line | EDJ-KQ54000 | Human | 4831 | Details Get a Quote |
| NME1-NME2 Knockout HeLa Cell Line | EDJ-KQ60668 | Human | 654364 | Details Get a Quote |
| NME2 Knockout A-549 Cell Line | EDJ-KQ62493 | Human | 4831 | Details Get a Quote |
| NME1-NME2 Knockout A-549 Cell Line | EDJ-KQ69142 | Human | 654364 | Details Get a Quote |
| NME2 Knockout HCT 116 Cell Line | EDJ-KQ70959 | Human | 4831 | Details Get a Quote |
| NME1-NME2 Knockout HCT 116 Cell Line | EDJ-KQ77494 | Human | 654364 | Details Get a Quote |
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