Nomenclature
Short Name:
NM23
Full Name:
Alias:
- EC 2.7.4.6
- Metastasis inhibition factor nm23
- NM23-H1
- NME1
- Non-metastatic cells 1, protein (NM23A) expressed in
- Tumor metastatic process-associated protein; Tumour metastatic process-associated protei
- NDK A
- NDKA
- NDP kinase A
- NDPKA
Classification
Type:
Group:
Family:
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
17,149
# Amino Acids:
# mRNA Isoforms:
2
mRNA Isoforms:
19,654 Da (177 AA; P15531-2); 17,149 Da (152 AA; P15531)
4D Structure:
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K12, K26, K31, K49, K56, K66, K85, K100.
Serine phosphorylated:
S44, S99, S120, S122, S125, S144.
Threonine phosphorylated:
T94, T103.
Tyrosine phosphorylated:
Y52, Y67.
Ubiquitinated:
K12, K26, K31, K39, K49, K56, K66, K85, K100.
Distribution
Based on gene microarray analysis from the NCBI
Human Tissue Distribution
% Max Expression:
Mean Expression:
Number of Samples:
Standard Deviation:
% Max Expression:
Mean Expression:
Number of Samples:
Standard Deviation:
3
237
6
251
7
516
3
19
2
159
4
70
50
3611
19
2733
5
389
3
6
9
625
12
474
4
284
3
18
100
7176
17
7721
4
304
3
4
3
215
7
111
5
360
7
146
7
470
18
293
2
164
4
77
3
221
3
5
7
485
3
16
-
-
-
-
79
5665
12
11811
4
268
7
112
2
165
7
37
4
279
3
5
4
308
7
131
2
162
7
60
4
311
4
178
2
129
7
50
4
298
7
105
94
6739
16
6525
5
362
7
120
3
229
7
81
3
251
7
86
-
-
-
-
23
1629
12
52
0
0
6
0
88
6283
37
1711
-
-
-
-
1.3
94
18
106
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
41.2
45.1
99
62
62.5
-
-
-
93
-
-
-
88.8
92.7
93
-
-
-
94
96
94
95.3
97.3
95
-
-
-
52
53.9
-
87.5
94.1
84.5
81.8
91.5
-
84.3
90.8
85
-
-
-
77.1
86.9
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
63
40.9
50.6
64
58.8
76.4
-
62.5
77.6
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Regulation
Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
Known Upstream Kinases
For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET
predictions.
Based on in vitro and/or in vivo phosphorylation data
| Kinase Short Name | UniProt ID (Human) | Phosphosite Location | Phosphosite Sequence | Effect of Phosphorylation |
|---|
Known Downstream Substrates
For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET
predictions.
Based on in vitro and/or in vivo phosphorylation data
| Substrate Short Name | UniProt ID (Human) | Phosphosite Location | Phosphosite Sequence | Effect of Phosphorylation |
|---|
| Ksr1 (KSR) | Q8IVT5 | S404 | TRLRRTESVPSDINN | |
| Ksr1 (KSR) | Q8IVT5 | S447 | LDSSSNPSSTTSSTP | |
| NM23 (NME1) | P15531 | H118 | QVGRNIIHGSDSVES | + |
| NM23 (NME1) | P15531 | S120 | GRNIIHGSDSVESAE | |
| NM23 (NME1) | P15531 | S44 | GLKFMQASEDLLKEH |
Disease Linkage
General Disease Association:
Cancer, genetic disorders
Specific Diseases (Non-cancerous):
Malignant hyperthermia; Malignant hyperthermia susceptibility
Comments:
Malignant hyperthermia, also known as anesthesia related hyperthermia, is a genetic disease characterized by a severe reaction to certain drugs that are often used for anesthesia purposes during surgical procedures. Symptoms of this disease include hyperthermia, rapid heart rate (tachycardia), rapid breathing, respiratory acidosis, muscle rigidity, and breakdown of muscle (rhabdomyolysis). Mutations in several genes, including NM23, which are inherited in a dominant autosomal manner are associated with the pathogenesis of the disease.
Specific Cancer Types:
Neuroblastomas (NB); Acute monocytic leukemias (AMoL); Laryngeal carcinomas; Monocytic leukemias; Laryngeal squamous cell carcinomas; Cervical adenocarcinomas; Keratoacanthomas; Smooth muscle tumours; Cervical intraepithelial neoplasias; Soft tissue sarcomas; Breast cancer; Ovarian cancer; Lung cancer (LC); Hepatocellular carcinomas; Follicular thyroid carcinomas; Adenocarcinomas; Anal canal carcinomas; Peripheral T-cell lymphomas; Papillary adenocarcinomas; Lung giant cell carcinomas; Skin melanomas; Gallbladder adenocarcinomas; Neuroblastomas, susceptibility; ALK-related neuroblastomas susceptibility; Acute myeloid leukemias (AML)
Comments:
NM23 appears to be a tumour suppressor protein (TSP). Loss-of-function mutations in the NM23 protein have been observed in various human cancers types. Several observations suggests that NM23 may function as an inhibitor of the tumour metatastic process. Additionally, expression of the NM23 gene may be related to tumour differentiation as low levels of transcript expression is correlated with reduced efficacy of differentiation in breast carcinoma, pancreatic adenocarcinoma, and ovarian carcinoma cancer specimens.
Gene Expression in Cancers:
The COSMIC website notes an up-regulated expression score for NM23 in diverse human cancers of 606, which is 1.3-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 3 for this protein kinase in human cancers was 0.1-fold of the average score of 60 for the human protein kinases.
Mutagenesis Experiments:
Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.05 % in 24640 diverse cancer specimens. This rate is only -29 % lower than the average rate of 0.075 % calculated for human protein kinases in general.
Mutation Rate in Specific Cancers:
Highest percent mutation rates per 100 amino acids length in human cancers: 0.33 % in 603 endometrium cancers tested; 0.23 % in 864 skin cancers tested; 0.21 % in 1270 large intestine cancers tested; 0.2 % in 1634 lung cancers tested; 0.12 % in 548 urinary tract cancers tested; 0.09 % in 710 oesophagus cancers tested; 0.09 % in 1512 liver cancers tested; 0.05 % in 1276 kidney cancers tested.
Frequency of Mutated Sites:
None > 2 in 19,923 cancer specimens
Comments:
No deletions, insertions or complex mutations are noted on the COSMIC website.