Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T42533
(Former ID: TTDI00226)
|
|||||
| Target Name |
Nucleoside diphosphate kinase A (NM23-H1)
|
|||||
| Synonyms |
nm23H1; Tumor metastatic processassociated protein; Tumor metastatic process-associated protein; NM23; NDPKA; NDP kinase A; NDK A; Metastasis inhibition factor nm23; Granzyme Aactivated DNase; Granzyme A-activated DNase; GAAD
Click to Show/Hide
|
|||||
| Gene Name |
NME1
|
|||||
| Target Type |
Literature-reported target
|
[1] | ||||
| Function |
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. Major role in the synthesis of nucleoside triphosphates other than ATP.
Click to Show/Hide
|
|||||
| BioChemical Class |
Kinase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 2.7.4.6
|
|||||
| Sequence |
MANCERTFIAIKPDGVQRGLVGEIIKRFEQKGFRLVGLKFMQASEDLLKEHYVDLKDRPF
FAGLVKYMHSGPVVAMVWEGLNVVKTGRVMLGETNPADSKPGTIRGDFCIQVGRNIIHGS DSVESAEKEIGLWFHPEELVDYTSCAQNWIYE Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T92X7D | |||||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | X-ray structure of human nucleoside diphosphate kinase A complexed with ADP at 2 A resolution | PDB:1UCN | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
ANCERTFIAI
11 KPDGVQRGLV21 GEIIKRFEQK31 GFRLVGLKFM41 QASEDLLKEH51 YVDLKDRPWF 61 AGLVKYMHSG71 PVVAMVWEGL81 NVVKTGRVML91 GETNPADSKP101 GTIRGDFCIQ 111 VGRNIIGGSD121 SVESAEKEIG131 LWFHPEELVD141 YTSCAQNWIY151 E |
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 4-[5-(3-Methoxyphenyl)-3-(prop-2-yn-1-yl)imidazol-4-yl]phenyl sulfurofluoridate | Ligand Info | |||||
| Structure Description | Structure of NME1 covalently conjugated to imidazole fluorosulfate | PDB:5UI4 | ||||
| Method | X-ray diffraction | Resolution | 2.75 Å | Mutation | No | [3] |
| PDB Sequence |
NCERTFIAIK
12 PDGVQRGLVG22 EIIKRFEQKG32 FRLVGLKFMQ42 ASEDLLKEHY52 VDLKDRPFFA 62 GLVKYMHSGP72 VVAMVWEGLN82 VVKTGRVMLG92 ETNPADSKPG102 TIRGDFCIQV 112 GRNIIHGSDS122 VESAEKEIGL132 WFHPEELVDY142 TSCAQNWIY
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Purine metabolism | hsa00230 | Affiliated Target |
|
| Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
| Pyrimidine metabolism | hsa00240 | Affiliated Target |
|
| Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
| Drug metabolism - other enzymes | hsa00983 | Affiliated Target |
|
| Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy | ||
| Degree | 14 | Degree centrality | 1.50E-03 | Betweenness centrality | 1.63E-03 |
|---|---|---|---|---|---|
| Closeness centrality | 2.21E-01 | Radiality | 1.39E+01 | Clustering coefficient | 9.89E-02 |
| Neighborhood connectivity | 1.36E+01 | Topological coefficient | 8.98E-02 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-interacting Proteins | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Metastasis suppressor Nm23-H1 inhibits STAT3 signaling via a negative feedback mechanism. Biochem Biophys Res Commun. 2013 May 10;434(3):541-6. | |||||
| REF 2 | Nucleotide binding to nucleoside diphosphate kinases: X-ray structure of human NDPK-A in complex with ADP and comparison to protein kinases. J Mol Biol. 2003 Sep 26;332(4):915-26. | |||||
| REF 3 | Inverse Drug Discovery Strategy To Identify Proteins That Are Targeted by Latent Electrophiles As Exemplified by Aryl Fluorosulfates. J Am Chem Soc. 2018 Jan 10;140(1):200-210. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.