Target Information
Target General Information | Top | |||||
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Target ID |
T45591
(Former ID: TTDI02137)
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Target Name |
Nucleophosmin (NPM1)
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Synonyms |
Numatrin; Nucleolar protein NO38; Nucleolar phosphoprotein B23; NPM
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Gene Name |
NPM1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade. In complex with MYC enhances the transcription of MYC target genes. Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF.
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UniProt ID | ||||||
Sequence |
MEDSMDMDMSPLRPQNYLFGCELKADKDYHFKVDNDENEHQLSLRTVSLGAGAKDELHIV
EAEAMNYEGSPIKVTLATLKMSVQPTVSLGGFEITPPVVLRLKCGSGPVHISGQHLVAVE EDAESEDEEEEDVKLLSISGKRSAPGGGSKVPQKKVKLAADEDDDDDDEEDDDEDDDDDD FDDEEAEEKAPVKKSIRDTPAKNAQKSNQNGKDSKPSSTPRSKGQESFKKQEKTPKTPKG PSSVEDIKAKMQASIEKGGSLPKVEAKFINYVKNCFRMTDQEAIQDLWQWRKSL Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
HIT2.0 ID | T81I6O |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | IPP-204106 | Drug Info | Phase 1/2 | Solid tumour/cancer | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | IPP-204106 | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: L-serine-O-phosphate | Ligand Info | |||||
Structure Description | Crystal structure of 14-3-3 sigma in complex with NPM1 phosphopeptide and stabilizer Fusicoccin-A | PDB:7OBH | ||||
Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
PDB Sequence |
QWRKL
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Ligand Name: Fusicoccin | Ligand Info | |||||
Structure Description | Crystal structure of 14-3-3 sigma in complex with NPM1 phosphopeptide and stabilizer Fusicoccin-A | PDB:7OBH | ||||
Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
PDB Sequence |
QWRKL
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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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).
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
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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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.
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Degree | 19 | Degree centrality | 2.04E-03 | Betweenness centrality | 1.80E-03 |
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Closeness centrality | 2.53E-01 | Radiality | 1.44E+01 | Clustering coefficient | 1.05E-01 |
Neighborhood connectivity | 4.96E+01 | Topological coefficient | 6.91E-02 | Eccentricity | 11 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-interacting Proteins |
Target Affiliated Biological Pathways | Top | |||||
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PID Pathway | [+] 4 PID Pathways | + | ||||
1 | Aurora B signaling | |||||
2 | Validated targets of C-MYC transcriptional activation | |||||
3 | HIF-1-alpha transcription factor network | |||||
4 | BARD1 signaling events | |||||
WikiPathways | [+] 2 WikiPathways | + | ||||
1 | Host Interactions of HIV factors | |||||
2 | Nucleosome assembly |
References | Top | |||||
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REF 1 | Company report (ImmuPharma) | |||||
REF 2 | ClinicalTrials.gov (NCT01711398) Dose-finding Adaptive Phase I/IIa Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of IPP-204106N on Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
REF 3 | IFN-alpha primes cancer cells for Fusicoccin-induced cell death via 14-3-3 PPI stabilization. Cell Chem Biol. 2023 Jun 15;30(6):573-590.e6. |
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