Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTHBS98)

• DTT Name: Nucleophosmin (NPM1)
• Synonyms: Numatrin; Nucleolar protein NO38; Nucleolar phosphoprotein B23; NPM
• Gene Name: NPM1
• DTT Type: Clinical trial target; [1]
• UniProt ID: NPM_HUMAN
• TTD ID: T45591
• Sequence:
  MEDSMDMDMSPLRPQNYLFGCELKADKDYHFKVDNDENEHQLSLRTVSLGAGAKDELHIV
  EAEAMNYEGSPIKVTLATLKMSVQPTVSLGGFEITPPVVLRLKCGSGPVHISGQHLVAVE
  EDAESEDEEEEDVKLLSISGKRSAPGGGSKVPQKKVKLAADEDDDDDDEEDDDEDDDDDD
  FDDEEAEEKAPVKKSIRDTPAKNAQKSNQNGKDSKPSSTPRSKGQESFKKQEKTPKTPKG
  PSSVEDIKAKMQASIEKGGSLPKVEAKFINYVKNCFRMTDQEAIQDLWQWRKSL
• 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.
• Reactome Pathway:
  SUMOylation of transcription cofactors (R-HSA-3899300)
  Deposition of new CENPA-containing nucleosomes at the centromere (R-HSA-606279)
  TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain (R-HSA-6804115)
  TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation (R-HSA-8869496)
  ALK mutants bind TKIs (R-HSA-9700645)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Nuclear events stimulated by ALK signaling in cancer (R-HSA-9725371)
  Nuclear import of Rev protein (R-HSA-180746)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IPP-204106	DM8E3N6	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[1]

References

• [1] Company report (ImmuPharma)