Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

NPM1 (P06748) - Overview - Molecular Target Synopsis

Protein


NPM1, Nucleophosmin
UniProt P06748

Also Known as NPM_HUMAN, NPM1, NPM

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. 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 (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). Decamer formed by two pentameric rings associated in a head-to-head fashion (By similarity). Disulfide-linked dimers under certain conditions (PubMed:25818168). The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70 (By similarity). Interacts with NSUN2 and SENP3. Interacts with the methylated form of RPS10. Interacts (via N-terminal domain) with APEX1; the interaction is RNA-dependent and decreases in hydrogen peroxide-damaged cells. Interacts with isoform 1 of NEK2. Interacts with ROCK2 and BRCA2. Interacts with RPGR. Interacts with CENPW. Interacts with EIF2AK2/PKR. Interacts with CEBPA (isoform 4) (PubMed:20075868). Interacts with DDX31; this interaction prevents interaction between NPM1 and HDM2 (PubMed:23019224). Interacts with MYC; competitive with NOP53 (PubMed:25956029). Interacts with NOP53; the interaction is direct and competitive with MYC (PubMed:25956029). Interacts with LRRC34 (By similarity). Interacts with RRP1B (PubMed:19710015, PubMed:20926688).

5EHD
CRYSTAL STRUCTURE OF HUMAN NUCLEOPHOSMIN-CORE IN COMPLEX WITH CYTOCHROME C
RCSB/PDB
Inspect Structure
See all 3D Structures for NPM1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: NPM1 is active in the following subcellular-locations: centrosome, cytoplasm, cytoskeleton, microtubule organizing center, nucleolus, nucleoplasm, nucleus.
GO terms: NPM1 is active in the following subcellular-locations: centrosome, cytoplasm, cytosol, focal adhesion, membrane, nucleolus, nucleoplasm, nucleus, protein-containing complex, protein-DNA complex, ribonucleoprotein complex, spindle pole centrosome.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project NPM1 has gain in 2 cell-lines, loss in 3 cell-lines and no signal in 1000 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: NCI_H460, HL_60, MCF7

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: RKN, SNU-423, UKE-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HMEC, HSMM

(see details)

RNA Interference


NPM1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: . (see details)

3D Structures


For NPM1 there are:
5 structures (37 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


NPM1 has been screened with 68 compounds (106 bioactivities), 30 compounds have bioactivities that show binding affinity of <= 500nM (32 bioactivities). (see details)