NPM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LLH, 2P1B, 2VXD
Identifiers
Aliases	NPM1, B23, NPM, nucleophosmin (nucleolar phosphoprotein B23, numatrin), nucleophosmin, nucleophosmin 1
External IDs	OMIM: 164040 MGI: 106184 HomoloGene: 81697 GeneCards: NPM1
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q35.1 Start 171,387,116 bp[1] End 171,411,810 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 A4 Start 33,102,287 bp[2] End 33,113,206 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon canal of the cervix ganglionic eminence body of pancreas right uterine tube gastric mucosa left uterine tube gallbladder stromal cell of endometrium body of stomach Top expressed in morula secondary oocyte ovary yolk sac placenta uterus ganglionic eminence thymus neural tube spleen More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ribosomal large subunit binding protein homodimerization activity ribosomal small subunit binding unfolded protein binding transcription coactivator activity protein kinase inhibitor activity histone binding Tat protein binding NF-kappaB binding protein binding RNA binding protein heterodimerization activity nucleic acid binding protein kinase binding transcription factor binding rRNA binding protein N-terminus binding chromatin binding Cellular component cytoplasm membrane focal adhesion spindle pole centrosome nucleoplasm microtubule organizing center nucleolus cytoskeleton nucleus protein-DNA complex granular component centrosome cytosol large ribosomal subunit small ribosomal subunit nuclear speck protein-containing complex ribonucleoprotein complex Biological process centrosome cycle regulation of eIF2 alpha phosphorylation by dsRNA positive regulation of cell cycle G2/M phase transition negative regulation of centrosome duplication regulation of centriole replication response to stress positive regulation of translation CENP-A containing chromatin assembly positive regulation of transcription, DNA-templated positive regulation of NF-kappaB transcription factor activity protein complex oligomerization negative regulation of protein kinase activity by regulation of protein phosphorylation regulation of endodeoxyribonuclease activity regulation of endoribonuclease activity ribosome assembly intracellular protein transport DNA repair signal transduction negative regulation of cell population proliferation nucleosome assembly viral process DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest regulation of transcription by RNA polymerase II cellular response to UV ribosomal large subunit export from nucleus ribosomal small subunit export from nucleus rRNA export from nucleus cell volume homeostasis nucleocytoplasmic transport protein localization positive regulation of cell population proliferation posttranscriptional regulation of gene expression negative regulation of gene expression regulation of centrosome duplication positive regulation of centrosome duplication cell growth positive regulation of cellular biosynthetic process positive regulation of protein ubiquitination regulation of protein stability ribosomal large subunit biogenesis ribosomal small subunit biogenesis negative regulation of apoptotic process regulation of DNA damage response, signal transduction by p53 class mediator positive regulation of protein kinase activity positive regulation of transcription by RNA polymerase II negative regulation of mRNA splicing, via spliceosome protein stabilization protein homooligomerization regulation of cell cycle positive regulation of protein localization to nucleolus chromatin remodeling regulation of mRNA stability involved in cellular response to UV Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4869 18148 Ensembl ENSG00000181163 ENSMUSG00000057113 UniProt P06748 Q61937 RefSeq (mRNA) NM_001037738 NM_002520 NM_199185 NM_001355006 NM_001355009 NM_001355007 NM_001355010 NM_001252260 NM_001252261 NM_008722 RefSeq (protein) NP_001032827 NP_002511 NP_954654 NP_001341935 NP_001341938 NP_001341936 NP_001341939 NP_001239189 NP_001239190 NP_032748 Location (UCSC) Chr 5: 171.39 – 171.41 Mb Chr 11: 33.1 – 33.11 Mb PubMed search [3] [4]
Wikidata
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Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1 gene.^[5][6]

Function

NPM1 is associated with nucleolar ribonucleoprotein structures and binds single-stranded and double-stranded nucleic acids, but it binds preferentially G-quadruplex forming nucleic acids. It is involved in the biogenesis of ribosomes and may assist small basic proteins in their transport to the nucleolus. Its regulation through SUMOylation (by SENP3 and SENP5) is another facet of the protein's regulation and cellular functions.

It is located in the nucleolus, but it can be translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. The protein is phosphorylated.

Nucleophosmin has multiple functions:^[7]

1. Histone chaperones
2. Ribosome biogenesis and transport
3. Genomic stability and DNA repair
4. Endoribonuclease activity
5. Centrosome duplication during cell cycle
6. Regulation of ARF-p53 tumor suppressor pathway
7. RNA helix destabilizing activity
8. Inhibition of caspase-activated DNase
9. Prevents apoptosis when located in nucleolus

Clinical significance

The NPM1 gene is up-regulated, mutated and chromosomally translocated in many tumor types. Chromosomal aberrations involving NPM1 were found in patients with non-Hodgkin lymphoma, acute promyelocytic leukemia, myelodysplastic syndrome, and acute myelogenous leukemia.^[8] Heterozygous mice for NPM1 are vulnerable to tumor development. In solid tumors NPM1 is frequently found overexpressed, and it is thought that NPM1 could promote tumor growth by inactivation of the tumor suppressor p53/ARF pathway; on the contrary, when expressed at low levels, NPM1 could suppress tumor growth by the inhibition of centrosome duplication.

Of high importance is NPM involvement in acute myelogenous leukemia,^[9] where a mutated protein lacking a folded C-terminal domain (NPM1c+) has been found in the cytoplasm in patients. This aberrant localization has been linked to the development of the disease, and is associated with improved clinical outcomes. Strategies against this subtype of acute myelogenous leukemia include the refolding of the C-terminal domain using pharmalogical chaperones and the displacement of the protein from nucleolus to nucleoplasm, which has been linked to apoptotic mechanisms. It has also been shown that in the context of clonal hematopoiesis of undetermined significance harboring a DNMT3A mutation, subsequent NPM1 mutations drive progression into overt myeloproliferative neoplasm.^[10]

Interactions

NPM1 has been shown to interact with

• AKT1,^[11]
• BARD1,^[12]
• BRCA1,^[12] and
• nucleolin.^[13]

Nucleophosmin has multiple binding partners:^[7]

1. rRNA
2. HIV Rev and Rex peptide
3. p53 tumor suppressor
4. ARF tumor suppressor
5. MDM2 (mouse double minute 2, ubiquitin ligase)
6. Ribosome protein S9
7. Phosphatidylinositol 3,4,5-triphosphate (PIP3)
8. Exportin-1 (CRM1, chromosome region maintenance)
9. Nucleolin/C23
10. Transcription target of myc oncogene

References

Further reading