NPM1

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)
External IDs	MGI: 106184 HomoloGene: 81697 GeneCards: NPM1
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 • poly(A) RNA binding • protein kinase binding • phosphatidylinositol-3,4,5-trisphosphate binding • DNA binding • enzyme binding Cellular component • cytoplasm • cytosol • centrosome • membrane • focal adhesion • spindle pole centrosome • intracellular ribonucleoprotein complex • nucleoplasm • microtubule organizing center • nucleolus • cytoskeleton • nucleus Biological process • protein localization • 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 • negative regulation of apoptotic process • positive regulation of translation • CENP-A containing nucleosome assembly • positive regulation of transcription, DNA-templated • cell aging • positive regulation of NF-kappaB transcription factor activity • protein oligomerization • nucleocytoplasmic transport • positive regulation of cell proliferation • 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 proliferation • positive regulation of DNA metabolic process • positive regulation of DNA replication • nucleosome assembly • positive regulation of catalytic activity • viral process • protein homooligomerization • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest • regulation of neuron apoptotic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4869	18148
Ensembl	ENSG00000181163	ENSMUSG00000057113
UniProt	P06748	Q61937
RefSeq (mRNA)	NM_001037738 NM_002520 NM_199185	NM_001252260 NM_001252261 NM_008722
RefSeq (protein)	NP_001032827.1 NP_002511.1 NP_954654.1	NP_032748.1
Location (UCSC)	Chr 5: 171.39 – 171.41 Mb	Chr 11: 33.15 – 33.16 Mb
PubMed search	[1]	[2]
Wikidata

Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the NPM1 gene.^[3][4]

Function

NPM1 is associated with nucleolar ribonucleoprotein structures and bind 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 proteins'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:^[5]

1. Histone chaperons
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

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.^[6] 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,^[7]

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. 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.

Interactions

NPM1 has been shown to interact with

• AKT1,^[8]
• BARD1,^[9]
• BRCA1,^[9] and
• nucleolin.^[10]

Nucleophosmin has multiple binding partners:^[5]

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

PDB gallery
2p1b: Crystal structure of human nucleophosmin-core