Nucleophosmin (NPM1)
The protein contains 294 amino acids for an estimated molecular weight of 32575 Da.
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). (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Cell aging
Cell volume homeostasis
Cellular response to UV
CENP-A containing nucleosome assembly
Centrosome cycle
Chromatin remodeling
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
DNA repair
Intracellular protein transport
Negative regulation of apoptotic process
Negative regulation of cell population proliferation
Negative regulation of centrosome duplication
Negative regulation of mRNA splicing, via spliceosome
Negative regulation of protein kinase activity by regulation of protein phosphorylation
Nucleocytoplasmic transport
Nucleosome assembly
Positive regulation of cell cycle G2/M phase transition
Positive regulation of cell population proliferation
Positive regulation of centrosome duplication
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of protein kinase activity
Positive regulation of protein localization to nucleolus
Positive regulation of protein ubiquitination
Positive regulation of transcription by RNA polymerase II
Positive regulation of transcription, DNA-templated
Positive regulation of translation
Protein complex oligomerization
Protein localization
Protein stabilization
Regulation of cell growth
Regulation of centriole replication
Regulation of centrosome duplication
Regulation of DNA damage response, signal transduction by p53 class mediator
Regulation of eIF2 alpha phosphorylation by dsRNA
Regulation of endodeoxyribonuclease activity
Regulation of endoribonuclease activity
Regulation of mRNA stability involved in cellular response to UV
Regulation of transcription by RNA polymerase II
Response to stress
Ribosomal large subunit biogenesis
Ribosomal large subunit export from nucleus
Ribosomal small subunit biogenesis
Ribosomal small subunit export from nucleus
Ribosome assembly
RRNA export from nucleus
Signal transduction
Viral process
Cellular Component
Centrosome
Cytoplasm
Cytosol
Focal adhesion
Granular component
Intracellular ribonucleoprotein complex
Large ribosomal subunit
Membrane
Nuclear speck
Nucleolus
Nucleoplasm
Nucleus
Obsolete cell
Protein complex
Protein-containing complex
Protein-DNA complex
Ribonucleoprotein complex
Small ribosomal subunit
Spindle pole centrosome
Molecular Function
Activating transcription factor binding
Chromatin binding
Core promoter binding
Core promoter sequence-specific DNA binding
Histone binding
NF-kappaB binding
Poly(A) RNA binding
Protein heterodimerization activity
Protein homodimerization activity
Protein kinase binding
Protein kinase inhibitor activity
Protein N-terminus binding
Ribosomal large subunit binding
Ribosomal small subunit binding
RNA binding
RNA polymerase II transcription coactivator activity
RRNA binding
Tat protein binding
Transcription coactivator activity
Transcription factor binding
Unfolded protein binding
The reference OMIM entry for this protein is 164040
Nucleophosmin/nucleoplasmin family, member 1; npm1
Nucleophosmin; npm
Nucleolar phosphoprotein b23
Numatrin npm1/alk fusion gene, included
DESCRIPTION
NPM1 is a ubiquitously expressed nucleolar protein that shuttles between the nucleus and cytoplasm. It is implicated in multiple functions, including ribosomal protein assembly and transport, control of centrosome duplication, and regulation of the tumor suppressor ARF (600160). NPM1 mutations that relocalize NPM1 from the nucleus into the cytoplasm are associated with development of acute myeloid leukemia (AML; 601626) (Garzon et al., 2008).CLONING
Chan et al. (1989) reported the nucleotide sequence of a cDNA of human nucleophosmin. The cDNA has a coding sequence equivalent to a protein of 294 amino acids. When protein levels were compared with Western blot immunoassays, Novikoff hepatoma showed 20 times more nucleophosmin than normal, and hypertrophic rat liver showed about 5 times more nucleophosmin than unstimulated normal liver. Dalenc et al. (2002) developed a HeLa cell line that overexpressed FGF2 (134920) and showed radioresistance following exposure to ionizing radiation. By differential display, they determined that the radioresistant cells upregulated expression of an NPM1 splice variant. This variant, which Dalenc et al. (2002) designated NPM2, encodes a deduced 259-amino acid protein that differs from the original isolate only at the C terminus. Western blot analysis of HeLa cells detected both NPM isoforms, which migrated with apparent molecular masses of 38 and 34 kD. The amount of the shorter isoform increased following FGF2 overexpression.GENE FUNCTION
Chan et al. (1989) found that nucleophosmin is a nucleolar phosphoprotein that is more abundant in tumor cells than in normal resting cells. Stimulation of the growth of normal cells, e.g., mitogen activation of B lymphocytes, was accompanied by an increase in nucleophosmin protein level. They stated that nucleophosmin is likely involved in the assembly of ribosomal proteins into ribosomes. Electron microscopic study indicated that nucleophosmin is concentrated in the granular region of the nucleolus, where ribosome assembly occurs. Okuda et al. (2000) identified nucleophosmin as a substrate of CDK2 (116953)/cyclin E (123837) in centrosome duplication. NPM1 associated with unduplicated centrosomes, and dissociated from centrosomes by CDK2/cyclin E-mediated phosphorylation. An anti-NPM1 antibody, which blocked this phosphorylation, suppressed the initiation of centrosome duplication in vivo. Moreover, expression of a nonphosphorylatable mutant NPM1 in cells effectively blocked centrosome duplication. Okuda et al. (2000) concluded that NPM1 is a target of CDK2/cyclin E in the initiation of centrosome duplication. By immunohistochemistry using antibodies that did not differentiate between NPM1 isoforms, Dalenc et al. (2002) found nuclear staining for NPM1 in control HeLa cells and cytoplasmic staining following transfection with FGF2. They concluded that overexpression of FGF2 caused the redistribution of both NPM1 isoforms. By transfection of the C-terminally truncated NPM1 variant (NPM2) into radiosensitive HeLa cells, Dalenc et al. (2002) showed that the radioresistance associated with FGF2 overexpression was mediated by increased expression of this NPM1 isoform. - NPM1/ALK Fusion Protein Zhang et al. (2007) stated that ALK (105590) tyrosine kinase expression is normally confined to neural cells, but chromosomal translocations involving ALK and various partners, most frequently NPM1, result in ectopic expression of ALK in a s ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 164040 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed