Nucleophosmin

Function

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. In complex with MYC enhances the transcription of MYC target genes. May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity).

Classification

Family (Pfam)

PF16276 NPM1-C, PF03066 Nucleoplasmin

InterPro

NPM1_C, Nucleoplasmin, Nucleoplasmin_core_dom, Nucleoplasmin_core_dom_sf

Functional cluster

Ribosomal Protein L12 & Acyl Carriers

Experimental structures · PDB · 8

• 2LLH NMR
• 2P1B X-ray 2.75A
• 2VXD NMR
• 5EHD X-ray 2.55A
• 7OBG X-ray 1.80A
• 7OBH X-ray 2.00A
• 8AH2 X-ray 2.90A
• 8AS5 EM 2.50A

A predicted model is available from AlphaFold.

Gene Ontology · 62

• GO:0005813 centrosome
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005925 focal adhesion
• GO:0001652 granular component
• GO:0015934 large ribosomal subunit
• GO:0016020 membrane
• GO:0016607 nuclear speck
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0032991 protein-containing complex
• GO:0032993 protein-DNA complex
• GO:1990904 ribonucleoprotein complex
• GO:0015935 small ribosomal subunit
• GO:0031616 spindle pole centrosome
• GO:0003682 chromatin binding
• GO:0001046 core promoter sequence-specific DNA binding
• GO:0140297 DNA-binding transcription factor binding
• GO:0042393 histone binding
• GO:0060090 molecular adaptor activity
• GO:0051059 NF-kappaB binding
• GO:0042803 protein homodimerization activity
• GO:0019901 protein kinase binding
• GO:0004860 protein kinase inhibitor activity
• GO:0043023 ribosomal large subunit binding
• GO:0043024 ribosomal small subunit binding
• GO:0003723 RNA binding
• GO:0019843 rRNA binding
• GO:0030957 Tat protein binding
• GO:0003713 transcription coactivator activity
• GO:0051082 unfolded protein binding
• GO:0007249 canonical NF-kappaB signal transduction
• GO:0034644 cellular response to UV
• GO:0090398 cellular senescence
• GO:0007098 centrosome cycle
• GO:0006338 chromatin remodeling
• GO:0006281 DNA repair
• GO:0008104 intracellular protein localization
• GO:0006886 intracellular protein transport
• GO:0030225 macrophage differentiation
• GO:0043066 negative regulation of apoptotic process
• GO:0008285 negative regulation of cell population proliferation
• GO:0010826 negative regulation of centrosome duplication
• GO:0006913 nucleocytoplasmic transport
• GO:0006334 nucleosome assembly
• GO:1902751 positive regulation of cell cycle G2/M phase transition
• GO:0008284 positive regulation of cell population proliferation
• GO:2000767 positive regulation of cytoplasmic translation
• GO:0045893 positive regulation of DNA-templated transcription
• GO:1904751 positive regulation of protein localization to nucleolus
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0006606 protein import into nucleus
• GO:0046599 regulation of centriole replication
• GO:0010824 regulation of centrosome duplication
• GO:1902629 regulation of mRNA stability involved in cellular response to UV
• GO:0042273 ribosomal large subunit biogenesis
• GO:0000055 ribosomal large subunit export from nucleus
• GO:0042274 ribosomal small subunit biogenesis
• GO:0000056 ribosomal small subunit export from nucleus
• GO:0042255 ribosome assembly
• GO:0007165 signal transduction

Drugs targeting this protein · 2

• CERITINIB inhibitor
• CRIZOTINIB inhibitor

Related proteins · sequence + function similarity

• Nucleophosmin 0.99
• Nucleophosmin 0.99
• Nucleophosmin 0.99
• Nucleophosmin 0.95
• Nucleophosmin 0.95
• Nucleoplasmin 0.85
• Nucleoplasmin 0.83
• Nucleoplasmin 0.82
• Nucleoplasmin-like protein ANO39 0.81
• Histone deacetylase HDT2 0.78
• Mitotic apparatus protein p62 0.77
• Nucleoplasmin-2 0.76

Co-cited proteins · studied together in the literature

• ATP-dependent DNA helicase DDX31 1 shared papers
• Nucleoplasmin-3 1 shared papers
• AT-rich interactive domain-containing protein 3C 1 shared papers
• Myeloid leukemia factor 1 1 shared papers
• Serine/threonine-protein kinase PLK2 1 shared papers
• Sentrin-specific protease 3 2 shared papers
• 28S rRNA (cytosine(4447)-C(5))-methyltransferase 2 shared papers
• Ribosome biogenesis protein NOP53 2 shared papers
• Centromere protein W 1 shared papers
• Small delta antigen 1 shared papers
• 28S rRNA/ribosome and sororin micro-cofactor 1 shared papers
• Cyclin-dependent kinase 6 1 shared papers

Literature · 82 cited papers

• ARID3C Acts as a Regulator of Monocyte-to-Macrophage Differentiation Interacting with NPM1. J. Proteome Res. · 2024
• Identification of Microprotein-Protein Interactions via APEX Tagging. Biochemistry · 2017
• Serine ADP-ribosylation depends on HPF1. Mol. Cell · 2017
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• The nucleolar protein GLTSCR2 is an upstream negative regulator of the oncogenic Nucleophosmin-MYC axis. Am. J. Pathol. · 2015
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• GLTSCR2 is an upstream negative regulator of nucleophosmin in cervical cancer. J. Cell. Mol. Med. · 2015
• SUMO-2 orchestrates chromatin modifiers in response to DNA damage. Cell Rep. · 2015
• System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability. Mol. Cell. Proteomics · 2015
• Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
• Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli. Proc. Natl. Acad. Sci. U.S.A. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• … and 70 more in the literature graph