InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NPM1

Summary

InnateDB Protein

IDBP-242817.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NPM1

Protein Name

nucleophosmin (nucleolar phosphoprotein B23, numatrin)

Synonyms

B23; NPM;

Species

Homo sapiens

Ensembl Protein

ENSP00000377408

InnateDB Gene

IDBG-57453 (NPM1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:12882984, ECO:0000269PubMed:16107701, ECO:0000269PubMed:17015463, ECO:0000269PubMed:18809582, ECO:0000269PubMed:19188445, ECO:0000269PubMed:20352051, ECO:0000269PubMed:21084279, ECO:0000269PubMed:22002061}.

Subcellular Localization

Nucleus, nucleolus. Nucleus, nucleoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Generally nucleolar, but is translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. Has been found in the cytoplasm in patients with primary acute myelogenous leukemia (AML), but not with secondary AML. Can shuttle between cytoplasm and nucleus. Co- localizes with the methylated form of RPS10 in the granular component (GC) region of the nucleolus. Colocalized with nucleolin and APEX1 in nucleoli. Isoform 1 of NEK2 is required for its localization to the centrosome during mitosis.

Disease Associations

Note=A chromosomal aberration involving NPM1 is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with ALK. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated.Note=A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) with RARA.Note=A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with MLF1.Note=Defects in NPM1 are associated with acute myelogenous leukemia (AML). Mutations in exon 12 affecting the C- terminus of the protein are associated with an aberrant cytoplasmic location.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 440 experimentally validated interaction(s) in this database.
They are also associated with 38 interaction(s) predicted by orthology.

Experimentally validated
Total	441 [view]
Protein-Protein	438 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	38 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003676	nucleic acid binding
GO:0003713	transcription coactivator activity
GO:0003723	RNA binding
GO:0004860	protein kinase inhibitor activity
GO:0005515	protein binding
GO:0019901	protein kinase binding
GO:0030957	Tat protein binding
GO:0042393	histone binding
GO:0042803	protein homodimerization activity
GO:0043023	ribosomal large subunit binding
GO:0043024	ribosomal small subunit binding
GO:0044822	poly(A) RNA binding
GO:0046982	protein heterodimerization activity
GO:0051059	NF-kappaB binding
GO:0051082	unfolded protein binding

Biological Process

GO:0006281	DNA repair
GO:0006334	nucleosome assembly
GO:0006886	intracellular protein transport
GO:0006913	nucleocytoplasmic transport
GO:0006950	response to stress
GO:0007098	centrosome cycle
GO:0007165	signal transduction
GO:0007569	cell aging
GO:0008104	protein localization
GO:0008285	negative regulation of cell proliferation
GO:0010826	negative regulation of centrosome duplication
GO:0016032	viral process
GO:0032071	regulation of endodeoxyribonuclease activity
GO:0034080	centromere-specific nucleosome assembly
GO:0042255	ribosome assembly
GO:0043066	negative regulation of apoptotic process
GO:0044387	negative regulation of protein kinase activity by regulation of protein phosphorylation
GO:0045727	positive regulation of translation
GO:0046599	regulation of centriole replication
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051259	protein oligomerization
GO:0060699	regulation of endoribonuclease activity
GO:0060735	regulation of eIF2 alpha phosphorylation by dsRNA

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0005829	cytosol
GO:0016020	membrane
GO:0030529	ribonucleoprotein complex
GO:0031616	spindle pole centrosome