NPM1

The protein encoded by this gene is involved in several cellular processes, including centrosome duplication, protein chaperoning, and cell proliferation. The encoded phosphoprotein shuttles between the nucleolus, nucleus, and cytoplasm, chaperoning ribosomal proteins and core histones from the nucleus to the cytoplasm. This protein is also known to sequester the tumor suppressor ARF in the nucleolus, protecting it from degradation until it is needed. Mutations in this gene are associated with acute myeloid leukemia. Dozens of pseudogenes of this gene have been identified. [provided by RefSeq, Aug 2017]

Nucleophosmin 1

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).

Cell agingManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to UVManual Assertion Based On ExperimentIDA:CAFA
Centrosome cycleManual Assertion Based On ExperimentIMP:UniProtKB
Chromatin remodelingManual Assertion Based On ExperimentIBA:GO_Central
DNA repairManual Assertion Based On ExperimentIDA:UniProtKB
Intracellular protein transportManual Assertion Based On ExperimentTAS:UniProtKB
Negative regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of centrosome duplicationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of protein kinase activity by regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Nucleocytoplasmic transportManual Assertion Based On ExperimentIDA:UniProtKB
Nucleosome assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cell cycle G2/M phase transitionManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:CAFA
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of translationManual Assertion Based On ExperimentIDA:UniProtKB
Protein localizationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of centriole replicationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of centrosome duplicationManual Assertion Based On ExperimentIBA:GO_Central
Regulation of eIF2 alpha phosphorylation by dsRNAManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of endodeoxyribonuclease activityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of endoribonuclease activityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of mRNA stability involved in cellular response to UVManual Assertion Based On ExperimentIMP:UniProtKB
Ribosomal large subunit biogenesisManual Assertion Based On ExperimentIBA:GO_Central
Ribosomal large subunit export from nucleusManual Assertion Based On ExperimentIBA:GO_Central
Ribosomal small subunit biogenesisManual Assertion Based On ExperimentIBA:GO_Central
Ribosomal small subunit export from nucleusManual Assertion Based On ExperimentIBA:GO_Central
Ribosome assemblyManual Assertion Based On ExperimentTAS:UniProtKB
rRNA export from nucleusManual Assertion Based On ExperimentIBA:GO_Central
Signal transduction1 PublicationNAS:UniProtKB

Nucleus, nucleolus
Nucleus, nucleoplasm
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
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.

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.
A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) with RARA.
A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with MLF1.
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.

Acetylated at C-terminal lysine residues, thereby increasing affinity to histones.
ADP-ribosylated.
Phosphorylated at Ser-4 by PLK1 and PLK2. Phosphorylation at Ser-4 by PLK2 in S phase is required for centriole duplication and is sufficient to trigger centriole replication. Phosphorylation at Ser-4 by PLK1 takes place during mitosis. Phosphorylated by CDK2 at Ser-125 and Thr-199. Phosphorylation at Thr-199 may trigger initiation of centrosome duplication. Phosphorylated by CDK1 at Thr-199, Thr-219, Thr-234 and Thr-237 during cell mitosis. When these four sites are phosphorated, RNA-binding activity seem to be abolished. May be phosphorylated at Ser-70 by NEK2. The Thr-199 phosphorylated form has higher affinity for ROCK2. CDK6 triggers Thr-199 phosphorylation when complexed to Kaposi's sarcoma herpesvirus (KSHV) V-cyclin, leading to viral reactivation by reducing viral LANA levels.
Sumoylated by ARF.
Ubiquitinated. Ubiquitination leads to proteasomal degradation. Deubiquitinated by USP36 (PubMed:19208757).