Npm1 citrulline R196
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 (PubMed:20513429).
Post-translational modifications
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-198. Phosphorylation at Thr-198 may trigger initiation of centrosome duplication. Phosphorylated by CDK1 at Thr-198, Thr-217, Thr-232 and Thr-235 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-198 phosphorylated form has higher affinity for ROCK2 (By similarity).
Sumoylated by ARF.
Ubiquitinated. Ubiquitination leads to proteasomal degradation. Deubiquitinated by USP36.
Sequence Similarities
Belongs to the nucleoplasmin family.
Tissue Specificity
Expressed in B-cells that have been induced to switch to various Ig isotypes.
Cellular localization
- 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. 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. Can shuttle between cytoplasm and nucleus.
Alternative names
Nucleophosmin, NPM, Nucleolar phosphoprotein B23, Nucleolar protein NO38, Numatrin, Npm1