nucleophosmin; NPM; nucleolar phosphoprotein B23; numatrin; nucleolar protein NO38; nucleoplasmin 1 (NPM1, NPM)

Function

• role in diverse cellular processes including:
  • ribosome biogenesis
  • centrosome duplication
  • protein chaperoning
  • histone assembly
  • cell proliferation
  • regulation of tumor suppressors TP53/p53 & ARF
• binds ribosomes presumably to drive ribosome nuclear export associated with nucleolar ribonucleoprotein structures
• binds single-stranded nucleic acids
• acts as a chaperonin for the core histones histoneH3, histone H2B & histone H4
• acetylated at C-terminal Lys, thereby increasing affinity to histones
• ADP-ribosylated
• phosphorylated at Ser-4 by PLK1
• phosphorylated by CDK2 at Ser-125 & Thr-199
• phosphorylation at Thr-199 may trigger initiation of centrosome duplication
• phosphorylated by CDC2 at Thr-199, Thr-219, Thr-234 & Thr-237 during cell mitosis; when these 4 sites are phosphorated, RNA-binding activity seems to be abolished
• may be phosphoryled at Ser-70 by NEK2
• sumoylated by ARF
• component of SWAP complex
• interacts with NSUN2
• interacts with hepatitis delta virus S-HDAg

Structure

• decamer formed by two pentameric rings associated in a head-to-head fashion
• disulfide-linked dimers under certain conditions
• belongs to the nucleoplasmin family

Compartment

• nucleus, nucleolus
• 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 & nucleus

Alternative splicing

named isoforms=2

Pathology

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

More general terms

• nucleoplasmin
• phosphoprotein

Component of

• SWAP complex

Database

• UniProt: http://www.uniprot.org/uniprot/P06748.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4869
• OMIM: https://mirror.omim.org/entry/164040