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

Function: - role in diverse cellular processes including: a) ribosome biogenesis b) centrosome duplication c) protein chaperoning d) histone assembly e) cell proliferation f) 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

General

nucleoplasmin phosphoprotein

Properties

SIZE: entity length = 294 aa MW = 33 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl Ser phosphorylation site {S4} Ser phosphorylation site {S10} Ser phosphorylation site {S70} Thr phosphorylation site {T75} Ser phosphorylation site {S88} Thr phosphorylation site {T95} Ser phosphorylation site {S106} acidic region {120-132} MOTIF: acidic residue (SEVERAL) Ser phosphorylation site {S125} Ser phosphorylation site {S137} Ser phosphorylation site {S139} nuclear translocation signal {152-157} acidic region {161-188} MOTIF: acidic residue (SEVERAL) breakpoint {175-176} nuclear translocation signal {191-197} Thr phosphorylation site {T199} Thr phosphorylation site {T219} Thr phosphorylation site {T234} Thr phosphorylation site {T237} Ser phosphorylation site {S243} Ser phosphorylation site {S254} Ser phosphorylation site {S260} Thr phosphorylation site {T279}

Database Correlations

OMIM 164040 UniProt P06748 Pfam PF03066 Entrez Gene 4869