Disease:A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS) . Translocation t (3;5) (q25.1;q34) with MLF1. ,Disease:A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t (5;17) (q32;q11) with RARA. ,Disease: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. ,Disease: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. ,Function:Involved in diverse cellular processes such as ribosome biogenesis , centrosome duplication , protein chaperoning , histone assembly , cell proliferation , and regulation of tumor suppressors TP53/p53 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. ,PTM:Acetylated at C-terminal lysine residues , thereby increasing affinity to histones. ,PTM:ADP-ribosylated. ,PTM:Phosphorylated at Ser-4 by PLK1. Phosphorylated by CDK2 at Ser-125 and Thr-199. Phosphorylation at Thr-199 may trigger initiation of centrosome duplication. Phosphorylated by CDC2 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 phosphoryled at Ser-70 by NEK2. ,PTM:Sumoylated by ARF. ,similarity:Belongs to the nucleoplasmin family. ,subcellular location: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. ,subunit:Decamer formed by two pentameric rings associated in a head-to-head fashion. Disulfide-linked dimers under certain conditions. The SWAP complex consists of NPM1 , NCL , PARP1 and SWAP70 (By similarity) . Interacts with NSUN2. Interacts with hepatitis delta virus S-HDAg. ,
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