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Symbol NPM1 contributors: mct/npt/pgu - updated : 25-04-2018
HGNC name nucleophosmin (nucleolar phosphoprotein B23, numatrin)
HGNC id 7910
Corresponding disease
NPM1 acute promyelocytic leukemia (APL) gene
Location 5q35.1      Physical location : 170.814.707 - 170.837.887
Synonym name
  • nucleophosmin 1
  • nucleolar phosphoprotein B23
  • numatrin
  • nucleophosmin/nucleoplasmin family, member 1
  • nucleolar protein NO38
  • Synonym symbol(s) B23, NPM, MGC104254
    TYPE functioning gene
    STRUCTURE 23.09 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1373 37 294 - 2012 22467873
  • B23.1, containing an additional 35 amino acids in the C terminus
  • contains domains involved in oligomerization (AAs 1–119), histone binding (AAs 119–190), and DNA/RNA binding (AAs 190–294)
  • 10 - 1286 - 265 - 2012 22467873
    10 - 1274 - 259 - 2012 22467873
  • B23.2
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Urinarybladder   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    at STAGE
  • N-terminal core structure, which is required for oligomerization, is shared within members of this family , and is also involved in the interaction with GAPDH but not required for SIAH1 interaction
  • two acidic domains rich in aspartic and glutamic acid
  • a central domain with ribonuclease activity and catalytic site, that contains the acidic clusters and is required for interaction with both SIAH1 and GAPDH
  • conjugated PhosphoP
    interspecies homolog to rattus B23
    homolog to Xenopus NO38
    ortholog to murine Npm1
  • nucleoplasmin family
  • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
  • localizes mainly in the nucleolus, where it forms a complex with different cellular proteins
  • citrullination of NPM1 by PADI4 resulted in its translocation from the nucleoli to the nucleoplasm
  • mainly localizes in nucleole, but it shuttles between the nucleolus/nucleoplasm and nucleus/cytoplasm (
  • basic FUNCTION
  • nucleus-cytoplasmic shuttling protein that is implicated in centrosome duplication, cell cycle progression and stress response
  • target of CDK2/cyclin E in the initiation of centrosome duplication
  • promoting the biogenesis of the ribosome by acting as a chaperone that carries preribosomal particles from the nucleolus to the cytoplasm
  • modulating the function of tumor suppressor transcription factors such as IRF1 and TP53
  • being essential for embryonic development and the maintenance of genomic stability
  • multifunctional protein, involving in a wide variety of basic cellular processes, including ribosome assembly, DNA duplication, nucleocytoplasmic trafficking, and centrosome duplication
  • may be playing a role in the centriole pairing
  • being critically involved in 28S rRNA maturation after deconjugation of SUMO2 by SENP3
  • abundant shuttling phosphoprotein, which plays important roles in ribosome biogenesis and which has been strongly implicated in hematopoietic malignancies
  • may be involved in regulation of SUMO deconjugation
  • acetylated protein localized to the nucleoplasm and regulates transcriptional activation of genes involved in oral cancer manifestation
  • may act as an oncogene or an oncosuppressor depending on the cell context
  • exhibited remarkable linker histone HIST1HA1 chaperone activity
  • important member of the linker histone chaperone family
  • may function in the assembly of the kinetochore complex by interacting with CENPW during interphase
  • NPM1 and NPM2 mediated nucleosome assembly independently of other NPM proteins
  • the NPM proteins (NPM1, NPM2, NPM3) cooperatively regulate chromatin disassembly and assembly in the early embryo and in somatic cells
  • is a nuclear protein that regulates a variety of cell functions including centrosomal duplication, cell cycle control, and apoptosis
  • involved in a variety of functions, including the regulation of centrosomal duplication, the cell cycle, mitosis, apoptosis, and RNA and DNA replication, and it also serves as a chaperone for proteins such as histones
  • is a multifunctional protein that participates in cell survival signaling by shuttling between the nucleolus/nucleoplasm and nucleus/cytoplasm
  • regulates neuronal survival by preventing SIAH1–GAPDH death signaling under stress-induced conditions in the brain
  • it is possible that NPM1 regulates ubiquitin dynamics by both deubiquitination and ubiquitination of nuclear proteins to provide rapid neuroprotection
  • novel mechanism that regulates telomerase activation through the interaction between NPM1, PINX1 and the telomerase complex
  • CELLULAR PROCESS cell organization/biogenesis
    a component
  • CDK2/CDK4/NPM1 pathway is a major guardian of centrosome dysfunction and genomic integrity
  • complex consisting of BRCA2, NPM1, and ROCK2 maintains the numerical integrity of centrosomes and accurate cell division and dysfunction of this regulation might be involved in the tumorigenesis of breast cancer
    small molecule nucleotide,
  • ATP via its K263
  • protein
  • interferon 1 (IRF1) binding and dissociating after phosphorylation by CDK2/CCNE
  • binding with SMN1
  • interacting with TP53
  • centrosomal association linked to XPO1 activity
  • binds SENP3 and SENP5
  • interaction with RPL5 mediated the colocalization of NPM1 with maturing nuclear 60S ribosomal subunits, as well as newly exported and assembled 80S ribosomes and polysomes
  • interacting with USP36 (binds to the deubiquitinating enzyme, USP36, enhancing its activity in the nucleolus)
  • BAX binding protein (interaction proposed to be a key event in the activation and translocation of BAX in mitochondrial dysfunction and apoptotic cell
  • by deubiquitylating various nucleolar substrate proteins including NPM1 and FBL, USP36 plays a crucial role in regulating the structure and function of nucleoli
  • interacting with PADI4 (citrullinated NPM1, at the arginine 197, and citrullination of NPM1 by PADI4 resulted in its translocation from the nucleoli to the nucleoplasm
  • death ubiquitylation/deubiquitylation
  • NPM1 directly interacts with KIF11, a member of the kinesin family, in the cytosol (NPM1 acts as an upstream regulator of KIF11 in promoting microtubule polymerization,
  • FUBP1 interacts specifically with the 3prime UTR of NPM1 to repress translation
  • novel BRCA2-associated protein
  • interacts with FOXM1 and their interaction is required for sustaining the level and localization of FOXM1
  • CENPW specifically interacts with the nucleolar phosphoprotein, nucleophosmin (NPM1)
  • NPM3 suppressed the RNA-binding activity of NPM1, which enhanced the nucleoplasm-nucleolus shuttling of NPM1 in somatic cell nuclei
  • GRK5 is able to interact with and phosphorylate nucleophosmin (NPM1) both in vitro and in intact cells
  • GRK5 and NPM1 interact directly, suggesting that the N-terminal RH domain of GRK5 interacts with the oligomerization domain of NPM1
  • NPM1 physiologically bound to both SIAH1 and GAPDH, disrupting the SIAH1–GAPDH complex in the nucleus in response to nitrosative stress
  • NPM1 did not compete with RILPL1 for GAPDH binding in the cytoplasm, although a small amount of NPM1 protein was able to reside in the cytoplasm
  • TMUB1 acts as a functional bridge in NPM1-CDKN2A interactions
  • nutrient-sensing MTOR kinase pathway controls the nucleolar targeting of SENP3 by regulating its interaction with NPM1
  • PPM1D regulates nucleolar formation by regulating NPM1 phosphorylation status through a novel signalling pathway, PPM1D-CDC25C-CDK1-PLK1
  • PINX1 directly interacts with nucleophosmin (NPM1), a protein that has been shown to positively correlate with telomerase activity
  • cell & other
  • associating specifically with unduplicated centrosomes
    inhibited by inhibited and phosphorylated by CDC2/cyclin E and dissociating from centrosome
    Phosphorylated by GRK5 both in vitro and in cells, with Ser-4 being the major phosphorylation site
    Other desumoylated by SENP3
    corresponding disease(s) NPM1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    translocation t(2;5)(p23;q35),(see ALK) in anaplastic nodal non Hodgkin lymphoma and B cell lymphoma
    tumoral somatic mutation     gain of function
    gain-of-function mutations in acute myeloid, that create functional nuclear export signal (NES), suggesting that alterations of nuclear export might represent a general mechanism of leukemogenesis
    tumoral somatic mutation      
    mutations in the exon 12 resulting in delocalization of NPM1 into the cytoplasm occur in 50 to 60p100 of acute myeloid leukemia cases with a normal karyotype (AML-NK)
    tumoral     --over  
    in papillary, follicular, undifferentiated thyroid cancer, and also in follicular benign adenomas, indicating it as an early event during thyroid tumorigenesis
    tumoral fusion      
    NPM1-HAUS1 in in acute myeloid leukemia
    Variant & Polymorphism
    Candidate gene
    Therapy target alterations of nuclear export might represent a general mechanism of leukemogenesis and a novel target for therapeutic intervention