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FLASH GENE
Symbol NPM1 contributors: mct/npt/pgu - updated : 26-05-2010
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
    DNA
    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
    Physical map
    FLJ20364 5q35.1 hypothetical protein FLJ20364 DOCK2 5q35.1 dedicator of cyto-kinesis 2 FOXI1 5q34 forkhead box I1 LOC345430 5q35.1 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC133874 5q35.1 hypothetical gene LOC133874 LCP2 5q34 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa) KCNMB1 5q34 potassium large conductance calcium-activated channel, subfamily M, beta member 1 KCNIP1 5q35.2 Kv channel interacting protein 1 LOC389343 5 LOC389343 GABRP 5q33-q34 gamma-aminobutyric acid (GABA) A receptor, pi RANBP17 5q31 RAN binding protein 17 USP12P1 5q33-q34 ubiquitin specific protease 12 pseudogene 1 TLX3 5q35.1 T-cell leukemia, homeobox 3 LOC391847 5 similar to hypothetical protein LOC391848 5 similar to 60S ribosomal protein L10 (QM protein homolog) NPM1 5q35 nucleophosmin (nucleolar phosphoprotein B23, numatrin) FGF18 5q34 fibroblast growth factor 18 FBXW1B 5q35.1 F-box and WD-40 domain protein 1B STK10 5q35.1 serine/threonine kinase 10 LOC285588 5q35.2 similar to RIKEN cDNA 1700007I06 DC-UbP 5q35.2 dendritic cell-derived ubiquitin-like protein KIAA1295 5q35.2 KIAA1295 protein LOC391849 5 similar to neuralized homolog LOC133539 5q35.2 similar to RIKEN cDNA 1810009O10 DUSP1 5q34 dual specificity phosphatase 1 KIAA1181 5q35.2 KIAA1181 protein LOC389344 5 LOC389344 RPL26L1 5q35.2 ribosomal protein L26-like 1 LOC285591 5q35.2 inorganic pyrophosphatase pseudogene ATP6V0E 5q35.3 ATPase, H+ transporting, lysosomal 9kDa, V0 subunit e LOC153222 5q35.2 adult retina protein BNIP1 5q33-q34 BCL2/adenovirus E1B 19kDa interacting protein 1 LOC391850 5 similar to 60S ribosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) NKX2-5 5q34-q35.3 NK2 transcription factor related, locus 5 (Drosophila) STC2 5p14.2-q15 stanniocalcin 2 LOC389345 5 LOC389345 LOC91272 5q35.2 hypothetical protein BC007436
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1373 37 294 - 2007 17616680
    10 - 1286 - 265 - 2007 17616680
    10 - 1274 - 259 - 2007 17616680
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two acidic domains rich in aspartic and glutamic acid
  • a central domain with ribonuclease activity and catalytic site
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to rattus B23
    homolog to Xenopus NO38
    ortholog to murine Npm1
    Homologene
    FAMILY
  • nucleoplasmin family
  • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text
  • 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
  • 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
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    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
  • INTERACTION
    DNA
    RNA
    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 (recruits USP36 to nucleoli, thereby serving as a platform for the regulation of nucleolar protein functions through
  • BAX binding protein (interaction proposed to be a key event in the activation and translocation of BAX in mitochondrial dysfunction and apoptotic cell
  • 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
  • cell & other
  • associating specifically with unduplicated centrosomes
  • REGULATION
    inhibited by inhibited and phosphorylated by CDC2/cyclin E and dissociating from centrosome
    Other desumoylated by SENP3
    ASSOCIATED DISORDERS
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target alterations of nuclear export might represent a general mechanism of leukemogenesis and a novel target for therapeutic intervention
    ANIMAL & CELL MODELS