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NPM1 (nucleophosmin)

Identity

Other namesNPM
B23
Numatrin
NO38
HGNC (Hugo) NPM1
LocusID (NCBI) 4869
Location 5q35.1
Location_base_pair Starts at 170814708 and ends at 170833731 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  NPM1 (5q35) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

DNA/RNA

Description 11 exons on 25 kb;
Transcription in a centromeric --> telomeric orientation; transcription is cell-cycle regulated, reaching peaks at G1/S transition and being baseline at S/G2 1.6 kb mRNA

Protein

 
  DNA Diagram
Description 294 amino acids, 32.5 kDa; contains in C-term an oligomerization domain (residues 1-83), a metal binding site (residues 104-115) , 2 domains rich in acidic amino acids (residues 120- 132 and 161-188) , and 2 nuclear localisation signals in C-term; forms homo-hexameres; binds to single and double strand nucleic acids
Expression wide
Localisation nuclear, mainly in the nucleolus
Function RNA binding nucleolar phosphoprotein involved in preribosomal assembly; transport ribonucleoproteins between cellular compartments
Homology with nucleoplasmin

Implicated in

Entity Anaplasic large cell lymphoma (ALCL) with t(2;5)(p23;q35) --> NPM1-ALK
Disease ALCL are high grade non Hodgkin lymphomas; ALK+ ALCL are ALCL where ALK is involved in a fusion gene; ALK+ ALCL represent 50 to 60 % of ALCL cases (they are CD30+, ALK+;); 80% of ALK+ ALCL cases bear a t(2;5)
Prognosis nonetheless, a 80% five yr survival may be associated with this anomaly
Cytogenetics additional anomalies are most often found
Hybrid/Mutated Gene 5' NPM1-3' ALK on der(5)
Abnormal Protein 680 amino acids, 80 kDa; N-term 116 amino acids from NPM1 fused to the 563 C-term aminoacids of ALK (i.e. composed of the oligomerization domain and the metal binding site of NPM1 ,and the entire cytoplasmic portion of ALK); no apparent expression of the ALK/NPM1 counterpart; Characteristic localisation both in the cytoplasm and in the nucleus, due to heterooligomerization of NPM-ALK and normal NPM whereas the normal NPM protein is confined to the nucleus; constitutive activation of the catalytic domain of ALK.
Oncogenesis via the kinase function activated by oligomerization of NPM1-ALK mediated by the NPM1 part
  
Entity t(3;5)(q25;q34)/in myeloid malignancies --> NPM - MLF1
Disease Acute non lymphocytic leukemia (ANLL), myelodysplasia (MDS), chronic myelogenous leukemia in blast crisis (BC-CML); trilineage involvement
Prognosis very poor
Cytogenetics location of breakpoints difficult to ascertain
Hybrid/Mutated Gene 5' NPM-3' MLF1 on der(5)
Abnormal Protein with the 175 N term amino acids of NPM1; nuclear protein
  
Entity t(5;17)(q34;q21)/M3-ANLL --> NPM1-RARa
Disease promyelocytic ANLL (M3-ANLL)
Cytogenetics variant translocation of the well known t(15;17)
Hybrid/Mutated Gene 5' NPM1-3' RARa on der(5)
Abnormal Protein with the 117 N term amino acids of NPM1
  

Breakpoints

 
 
Note within the 4th intron in the cases of t(2;5) or t(5;17), within the 6th intron in case of t(3;5)

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias t0817q24q22ID1494 t1119q23p13ID1540 t614p25q32IRF4IGHID1175 t1213p13q14ID1323 t1117q23q12AF17ID1027
t1117p15p13ID2134 t1114ID1070 dic920ID1143 dic0709p11p12ID1554 i17qID1038
t0109p34q34ID2143 t0109q24q34ID2109 t0112ID1147 t0411q35q23ID1423

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors ProstateOverviewID5041

External links

Nomenclature
HGNC (Hugo)NPM1   7910
Cards
AtlasNPM1
Entrez_Gene (NCBI)NPM1  4869  nucleophosmin (nucleolar phosphoprotein B23, numatrin)
GeneCards (Weizmann)NPM1
Ensembl (Hinxton)ENSG00000181163 [Gene_View]  chr5:170814708-170833731 [Contig_View]  NPM1 [Vega]
ICGC DataPortalENSG00000181163
cBioPortalNPM1
AceView (NCBI)NPM1
Genatlas (Paris)NPM1
WikiGenes4869
SOURCE (Princeton)NM_001037738 NM_002520 NM_199185
Genomic and cartography
GoldenPath (UCSC)NPM1  -  5q35.1   chr5:170814708-170833731 +  5q35.1   [Description]    (hg19-Feb_2009)
EnsemblNPM1 - 5q35.1 [CytoView]
Mapping of homologs : NCBINPM1 [Mapview]
OMIM164040   
Gene and transcription
Genbank (Entrez)AB042278 AB451236 AB451361 AI687394 AK000472
RefSeq transcript (Entrez)NM_001037738 NM_002520 NM_199185
RefSeq genomic (Entrez)AC_000137 NC_000005 NC_018916 NG_016018 NT_023133 NW_001838954 NW_004929325
Consensus coding sequences : CCDS (NCBI)NPM1
Cluster EST : UnigeneHs.557550 [ NCBI ]
CGAP (NCI)Hs.557550
Alternative Splicing : Fast-db (Paris)GSHG0024462
Alternative Splicing GalleryENSG00000181163
Gene ExpressionNPM1 [ NCBI-GEO ]     NPM1 [ SEEK ]   NPM1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP06748 (Uniprot)
NextProtP06748  [Medical]
With graphics : InterProP06748
Splice isoforms : SwissVarP06748 (Swissvar)
Domains : Interpro (EBI)Nucleoplasmin [organisation]   Nucleoplasmin_core_dom [organisation]  
Related proteins : CluSTrP06748
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
DMDM Disease mutations4869
Blocks (Seattle)P06748
PDB (SRS)2LLH    2P1B    2VXD   
PDB (PDBSum)2LLH    2P1B    2VXD   
PDB (IMB)2LLH    2P1B    2VXD   
PDB (RSDB)2LLH    2P1B    2VXD   
Human Protein AtlasENSG00000181163 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP06748
HPRD01246
IPIIPI00549248   IPI00220740   IPI00604504   IPI00658013   IPI00985410   IPI00983818   
Protein Interaction databases
DIP (DOE-UCLA)P06748
IntAct (EBI)P06748
FunCoupENSG00000181163
BioGRIDNPM1
InParanoidP06748
Interologous Interaction database P06748
IntegromeDBNPM1
STRING (EMBL)NPM1
Ontologies - Pathways
Ontology : AmiGOtranscription coactivator activity  RNA binding  protein kinase inhibitor activity  protein binding  nucleus  nucleus  nucleoplasm  nucleoplasm  nucleolus  cytoplasm  cytoplasm  centrosome  centrosome  cytosol  DNA repair  nucleosome assembly  nucleosome assembly  intracellular protein transport  nucleocytoplasmic transport  nucleocytoplasmic transport  response to stress  centrosome cycle  centrosome cycle  signal transduction  cell aging  cell aging  protein localization  negative regulation of cell proliferation  negative regulation of cell proliferation  negative regulation of centrosome duplication  membrane  viral process  protein kinase binding  ribonucleoprotein complex  Tat protein binding  spindle pole centrosome  regulation of endodeoxyribonuclease activity  centromere-specific nucleosome assembly  ribosome assembly  histone binding  protein homodimerization activity  ribosomal large subunit binding  ribosomal small subunit binding  negative regulation of apoptotic process  negative regulation of apoptotic process  negative regulation of protein kinase activity by regulation of protein phosphorylation  poly(A) RNA binding  positive regulation of translation  regulation of centriole replication  protein heterodimerization activity  NF-kappaB binding  NF-kappaB binding  unfolded protein binding  unfolded protein binding  positive regulation of NF-kappaB transcription factor activity  protein oligomerization  regulation of endoribonuclease activity  regulation of eIF2 alpha phosphorylation by dsRNA  
Ontology : EGO-EBItranscription coactivator activity  RNA binding  protein kinase inhibitor activity  protein binding  nucleus  nucleus  nucleoplasm  nucleoplasm  nucleolus  cytoplasm  cytoplasm  centrosome  centrosome  cytosol  DNA repair  nucleosome assembly  nucleosome assembly  intracellular protein transport  nucleocytoplasmic transport  nucleocytoplasmic transport  response to stress  centrosome cycle  centrosome cycle  signal transduction  cell aging  cell aging  protein localization  negative regulation of cell proliferation  negative regulation of cell proliferation  negative regulation of centrosome duplication  membrane  viral process  protein kinase binding  ribonucleoprotein complex  Tat protein binding  spindle pole centrosome  regulation of endodeoxyribonuclease activity  centromere-specific nucleosome assembly  ribosome assembly  histone binding  protein homodimerization activity  ribosomal large subunit binding  ribosomal small subunit binding  negative regulation of apoptotic process  negative regulation of apoptotic process  negative regulation of protein kinase activity by regulation of protein phosphorylation  poly(A) RNA binding  positive regulation of translation  regulation of centriole replication  protein heterodimerization activity  NF-kappaB binding  NF-kappaB binding  unfolded protein binding  unfolded protein binding  positive regulation of NF-kappaB transcription factor activity  protein oligomerization  regulation of endoribonuclease activity  regulation of eIF2 alpha phosphorylation by dsRNA  
Protein Interaction DatabaseNPM1
Wikipedia pathwaysNPM1
Gene fusion - rearrangments
Rearrangement : COSMICNPM1 [5q35.1]  -  ALK [2p23.2]  
  [COSF198] [COSF199] [COSF200] [COSF201] [COSF420] [COSF448] [COSF449] [COSF450] [COSF451] 
  [COSF452] [COSF453] [COSF454] [COSF455] [COSF456] [COSF457] [COSF458] 
Rearrangement : TICdbNPM1 [5q35.1]  -  ALK [12p13.33]
Rearrangement : TICdbNPM1 [5q35.1]  -  MLF1 [11q23.3]
Rearrangement : TICdbNPM1 [5q35.1]  -  RARA [3q12.2]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)NPM1
snp3D : Map Gene to Disease4869
SNP (GeneSNP Utah)NPM1
SNP : HGBaseNPM1
Genetic variants : HAPMAPNPM1
Exome VariantNPM1
1000_GenomesNPM1 
ICGC programENSG00000181163 
Cancer Gene: CensusNPM1 
Somatic Mutations in Cancer : COSMICNPM1 
CONAN: Copy Number AnalysisNPM1 
Mutations and Diseases : HGMDNPM1
Genomic VariantsNPM1  NPM1 [DGVbeta]
dbVarNPM1
ClinVarNPM1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM164040   
MedgenNPM1
GENETestsNPM1
Disease Genetic AssociationNPM1
Huge Navigator NPM1 [HugePedia]  NPM1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneNPM1
Homology/Alignments : Family Browser (UCSC)NPM1
Phylogenetic Trees/Animal Genes : TreeFamNPM1
Chemical/Protein Interactions : CTD4869
Chemical/Pharm GKB GenePA31712
Clinical trialNPM1
Cancer Resource (Charite)ENSG00000181163
Other databases
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=NPM1
Probes
ProbeCancer Cytogenetics (Bari)
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineNPM1
iHOPNPM1
OncoSearchNPM1

Bibliography

Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.
Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, Look AT
Science (New York, N.Y.). 1994 ; 263 (5151) : 1281-1284.
PMID 8122112
 
The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1.
Yoneda-Kato N, Look AT, Kirstein MN, Valentine MB, Raimondi SC, Cohen KJ, Carroll AJ, Morris SW
Oncogene. 1996 ; 12 (2) : 265-275.
PMID 8570204
 
The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion.
Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ
Blood. 1996 ; 87 (3) : 882-886.
PMID 8562957
 
The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion.
Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ
Blood. 1996 ; 87 (3) : 882-886.
PMID 8562957
 
Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: identification of the YY1 binding site at the 5' enhancer region.
Chan PK, Chan FY, Morris SW, Xie Z
Nucleic acids research. 1997 ; 25 (6) : 1225-1232.
PMID 9092633
 
Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis.
Bischof D, Pulford K, Mason DY, Morris SW
Molecular and cellular biology. 1997 ; 17 (4) : 2312-2325.
PMID 9121481
 
CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.
Stein H, Foss HD, Dł║rkop H, Marafioti T, Delsol G, Pulford K, Pileri S, Falini B
Blood. 2000 ; 96 (12) : 3681-3695.
PMID 11090048
 
Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.
Drexler HG, Gignac SM, von Wasielewski R, Werner M, Dirks WG
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (9) : 1533-1559.
PMID 10994999
 
Anaplastic large cell lymphomas, Primary systemic (T/Null cell type).
Delsol G, Ralfkiaer E, Stein H, Wright D, Jaffe E
World Health Organization (WHO) Classification of Tumors..
 
Alk+ CD30+ lymphomas: a distinct molecular genetic subtype of non-Hodgkin's lymphoma.
Morris SW, Xue L, Ma Z, Kinney MC
British journal of haematology. 2001 ; 113 (2) : 275-295.
PMID 11380391
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written12-1997Jean-Loup Huret
Updated08-2001Jean-Loup Huret

Citation

This paper should be referenced as such :
Huret, JL
NPM1 (nucleophosmin)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):265-267.
Free online version   Free pdf version   [Bibliographic record ]
Atlas Genet Cytogenet Oncol Haematol. December 1997
http://documents.irevues.inist.fr/bitstream/handle/2042/32058/12-1997-NPM1.pdf
URL : http://AtlasGeneticsOncology.org/Genes/NPM1.html

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indexed on : Sat Jul 26 15:16:35 CEST 2014

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