ID:NPM_HUMAN DESCRIPTION: RecName: Full=Nucleophosmin; Short=NPM; AltName: Full=Nucleolar phosphoprotein B23; AltName: Full=Nucleolar protein NO38; AltName: Full=Numatrin; FUNCTION: Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 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. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double- stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. 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 and SENP3. Interacts with hepatitis delta virus S-HDAg. Interacts with HTLV1 Rex protein (via N-terminal nuclear localization signal). Interacts with the methylated form of RPS10. Interacts (via N-terminal domain) with APEX1; the interaction is RNA-dependent and decreases in hydrogen peroxide-damaged cells. Interacts with isoform 1 of NEK2. Interacts with ROCK2 and BRCA2. Interacts with RPGR. Interacts with CENPW. INTERACTION: Q98147:- (xeno); NbExp=2; IntAct=EBI-78579, EBI-626601; Q00987:MDM2; NbExp=3; IntAct=EBI-78579, EBI-389668; P04637:TP53; NbExp=3; IntAct=EBI-354150, EBI-366083; SUBCELLULAR LOCATION: Nucleus, nucleolus. Nucleus, nucleoplasm. Cytoplasm, cytoskeleton, centrosome. Note=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. Co- localizes with the methylated form of RPS10 in the granular component (GC) region of the nucleolus. Colocalized with nucleolin and APEX1 in nucleoli. Isoform 1 of NEK2 is required for its localization to the centrosome during mitosis. PTM: Acetylated at C-terminal lysine residues, thereby increasing affinity to histones. PTM: ADP-ribosylated. PTM: Phosphorylated at Ser-4 by PLK1 and PLK2. Phosphorylation at Ser-4 by PLK2 in S phase is required for centriole duplication and is sufficient to trigger centriole replication. Phosphorylation at Ser-4 by PLK1 takes place during mitosis. Phosphorylated by CDK2 at Ser-125 and Thr-199. Phosphorylation at Thr-199 may trigger initiation of centrosome duplication. Phosphorylated by CDK1 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 phosphorylated at Ser-70 by NEK2. The Thr-199 phosphorylated form has higher affinity for ROCK2. CDK6 triggers Thr-199 phosphorylation when complexed to Kaposi's sarcoma herpesvirus (KSHV) V-cyclin, leading to viral reactivation by reducing viral LANA levels. PTM: Sumoylated by ARF. DISEASE: Note=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: Note=A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) with RARA. DISEASE: Note=A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with MLF1. DISEASE: Note=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. SIMILARITY: Belongs to the nucleoplasmin family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NPM1.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P06748
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006281 DNA repair GO:0006334 nucleosome assembly GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0006886 intracellular protein transport GO:0006913 nucleocytoplasmic transport GO:0007098 centrosome cycle GO:0007165 signal transduction GO:0007569 cell aging GO:0008104 protein localization GO:0008284 positive regulation of cell proliferation GO:0008285 negative regulation of cell proliferation GO:0010826 negative regulation of centrosome duplication GO:0016032 viral process GO:0032071 regulation of endodeoxyribonuclease activity GO:0034080 CENP-A containing nucleosome assembly GO:0034644 cellular response to UV GO:0042255 ribosome assembly GO:0043066 negative regulation of apoptotic process GO:0044387 negative regulation of protein kinase activity by regulation of protein phosphorylation GO:0045727 positive regulation of translation GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046599 regulation of centriole replication GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051259 protein oligomerization GO:0060699 regulation of endoribonuclease activity GO:0060735 regulation of eIF2 alpha phosphorylation by dsRNA GO:1902629 regulation of mRNA stability involved in cellular response to UV GO:1902751 positive regulation of cell cycle G2/M phase transition
AY347529 - Homo sapiens nucleophosmin mRNA, complete cds. HM005441 - Homo sapiens clone HTL-T-128 testicular tissue protein Li 128 mRNA, complete cds. D28343 - Homo sapiens mRNA for nucleolar phosphoprotein B23, 5'UTR region. AK290652 - Homo sapiens cDNA FLJ76122 complete cds, highly similar to Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1), transcript variant 1, mRNA. BC107754 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:104254 IMAGE:6736004), complete cds. BC008495 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:14826 IMAGE:4276604), complete cds. BC012566 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:13433 IMAGE:4097025), complete cds. BC021668 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:22695 IMAGE:3930893), complete cds. DQ303464 - Homo sapiens mutant nucleolar phosphoprotein B23 (NPM1) mRNA, complete cds. BC016768 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:22724 IMAGE:4081364), complete cds. BC016824 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:24544 IMAGE:4106286), complete cds. BC016716 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:24404 IMAGE:4068167), complete cds. BC021983 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:22736 IMAGE:4106023), complete cds. BC014349 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:24185 IMAGE:3511037), complete cds. BC009623 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:17308 IMAGE:3877633), complete cds. LP947257 - Sequence 3 from Patent EP3203239. LZ177443 - JP 2017138189-A/1: Determination method of atrial fibrillation. M23613 - Human nucleophosmin mRNA, complete cds. M26697 - Human nucleolar protein (B23) mRNA, complete cds. BC002398 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:8463 IMAGE:2821577), complete cds. BC050628 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone MGC:60104 IMAGE:5575414), complete cds. BC020467 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone IMAGE:3872185). BC071891 - Homo sapiens cDNA clone IMAGE:4579479, **** WARNING: chimeric clone ****. M28699 - Homo sapiens nucleolar phosphoprotein B23 (NPM1) mRNA, complete cds. AY740634 - Homo sapiens nucleophosmin (NPM1) mRNA, NPM1-A allele, complete cds. AY740635 - Homo sapiens nucleophosmin (NPM1) mRNA, complete cds. AY740636 - Homo sapiens nucleophosmin (NPM1) mRNA, complete cds. AY740637 - Homo sapiens nucleophosmin (NPM1) mRNA, complete cds. AY740638 - Homo sapiens nucleophosmin (NPM1) mRNA, complete cds. AY740639 - Homo sapiens nucleophosmin (NPM1) mRNA, complete cds. AY740640 - Homo sapiens nucleophosmin (NPM1) mRNA, complete cds. LP947258 - Sequence 4 from Patent EP3203239. LZ177444 - JP 2017138189-A/2: Determination method of atrial fibrillation. BC063542 - Homo sapiens cDNA clone IMAGE:4525305, **** WARNING: chimeric clone ****. CU676967 - Synthetic construct Homo sapiens gateway clone IMAGE:100016987 5' read NPM1 mRNA. CU677717 - Synthetic construct Homo sapiens gateway clone IMAGE:100018085 5' read NPM1 mRNA. AB042278 - Homo sapiens mRNA for nucleophosmin/B23.2, complete cds. EF429251 - Homo sapiens truncated nucleolar phosphoprotein B23 (NPM1) mRNA, complete cds. CU680364 - Synthetic construct Homo sapiens gateway clone IMAGE:100023350 5' read NPM1 mRNA. CU692436 - Synthetic construct Homo sapiens gateway clone IMAGE:100018083 5' read NPM1 mRNA. AB451361 - Homo sapiens NPM1 mRNA for nucleophosmin 1 isoform 1, partial cds, clone: FLJ08034AAAF. AB463949 - Synthetic construct DNA, clone: pF1KB8236, Homo sapiens NPM1 gene for nucleophosmin, without stop codon, in Flexi system. KU178236 - Homo sapiens nucleophosmin isoform 1 (NPM1) mRNA, partial cds. KU178237 - Homo sapiens nucleophosmin isoform 2 (NPM1) mRNA, partial cds. DQ895223 - Synthetic construct Homo sapiens clone IMAGE:100009683; FLH182507.01L; RZPDo839G12137D nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1) gene, encodes complete protein. KJ905840 - Synthetic construct Homo sapiens clone ccsbBroadEn_15510 NPM1 gene, encodes complete protein. KJ905841 - Synthetic construct Homo sapiens clone ccsbBroadEn_15511 NPM1 gene, encodes complete protein. BT007011 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin) mRNA, complete cds. DQ892032 - Synthetic construct clone IMAGE:100004662; FLH182511.01X; RZPDo839G12138D nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1) gene, encodes complete protein. KJ891713 - Synthetic construct Homo sapiens clone ccsbBroadEn_01107 NPM1 gene, encodes complete protein. KJ897260 - Synthetic construct Homo sapiens clone ccsbBroadEn_06654 NPM1 gene, encodes complete protein. KJ897261 - Synthetic construct Homo sapiens clone ccsbBroadEn_06655 NPM1 gene, encodes complete protein. AB451236 - Homo sapiens NPM1 mRNA for nucleophosmin 1 isoform 1, complete cds, clone: FLJ08034AAAN. X16934 - Human hB23 gene for B23 nucleophosmin. DQ579020 - Homo sapiens piRNA piR-47132, complete sequence. AK000472 - Homo sapiens cDNA FLJ20465 fis, clone KAT06236. BC003670 - Homo sapiens nucleophosmin (nucleolar phosphoprotein B23, numatrin), mRNA (cDNA clone IMAGE:3932340), partial cds. KJ905842 - Synthetic construct Homo sapiens clone ccsbBroadEn_15512 NPM1 gene, encodes complete protein. DL492405 - Novel nucleic acids. DL492406 - Novel nucleic acids. DL490887 - Novel nucleic acids. JD437096 - Sequence 418120 from Patent EP1572962. JD310793 - Sequence 291817 from Patent EP1572962. M31004 - Human nuclear phosphoprotein B23 mRNA, clone hpB2. J02590 - Human nucleolar phosphoprotein B23 mRNA, clone hpB1. BC024716 - Homo sapiens cDNA clone IMAGE:3856933, with apparent retained intron. JD299587 - Sequence 280611 from Patent EP1572962. JD299586 - Sequence 280610 from Patent EP1572962. JD233784 - Sequence 214808 from Patent EP1572962. JD562621 - Sequence 543645 from Patent EP1572962. JD562620 - Sequence 543644 from Patent EP1572962. JD449611 - Sequence 430635 from Patent EP1572962. JD354959 - Sequence 335983 from Patent EP1572962. JD336921 - Sequence 317945 from Patent EP1572962. JD492400 - Sequence 473424 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P06748 (Reactome details) participates in the following event(s):
R-HSA-8869568 NPM1 binds TFAP2A homodimer R-HSA-180736 Disassembly of the Rev-importin beta-B23:Ran-GTP complex R-HSA-180725 Rev associates with B23 R-HSA-6801675 PLK2 phosphorylates NPM1 R-HSA-180728 Association of Ran-GTP with importin-beta R-HSA-180732 Translocation of Rev:importin-beta:B23 to the nucleus R-HSA-606326 HJURP:CENPA complex localizes to the centromere R-HSA-8869542 TFPA2A homodimer and NPM1 bind the HSPD1 gene promoter R-HSA-8869543 TFPA2A homodimer and NPM1 bind the NOP2 gene promoter R-HSA-8869549 TFPA2A homodimer and NPM1 bind the MYBL2 gene promoter R-HSA-180710 Rev:importin beta:B23 recruited to the nuclear pore R-HSA-8869496 TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation R-HSA-180746 Nuclear import of Rev protein R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors R-HSA-177243 Interactions of Rev with host cellular proteins R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes R-HSA-774815 Nucleosome assembly R-HSA-212436 Generic Transcription Pathway R-HSA-162909 Host Interactions of HIV factors R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-73886 Chromosome Maintenance R-HSA-73857 RNA Polymerase II Transcription R-HSA-162906 HIV Infection R-HSA-1640170 Cell Cycle R-HSA-74160 Gene expression (Transcription) R-HSA-5663205 Infectious disease R-HSA-1643685 Disease
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
