MGP Database

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MGP002124

UniProt Annotations

Entry Information
Gene Namenucleophosmin (nucleolar phosphoprotein B23, numatrin)
Protein EntryNPM_HUMAN
UniProt IDP06748
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=P06748-1; Sequence=Displayed; Name=2; IsoId=P06748-2; Sequence=VSP_003616; Name=3; IsoId=P06748-3; Sequence=VSP_043599; Note=Contains a N6-acetyllysine at position 257.;
DiseaseNote=A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with MLF1.
DiseaseNote=A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) with RARA.
DiseaseNote=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.
DiseaseNote=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.
FunctionInvolved 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. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. {ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061}.
InteractionQ98147:- (xeno); NbExp=2; IntAct=EBI-78579, EBI-626601; O14965:AURKA; NbExp=3; IntAct=EBI-78579, EBI-448680; Q96GD4:AURKB; NbExp=5; IntAct=EBI-78579, EBI-624291; Q8N726:CDKN2A; NbExp=2; IntAct=EBI-78579, EBI-625922; Q10570:CPSF1; NbExp=2; IntAct=EBI-78579, EBI-347859; P19525:EIF2AK2; NbExp=3; IntAct=EBI-78579, EBI-640775; Q9BZQ8:FAM129A; NbExp=7; IntAct=EBI-78579, EBI-6916466; Q13547:HDAC1; NbExp=2; IntAct=EBI-78579, EBI-301834; Q92769:HDAC2; NbExp=2; IntAct=EBI-78579, EBI-301821; Q9BXL5:HEMGN; NbExp=7; IntAct=EBI-78579, EBI-3916399; P24938:L2 (xeno); NbExp=4; IntAct=EBI-78579, EBI-7481199; P68951:L2 (xeno); NbExp=5; IntAct=EBI-78579, EBI-7481182; Q00987:MDM2; NbExp=5; IntAct=EBI-78579, EBI-389668; Q8IZL8:PELP1; NbExp=3; IntAct=EBI-78579, EBI-716449; B1Q2W9:pre-C/C (xeno); NbExp=8; IntAct=EBI-78579, EBI-9081051; Q9H4L4:SENP3; NbExp=6; IntAct=EBI-78579, EBI-2880236; P05549:TFAP2A; NbExp=6; IntAct=EBI-78579, EBI-347351; P04637:TP53; NbExp=6; IntAct=EBI-78579, EBI-366083; P63104:YWHAZ; NbExp=2; IntAct=EBI-78579, EBI-347088;
PtmAcetylated at C-terminal lysine residues, thereby increasing affinity to histones. {ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:16916647, ECO:0000269|PubMed:19413330, ECO:0000269|PubMed:19608861, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:22223895, ECO:0000269|Ref.17}.
PtmADP-ribosylated.
PtmPhosphorylated 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. {ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:12058066, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:15190079, ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:17924679, ECO:0000269|PubMed:18220336, ECO:0000269|PubMed:18318008, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:19369195, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21406692, ECO:0000269|Ref.17}.
PtmSumoylated by ARF. {ECO:0000269|PubMed:15897463}.
SimilarityBelongs to the nucleoplasmin family. {ECO:0000305}.
Subcellular LocationNucleus, nucleolus. Nucleus, nucleoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, 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.
SubunitDecamer 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. Interacts with EIF2AK2/PKR. {ECO:0000250, ECO:0000269|PubMed:11309377, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:15772089, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:17215513, ECO:0000269|PubMed:18259216, ECO:0000269|PubMed:19015314, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20159986, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:8314759}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NPM1ID22.html";
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