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Protein

Nucleophosmin

Gene

Npm1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade.By similarity

GO - Molecular functioni

  • ATP binding Source: RGD
  • DNA binding Source: RGD
  • enzyme binding Source: RGD
  • NF-kappaB binding Source: UniProtKB
  • p53 binding Source: RGD
  • phosphatidylinositol-3,4,5-trisphosphate binding Source: RGD
  • protein kinase B binding Source: RGD
  • protein kinase inhibitor activity Source: UniProtKB
  • rRNA binding Source: Ensembl
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone

Keywords - Ligandi

DNA-binding, RNA-binding

Enzyme and pathway databases

ReactomeiR-RNO-606279. Deposition of new CENPA-containing nucleosomes at the centromere.
R-RNO-6804115. TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
R-RNO-8869496. TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation.

Names & Taxonomyi

Protein namesi
Recommended name:
Nucleophosmin
Short name:
NPM
Alternative name(s):
Nucleolar phosphoprotein B23
Nucleolar protein NO38
Numatrin
Gene namesi
Name:Npm1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi3192. Npm1.

Subcellular locationi

  • Nucleusnucleolus
  • Nucleusnucleoplasm By similarity
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity

  • Note: Generally nucleolar, but is translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. Colocalizes with the methylated form of RPS10 in the granular component (GC) region of the nucleolus. Colocalized with nucleolin and APEX1 in nucleoli. NEK2 is required for its localization to the centrosome during mitosis (By similarity).By similarity

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Ensembl
  • granular component Source: Ensembl
  • large ribosomal subunit Source: Ensembl
  • nuclear matrix Source: RGD
  • nuclear speck Source: Ensembl
  • nucleolus Source: RGD
  • nucleoplasm Source: RGD
  • nucleus Source: UniProtKB
  • small ribosomal subunit Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002194831 – 292NucleophosminAdd BLAST292

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei4Phosphoserine; by PLK1 and PLK2By similarity1
Modified residuei10PhosphoserineBy similarity1
Cross-linki27Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei32N6-acetyllysine; alternateBy similarity1
Cross-linki32Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki32Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei43PhosphoserineBy similarity1
Modified residuei70PhosphoserineBy similarity1
Modified residuei75PhosphothreonineBy similarity1
Modified residuei95PhosphothreonineBy similarity1
Modified residuei125Phosphoserine; by CDK2By similarity1
Modified residuei139PhosphoserineBy similarity1
Modified residuei150N6-acetyllysineBy similarity1
Modified residuei154N6-acetyllysineBy similarity1
Modified residuei198Phosphothreonine; by CDK1 and CDK2By similarity1
Modified residuei211N6-acetyllysineBy similarity1
Cross-linki214Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei217Phosphothreonine; by CDK1By similarity1
Modified residuei225PhosphoserineBy similarity1
Modified residuei227N6-acetyllysineBy similarity1
Modified residuei228N6-acetyllysine; alternateBy similarity1
Cross-linki228Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Modified residuei232Phosphothreonine; by CDK1By similarity1
Modified residuei235Phosphothreonine; by CDK1By similarity1
Modified residuei240PhosphoserineBy similarity1
Modified residuei241PhosphoserineBy similarity1
Cross-linki246Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki246Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei248N6-acetyllysine; alternateBy similarity1
Cross-linki248Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei252PhosphoserineBy similarity1
Modified residuei255N6-acetyllysine; alternateBy similarity1
Cross-linki255Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki255Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei258PhosphoserineBy similarity1
Cross-linki261Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei265N6-acetyllysine; alternateBy similarity1
Cross-linki265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Modified residuei271N6-acetyllysineBy similarity1
Modified residuei277PhosphothreonineBy similarity1
Modified residuei290N6-acetyllysineBy similarity1

Post-translational modificationi

Acetylated at C-terminal lysine residues, thereby increasing affinity to histones.By similarity
ADP-ribosylated.By similarity
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-198. Phosphorylation at Thr-198 may trigger initiation of centrosome duplication. Phosphorylated by CDK1 at Thr-198, Thr-217, Thr-232 and Thr-235 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-198 phosphorylated form has higher affinity for ROCK2 (By similarity).By similarity
Sumoylated by ARF.By similarity
The N-terminus is blocked.

Keywords - PTMi

Acetylation, ADP-ribosylation, Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP13084.
PRIDEiP13084.

2D gel databases

World-2DPAGE0004:P13084.

PTM databases

iPTMnetiP13084.
PhosphoSitePlusiP13084.
SwissPalmiP13084.

Expressioni

Gene expression databases

BgeeiENSRNOG00000004616.
GenevisibleiP13084. RN.

Interactioni

Subunit structurei

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. Interacts with NSUN2 and SENP3. 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 NEK2. Interacts with ROCK2 and BRCA2 (By similarity). Interacts with RPGR. Interacts with CENPW (By similarity). Interacts with EIF2AK2/PKR (By similarity). Interacts with CEBPA (isoform 4) (PubMed:20075868). Interacts with DDX31; this interaction prevents interaction between NPM1 and HDM2 (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei55Interaction between pentamersBy similarity1
Sitei80Interaction between pentamersBy similarity1

GO - Molecular functioni

  • enzyme binding Source: RGD
  • NF-kappaB binding Source: UniProtKB
  • p53 binding Source: RGD
  • protein kinase B binding Source: RGD
  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi247531. 3 interactors.
IntActiP13084. 1 interactor.
MINTiMINT-4587645.
STRINGi10116.ENSRNOP00000006591.

Structurei

3D structure databases

ProteinModelPortaliP13084.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 185Required for interaction with SENP3By similarityAdd BLAST185
Regioni1 – 117Necessary for interaction with APEX1By similarityAdd BLAST117
Regioni241 – 292Required for nucleolar localizationBy similarityAdd BLAST52

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi152 – 157Nuclear localization signalSequence analysis6
Motifi190 – 196Nuclear localization signalSequence analysis7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1 – 9Met-rich9
Compositional biasi120 – 132Asp/Glu-rich (acidic)Add BLAST13
Compositional biasi158 – 187Asp/Glu-rich (highly acidic)Add BLAST30

Sequence similaritiesi

Belongs to the nucleoplasmin family.Curated

Phylogenomic databases

eggNOGiENOG410IHZM. Eukaryota.
ENOG4111IKX. LUCA.
GeneTreeiENSGT00440000034554.
HOGENOMiHOG000013061.
HOVERGENiHBG001860.
InParanoidiP13084.
KOiK11276.
OMAiKMQASVD.
OrthoDBiEOG091G0NLY.
PhylomeDBiP13084.
TreeFamiTF327704.

Family and domain databases

Gene3Di2.60.120.340. 1 hit.
InterProiIPR032569. NPM1_C.
IPR004301. Nucleoplasmin.
IPR024057. Nucleoplasmin_core_dom.
[Graphical view]
PANTHERiPTHR22747. PTHR22747. 1 hit.
PfamiPF16276. NPM1-C. 1 hit.
PF03066. Nucleoplasmin. 1 hit.
[Graphical view]
SUPFAMiSSF69203. SSF69203. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform B23.1 (identifier: P13084-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEDSMDMDMS PLRPQNYLFG CELKADKDYH FKVDNDENEH QLSLRTVSLG
60 70 80 90 100
AGAKDELHIV EAEAMNYEGS PIKVTLATLK MSVQPTVSLG GFEITPPVVL
110 120 130 140 150
RLKCGSGPVH ISGQHLVAVE EDAESEDEDE EDVKLLGMSG KRSAPGGGNK
160 170 180 190 200
VPQKKVKLDE DDDEDDEDDE DDEDDDDDDF DEEETEEKVP VKKSVRDTPA
210 220 230 240 250
KNAQKSNQNG KDLKPSTPRS KGQESFKKQE KTPKTPKGPS SVEDIKAKMQ
260 270 280 290
ASIEKGGSLP KVEAKFINYV KNCFRMTDQE AIQDLWQWRK SL
Length:292
Mass (Da):32,560
Last modified:January 1, 1990 - v1
Checksum:i1372A474F9ED2457
GO
Isoform B23.2 (identifier: P13084-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     256-292: GGSLPKVEAKFINYVKNCFRMTDQEAIQDLWQWRKSL → AH

Show »
Length:257
Mass (Da):28,385
Checksum:i7271F6D962A63D6C
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003617256 – 292GGSLP…WRKSL → AH in isoform B23.2. 2 PublicationsAdd BLAST37

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03969 mRNA. Translation: AAA40796.1.
M37039
, M37035, M37036, M37037, M37038 Genomic DNA. Translation: AAA41730.1.
M37041
, M37035, M37036, M37037, M37038, M37040 Genomic DNA. Translation: AAA41731.1.
M25062 Genomic DNA. Translation: AAA40795.1.
J04943 mRNA. Translation: AAA40794.1.
J04944 Genomic DNA. Translation: AAA40793.1.
BC060579 mRNA. Translation: AAH60579.1.
BC088088 mRNA. Translation: AAH88088.1.
PIRiA28939.
A36089.
B36089. A34168.
RefSeqiNP_037124.1. NM_012992.4. [P13084-1]
UniGeneiRn.54537.

Genome annotation databases

EnsembliENSRNOT00000006591; ENSRNOP00000006591; ENSRNOG00000004616. [P13084-1]
ENSRNOT00000064744; ENSRNOP00000062356; ENSRNOG00000004616. [P13084-2]
GeneIDi25498.
KEGGirno:25498.
UCSCiRGD:3192. rat. [P13084-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J03969 mRNA. Translation: AAA40796.1.
M37039
, M37035, M37036, M37037, M37038 Genomic DNA. Translation: AAA41730.1.
M37041
, M37035, M37036, M37037, M37038, M37040 Genomic DNA. Translation: AAA41731.1.
M25062 Genomic DNA. Translation: AAA40795.1.
J04943 mRNA. Translation: AAA40794.1.
J04944 Genomic DNA. Translation: AAA40793.1.
BC060579 mRNA. Translation: AAH60579.1.
BC088088 mRNA. Translation: AAH88088.1.
PIRiA28939.
A36089.
B36089. A34168.
RefSeqiNP_037124.1. NM_012992.4. [P13084-1]
UniGeneiRn.54537.

3D structure databases

ProteinModelPortaliP13084.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247531. 3 interactors.
IntActiP13084. 1 interactor.
MINTiMINT-4587645.
STRINGi10116.ENSRNOP00000006591.

PTM databases

iPTMnetiP13084.
PhosphoSitePlusiP13084.
SwissPalmiP13084.

2D gel databases

World-2DPAGE0004:P13084.

Proteomic databases

PaxDbiP13084.
PRIDEiP13084.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000006591; ENSRNOP00000006591; ENSRNOG00000004616. [P13084-1]
ENSRNOT00000064744; ENSRNOP00000062356; ENSRNOG00000004616. [P13084-2]
GeneIDi25498.
KEGGirno:25498.
UCSCiRGD:3192. rat. [P13084-1]

Organism-specific databases

CTDi4869.
RGDi3192. Npm1.

Phylogenomic databases

eggNOGiENOG410IHZM. Eukaryota.
ENOG4111IKX. LUCA.
GeneTreeiENSGT00440000034554.
HOGENOMiHOG000013061.
HOVERGENiHBG001860.
InParanoidiP13084.
KOiK11276.
OMAiKMQASVD.
OrthoDBiEOG091G0NLY.
PhylomeDBiP13084.
TreeFamiTF327704.

Enzyme and pathway databases

ReactomeiR-RNO-606279. Deposition of new CENPA-containing nucleosomes at the centromere.
R-RNO-6804115. TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
R-RNO-8869496. TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation.

Miscellaneous databases

PROiP13084.

Gene expression databases

BgeeiENSRNOG00000004616.
GenevisibleiP13084. RN.

Family and domain databases

Gene3Di2.60.120.340. 1 hit.
InterProiIPR032569. NPM1_C.
IPR004301. Nucleoplasmin.
IPR024057. Nucleoplasmin_core_dom.
[Graphical view]
PANTHERiPTHR22747. PTHR22747. 1 hit.
PfamiPF16276. NPM1-C. 1 hit.
PF03066. Nucleoplasmin. 1 hit.
[Graphical view]
SUPFAMiSSF69203. SSF69203. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNPM_RAT
AccessioniPrimary (citable) accession number: P13084
Secondary accession number(s): Q63698, Q64269
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: November 30, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.