Q61937 (NPM_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nucleophosmin
Short name=NPM

Alternative name(s):
Nucleolar phosphoprotein B23
Nucleolar protein NO38
Numatrin

Gene names

Name:

Npm1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	292 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. 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 By similarity. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication By similarity.
Subunit structure	Decamer formed by two pentameric rings associated in a head-to-head fashion. Disulfide-linked dimers under certain conditions. Interacts with NSUN2 and SENP3 By similarity. The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70. Interacts with the methylated form of RPS10. Interacts (via N-terminal domain) with APEX1; the interaction is RNA-dependent and decreases peroxide-damaged cells. Interacts with NEK2. Interacts with ROCK2 and BRCA2 By similarity. Interacts with RPGR. Interacts with CENPW By similarity. Ref.5
Subcellular location	Nucleus › nucleolus. Nucleus › nucleoplasm By similarity. Cytoplasm › cytoskeleton › centrosome By similarity. Note: Generally nucleolar, but is translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. Co-localizes 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.
Tissue specificity	Expressed in B-cells that have been induced to switch to various Ig isotypes. Ref.5
Post-translational modification	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. Sumoylated by ARF By similarity.
Sequence similarities	Belongs to the nucleoplasmin family.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Nucleus
Ligand	DNA-binding RNA-binding
Molecular function	Chaperone
PTM	ADP-ribosylation Acetylation Disulfide bond Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from sequence or structural similarity. Source: UniProtKB cell aging Inferred from sequence or structural similarity. Source: UniProtKB cell growth Inferred from direct assay PubMed 18809582. Source: MGI cell volume homeostasis Inferred from direct assay PubMed 18809582. Source: MGI centrosome cycle Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of mRNA splicing, via spliceosome Inferred from direct assay PubMed 16376875. Source: MGI positive regulation of DNA replication Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from direct assay PubMed 18809582. Source: MGI positive regulation of cellular biosynthetic process Inferred from direct assay PubMed 18809582. Source: MGI positive regulation of centrosome duplication Inferred from genetic interaction PubMed 17015463. Source: MGI positive regulation of protein kinase activity Inferred from direct assay PubMed 17015463. Source: MGI protein homooligomerization Inferred from electronic annotation. Source: Compara protein localization Inferred from mutant phenotype PubMed 16199867. Source: MGI protein oligomerization Inferred from sequence orthology PubMed 18809582. Source: MGI rRNA export from nucleus Inferred from direct assay PubMed 18809582. Source: MGI regulation of DNA damage response, signal transduction by p53 class mediator Inferred from genetic interaction PubMed 16199867. Source: MGI regulation of centriole replication Inferred from sequence or structural similarity. Source: UniProtKB regulation of endodeoxyribonuclease activity Inferred from sequence or structural similarity. Source: UniProtKB regulation of endoribonuclease activity Inferred from sequence or structural similarity. Source: UniProtKB ribosomal large subunit biogenesis Inferred from mutant phenotype PubMed 18809582. Source: MGI ribosomal large subunit export from nucleus Inferred from mutant phenotype PubMed 18809582. Source: MGI ribosomal small subunit biogenesis Inferred from mutant phenotype PubMed 18809582. Source: MGI ribosomal small subunit export from nucleus Inferred from direct assay PubMed 18809582. Source: MGI
Cellular_component	centrosome Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from direct assay PubMed 18809582. Source: MGI granular component Inferred from direct assay PubMed 15485902. Source: MGI large ribosomal subunit Inferred from direct assay PubMed 18809582. Source: MGI nuclear speck Inferred from direct assay PubMed 16376875. Source: MGI small ribosomal subunit Inferred from direct assay PubMed 18809582. Source: MGI
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW NF-kappaB binding Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol-3,4,5-trisphosphate binding Inferred from electronic annotation. Source: Compara rRNA binding Inferred from direct assay PubMed 15596447PubMed 18809582. Source: MGI ribosomal large subunit binding Inferred from sequence orthology PubMed 18809582. Source: MGI ribosomal small subunit binding Inferred from sequence orthology PubMed 18809582. Source: MGI unfolded protein binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	2	EBI-626362,EBI-389668	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 292	292	Nucleophosmin		PRO_0000219482
Regions
	Region	1 – 185	185	Required for interaction with SENP3 By similarity
	Region	1 – 117	117	Necessary for interaction with APEX1 By similarity
	Region	241 – 292	52	Required for nucleolar localization By similarity
	Motif	152 – 157	6	Nuclear localization signal Potential
	Motif	190 – 196	7	Nuclear localization signal Potential
	Compositional bias	1 – 9	9	Met-rich
	Compositional bias	120 – 132	13	Asp/Glu-rich (acidic)
	Compositional bias	158 – 187	30	Asp/Glu-rich (highly acidic)
Sites
	Site	55	1	Interaction between pentamers By similarity
	Site	80	1	Interaction between pentamers By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine By similarity
	Modified residue	4	1	Phosphoserine; by PLK1 and PLK2 By similarity
	Modified residue	10	1	Phosphoserine By similarity
	Modified residue	32	1	N6-acetyllysine By similarity
	Modified residue	70	1	Phosphoserine Ref.10 Ref.11
	Modified residue	75	1	Phosphothreonine By similarity
	Modified residue	95	1	Phosphothreonine By similarity
	Modified residue	106	1	Phosphoserine By similarity
	Modified residue	125	1	Phosphoserine Ref.7 Ref.9 Ref.11 Ref.12
	Modified residue	139	1	Phosphoserine By similarity
	Modified residue	150	1	N6-acetyllysine By similarity
	Modified residue	154	1	N6-acetyllysine By similarity
	Modified residue	198	1	Phosphothreonine; by CDK1 and CDK2 By similarity
	Modified residue	211	1	N6-acetyllysine By similarity
	Modified residue	217	1	Phosphothreonine; by CDK1 By similarity
	Modified residue	225	1	Phosphoserine By similarity
	Modified residue	227	1	N6-acetyllysine By similarity
	Modified residue	228	1	N6-acetyllysine By similarity
	Modified residue	232	1	Phosphothreonine; by CDK1 By similarity
	Modified residue	235	1	Phosphothreonine; by CDK1 By similarity
	Modified residue	240	1	Phosphoserine By similarity
	Modified residue	241	1	Phosphoserine By similarity
	Modified residue	248	1	N6-acetyllysine By similarity
	Modified residue	252	1	Phosphoserine Ref.6
	Modified residue	255	1	N6-acetyllysine By similarity
	Modified residue	258	1	Phosphoserine Ref.6 Ref.8
	Modified residue	265	1	N6-acetyllysine By similarity
	Modified residue	271	1	N6-acetyllysine By similarity
	Modified residue	277	1	Phosphothreonine By similarity
	Modified residue	290	1	N6-acetyllysine By similarity
	Cross-link	228		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	261		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q61937 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: E68750C549ED25E6	FASTA	292	32,560
	10 20 30 40 50 60 MEDSMDMDMS PLRPQNYLFG CELKADKDYH FKVDNDENEH QLSLRTVSLG AGAKDELHIV 70 80 90 100 110 120 EAEAMNYEGS PIKVTLATLK MSVQPTVSLG GFEITPPVVL RLKCGSGPVH ISGQHLVAVE 130 140 150 160 170 180 EDAESEDEDE EDVKLLGMSG KRSAPGGGNK VPQKKVKLDE DDEDDDEDDE DDEDDDDDDF 190 200 210 220 230 240 DEEETEEKVP VKKSVRDTPA KNAQKSNQNG KDLKPSTPRS KGQESFKKQE KTPKTPKGPS 250 260 270 280 290 SVEDIKAKMQ ASIEKGGSLP KVEAKFINYV KNCFRMTDQE AIQDLWQWRK SL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DNA cloning and amino acid sequence determination of a major constituent protein of mammalian nucleoli. Correspondence of the nucleoplasmin-related protein NO38 to mammalian protein B23." Schmidt-Zachmann M.S., Franke W.W. Chromosoma 96:417-426(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Embryo.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[4]	Lubec G., Yang J.W., Zigmond M. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 33-45. Tissue: Brain.
[5]	"A B-cell-specific DNA recombination complex." Borggrefe T., Wabl M., Akhmedov A.T., Jessberger R. J. Biol. Chem. 273:17025-17035(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 46-52 AND 266-271, SUBUNIT, TISSUE SPECIFICITY. Strain: C57BL/6. Tissue: Spleen.
[6]	"Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line." Shu H., Chen S., Bi Q., Mumby M., Brekken D.L. Mol. Cell. Proteomics 3:279-286(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252 AND SER-258, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[7]	"Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, MASS SPECTROMETRY. Tissue: Brain.
[8]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, MASS SPECTROMETRY. Tissue: Liver.
[9]	"Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis." Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H. J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, MASS SPECTROMETRY. Tissue: Melanoma.
[11]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70 AND SER-125, MASS SPECTROMETRY. Tissue: Macrophage.
[12]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M33212 mRNA. Translation: AAA39801.1. AK028253 mRNA. Translation: BAC25844.1. BC054755 mRNA. Translation: AAH54755.1.
IPI	IPI00127415.
PIR	I52858.
RefSeq	NP_032748.1. NM_008722.3.
UniGene	Mm.485384.
3D structure databases
ProteinModelPortal	Q61937.
SMR	Q61937. Positions 15-118, 223-292.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q61937. 2 interactions.
MINT	MINT-270928.
PTM databases
PhosphoSite	Q61937.
Proteomic databases
PaxDb	Q61937.
PRIDE	Q61937.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000075641; ENSMUSP00000075067; ENSMUSG00000057113.
GeneID	18148.
KEGG	mmu:18148.
Organism-specific databases
CTD	4869.
MGI	MGI:106184. Npm1.
Phylogenomic databases
eggNOG	NOG79897.
GeneTree	ENSGT00440000034554.
HOGENOM	HOG000013061.
HOVERGEN	HBG001860.
InParanoid	Q61937.
KO	K11276.
OMA	NCFRTED.
OrthoDB	EOG4W3SNZ.
Gene expression databases
ArrayExpress	Q61937.
Bgee	Q61937.
CleanEx	MM_NPM1.
Genevestigator	Q61937.
GermOnline	ENSMUSG00000057113. Mus musculus.
Family and domain databases
Gene3D	2.60.120.340. 1 hit.
InterPro	IPR004301. Nucleoplasmin. IPR024057. Nucleoplasmin_core_dom. [Graphical view]
PANTHER	PTHR22747. PTHR22747. 1 hit.
SUPFAM	SSF69203. Nucleoplasmin. 1 hit.
ProtoNet	Search...
Other
ChEMBL	CHEMBL5386.
NextBio	293410.
SOURCE	Search...

Entry information

Entry name

NPM_MOUSE

Accession

Primary (citable) accession number: Q61937

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program