P13084 (NPM_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

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. 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.
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.
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. The N-terminus is blocked.
Sequence similarities	Belongs to the nucleoplasmin family.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Alternative splicing
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 electronic annotation. Source: Compara cell volume homeostasis Inferred from electronic annotation. Source: Compara 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 electronic annotation. Source: Compara positive regulation of DNA replication Inferred from direct assay PubMed 11481036. Source: RGD positive regulation of catalytic activity Inferred from direct assay PubMed 11481036. Source: RGD positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of centrosome duplication Inferred from electronic annotation. Source: Compara positive regulation of protein kinase activity Inferred from electronic annotation. Source: Compara protein homooligomerization Inferred from direct assay PubMed 8611572. Source: RGD protein localization Inferred from electronic annotation. Source: Compara rRNA export from nucleus Inferred from electronic annotation. Source: Compara regulation of DNA damage response, signal transduction by p53 class mediator Inferred from electronic annotation. Source: Compara 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 regulation of neuron apoptotic process Inferred from mutant phenotype PubMed 15893727. Source: RGD ribosomal large subunit biogenesis Inferred from electronic annotation. Source: Compara ribosomal large subunit export from nucleus Inferred from electronic annotation. Source: Compara ribosomal small subunit biogenesis Inferred from electronic annotation. Source: Compara ribosomal small subunit export from nucleus Inferred from electronic annotation. Source: Compara
Cellular_component	centrosome Inferred from sequence or structural similarity. Source: UniProtKB cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB cytosol Inferred from electronic annotation. Source: Compara granular component Inferred from electronic annotation. Source: Compara large ribosomal subunit Inferred from electronic annotation. Source: Compara nuclear speck Inferred from electronic annotation. Source: Compara nucleolus Inferred from direct assay PubMed 12450141. Source: RGD small ribosomal subunit Inferred from electronic annotation. Source: Compara
Molecular_function	DNA binding Inferred from direct assay PubMed 8611572. Source: RGD NF-kappaB binding Inferred from sequence or structural similarity. Source: UniProtKB enzyme binding Inferred from direct assay PubMed 11481036. Source: RGD phosphatidylinositol-3,4,5-trisphosphate binding Inferred from physical interaction PubMed 15893727. Source: RGD rRNA binding Inferred from electronic annotation. Source: Compara unfolded protein binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform B23.1 (identifier: P13084-1)

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.

Isoform B23.2 (identifier: P13084-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 292	292	Nucleophosmin		PRO_0000219483
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 By similarity
	Modified residue	75	1	Phosphothreonine By similarity
	Modified residue	95	1	Phosphothreonine By similarity
	Modified residue	106	1	Phosphoserine Ref.6
	Modified residue	125	1	Phosphoserine; by CDK2 Ref.6
	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 By similarity
	Modified residue	255	1	N6-acetyllysine By similarity
	Modified residue	258	1	Phosphoserine By similarity
	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
Natural variations
	Alternative sequence	256 – 292	37	GGSLP…WRKSL → AH in isoform B23.2.		VSP_003617

Sequences

	Sequence		Length	Mass (Da)
	Isoform B23.1 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: 1372A474F9ED2457	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 DDDEDDEDDE DDEDDDDDDF 190 200 210 220 230 240 DEEETEEKVP VKKSVRDTPA KNAQKSNQNG KDLKPSTPRS KGQESFKKQE KTPKTPKGPS 250 260 270 280 290 SVEDIKAKMQ ASIEKGGSLP KVEAKFINYV KNCFRMTDQE AIQDLWQWRK SL
	Isoform B23.2 [UniParc]. Checksum: 7271F6D962A63D6C	FASTA	257	28,385
	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 DDDEDDEDDE DDEDDDDDDF 190 200 210 220 230 240 DEEETEEKVP VKKSVRDTPA KNAQKSNQNG KDLKPSTPRS KGQESFKKQE KTPKTPKGPS 250 SVEDIKAKMQ ASIEKAH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA and deduced primary structure of rat protein B23, a nucleolar protein containing highly conserved sequences." Chang J.-H., Dumbar T.S., Olson M.O.J. J. Biol. Chem. 263:12824-12827(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B23.1 AND B23.2), PARTIAL PROTEIN SEQUENCE.
[2]	"A single gene codes for two forms of rat nucleolar protein B23 mRNA." Chang J.-H., Olson M.O.J. J. Biol. Chem. 264:11732-11737(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM B23.2).
[3]	"Structure of the gene for rat nucleolar protein B23." Chang J.-H., Olson M.O.J. J. Biol. Chem. 265:18227-18233(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS B23.1 AND B23.2).
[4]	"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] (ISOFORM B23.1). Tissue: Pituitary and Thymus.
[5]	Lubec G., Chen W.-Q. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 55-101; 238-246 AND 266-271, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus.
[6]	"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites." Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A. Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106 AND SER-125, MASS SPECTROMETRY. Tissue: Renal collecting duct.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00197553. IPI00230893.
PIR	A28939. A36089. A34168. B36089.
RefSeq	NP_037124.1. NM_012992.4.
UniGene	Rn.54537.
3D structure databases
ProteinModelPortal	P13084.
SMR	P13084. Positions 15-118, 241-292.
ModBase	Search...
PTM databases
PhosphoSite	P13084.
2D gel databases
World-2DPAGE	0004:P13084.
Proteomic databases
PaxDb	P13084.
PRIDE	P13084.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000006591; ENSRNOP00000006591; ENSRNOG00000004616. ENSRNOT00000064744; ENSRNOP00000062356; ENSRNOG00000004616.
GeneID	25498.
KEGG	rno:25498.
UCSC	RGD:3192. rat.
Organism-specific databases
CTD	4869.
RGD	3192. Npm1.
Phylogenomic databases
eggNOG	NOG79897.
GeneTree	ENSGT00440000034554.
HOGENOM	HOG000013061.
HOVERGEN	HBG001860.
InParanoid	P13084.
KO	K11276.
OMA	NCFRTED.
OrthoDB	EOG4W3SNZ.
Gene expression databases
ArrayExpress	P13084.
Genevestigator	P13084.
GermOnline	ENSRNOG00000004616. Rattus norvegicus.
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
NextBio	606897.

Entry information

Entry name

NPM_RAT

Accession

Primary (citable) accession number: P13084
Secondary accession number(s): Q63698, Q64269

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	May 1, 2013
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program