UniProt Accession

 NPM_HUMAN; P06748; A8K3N7; B5BU00; D3DQL6; P08693; Q12826; Q13440; Q13441; Q14115; Q5EU94; Q5EU95; Q5EU96; Q5EU97; Q5EU98; Q5EU99; Q6V962; Q8WTW5; Q96AT6; Q96DC4; Q96EA5; Q9BYG9; Q9UDJ7 

Genbank Protein ID

 M23613; M28699; M26697; U89321; U89309; U89310; U89311; U89313; U89314; U89317; U89319; AB042278; AY740634; AY740635; AY740636; AY740637; AY740638; AY740639; AY740640; DQ303464; AY347529; BT007011; AK290652; AB451236; AB451361; CH471062; CH471062; BC002398; BC008495; BC009623; BC012566; BC014349; BC016716; BC016768; BC016824; BC021668; BC021983; BC050628; BC107754; U41742; U41743; U04946; D45915; X16934; J02590; M31004 

Genbank Nucleotide ID

 AAA36380.1; AAA58386.1; AAA36385.1; AAB94739.1; AAB94739.1; AAB94739.1; AAB94739.1; AAB94739.1; AAB94739.1; AAB94739.1; AAB94739.1; BAB40600.1; AAW67752.1; AAW67753.1; AAW67754.1; AAW67755.1; AAW67756.1; AAW67757.1; AAW67758.1; ABC40399.1; AAQ24860.1; AAP35657.1; BAF83341.1; BAG70050.1; BAG70175.1; EAW61443.1; EAW61446.1; AAH02398.1; AAH08495.1; AAH09623.1; AAH12566.1; AAH14349.1; AAH16716.1; AAH16768.1; AAH16824.1; AAH21668.1; AAH21983.1; AAH50628.1; AAI07755.1; AAB00112.1; AAB00113.1; AAA58698.1; BAA08343.1; CAA34809.1; AAA36473.1; AAA36474.1 

Protein Name

 Nucleophosmin 

Protein Synonyms/Alias

 NPM; Nucleolar phosphoprotein B23; Nucleolar protein NO38; Numatrin 

Gene Name

 NPM1 

Gene Synonyms/Alias

 NPM 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
27	GCELKADKDYHFKVD	acetylation	[1, 2]
27	GCELKADKDYHFKVD	ubiquitination	[2, 3, 4]
32	ADKDYHFKVDNDENE	acetylation	[1, 2]
32	ADKDYHFKVDNDENE	ubiquitination	[2, 3, 4, 5, 6, 7, 8, 9]
54	VSLGAGAKDELHIVE	acetylation	[2, 10, 11]
54	VSLGAGAKDELHIVE	ubiquitination	[3, 6, 7]
141	KLLSISGKRSAPGGG	acetylation	[12]
141	KLLSISGKRSAPGGG	ubiquitination	[3, 5, 6, 8, 9]
150	SAPGGGSKVPQKKVK	acetylation	[1, 13]
154	GGSKVPQKKVKLAAD	acetylation	[13]
155	GSKVPQKKVKLAADE	ubiquitination	[6]
157	KVPQKKVKLAADEDD	ubiquitination	[6]
189	DDEEAEEKAPVKKSI	ubiquitination	[6]
193	AEEKAPVKKSIRDTP	ubiquitination	[6]
202	SIRDTPAKNAQKSNQ	acetylation	[14]
202	SIRDTPAKNAQKSNQ	ubiquitination	[3, 6]
212	QKSNQNGKDSKPSST	acetylation	[2, 13, 15, 16]
215	NQNGKDSKPSSTPRS	acetylation	[2, 16]
215	NQNGKDSKPSSTPRS	sumoylation	[17]
223	PSSTPRSKGQESFKK	acetylation	[2]
229	SKGQESFKKQEKTPK	acetylation	[2, 15, 16]
229	SKGQESFKKQEKTPK	ubiquitination	[6]
230	KGQESFKKQEKTPKT	acetylation	[15, 16]
230	KGQESFKKQEKTPKT	sumoylation	[18, 19]
239	EKTPKTPKGPSSVED	ubiquitination	[2, 3]
248	PSSVEDIKAKMQASI	acetylation	[2, 10]
248	PSSVEDIKAKMQASI	sumoylation	[17]
248	PSSVEDIKAKMQASI	ubiquitination	[2, 3, 6, 7, 8, 20]
250	SVEDIKAKMQASIEK	acetylation	[15]
250	SVEDIKAKMQASIEK	ubiquitination	[2, 3, 6, 8]
257	KMQASIEKGGSLPKV	acetylation	[1, 2, 10, 15, 16]
257	KMQASIEKGGSLPKV	ubiquitination	[2, 3, 6, 8]
263	EKGGSLPKVEAKFIN	sumoylation	[18, 19, 21, 22]
263	EKGGSLPKVEAKFIN	ubiquitination	[2, 3, 8]
267	SLPKVEAKFINYVKN	acetylation	[1, 2, 10, 11, 14, 16, 23, 24]
267	SLPKVEAKFINYVKN	ubiquitination	[2, 3, 4, 5, 8, 9, 25]
273	AKFINYVKNCFRMTD	acetylation	[1, 10, 24]
273	AKFINYVKNCFRMTD	ubiquitination	[3, 5, 7, 8, 9, 25]
292	QDLWQWRKSL*****	acetylation	[15, 16]

Reference

 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [9] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [10] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [11] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [12] Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.
 Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, López-Otín C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G.
 J Cell Biol. 2011 Feb 21;192(4):615-29. [PMID: 21339330]
 [13] Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
 Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J, Cheng T, Kho Y, Xiao H, Xiao L, Grishin NV, White M, Yang XJ, Zhao Y.
 Mol Cell. 2006 Aug;23(4):607-18. [PMID: 16916647]
 [14] Proteome-wide prediction of acetylation substrates.
 Basu A, Rose KL, Zhang J, Beavis RC, Ueberheide B, Garcia BA, Chait B, Zhao Y, Hunt DF, Segal E, Allis CD, Hake SB.
 Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13785-90. [PMID: 19666589]
 [15] Human histone chaperone nucleophosmin enhances acetylation-dependent chromatin transcription.
 Swaminathan V, Kishore AH, Febitha KK, Kundu TK.
 Mol Cell Biol. 2005 Sep;25(17):7534-45. [PMID: 16107701]
 [16] Acetylated NPM1 localizes in the nucleoplasm and regulates transcriptional activation of genes implicated in oral cancer manifestation.
 Shandilya J, Swaminathan V, Gadad SS, Choudhari R, Kodaganur GS, Kundu TK.
 Mol Cell Biol. 2009 Sep;29(18):5115-27. [PMID: 19581289]
 [17] Targeted identification of SUMOylation sites in human proteins using affinity enrichment and paralog-specific reporter ions.
 Lamoliatte F, Bonneil E, Durette C, Caron-Lizotte O, Wildemann D, Zerweck J, Wenschuh H, Thibault P.
 Mol Cell Proteomics. 2013 Jun 7;. [PMID: 23750026]
 [18] Sumoylation of nucleophosmin/B23 regulates its subcellular localization, mediating cell proliferation and survival.
 Liu X, Liu Z, Jang SW, Ma Z, Shinmura K, Kang S, Dong S, Chen J, Fukasawa K, Ye K.
 Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9679-84. [PMID: 17535915]
 [19] Nuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival.
 Lee SB, Xuan Nguyen TL, Choi JW, Lee KH, Cho SW, Liu Z, Ye K, Bae SS, Ahn JY.
 Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16584-9. [PMID: 18931307]
 [20] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [21] Ebp1 association with nucleophosmin/B23 is essential for regulating cell proliferation and suppressing apoptosis.
 Okada M, Jang SW, Ye K.
 J Biol Chem. 2007 Dec 14;282(50):36744-54. [PMID: 17951246]
 [22] Lysine 263 residue of NPM/B23 is essential for regulating ATP binding and B23 stability.
 Choi JW, Lee SB, Kim CK, Lee KH, Cho SW, Ahn JY.
 FEBS Lett. 2008 Apr 2;582(7):1073-80. [PMID: 18319061]
 [23] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [24] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
 [25] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 

Functional Description

 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. 

Sequence Annotation

 REGION 1 186 Required for interaction with SENP3.
 REGION 1 117 Necessary for interaction with APEX1.
 REGION 243 294 Required for nucleolar localization.
 MOTIF 152 157 Nuclear localization signal (Potential).
 MOTIF 191 197 Nuclear localization signal (Potential).
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 4 4 Phosphoserine; by PLK1 and PLK2.
 MOD_RES 10 10 Phosphoserine.
 MOD_RES 32 32 N6-acetyllysine.
 MOD_RES 70 70 Phosphoserine.
 MOD_RES 75 75 Phosphothreonine.
 MOD_RES 95 95 Phosphothreonine.
 MOD_RES 125 125 Phosphoserine; by CDK2.
 MOD_RES 137 137 Phosphoserine.
 MOD_RES 139 139 Phosphoserine.
 MOD_RES 150 150 N6-acetyllysine.
 MOD_RES 154 154 N6-acetyllysine.
 MOD_RES 199 199 Phosphothreonine; by CDK1, CDK2 and CDK6.
 MOD_RES 212 212 N6-acetyllysine.
 MOD_RES 219 219 Phosphothreonine; by CDK1.
 MOD_RES 227 227 Phosphoserine.
 MOD_RES 229 229 N6-acetyllysine.
 MOD_RES 230 230 N6-acetyllysine; alternate.
 MOD_RES 234 234 Phosphothreonine; by CDK1.
 MOD_RES 237 237 Phosphothreonine; by CDK1.
 MOD_RES 242 242 Phosphoserine.
 MOD_RES 243 243 Phosphoserine.
 MOD_RES 250 250 N6-acetyllysine.
 MOD_RES 254 254 Phosphoserine.
 MOD_RES 257 257 N6-acetyllysine.
 MOD_RES 260 260 Phosphoserine.
 MOD_RES 267 267 N6-acetyllysine.
 MOD_RES 273 273 N6-acetyllysine.
 MOD_RES 279 279 Phosphothreonine.
 MOD_RES 292 292 N6-acetyllysine.
 CROSSLNK 230 230 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 263 263 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; ADP-ribosylation; Alternative splicing; Chaperone; Chromosomal rearrangement; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Disulfide bond; Host-virus interaction; Isopeptide bond; Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; RNA-binding; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 294 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; IDA:UniProtKB.
 GO:0030529; C:ribonucleoprotein complex; IDA:MGI.
 GO:0031616; C:spindle pole centrosome; IDA:UniProtKB.
 GO:0042393; F:histone binding; IDA:UniProtKB.
 GO:0051059; F:NF-kappaB binding; IDA:UniProtKB.
 GO:0046982; F:protein heterodimerization activity; IMP:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0004860; F:protein kinase inhibitor activity; IDA:UniProtKB.
 GO:0043023; F:ribosomal large subunit binding; IDA:MGI.
 GO:0043024; F:ribosomal small subunit binding; IDA:MGI.
 GO:0003723; F:RNA binding; IDA:UniProtKB.
 GO:0030957; F:Tat protein binding; IDA:UniProtKB.
 GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
 GO:0051082; F:unfolded protein binding; IDA:UniProtKB.
 GO:0007569; P:cell aging; IMP:UniProtKB.
 GO:0034080; P:CENP-A containing nucleosome assembly at centromere; TAS:Reactome.
 GO:0007098; P:centrosome cycle; IMP:UniProtKB.
 GO:0006281; P:DNA repair; IDA:UniProtKB.
 GO:0006886; P:intracellular protein transport; TAS:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; IMP:UniProtKB.
 GO:0010826; P:negative regulation of centrosome duplication; IMP:UniProtKB.
 GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; IDA:UniProtKB.
 GO:0006913; P:nucleocytoplasmic transport; IDA:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
 GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
 GO:0051259; P:protein oligomerization; IDA:MGI.
 GO:0046599; P:regulation of centriole replication; IMP:UniProtKB.
 GO:0060735; P:regulation of eIF2 alpha phosphorylation by dsRNA; IDA:UniProtKB.
 GO:0032071; P:regulation of endodeoxyribonuclease activity; IDA:UniProtKB.
 GO:0060699; P:regulation of endoribonuclease activity; IDA:UniProtKB.
 GO:0042255; P:ribosome assembly; TAS:UniProtKB.
 GO:0007165; P:signal transduction; NAS:UniProtKB.
 GO:0016032; P:viral reproduction; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR004301; Nucleoplasmin.
 IPR024057; Nucleoplasmin_core_dom. 

Pfam

  

SMART

  

PROSITE

  

PRINTS