IED Industry Enzyme Database

Detail Information for IndEnz0002015643
IED ID IndEnz0002015643
Enzyme Type ID protease015643
Protein Name Nucleophosmin
NPM
Nucleolar phosphoprotein B23
Nucleolar protein NO38
Numatrin
Gene Name NPM1 NPM
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MEDSMDMDMSPLRPQNYLFGCELKADKDYHFKVDNDENEHQLSLRTVSLGAGAKDELHIVEAEAMNYEGSPIKVTLATLKMSVQPTVSLGGFEITPPVVLRLKCGSGPVHISGQHLVAVEEDAESEDEEEEDVKLLSISGKRSAPGGGSKVPQKKVKLAADEDDDDDDEEDDDEDDDDDDFDDEEAEEKAPVKKSIRDTPAKNAQKSNQNGKDSKPSSTPRSKGQESFKKQEKTPKTPKGPSSVEDIKAKMQASIEKGGSLPKVEAKFINYVKNCFRMTDQEAIQDLWQWRKSL
Enzyme Length 294
Uniprot Accession Number P06748
Absorption
Active Site
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding
EC Number
Enzyme Function 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. 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 (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). {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, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Alternative sequence (2); Beta strand (8); Chain (1); Compositional bias (2); Cross-link (17); Helix (3); Modified residue (36); Motif (2); Mutagenesis (17); Region (4); Sequence conflict (21); Site (3); Turn (1)
Keywords 3D-structure;ADP-ribosylation;Acetylation;Alternative splicing;Chaperone;Chromosomal rearrangement;Cytoplasm;Cytoskeleton;Direct protein sequencing;Disulfide bond;Host-virus interaction;Isopeptide bond;Nucleus;Phosphoprotein;Proto-oncogene;RNA-binding;Reference proteome;Ubl conjugation
Interact With O14965; Q96GD4; Q8N726; P10176; Q10570; P19525; Q13547; Q92769; Q9BXL5; Q92876; Q71RC2; Q00987; Q9BZQ8; Q86SE8; Q86SE8-2; Q8IZL8; Q96BK5; P62753; Q9H4L4; O14746; P05549; P04637; P63104; Q64364; P24938; P68951; P0DOE7; Q6UPD4; P03427; B1Q2W9; Q98147; P49450-1; P63165; P04637; Q14669; Q86SE8-2
Induction
Subcellular Location SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25818168, ECO:0000269|PubMed:25956029}. Nucleus, nucleoplasm {ECO:0000269|PubMed:25818168}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:14654843}. 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.
Modified Residue MOD_RES 1; /note="N-acetylmethionine"; /evidence="ECO:0000269|Ref.17, ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22223895"; MOD_RES 4; /note="Phosphoserine; by PLK1 and PLK2"; /evidence="ECO:0000269|PubMed:15190079, ECO:0000269|PubMed:20352051, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 10; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 32; /note="N6-acetyllysine; alternate"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 43; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 67; /note="Phosphotyrosine"; /evidence="ECO:0000250|UniProtKB:Q61937"; MOD_RES 70; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 75; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18669648"; MOD_RES 95; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 125; /note="Phosphoserine; by CDK2"; /evidence="ECO:0000269|Ref.17, ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 137; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231"; MOD_RES 139; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 150; /note="N6-acetyllysine; alternate"; /evidence="ECO:0007744|PubMed:16916647, ECO:0007744|PubMed:19608861"; MOD_RES 154; /note="N6-acetyllysine"; /evidence="ECO:0007744|PubMed:16916647"; MOD_RES 199; /note="Phosphothreonine; by CDK1, CDK2 and CDK6"; /evidence="ECO:0000269|PubMed:12058066, ECO:0000269|PubMed:20333249, ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:20068231"; MOD_RES 207; /note="ADP-ribosylserine"; /evidence="ECO:0000269|PubMed:28190768"; MOD_RES 212; /note="N6-acetyllysine"; /evidence="ECO:0000269|PubMed:16107701, ECO:0007744|PubMed:16916647"; MOD_RES 219; /note="Phosphothreonine; by CDK1"; /evidence="ECO:0000305|PubMed:12058066"; MOD_RES 227; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21406692"; MOD_RES 229; /note="N6-acetyllysine"; /evidence="ECO:0000269|PubMed:16107701"; MOD_RES 230; /note="N6-acetyllysine; alternate"; /evidence="ECO:0000269|PubMed:16107701"; MOD_RES 234; /note="Phosphothreonine; by CDK1"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 237; /note="Phosphothreonine; by CDK1"; /evidence="ECO:0000269|PubMed:12058066, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"; MOD_RES 242; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 243; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"; MOD_RES 250; /note="N6-acetyllysine; alternate"; /evidence="ECO:0000269|PubMed:16107701"; MOD_RES 254; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"; MOD_RES 257; /note="N6-acetyllysine; alternate"; /evidence="ECO:0000269|PubMed:16107701, ECO:0007744|PubMed:19608861"; MOD_RES 260; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"; MOD_RES 267; /note="N6-acetyllysine; alternate"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 267; /note="N6-succinyllysine; alternate"; /evidence="ECO:0000250|UniProtKB:Q61937"; MOD_RES 273; /note="N6-acetyllysine; alternate"; /evidence="ECO:0007744|PubMed:19608861"; MOD_RES 279; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:20068231"; MOD_RES 292; /note="N6-acetyllysine"; /evidence="ECO:0000269|PubMed:16107701"; MOD_RES P06748-3:254; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:20068231"; MOD_RES P06748-3:257; /note="N6-acetyllysine"; /evidence="ECO:0007744|PubMed:19608861"
Post Translational Modification PTM: Acetylated at C-terminal lysine residues, thereby increasing affinity to histones. {ECO:0000269|PubMed:16107701, ECO:0000269|Ref.17}.; PTM: ADP-ribosylated.; PTM: 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-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:20333249, ECO:0000269|PubMed:20352051, ECO:0000269|Ref.17}.; PTM: Sumoylated by ARF. {ECO:0000269|PubMed:15897463}.; PTM: Ubiquitinated. Ubiquitination leads to proteasomal degradation. Deubiquitinated by USP36 (PubMed:19208757). {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:25818168}.
Signal Peptide
Structure 3D NMR spectroscopy (2); X-ray crystallography (2)
Cross Reference PDB 2LLH; 2P1B; 2VXD; 5EHD;
Mapped Pubmed ID 10216106; 10556217; 10702393; 10706082; 10706887; 10866662; 10934142; 11110708; 11278991; 11280786; 11310834; 11751994; 11850821; 11943732; 12031912; 12039952; 12057857; 12080348; 12112524; 12185581; 12374805; 12424201; 12577067; 12748172; 12750159; 12920229; 12934099; 14506644; 14519847; 14559993; 14563642; 14636574; 14656879; 14670079; 14730621; 14743216; 14962911; 14968112; 15047060; 15064750; 15082766; 15087454; 15144954; 15161933; 15175163; 15184379; 15208656; 15310764; 15374880; 15514966; 15588951; 15589822; 15644315; 15665273; 15684379; 15831697; 15848144; 15870172; 15872011; 15895073; 15964625; 15989956; 15994285; 16009132; 16041368; 16046528; 16076867; 16153455; 16161041; 16170336; 16170350; 16205118; 16376875; 16376884; 16415342; 16455950; 16455956; 16541144; 16547420; 16622420; 16645213; 16678898; 16679321; 16709933; 16720834; 16725311; 16766651; 16825495; 16835382; 16855788; 16857742; 16870548; 16871283; 16912078; 16926303; 16939498; 16957780; 17076533; 17086210; 17110082; 17111047; 17147251; 17151698; 17185414; 17199038; 17277230; 17306368; 17315018; 17318229; 17353907; 17353931; 17416736; 17440048; 17483340; 17488663; 17504301; 17531812; 17535915; 17537995; 17546053; 17549383; 17569113; 17597811; 17598835; 17602943; 17616680; 17620599; 17625570; 17637812; 17637816; 17639390; 17690253; 17690700; 17715399; 17875528; 17877154; 17922009; 17932509; 17942908; 17943167; 17951246; 17957027; 17968318; 17972951; 17990177; 17998938; 18037965; 18059485; 18081718; 18097461; 18165222; 18180033; 18192111; 18200037; 18214681; 18226242; 18234856; 18243139; 18261272; 18268276; 18273044; 18298902; 18308931; 18316603; 18332108; 18367491; 18371977; 18420587; 18448670; 18452557; 18454140; 18478020; 18559874; 18590714; 18593892; 18594010; 18596743; 18603563; 18639523; 18641025; 18701132; 18726096; 18729828; 18845790; 18847512; 18923523; 18923524; 18923525; 18951898; 19005479; 19020547; 19052985; 19059939; 19066330; 19103589; 19131589; 19151774; 19160485; 19221506; 19240082; 19242062; 19279329; 19286999; 19289604; 19309322; 19351769; 19365794; 19367725; 19369962; 19379554; 19398759; 19410544; 19410545; 19423729; 19429869; 19456272; 19459784; 19463016; 19484332; 19522705; 19523114; 19531656; 19535344; 19536888; 19540590; 19557552; 19569254; 19581289; 19587375; 19637342; 19638589; 19642896; 19672946; 19679565; 19679658; 19694479; 19734942; 19738201; 19770764; 19775300; 19805454; 19824900; 19843866; 19862764; 19865112; 19887368; 19901261; 19965647; 20001230; 20011973; 20023256; 20026798; 20027629; 20073075; 20080577; 20127469; 20145123; 2017166; 20172040; 20203266; 20212148; 20237420; 20306250; 20338617; 20368469; 20368538; 20393185; 20404347; 20424160; 20428199; 20439648; 20454865; 20464055; 20467437; 20471513; 20494930; 20506166; 20508983; 20513120; 20515654; 20520634; 20533335; 20546020; 20554525; 20562859; 20566683; 20592250; 20606168; 20616361; 20618440; 20634376; 20651067; 20673208; 20678218; 20684989; 20711500; 20713446; 20713529; 20724983; 20802533; 20803351; 20807181; 20849383; 20855646; 20858903; 20864535; 20872983; 20875872; 20877721; 20880116; 20924036; 20962268; 20965181; 20979630; 20981679; 21030560; 21045017; 21048921; 21102525; 21122805; 21134980; 21164297; 21173125; 21182205; 21182834; 21183700; 21213368; 21233837; 21242972; 21245151; 21245599; 21258971; 21278791; 21282530; 21297583; 21310483; 21316727; 21326211; 21331074; 21338238; 21393327; 21415216; 21418451; 21425800; 21441929; 21472563; 21492127; 21494621; 21502504; 21518927; 21537333; 21537492; 21555683; 21577323; 21606167; 21621842; 21656749; 21660047; 21666141; 21689627; 21703420; 21705779; 21719597; 21744003; 21763502; 21765024; 21768289; 21784052; 21789382; 21809990; 21822216; 21860418; 21880628; 21904378; 21911578; 21933585; 21948233; 21979956; 21986840; 21988832; 22099964; 22102817; 22104247; 22126574; 22174271; 22193965; 22249260; 22327622; 22337638; 22347464; 22362118; 22374696; 22397365; 22451695; 22454318; 22467873; 22475129; 22481022; 22487825; 22494415; 22496234; 22510990; 22570254; 22573554; 22592607; 22623428; 22631075; 22658521; 22665062; 22707729; 22712502; 22733614; 22745010; 22761710; 22791379; 22810585; 22851180; 22863774; 22906848; 22911473; 22914610; 22926011; 22955283; 22968966; 22996295; 23020761; 23064464; 23065518; 23075850; 23104988; 23139213; 23154527; 23183427; 23201355; 23232117; 23238897; 23239810; 23271972; 23285058; 23301224; 23328624; 23338972; 23393136; 23403313; 23435463; 23436734; 23455153; 23483572; 23489260; 23496932; 23511494; 23536448; 23540998; 23544830; 23590662; 23591014; 23601747; 23618861; 23656730; 23661334; 23666693; 23704090; 23716555; 23730215; 23742937; 23753029; 23763915; 23797873; 23831574; 23851489; 23874639; 23877794; 23892143; 23902751; 23907410; 23927396; 23929838; 23957430; 23998253; 24004182; 24035716; 24060861; 24097631; 24106084; 24164801; 24183235; 24189400; 24192815; 24220271; 24288427; 24289551; 24413856; 24443894; 24445538; 24462683; 24475247; 24496003; 24502978; 24515769; 24518094; 24573385; 24576674; 24596420; 24613930; 24616519; 24675041; 24716928; 24724782; 24736082; 24743218; 24780295; 24787960; 24793791; 24796332; 24801015; 24816240; 24857377; 24859829; 24867636; 24895580; 24991885; 24998852; 25026287; 25033841; 25039748; 25071014; 25079101; 25083817; 25228534; 25242579; 25281355; 25288641; 25299584; 25342631; 25348016; 25349176; 25349213; 25381129; 25384962; 25389240; 25393796; 25416956; 25421715; 25421750; 25457413; 25468431; 25527567; 25531824; 25543261; 25609649; 25648021; 25711412; 25713434; 25749034; 25754892; 25779376; 25791120; 25805179; 25809997; 25813404; 25907517; 25908633; 25918010; 25961029; 25977257; 25992555; 26001147; 26055329; 26062823; 26068981; 26101160; 26123729; 26200838; 26205693; 26231209; 26301689; 26343305; 26447856; 26464158; 26471486; 26496610; 26526573; 26536659; 26559910; 26634271; 26642331; 26642792; 26657151; 26666953; 26669619; 26754533; 26789727; 26836305; 26847745; 26884713; 26894557; 26939704; 26993766; 26997274; 27071442; 27142525; 27191933; 27245569; 27416910; 27436336; 27471865; 27501253; 27553022; 27573755; 27619510; 27636548; 27643573; 27669739; 27732946; 27748301; 27798920; 27874193; 27879258; 27886181; 27983985; 28005077; 28045037; 28111462; 28259962; 28262969; 28294102; 28318150; 28370403; 28384310; 28404650; 28432080; 28513872; 28557340; 28589727; 28659337; 28707414; 28740552; 28741662; 28790338; 29079128; 29183886; 29224316; 29274134; 29283500; 29330024; 29343273; 29455642; 29466670; 29483575; 29507312; 29530994; 29535419; 29588546; 29684564; 29724895; 29746960; 29748442; 29806051; 29806702; 29873274; 29903758; 30015632; 30082225; 30085406; 30126359; 30126426; 30130654; 30205049; 30214626; 30453269; 30632059; 30692217; 30706524; 30710643; 30836427; 30838674; 30921500; 30926392; 30981631; 30998139; 31048683; 31113615; 31177400; 31186273; 31209279; 31244296; 31291378; 31307523; 31330844; 31366041; 31388026; 31397440; 31430225; 31434245; 31462227; 31571325; 31575857; 31650162; 31675375; 31694106; 31751897; 31755865; 31764996; 31767858; 31831844; 31855575; 31907961; 31915364; 32007256; 32022605; 32027259; 32092641; 32093728; 32193476; 32194167; 32234886; 32378344; 32385931; 32388535; 32452083; 32458446; 32495317; 32510599; 32545659; 32606971; 32646968; 32668024; 32686519; 32712325; 32856112; 32860479; 32898396; 33039556; 33073687; 33077765; 33089315; 33099879; 33201521; 33255988; 33301193; 33310759; 33358698; 33367545; 33371116; 33372822; 33400143; 33507833; 33594052; 33618432; 33711909; 33777934; 33782403; 33813791; 33879827; 34044346; 34053184; 34131282; 34153064; 34193978; 34238278; 34335635; 34343258; 34364939; 34438119; 34555849; 34576201; 34893102; 7824924; 9092824; 9405152; 9819383;
Motif MOTIF 152..157; /note=Nuclear localization signal; /evidence=ECO:0000255; MOTIF 191..197; /note=Nuclear localization signal; /evidence=ECO:0000255
Gene Encoded By
Mass 32,575
Kinetics
Metal Binding
Rhea ID
Cross Reference Brenda