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| | <StructureSection load='2p1b' size='340' side='right'caption='[[2p1b]], [[Resolution|resolution]] 2.75Å' scene=''> | | <StructureSection load='2p1b' size='340' side='right'caption='[[2p1b]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2p1b]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P1B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2P1B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2p1b]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P1B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P1B FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2p1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p1b OCA], [http://pdbe.org/2p1b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2p1b RCSB], [http://www.ebi.ac.uk/pdbsum/2p1b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2p1b ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2p1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p1b OCA], [https://pdbe.org/2p1b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p1b RCSB], [https://www.ebi.ac.uk/pdbsum/2p1b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p1b ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/NPM_HUMAN NPM_HUMAN]] Note=A chromosomal aberration involving NPM1 is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with ALK. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. Note=A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) with RARA. Note=A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with MLF1. Note=Defects in NPM1 are associated with acute myelogenous leukemia (AML). Mutations in exon 12 affecting the C-terminus of the protein are associated with an aberrant cytoplasmic location. | + | [https://www.uniprot.org/uniprot/NPM_HUMAN NPM_HUMAN] Note=A chromosomal aberration involving NPM1 is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with ALK. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. Note=A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) with RARA. Note=A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with MLF1. Note=Defects in NPM1 are associated with acute myelogenous leukemia (AML). Mutations in exon 12 affecting the C-terminus of the protein are associated with an aberrant cytoplasmic location. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NPM_HUMAN NPM_HUMAN]] 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.<ref>PMID:16107701</ref> <ref>PMID:17015463</ref> <ref>PMID:18809582</ref> <ref>PMID:19188445</ref> <ref>PMID:20352051</ref> <ref>PMID:21084279</ref> <ref>PMID:22002061</ref> | + | [https://www.uniprot.org/uniprot/NPM_HUMAN NPM_HUMAN] 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.<ref>PMID:16107701</ref> <ref>PMID:17015463</ref> <ref>PMID:18809582</ref> <ref>PMID:19188445</ref> <ref>PMID:20352051</ref> <ref>PMID:21084279</ref> <ref>PMID:22002061</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ha, J Y]] | + | [[Category: Ha JY]] |
| - | [[Category: Jung, G]] | + | [[Category: Jung G]] |
| - | [[Category: Kang, J Y]] | + | [[Category: Kang JY]] |
| - | [[Category: Kim, H S]] | + | [[Category: Kim HS]] |
| - | [[Category: Lee, B I]] | + | [[Category: Lee BI]] |
| - | [[Category: Lee, H H]] | + | [[Category: Lee HH]] |
| - | [[Category: Lim, S O]] | + | [[Category: Lim SO]] |
| - | [[Category: Suh, S W]] | + | [[Category: Suh SW]] |
| - | [[Category: Yoon, H J]] | + | [[Category: Yoon HJ]] |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Decamer]]
| + | |
| Structural highlights
Disease
NPM_HUMAN Note=A chromosomal aberration involving NPM1 is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with ALK. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. Note=A chromosomal aberration involving NPM1 is found in a form of acute promyelocytic leukemia. Translocation t(5;17)(q32;q11) with RARA. Note=A chromosomal aberration involving NPM1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with MLF1. Note=Defects in NPM1 are associated with acute myelogenous leukemia (AML). Mutations in exon 12 affecting the C-terminus of the protein are associated with an aberrant cytoplasmic location.
Function
NPM_HUMAN 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.[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Swaminathan V, Kishore AH, Febitha KK, Kundu TK. Human histone chaperone nucleophosmin enhances acetylation-dependent chromatin transcription. Mol Cell Biol. 2005 Sep;25(17):7534-45. PMID:16107701 doi:10.1128/MCB.25.17.7534-7545.2005
- ↑ Ma Z, Kanai M, Kawamura K, Kaibuchi K, Ye K, Fukasawa K. Interaction between ROCK II and nucleophosmin/B23 in the regulation of centrosome duplication. Mol Cell Biol. 2006 Dec;26(23):9016-34. Epub 2006 Oct 2. PMID:17015463 doi:10.1128/MCB.01383-06
- ↑ Maggi LB Jr, Kuchenruether M, Dadey DY, Schwope RM, Grisendi S, Townsend RR, Pandolfi PP, Weber JD. Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome. Mol Cell Biol. 2008 Dec;28(23):7050-65. Epub 2008 Sep 22. PMID:18809582 doi:MCB.01548-07
- ↑ Vascotto C, Fantini D, Romanello M, Cesaratto L, Deganuto M, Leonardi A, Radicella JP, Kelley MR, D'Ambrosio C, Scaloni A, Quadrifoglio F, Tell G. APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. Mol Cell Biol. 2009 Apr;29(7):1834-54. doi: 10.1128/MCB.01337-08. Epub 2009 Feb, 2. PMID:19188445 doi:10.1128/MCB.01337-08
- ↑ Krause A, Hoffmann I. Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication. PLoS One. 2010 Mar 24;5(3):e9849. doi: 10.1371/journal.pone.0009849. PMID:20352051 doi:10.1371/journal.pone.0009849
- ↑ Wang HF, Takenaka K, Nakanishi A, Miki Y. BRCA2 and nucleophosmin coregulate centrosome amplification and form a complex with the Rho effector kinase ROCK2. Cancer Res. 2011 Jan 1;71(1):68-77. doi: 10.1158/0008-5472.CAN-10-0030. Epub 2010, Nov 16. PMID:21084279 doi:10.1158/0008-5472.CAN-10-0030
- ↑ Chun Y, Park B, Koh W, Lee S, Cheon Y, Kim R, Che L, Lee S. New centromeric component CENP-W is an RNA-associated nuclear matrix protein that interacts with nucleophosmin/B23 protein. J Biol Chem. 2011 Dec 9;286(49):42758-69. doi: 10.1074/jbc.M111.228411. Epub 2011, Oct 14. PMID:22002061 doi:10.1074/jbc.M111.228411
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