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| | <StructureSection load='1xni' size='340' side='right'caption='[[1xni]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='1xni' size='340' side='right'caption='[[1xni]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1xni]] 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=1XNI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1XNI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1xni]] 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=1XNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XNI FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TP53BP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=1xni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xni OCA], [https://pdbe.org/1xni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xni RCSB], [https://www.ebi.ac.uk/pdbsum/1xni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xni ProSAT]</span></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=1xni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xni OCA], [http://pdbe.org/1xni PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xni RCSB], [http://www.ebi.ac.uk/pdbsum/1xni PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xni ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TP53B_HUMAN TP53B_HUMAN]] Note=A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein. | + | [https://www.uniprot.org/uniprot/TP53B_HUMAN TP53B_HUMAN] Note=A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TP53B_HUMAN TP53B_HUMAN]] Plays a key role in the response to DNA damage. May have a role in checkpoint signaling during mitosis. Enhances TP53-mediated transcriptional activation.<ref>PMID:12364621</ref> <ref>PMID:17190600</ref> | + | [https://www.uniprot.org/uniprot/TP53B_HUMAN TP53B_HUMAN] Plays a key role in the response to DNA damage. May have a role in checkpoint signaling during mitosis. Enhances TP53-mediated transcriptional activation.<ref>PMID:12364621</ref> <ref>PMID:17190600</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: DiTullio, R A]] | + | [[Category: DiTullio Jr RA]] |
| - | [[Category: Gorgoulis, V G]] | + | [[Category: Gorgoulis VG]] |
| - | [[Category: Halazonetis, T D]] | + | [[Category: Halazonetis TD]] |
| - | [[Category: Huyen, Y]] | + | [[Category: Huyen Y]] |
| - | [[Category: Mellert, H S]] | + | [[Category: Mellert HS]] |
| - | [[Category: Petty, T J]] | + | [[Category: Petty TJ]] |
| - | [[Category: Sheston, E A]] | + | [[Category: Sheston EA]] |
| - | [[Category: Stavridi, E S]] | + | [[Category: Stavridi ES]] |
| - | [[Category: Zacharatos, P]] | + | [[Category: Zacharatos P]] |
| - | [[Category: Zgheib, O]] | + | [[Category: Zgheib O]] |
| - | [[Category: Bent beta-sheet]]
| + | |
| - | [[Category: Beta-barrel]]
| + | |
| - | [[Category: Cell cycle]]
| + | |
| Structural highlights
Disease
TP53B_HUMAN Note=A chromosomal aberration involving TP53BP1 is found in a form of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;15)(q33;q22) with PDGFRB creating a TP53BP1-PDGFRB fusion protein.
Function
TP53B_HUMAN Plays a key role in the response to DNA damage. May have a role in checkpoint signaling during mitosis. Enhances TP53-mediated transcriptional activation.[1] [2]
Publication Abstract from PubMed
The mechanisms by which eukaryotic cells sense DNA double-strand breaks (DSBs) in order to initiate checkpoint responses are poorly understood. 53BP1 is a conserved checkpoint protein with properties of a DNA DSB sensor. Here, we solved the structure of the domain of 53BP1 that recruits it to sites of DSBs. This domain consists of two tandem tudor folds with a deep pocket at their interface formed by residues conserved in the budding yeast Rad9 and fission yeast Rhp9/Crb2 orthologues. In vitro, the 53BP1 tandem tudor domain bound histone H3 methylated on Lys 79 using residues that form the walls of the pocket; these residues were also required for recruitment of 53BP1 to DSBs. Suppression of DOT1L, the enzyme that methylates Lys 79 of histone H3, also inhibited recruitment of 53BP1 to DSBs. Because methylation of histone H3 Lys 79 was unaltered in response to DNA damage, we propose that 53BP1 senses DSBs indirectly through changes in higher-order chromatin structure that expose the 53BP1 binding site.
Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks.,Huyen Y, Zgheib O, Ditullio RA Jr, Gorgoulis VG, Zacharatos P, Petty TJ, Sheston EA, Mellert HS, Stavridi ES, Halazonetis TD Nature. 2004 Nov 18;432(7015):406-11. Epub 2004 Nov 3. PMID:15525939[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang B, Matsuoka S, Carpenter PB, Elledge SJ. 53BP1, a mediator of the DNA damage checkpoint. Science. 2002 Nov 15;298(5597):1435-8. Epub 2002 Oct 3. PMID:12364621 doi:10.1126/science.1076182
- ↑ Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell. 2006 Dec 29;127(7):1361-73. PMID:17190600 doi:10.1016/j.cell.2006.10.043
- ↑ Huyen Y, Zgheib O, Ditullio RA Jr, Gorgoulis VG, Zacharatos P, Petty TJ, Sheston EA, Mellert HS, Stavridi ES, Halazonetis TD. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature. 2004 Nov 18;432(7015):406-11. Epub 2004 Nov 3. PMID:15525939 doi:http://dx.doi.org/nature03114
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