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| - | {{STRUCTURE_3os5| PDB=3os5 | SCENE= }} | |
| - | ===SET7/9-Dnmt1 K142me1 complex=== | |
| - | {{ABSTRACT_PUBMED_21151116}} | |
| | | | |
| - | ==Function== | + | ==SET7/9-Dnmt1 K142me1 complex== |
| - | [[http://www.uniprot.org/uniprot/SETD7_HUMAN SETD7_HUMAN]] Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Has also methyltransferase activity toward non-histone proteins such as p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation.<ref>PMID:12588998</ref> <ref>PMID:15099517</ref> <ref>PMID:16141209</ref> <ref>PMID:17108971</ref> <ref>PMID:12540855</ref> <ref>PMID:15525938</ref> | + | <StructureSection load='3os5' size='340' side='right'caption='[[3os5]], [[Resolution|resolution]] 1.69Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[3os5]] is a 2 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=3OS5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OS5 FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.69Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></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=3os5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3os5 OCA], [https://pdbe.org/3os5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3os5 RCSB], [https://www.ebi.ac.uk/pdbsum/3os5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3os5 ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SETD7_HUMAN SETD7_HUMAN] Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Has also methyltransferase activity toward non-histone proteins such as p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation.<ref>PMID:12588998</ref> <ref>PMID:15099517</ref> <ref>PMID:16141209</ref> <ref>PMID:17108971</ref> <ref>PMID:12540855</ref> <ref>PMID:15525938</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The protein lysine methyltransferase SET7 regulates DNA methyltransferase-1 (DNMT1) activity in mammalian cells by promoting degradation of DNMT1 and thus allows epigenetic changes via DNA demethylation. Here we reveal an interplay between monomethylation of DNMT1 Lys142 by SET7 and phosphorylation of DNMT1 Ser143 by AKT1 kinase. These two modifications are mutually exclusive, and structural analysis suggests that Ser143 phosphorylation interferes with Lys142 monomethylation. AKT1 kinase colocalizes and directly interacts with DNMT1 and phosphorylates Ser143. Phosphorylated DNMT1 peaks during DNA synthesis, before DNMT1 methylation. Depletion of AKT1 or overexpression of dominant-negative AKT1 increases methylated DNMT1, resulting in a decrease in DNMT1 abundance. In mammalian cells, phosphorylated DNMT1 is more stable than methylated DNMT1. These results reveal cross-talk on DNMT1, through modifications mediated by AKT1 and SET7, that affects cellular DNMT1 levels. |
| | | | |
| - | ==About this Structure==
| + | A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability.,Esteve PO, Chang Y, Samaranayake M, Upadhyay AK, Horton JR, Feehery GR, Cheng X, Pradhan S Nat Struct Mol Biol. 2011 Jan;18(1):42-8. Epub 2010 Dec 12. PMID:21151116<ref>PMID:21151116</ref> |
| - | [[3os5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OS5 OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | <ref group="xtra">PMID:021151116</ref><references group="xtra"/><references/> | + | </div> |
| - | [[Category: Histone-lysine N-methyltransferase]] | + | <div class="pdbe-citations 3os5" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Chang, Y.]] | + | [[Category: Large Structures]] |
| - | [[Category: Cheng, X.]] | + | [[Category: Chang Y]] |
| - | [[Category: Esteve, P O.]] | + | [[Category: Cheng X]] |
| - | [[Category: Feehery, G R.]] | + | [[Category: Esteve P-O]] |
| - | [[Category: Horton, J R.]] | + | [[Category: Feehery GR]] |
| - | [[Category: Pradhan, S.]] | + | [[Category: Horton JR]] |
| - | [[Category: Samaranayake, M.]] | + | [[Category: Pradhan S]] |
| - | [[Category: Upadhyay, A K.]] | + | [[Category: Samaranayake M]] |
| - | [[Category: Dnmt1]]
| + | [[Category: Upadhyay AK]] |
| - | [[Category: Epigenetic modification]]
| + | |
| - | [[Category: K142]]
| + | |
| - | [[Category: Lysine mono-methylation]]
| + | |
| - | [[Category: Protein lysine methyltransferase]]
| + | |
| - | [[Category: Set domain]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
3os5 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.69Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
SETD7_HUMAN Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Has also methyltransferase activity toward non-histone proteins such as p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
The protein lysine methyltransferase SET7 regulates DNA methyltransferase-1 (DNMT1) activity in mammalian cells by promoting degradation of DNMT1 and thus allows epigenetic changes via DNA demethylation. Here we reveal an interplay between monomethylation of DNMT1 Lys142 by SET7 and phosphorylation of DNMT1 Ser143 by AKT1 kinase. These two modifications are mutually exclusive, and structural analysis suggests that Ser143 phosphorylation interferes with Lys142 monomethylation. AKT1 kinase colocalizes and directly interacts with DNMT1 and phosphorylates Ser143. Phosphorylated DNMT1 peaks during DNA synthesis, before DNMT1 methylation. Depletion of AKT1 or overexpression of dominant-negative AKT1 increases methylated DNMT1, resulting in a decrease in DNMT1 abundance. In mammalian cells, phosphorylated DNMT1 is more stable than methylated DNMT1. These results reveal cross-talk on DNMT1, through modifications mediated by AKT1 and SET7, that affects cellular DNMT1 levels.
A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability.,Esteve PO, Chang Y, Samaranayake M, Upadhyay AK, Horton JR, Feehery GR, Cheng X, Pradhan S Nat Struct Mol Biol. 2011 Jan;18(1):42-8. Epub 2010 Dec 12. PMID:21151116[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Martens JH, Verlaan M, Kalkhoven E, Zantema A. Cascade of distinct histone modifications during collagenase gene activation. Mol Cell Biol. 2003 Mar;23(5):1808-16. PMID:12588998
- ↑ Kouskouti A, Scheer E, Staub A, Tora L, Talianidis I. Gene-specific modulation of TAF10 function by SET9-mediated methylation. Mol Cell. 2004 Apr 23;14(2):175-82. PMID:15099517
- ↑ Francis J, Chakrabarti SK, Garmey JC, Mirmira RG. Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription. J Biol Chem. 2005 Oct 28;280(43):36244-53. Epub 2005 Sep 1. PMID:16141209 doi:M505741200
- ↑ Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T, Berger SL. Repression of p53 activity by Smyd2-mediated methylation. Nature. 2006 Nov 30;444(7119):629-32. Epub 2006 Nov 15. PMID:17108971 doi:10.1038/nature05287
- ↑ Xiao B, Jing C, Wilson JR, Walker PA, Vasisht N, Kelly G, Howell S, Taylor IA, Blackburn GM, Gamblin SJ. Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature. 2003 Feb 6;421(6923):652-6. Epub 2003 Jan 22. PMID:12540855 doi:10.1038/nature01378
- ↑ Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS, McKinney K, Tempst P, Prives C, Gamblin SJ, Barlev NA, Reinberg D. Regulation of p53 activity through lysine methylation. Nature. 2004 Nov 18;432(7015):353-60. Epub 2004 Nov 3. PMID:15525938 doi:10.1038/nature03117
- ↑ Esteve PO, Chang Y, Samaranayake M, Upadhyay AK, Horton JR, Feehery GR, Cheng X, Pradhan S. A methylation and phosphorylation switch between an adjacent lysine and serine determines human DNMT1 stability. Nat Struct Mol Biol. 2011 Jan;18(1):42-8. Epub 2010 Dec 12. PMID:21151116 doi:10.1038/nsmb.1939
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