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| | ==crystal structure of PHF2 PHD domain complexed with H3K4Me3 peptide== | | ==crystal structure of PHF2 PHD domain complexed with H3K4Me3 peptide== |
| - | <StructureSection load='3kqi' size='340' side='right' caption='[[3kqi]], [[Resolution|resolution]] 1.78Å' scene=''> | + | <StructureSection load='3kqi' size='340' side='right'caption='[[3kqi]], [[Resolution|resolution]] 1.78Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3kqi]] is a 2 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=3KQI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KQI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3kqi]] 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=3KQI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KQI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 1.78Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIAA0662, PHF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3kqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kqi OCA], [https://pdbe.org/3kqi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kqi RCSB], [https://www.ebi.ac.uk/pdbsum/3kqi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kqi ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kqi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kqi OCA], [http://pdbe.org/3kqi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kqi RCSB], [http://www.ebi.ac.uk/pdbsum/3kqi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kqi ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PHF2_HUMAN PHF2_HUMAN]] Lysine demethylase that demethylates both histones and non-histone proteins. Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B. Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA.<ref>PMID:21532585</ref> <ref>PMID:20129925</ref> <ref>PMID:21167174</ref> | + | [https://www.uniprot.org/uniprot/PHF2_HUMAN PHF2_HUMAN] Lysine demethylase that demethylates both histones and non-histone proteins. Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B. Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA.<ref>PMID:21532585</ref> <ref>PMID:20129925</ref> <ref>PMID:21167174</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kq/3kqi_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kq/3kqi_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lee, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, J Z]] | + | [[Category: Lee M]] |
| - | [[Category: Lu, M]] | + | [[Category: Li JZ]] |
| - | [[Category: Song, T]] | + | [[Category: Lu M]] |
| - | [[Category: Wen, H]] | + | [[Category: Song T]] |
| - | [[Category: Histone-binding]]
| + | [[Category: Wen H]] |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Nuclear protein]]
| + | |
| - | [[Category: Phd finger]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| Structural highlights
3kqi 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 1.78Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
PHF2_HUMAN Lysine demethylase that demethylates both histones and non-histone proteins. Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B. Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Distinct lysine methylation marks on histones create dynamic signatures deciphered by the "effector" modules, although the underlying mechanisms remain unclear. We identified the plant homeodomain- and Jumonji C domain-containing protein PHF2 as a novel histone H3K9 demethylase. We show in biochemical and crystallographic analyses that PHF2 recognizes histone H3K4 trimethylation through its plant homeodomain finger and that this interaction is essential for PHF2 occupancy and H3K9 demethylation at rDNA promoters. Our study provides molecular insights into the mechanism by which distinct effector domains within a protein cooperatively modulate the "cross-talk" of histone modifications.
Recognition of histone H3K4 trimethylation by the plant homeodomain of PHF2 modulates histone demethylation.,Wen H, Li J, Song T, Lu M, Kan PY, Lee MG, Sha B, Shi X J Biol Chem. 2010 Mar 26;285(13):9322-6. Epub 2010 Feb 2. PMID:20129925[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Baba A, Ohtake F, Okuno Y, Yokota K, Okada M, Imai Y, Ni M, Meyer CA, Igarashi K, Kanno J, Brown M, Kato S. PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B. Nat Cell Biol. 2011 Jun;13(6):668-75. doi: 10.1038/ncb2228. Epub 2011 May 1. PMID:21532585 doi:10.1038/ncb2228
- ↑ Wen H, Li J, Song T, Lu M, Kan PY, Lee MG, Sha B, Shi X. Recognition of histone H3K4 trimethylation by the plant homeodomain of PHF2 modulates histone demethylation. J Biol Chem. 2010 Mar 26;285(13):9322-6. Epub 2010 Feb 2. PMID:20129925 doi:10.1074/jbc.C109.097667
- ↑ Horton JR, Upadhyay AK, Hashimoto H, Zhang X, Cheng X. Structural Basis for Human PHF2 Jumonji Domain Interaction with Metal Ions. J Mol Biol. 2010 Dec 15. PMID:21167174 doi:10.1016/j.jmb.2010.12.013
- ↑ Wen H, Li J, Song T, Lu M, Kan PY, Lee MG, Sha B, Shi X. Recognition of histone H3K4 trimethylation by the plant homeodomain of PHF2 modulates histone demethylation. J Biol Chem. 2010 Mar 26;285(13):9322-6. Epub 2010 Feb 2. PMID:20129925 doi:10.1074/jbc.C109.097667
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