|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2pqw' size='340' side='right'caption='[[2pqw]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='2pqw' size='340' side='right'caption='[[2pqw]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2pqw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PQW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PQW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2pqw]] 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=2PQW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PQW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</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]] 2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2rjc|2rjc]], [[2rjd|2rjd]], [[2rje|2rje]], [[2rjf|2rjf]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">L3MBTL, KIAA0681, L3MBT ([https://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=2pqw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pqw OCA], [https://pdbe.org/2pqw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pqw RCSB], [https://www.ebi.ac.uk/pdbsum/2pqw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pqw ProSAT]</span></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=2pqw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pqw OCA], [https://pdbe.org/2pqw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pqw RCSB], [https://www.ebi.ac.uk/pdbsum/2pqw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pqw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/LMBL1_HUMAN LMBL1_HUMAN]] Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.<ref>PMID:17540172</ref> <ref>PMID:18408754</ref> <ref>PMID:20870719</ref> <ref>PMID:20870725</ref>
| + | [https://www.uniprot.org/uniprot/LMBL1_HUMAN LMBL1_HUMAN] Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.<ref>PMID:17540172</ref> <ref>PMID:18408754</ref> <ref>PMID:20870719</ref> <ref>PMID:20870725</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 35: |
Line 33: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Allali-Hassani, A]] | + | [[Category: Allali-Hassani A]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bochkarev, A]] | + | [[Category: Bochkarev A]] |
| - | [[Category: Crombet, L]] | + | [[Category: Crombet L]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Edwards AM]] |
| - | [[Category: Herzanych, N]] | + | [[Category: Herzanych N]] |
| - | [[Category: Kozieradzki, I]] | + | [[Category: Kozieradzki I]] |
| - | [[Category: Liu, Y]] | + | [[Category: Liu Y]] |
| - | [[Category: Loppnau, P]] | + | [[Category: Loppnau P]] |
| - | [[Category: Mackenzie, F]] | + | [[Category: Mackenzie F]] |
| - | [[Category: Min, J R]] | + | [[Category: Min JR]] |
| - | [[Category: Ouyang, H]] | + | [[Category: Ouyang H]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Sundstrom M]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Vedadi M]] |
| - | [[Category: Vedadi, M]] | + | [[Category: Weigelt J]] |
| - | [[Category: Weigelt, J]] | + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
LMBL1_HUMAN Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.[1] [2] [3] [4]
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
Crystal structures of the L3MBTL1 MBT repeats in complex with histone H4 peptides dimethylated on Lys20 (H4K20me2) show that only the second of the three MBT repeats can bind mono- and dimethylated histone peptides. Its binding pocket has similarities to that of 53BP1 and is able to recognize the degree of histone lysine methylation. An unexpected mode of peptide-mediated dimerization suggests a possible mechanism for chromatin compaction by L3MBTL1.
L3MBTL1 recognition of mono- and dimethylated histones.,Min J, Allali-Hassani A, Nady N, Qi C, Ouyang H, Liu Y, MacKenzie F, Vedadi M, Arrowsmith CH Nat Struct Mol Biol. 2007 Dec;14(12):1229-30. Epub 2007 Nov 18. PMID:18026117[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Trojer P, Li G, Sims RJ 3rd, Vaquero A, Kalakonda N, Boccuni P, Lee D, Erdjument-Bromage H, Tempst P, Nimer SD, Wang YH, Reinberg D. L3MBTL1, a histone-methylation-dependent chromatin lock. Cell. 2007 Jun 1;129(5):915-28. PMID:17540172 doi:10.1016/j.cell.2007.03.048
- ↑ Kalakonda N, Fischle W, Boccuni P, Gurvich N, Hoya-Arias R, Zhao X, Miyata Y, Macgrogan D, Zhang J, Sims JK, Rice JC, Nimer SD. Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1. Oncogene. 2008 Jul 17;27(31):4293-304. doi: 10.1038/onc.2008.67. Epub 2008 Apr, 14. PMID:18408754 doi:10.1038/onc.2008.67
- ↑ Saddic LA, West LE, Aslanian A, Yates JR 3rd, Rubin SM, Gozani O, Sage J. Methylation of the retinoblastoma tumor suppressor by SMYD2. J Biol Chem. 2010 Nov 26;285(48):37733-40. doi: 10.1074/jbc.M110.137612. Epub, 2010 Sep 24. PMID:20870719 doi:10.1074/jbc.M110.137612
- ↑ West LE, Roy S, Lachmi-Weiner K, Hayashi R, Shi X, Appella E, Kutateladze TG, Gozani O. The MBT repeats of L3MBTL1 link set8 mediated p53 methylation at lysine 382 to target gene repression. J Biol Chem. 2010 Sep 24. PMID:20870725 doi:10.1074/jbc.M110.139527
- ↑ Min J, Allali-Hassani A, Nady N, Qi C, Ouyang H, Liu Y, MacKenzie F, Vedadi M, Arrowsmith CH. L3MBTL1 recognition of mono- and dimethylated histones. Nat Struct Mol Biol. 2007 Dec;14(12):1229-30. Epub 2007 Nov 18. PMID:18026117 doi:10.1038/nsmb1340
|
