View source for 3b7b


==EuHMT1 (Glp) Ankyrin Repeat Domain (Structure 1)==
<StructureSection load='3b7b' size='340' side='right'caption='[[3b7b]], [[Resolution|resolution]] 2.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3b7b]] 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=3B7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B7B FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EHMT1, EUHMTASE1, KIAA1876 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </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=3b7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b7b OCA], [https://pdbe.org/3b7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b7b RCSB], [https://www.ebi.ac.uk/pdbsum/3b7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b7b ProSAT]</span></td></tr>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/EHMT1_HUMAN EHMT1_HUMAN]] Defects in EHMT1 are the cause of chromosome 9q subtelomeric deletion syndrome (9q- syndrome) [MIM:[https://omim.org/entry/610253 610253]]. Common features seen in these patients are severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, cupid bow or tented upper lip, everted lower lip, prognathism, macroglossia, conotruncal heart defects, and behavioral problems. 
== Function ==
[[https://www.uniprot.org/uniprot/EHMT1_HUMAN EHMT1_HUMAN]] Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53.<ref>PMID:12004135</ref> <ref>PMID:20118233</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b7/3b7b_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3b7b ConSurf].
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== Publication Abstract from PubMed ==
Histone modifications have important roles in transcriptional control, mitosis and heterochromatin formation. G9a and G9a-like protein (GLP) are euchromatin-associated methyltransferases that repress transcription by mono- and dimethylating histone H3 at Lys9 (H3K9). Here we demonstrate that the ankyrin repeat domains of G9a and GLP bind with strong preference to N-terminal H3 peptides containing mono- or dimethyl K9. X-ray crystallography revealed the basis for recognition of the methylated lysine by a partial hydrophobic cage with three tryptophans and one acidic residue. Substitution of key residues in the cage eliminated the H3 tail interaction. Hence, G9a and GLP contain a new type of methyllysine binding module (the ankyrin repeat domains) and are the first examples of protein (histone) methyltransferases harboring in a single polypeptide the activities that generate and read the same epigenetic mark.

The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules.,Collins RE, Northrop JP, Horton JR, Lee DY, Zhang X, Stallcup MR, Cheng X Nat Struct Mol Biol. 2008 Mar;15(3):245-50. Epub 2008 Feb 10. PMID:18264113<ref>PMID:18264113</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3b7b" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Histone-lysine N-methyltransferase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Cheng, X]]
[[Category: Collins, R E]]
[[Category: Horton, J R]]
[[Category: Alternative splicing]]
[[Category: Ank repeat]]
[[Category: Ankyrin repeat]]
[[Category: Chromatin regulator]]
[[Category: Methyltransferase]]
[[Category: Nucleus]]
[[Category: Phosphorylation]]
[[Category: Polymorphism]]
[[Category: S-adenosyl-l-methionine]]
[[Category: Transferase]]