View source for 3rc0


==Human SETD6 in complex with RelA Lys310 peptide==
<StructureSection load='3rc0' size='340' side='right'caption='[[3rc0]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3rc0]] is a 4 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=3RC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RC0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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;'>[[3qxy|3qxy]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SETD6 ([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=3rc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rc0 OCA], [https://pdbe.org/3rc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rc0 RCSB], [https://www.ebi.ac.uk/pdbsum/3rc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rc0 ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/SETD6_HUMAN SETD6_HUMAN]] Protein-lysine N-methyltransferase that specifically monomethylates 'Lys-310' of the RELA subunit of NF-kappa-B complex, leading to down-regulate NF-kappa-B transcription factor activity.<ref>PMID:21131967</ref>  [[https://www.uniprot.org/uniprot/TF65_HUMAN TF65_HUMAN]] NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression. The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1.<ref>PMID:10928981</ref> <ref>PMID:12748188</ref> <ref>PMID:17000776</ref> <ref>PMID:17620405</ref> <ref>PMID:19058135</ref> <ref>PMID:20547752</ref>  
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== Publication Abstract from PubMed ==
SET domain containing 6 (SETD6) monomethylates the RelA subunit of nuclear factor kappa B (NF-kappaB). The ankyrin repeats of G9a-like protein (GLP) recognizes RelA monomethylated at Lys310. Adjacent to Lys310 is Ser311, a known phosphorylation site of RelA. Ser311 phosphorylation inhibits Lys310 methylation by SETD6 as well as binding of Lys310me1 by GLP. The structure of SETD6 in complex with RelA peptide containing the methylation site, in the presence of S-adenosyl-l-methionine, reveals a V-like protein structure and suggests a model for NF-kappaB binding to SETD6. In addition, structural modeling of the GLP ankyrin repeats bound to Lys310me1 peptide provides insight into the molecular basis for inhibition of Lys310me1 binding by Ser311 phosphorylation. Together, these findings provide a structural explanation for a key cellular signaling pathway centered on RelA Lys310 methylation, which is generated by SETD6 and recognized by GLP, and incorporate a methylation-phosphorylation switch of adjacent lysine and serine residues. Finally, SETD6 is structurally similar to the Rubisco large subunit methyltransferase. Given the restriction of Rubisco to plant species, this particular appearance of the protein lysine methyltransferase has been evolutionarily well conserved.

Structural basis of SETD6-mediated regulation of the NF-kB network via methyl-lysine signaling.,Chang Y, Levy D, Horton JR, Peng J, Zhang X, Gozani O, Cheng X Nucleic Acids Res. 2011 Apr 22. PMID:21515635<ref>PMID:21515635</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 3rc0" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Chang, Y]]
[[Category: Cheng, X]]
[[Category: Gozani, O]]
[[Category: Horton, J R]]
[[Category: Levy, D]]
[[Category: Peng, J]]
[[Category: Zhang, X]]
[[Category: Epigenetic]]
[[Category: Protein lysine monomethylation]]
[[Category: Transferase]]