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| | ==Crystal Structure of NSD3 tandem PHD5-C5HCH domains complexed with H3 peptide 1-15== | | ==Crystal Structure of NSD3 tandem PHD5-C5HCH domains complexed with H3 peptide 1-15== |
| - | <StructureSection load='4gnf' size='340' side='right' caption='[[4gnf]], [[Resolution|resolution]] 1.55Å' scene=''> | + | <StructureSection load='4gnf' size='340' side='right'caption='[[4gnf]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gnf]] 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=4GNF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GNF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gnf]] 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=4GNF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GNF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gnd|4gnd]], [[4gne|4gne]], [[4gng|4gng]]</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=4gnf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gnf OCA], [https://pdbe.org/4gnf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gnf RCSB], [https://www.ebi.ac.uk/pdbsum/4gnf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gnf ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WHSC1L1, NSD3, DC28 ([http://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'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gnf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gnf OCA], [http://pdbe.org/4gnf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gnf RCSB], [http://www.ebi.ac.uk/pdbsum/4gnf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gnf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/NSD3_HUMAN NSD3_HUMAN]] Note=Defects in WHSC1L1 may be involved in non small cell lung carcinomas (NSCLC). Amplified or overexpressed in NSCLC.<ref>PMID:15983384</ref> Note=A chromosomal aberration involving WHSC1L1 is found in childhood acute myeloid leukemia. Translocation t(8;11)(p11.2;p15) with NUP98. | + | [https://www.uniprot.org/uniprot/NSD3_HUMAN NSD3_HUMAN] Note=Defects in WHSC1L1 may be involved in non small cell lung carcinomas (NSCLC). Amplified or overexpressed in NSCLC.<ref>PMID:15983384</ref> Note=A chromosomal aberration involving WHSC1L1 is found in childhood acute myeloid leukemia. Translocation t(8;11)(p11.2;p15) with NUP98. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NSD3_HUMAN NSD3_HUMAN]] Histone methyltransferase. Preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression.<ref>PMID:16682010</ref> | + | [https://www.uniprot.org/uniprot/NSD3_HUMAN NSD3_HUMAN] Histone methyltransferase. Preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression.<ref>PMID:16682010</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Histone methyltransferase|Histone methyltransferase]] | + | *[[Beta-N-acetylhexosaminidase 3D structures|Beta-N-acetylhexosaminidase 3D structures]] |
| | + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Histone-lysine N-methyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: He, C]] | + | [[Category: He C]] |
| - | [[Category: Li, F]] | + | [[Category: Li F]] |
| - | [[Category: Shi, Y]] | + | [[Category: Shi Y]] |
| - | [[Category: Wu, J]] | + | [[Category: Wu J]] |
| - | [[Category: Histone]]
| + | |
| - | [[Category: Nuclear protein]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transferase-nuclear protein complex]]
| + | |
| - | [[Category: Zinc finger]]
| + | |
| Structural highlights
Disease
NSD3_HUMAN Note=Defects in WHSC1L1 may be involved in non small cell lung carcinomas (NSCLC). Amplified or overexpressed in NSCLC.[1] Note=A chromosomal aberration involving WHSC1L1 is found in childhood acute myeloid leukemia. Translocation t(8;11)(p11.2;p15) with NUP98.
Function
NSD3_HUMAN Histone methyltransferase. Preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression.[2]
Publication Abstract from PubMed
The NSD (nuclear receptor SET domain-containing) family members, consisting of NSD1, NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1), are SET domain-containing methyltransferases and aberrant expression of each member has been implicated in multiple diseases. They have specific mono- and dimethylase activities for H3K36, whereas play nonredundant roles during development. Aside from the well characterized catalytic SET domain, NSD proteins have multiple potential chromatin-binding motifs that are clinically relevant, including the fifth plant homeodomain (PHD5) and the adjacent Cys-His-rich domain (C5HCH) located at the C terminus. Herein, we report the crystal structures of the PHD5-C5HCH module of NSD3, in the free state and in complex with H3(1-7) (H3 residues 1-7), H3(1-15) (H3 residues 1-15), and H3(1-15)K9me3 (H3 residues 1-15 with trimethylation on K9) peptides. These structures reveal that the PHD5 and C5HCH domains fold into a novel integrated PHD-PHD-like structural module with H3 peptide bound only on the surface of PHD5 and provide the molecular basis for the recognition of unmodified H3K4 and trimethylated H3K9 by NSD3 PHD5. Structural studies and binding assays show that differences exist in histone binding specificity of the PHD5 domain between three members of the NSD family. For NSD2, the PHD5-C5HCH:H3 N terminus interaction is largely conserved, although with a stronger preference for unmethylated H3K9 (H3K9me0) than trimethylated H3K9 (H3K9me3), and NSD1 PHD5-C5HCH does not bind to H3 peptides. Our results shed light on how NSD proteins that mediate H3K36 methylation are localized to specific genomic sites and provide implications for the mechanism of functional diversity of NSD proteins.
The methyltransferase NSD3 has chromatin-binding motifs, PHD5-C5HCH, that are distinct from other NSD (nuclear receptor SET domain) family members in their histone H3 recognition.,He C, Li F, Zhang J, Wu J, Shi Y J Biol Chem. 2013 Feb 15;288(7):4692-703. doi: 10.1074/jbc.M112.426148. Epub 2012, Dec 26. PMID:23269674[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tonon G, Wong KK, Maulik G, Brennan C, Feng B, Zhang Y, Khatry DB, Protopopov A, You MJ, Aguirre AJ, Martin ES, Yang Z, Ji H, Chin L, Depinho RA. High-resolution genomic profiles of human lung cancer. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9625-30. Epub 2005 Jun 27. PMID:15983384 doi:10.1073/pnas.0504126102
- ↑ Kim SM, Kee HJ, Eom GH, Choe NW, Kim JY, Kim YS, Kim SK, Kook H, Kook H, Seo SB. Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity. Biochem Biophys Res Commun. 2006 Jun 23;345(1):318-23. Epub 2006 Apr 27. PMID:16682010 doi:S0006-291X(06)00939-9
- ↑ He C, Li F, Zhang J, Wu J, Shi Y. The methyltransferase NSD3 has chromatin-binding motifs, PHD5-C5HCH, that are distinct from other NSD (nuclear receptor SET domain) family members in their histone H3 recognition. J Biol Chem. 2013 Feb 15;288(7):4692-703. doi: 10.1074/jbc.M112.426148. Epub 2012, Dec 26. PMID:23269674 doi:10.1074/jbc.M112.426148
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