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| | ==Solution structure of WW domain with polyproline stretch (PP2WW) of HYPB== | | ==Solution structure of WW domain with polyproline stretch (PP2WW) of HYPB== |
| - | <StructureSection load='2mdj' size='340' side='right' caption='[[2mdj]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='2mdj' size='340' side='right'caption='[[2mdj]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mdj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MDJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MDJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mdj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MDJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MDJ FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2mdc|2mdc]], [[2mdi|2mdi]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2mdc|2mdc]], [[2mdi|2mdi]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SETD2, HIF1, HYPB, KIAA1732, KMT3A, SET2, HSPC069 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SETD2, HIF1, HYPB, KIAA1732, KMT3A, SET2, HSPC069 ([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'>[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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mdj OCA], [http://pdbe.org/2mdj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mdj RCSB], [http://www.ebi.ac.uk/pdbsum/2mdj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mdj 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=2mdj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mdj OCA], [https://pdbe.org/2mdj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mdj RCSB], [https://www.ebi.ac.uk/pdbsum/2mdj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mdj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SETD2_HUMAN SETD2_HUMAN]] Histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. Probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. Binds DNA at promoters. May also act as a transcription activator that binds to promoters. Binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.<ref>PMID:16118227</ref> | + | [[https://www.uniprot.org/uniprot/SETD2_HUMAN SETD2_HUMAN]] Histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. Probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. Binds DNA at promoters. May also act as a transcription activator that binds to promoters. Binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.<ref>PMID:16118227</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]] | + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Histone-lysine N-methyltransferase]] | | [[Category: Histone-lysine N-methyltransferase]] |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Gao, Y]] | | [[Category: Gao, Y]] |
| | [[Category: Hu, H]] | | [[Category: Hu, H]] |
| Structural highlights
2mdj is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | |
| Gene: | SETD2, HIF1, HYPB, KIAA1732, KMT3A, SET2, HSPC069 (HUMAN) |
| Activity: | Histone-lysine N-methyltransferase, with EC number 2.1.1.43 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SETD2_HUMAN] Histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. Probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. Binds DNA at promoters. May also act as a transcription activator that binds to promoters. Binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.[1]
Publication Abstract from PubMed
Huntington's disease (HD) is an autosomally dominant neurodegenerative disorder caused by expansion of polyglutamine (polyQ) in the huntingtin (Htt) protein. Htt yeast two-hybrid protein B (HYPB/SETD2), a histone methyltransferase, directly interacts with Htt and is involved in HD pathology. Using NMR techniques, we characterized a polyproline (polyP) stretch at the C terminus of HYPB, which directly interacts with the following WW domain and leads this domain predominantly to be in a closed conformational state. The solution structure shows that the polyP stretch extends from the back and binds to the WW core domain in a typical binding mode. This autoinhibitory structure regulates interaction between the WW domain of HYPB and the proline-rich region (PRR) of Htt, as evidenced by NMR and immunofluorescence techniques. This work provides structural and mechanistic insights into the intramolecular regulation of the WW domain in Htt-interacting partners and will be helpful for understanding the pathology of HD.
Autoinhibitory structure of the WW domain of HYPB/SETD2 regulates its interaction with the proline-rich region of huntingtin.,Gao YG, Yang H, Zhao J, Jiang YJ, Hu HY Structure. 2014 Mar 4;22(3):378-86. doi: 10.1016/j.str.2013.12.005. Epub 2014 Jan, 9. PMID:24412394[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sun XJ, Wei J, Wu XY, Hu M, Wang L, Wang HH, Zhang QH, Chen SJ, Huang QH, Chen Z. Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem. 2005 Oct 21;280(42):35261-71. Epub 2005 Aug 22. PMID:16118227 doi:http://dx.doi.org/M504012200
- ↑ Gao YG, Yang H, Zhao J, Jiang YJ, Hu HY. Autoinhibitory structure of the WW domain of HYPB/SETD2 regulates its interaction with the proline-rich region of huntingtin. Structure. 2014 Mar 4;22(3):378-86. doi: 10.1016/j.str.2013.12.005. Epub 2014 Jan, 9. PMID:24412394 doi:http://dx.doi.org/10.1016/j.str.2013.12.005
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