2mtn
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2mtn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MTN FirstGlance]. <br> | <table><tr><td colspan='2'>[[2mtn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MTN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MTN FirstGlance]. <br> | ||
| - | </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=2mtn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mtn OCA], [https://pdbe.org/2mtn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mtn RCSB], [https://www.ebi.ac.uk/pdbsum/2mtn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mtn ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2mtn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mtn OCA], [https://pdbe.org/2mtn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mtn RCSB], [https://www.ebi.ac.uk/pdbsum/2mtn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mtn ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/PSIP1_HUMAN PSIP1_HUMAN] Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.<ref>PMID:15642333</ref> [https://www.uniprot.org/uniprot/KMT2A_HUMAN KMT2A_HUMAN] Histone methyltransferase that plays an essential role in early development and hematopoiesis. Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation. Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity. Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9'. Required for transcriptional activation of HOXA9. Promotes PPP1R15A-induced apoptosis.<ref>PMID:10490642</ref> <ref>PMID:12453419</ref> <ref>PMID:15960975</ref> <ref>PMID:19556245</ref> | [https://www.uniprot.org/uniprot/PSIP1_HUMAN PSIP1_HUMAN] Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration.<ref>PMID:15642333</ref> [https://www.uniprot.org/uniprot/KMT2A_HUMAN KMT2A_HUMAN] Histone methyltransferase that plays an essential role in early development and hematopoiesis. Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation. Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity. Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9'. Required for transcriptional activation of HOXA9. Promotes PPP1R15A-induced apoptosis.<ref>PMID:10490642</ref> <ref>PMID:12453419</ref> <ref>PMID:15960975</ref> <ref>PMID:19556245</ref> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Lens epithelium-derived growth factor (LEDGF) is a chromatin associated protein implicated in leukemia and HIV-1 infection. LEDGF associates with MLL fusion proteins and menin and is required for leukemic transformation. To better understand the molecular mechanism underlying the LEDGF IBD domain interaction with MLL fusion proteins in leukemia we determined the solution structure of the MLL-IBD complex. We found a novel MLL motif, IBM2 (Integrase Binding Motif 2), which binds to a well-defined site on IBD. Point mutations within IBM2 abolished leukemogenic transformation by MLL-AF9, validating that this newly identified motif is essential for the oncogenic activity of MLL fusion proteins. Interestingly, the IBM2 binding site on IBD overlaps with the binding site for the HIV integrase (IN) and IN was capable to efficiently sequester IBD from the menin-MLL complex. A short IBM2 peptide binds to the IBD domain directly and inhibits both the IBD-MLL/menin and IBD-IN interactions. Our findings show that the same site on IBD is involved in binding to MLL and HIV integrase, revealing an attractive approach to simultaneously target LEDGF in leukemia and HIV. | ||
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| - | The same site on LEDGF IBD domain represents therapeutic target for MLL leukemia and HIV.,Murai MJ, Pollock J, He S, Miao H, Purohit T, Yokom A, Hess JL, Muntean AG, Grembecka J, Cierpicki T Blood. 2014 Oct 10. pii: blood-2014-01-550079. PMID:25305204<ref>PMID:25305204</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 2mtn" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Solution structure of MLL-IBD complex
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