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2kyg

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{{STRUCTURE_2kyg| PDB=2kyg | SCENE= }}
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==Structure of the AML1-ETO Nervy Domain - PKA(RIIa) complex and its contribution to AML1-ETO activity==
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===Structure of the AML1-ETO Nervy Domain - PKA(RIIa) complex and its contribution to AML1-ETO activity===
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<StructureSection load='2kyg' size='340' side='right' caption='[[2kyg]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
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{{ABSTRACT_PUBMED_20708017}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2kyg]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KYG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KYG FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKAR2A, PKR2, PRKAR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), RUNX1T1, AML1T1, CBFA2T1, CDR, ETO, MTG8, ZMYND2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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=2kyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kyg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2kyg RCSB], [http://www.ebi.ac.uk/pdbsum/2kyg PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Note=A chromosomal aberration involving RUNX1T1 is a cause of acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1/AML1.<ref>PMID:8334990</ref> <ref>PMID:7541640</ref> <ref>PMID:8353289</ref> <ref>PMID:1423235</ref> Defects in RUNX1T1 may be a cause of colorectal cancer (CRC) [MIM:[http://omim.org/entry/114500 114500]].
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== Function ==
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[[http://www.uniprot.org/uniprot/KAP2_HUMAN KAP2_HUMAN]] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. [[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12.<ref>PMID:10973986</ref> <ref>PMID:16803958</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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AML1-ETO is the chimeric protein product of t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the nervy homology region (NHR) 3 domain, which shares homology with A-kinase anchoring proteins and interacts with the regulatory subunit of type II cAMP-dependent protein kinase A (PKA(RIIalpha)). We determined the solution structure of a complex between the AML1-ETO NHR3 domain and PKA(RIIalpha). Based on this structure, a key residue in AML1-ETO for PKA(RIIalpha) association was mutated. This mutation did not disrupt AML1-ETO's ability to enhance the clonogenic capacity of primary mouse bone marrow cells or its ability to repress proliferation or granulocyte differentiation. Introduction of the mutation into AML1-ETO had minimal impact on in vivo leukemogenesis. Therefore, the NHR3-PKA(RIIalpha) protein interaction does not appear to significantly contribute to AML1-ETO's ability to induce leukemia.
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==Disease==
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Structure of the AML1-ETO NHR3-PKA(RIIalpha) complex and its contribution to AML1-ETO activity.,Corpora T, Roudaia L, Oo ZM, Chen W, Manuylova E, Cai X, Chen MJ, Cierpicki T, Speck NA, Bushweller JH J Mol Biol. 2010 Sep 24;402(3):560-77. Epub 2010 Aug 11. PMID:20708017<ref>PMID:20708017</ref>
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[[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Note=A chromosomal aberration involving RUNX1T1 is a cause of acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1/AML1.<ref>PMID:8334990</ref><ref>PMID:7541640</ref><ref>PMID:8353289</ref><ref>PMID:1423235</ref> Defects in RUNX1T1 may be a cause of colorectal cancer (CRC) [MIM:[http://omim.org/entry/114500 114500]].
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/KAP2_HUMAN KAP2_HUMAN]] Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. [[http://www.uniprot.org/uniprot/MTG8_HUMAN MTG8_HUMAN]] Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12.<ref>PMID:10973986</ref><ref>PMID:16803958</ref>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[2kyg]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KYG OCA].
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__TOC__
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</StructureSection>
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==See Also==
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*[[CAMP-dependent protein kinase|CAMP-dependent protein kinase]]
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==Reference==
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<ref group="xtra">PMID:020708017</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Bushweller, J.]]
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[[Category: Bushweller, J]]
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[[Category: Cierpecki, T.]]
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[[Category: Cierpecki, T]]
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[[Category: Corpora, T A.]]
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[[Category: Corpora, T A]]
[[Category: Homodimer bound to monomer]]
[[Category: Homodimer bound to monomer]]
[[Category: Protein binding]]
[[Category: Protein binding]]
[[Category: Protein/protein]]
[[Category: Protein/protein]]

Revision as of 12:31, 18 December 2014

Structure of the AML1-ETO Nervy Domain - PKA(RIIa) complex and its contribution to AML1-ETO activity

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