|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of the AML1-ETO Nervy Domain - PKA(RIIa) complex and its contribution to AML1-ETO activity== | | ==Structure of the AML1-ETO Nervy Domain - PKA(RIIa) complex and its contribution to AML1-ETO activity== |
| - | <StructureSection load='2kyg' size='340' side='right'caption='[[2kyg]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='2kyg' size='340' side='right'caption='[[2kyg]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kyg]] is a 3 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=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> | + | <table><tr><td colspan='2'>[[2kyg]] is a 3 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=2KYG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KYG FirstGlance]. <br> |
| - | </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 HUMAN]), RUNX1T1, AML1T1, CBFA2T1, CDR, ETO, MTG8, ZMYND2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[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://pdbe.org/2kyg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kyg RCSB], [http://www.ebi.ac.uk/pdbsum/2kyg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kyg 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=2kyg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kyg OCA], [https://pdbe.org/2kyg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kyg RCSB], [https://www.ebi.ac.uk/pdbsum/2kyg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kyg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[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]]. | |
| | == Function == | | == Function == |
| - | [[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> | + | [https://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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bushweller, J]] | + | [[Category: Bushweller J]] |
| - | [[Category: Cierpecki, T]] | + | [[Category: Cierpecki T]] |
| - | [[Category: Corpora, T A]] | + | [[Category: Corpora TA]] |
| - | [[Category: Homodimer bound to monomer]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Protein/protein]]
| + | |
| Structural highlights
Function
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.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Corpora T, Roudaia L, Oo ZM, Chen W, Manuylova E, Cai X, Chen MJ, Cierpicki T, Speck NA, Bushweller JH. Structure of the AML1-ETO NHR3-PKA(RIIalpha) complex and its contribution to AML1-ETO activity. J Mol Biol. 2010 Sep 24;402(3):560-77. Epub 2010 Aug 11. PMID:20708017 doi:10.1016/j.jmb.2010.08.007
|
