7c4o

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==Solution structure of the Orange domain from human protein HES1==
==Solution structure of the Orange domain from human protein HES1==
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<StructureSection load='7c4o' size='340' side='right'caption='[[7c4o]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='7c4o' size='340' side='right'caption='[[7c4o]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7c4o]] is a 2 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=7C4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C4O FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7c4o]] is a 2 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=7C4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C4O FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HES1, BHLHB39, HL, HRY ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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</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=7c4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c4o OCA], [https://pdbe.org/7c4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c4o RCSB], [https://www.ebi.ac.uk/pdbsum/7c4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c4o ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7c4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c4o OCA], [https://pdbe.org/7c4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c4o RCSB], [https://www.ebi.ac.uk/pdbsum/7c4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c4o ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/HES1_HUMAN HES1_HUMAN]] Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity (By similarity). May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage.<ref>PMID:18550849</ref>
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[[https://www.uniprot.org/uniprot/HES1_HUMAN HES1_HUMAN]] Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity (By similarity). May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage.<ref>PMID:18550849</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Herein, we report that hairy and enhancer of split homolog-1 (HES1), known to repress gene transcription in progenitor cells of several cell lineages, is strongly expressed in cells and tissues of T-cell lymphoma expressing the oncogenic chimeric tyrosine kinase nucleophosmin (NPM)-anaplastic lymphoma kinase [ALK; ALK(+) T-cell lymphoma (TCL)]. The structure analysis of the Orange domain of HES1 indicates that HES1 forms a highly stable homodimer. Of note, repression of HES1 expression leads to inhibition of ALK(+) TCL cell growth in vivo. The expression of the HES1 gene is induced by NPM-ALK through activation of STAT3, which binds to the gene's promoter and induces the gene's transcription. NPM-ALK also directly phosphorylates HES1 protein. In turn, HES1 up-regulates and down-regulates in ALK(+) TCL cell expression of numerous genes, protein products of which are involved in key cell functions, such as cell proliferation and viability. Among the genes inhibited by HES1 is thioredoxin-interacting protein (TXNIP), encoding a protein implicated in promotion of cell death in various types of cells. Accordingly, ALK(+) TCL cells and tissues lack expression of TXNIP, and its transcription is co-inhibited by HES1 and STAT3 in an NPM-ALK-dependent manner. Finally, the induced expression of TXNIP induces massive apoptotic cell death of ALK(+) TCL cells. The results revealed a novel NPM-ALK-controlled pro-oncogenic regulatory network and document an important role of HES and TXNIP in the NPM-ALK-driven oncogenesis, with the former protein displaying oncogenic and the latter tumor suppressor properties.
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Induction of Transcriptional Inhibitor Hairy and Enhancer of Split Homolog-1 and the Related Repression of Tumor-Suppressor Thioredoxin-Interacting Protein Are Important Components of Cell-Transformation Program Imposed by Oncogenic Kinase Nucleophosmin-Anaplastic Lymphoma Kinase.,Zhang Q, Wang HY, Nayak A, Nunez-Cruz S, Slupianek A, Liu X, Basappa J, Fan JS, Chekol S, Nejati R, Bogusz AM, Turner SD, Swaminathan K, Wasik MA Am J Pathol. 2022 May 28. pii: S0002-9440(22)00148-1. doi:, 10.1016/j.ajpath.2022.05.005. PMID:35640677<ref>PMID:35640677</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7c4o" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Fan, J S]]
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[[Category: Fan JS]]
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[[Category: Nayak, A]]
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[[Category: Nayak A]]
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[[Category: Swaminathan, K]]
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[[Category: Swaminathan K]]
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[[Category: Dimer]]
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[[Category: Signaling protein]]
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[[Category: Solution structure]]
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Revision as of 07:12, 8 September 2022

Solution structure of the Orange domain from human protein HES1

PDB ID 7c4o

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