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| | ==Zinc finger of human CXXC5 in complex with CpG DNA== | | ==Zinc finger of human CXXC5 in complex with CpG DNA== |
| - | <StructureSection load='5w9s' size='340' side='right' caption='[[5w9s]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='5w9s' size='340' side='right'caption='[[5w9s]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w9s]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W9S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W9S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w9s]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W9S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CXXC5, HSPC195, TCCCIA00297 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5w9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w9s OCA], [http://pdbe.org/5w9s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w9s RCSB], [http://www.ebi.ac.uk/pdbsum/5w9s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w9s 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=5w9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w9s OCA], [https://pdbe.org/5w9s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w9s RCSB], [https://www.ebi.ac.uk/pdbsum/5w9s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w9s ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CXXC5_HUMAN CXXC5_HUMAN]] May indirectly participate in activation of the NF-kappa-B and MAPK pathways. Acts as a mediator of BMP4-mediated modulation of canonical Wnt signaling activity in neural stem cells (By similarity). Required for DNA damage-induced ATM phosphorylation, p53 activation and cell cycle arrest. Involved in myelopoiesis. Transcription factor. Binds to the oxygen responsive element of COX4I2 and represses its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen) (PubMed:23303788). May repress COX4I2 transactivation induced by CHCHD2 and RBPJ (PubMed:23303788).<ref>PMID:19182210</ref> <ref>PMID:19557330</ref> <ref>PMID:23303788</ref> | + | [https://www.uniprot.org/uniprot/CXXC5_HUMAN CXXC5_HUMAN] May indirectly participate in activation of the NF-kappa-B and MAPK pathways. Acts as a mediator of BMP4-mediated modulation of canonical Wnt signaling activity in neural stem cells (By similarity). Required for DNA damage-induced ATM phosphorylation, p53 activation and cell cycle arrest. Involved in myelopoiesis. Transcription factor. Binds to the oxygen responsive element of COX4I2 and represses its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen) (PubMed:23303788). May repress COX4I2 transactivation induced by CHCHD2 and RBPJ (PubMed:23303788).<ref>PMID:19182210</ref> <ref>PMID:19557330</ref> <ref>PMID:23303788</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Large Structures]] |
| - | [[Category: Bountra, C]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Liu, K]] | + | [[Category: Bountra C]] |
| - | [[Category: Min, J]] | + | [[Category: Edwards AM]] |
| - | [[Category: Structural genomic]] | + | [[Category: Liu K]] |
| - | [[Category: Tempel, W]] | + | [[Category: Min J]] |
| - | [[Category: Walker, J R]]
| + | [[Category: Tempel W]] |
| - | [[Category: Xu, C]] | + | [[Category: Walker JR]] |
| - | [[Category: Dna binding protein-dna complex]] | + | [[Category: Xu C]] |
| - | [[Category: Sgc]] | + | |
| Structural highlights
Function
CXXC5_HUMAN May indirectly participate in activation of the NF-kappa-B and MAPK pathways. Acts as a mediator of BMP4-mediated modulation of canonical Wnt signaling activity in neural stem cells (By similarity). Required for DNA damage-induced ATM phosphorylation, p53 activation and cell cycle arrest. Involved in myelopoiesis. Transcription factor. Binds to the oxygen responsive element of COX4I2 and represses its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen) (PubMed:23303788). May repress COX4I2 transactivation induced by CHCHD2 and RBPJ (PubMed:23303788).[1] [2] [3]
Publication Abstract from PubMed
The CXXC domain, first identified as the reader of unmodified CpG dinucleotide, plays important roles in epigenetic regulation by targeting various activities to CpG islands. Here we systematically measured and compared the DNA-binding selectivities of all known human CXXC domains by different binding assays, and complemented the existing function-based classification of human CXXC domains with a classification based on their DNA selectivities. Through a series of crystal structures of CXXC domains with DNA ligands, we unravel the molecular mechanisms of how these CXXC domains, including single CXXC domains and tandem CXXC-PHD domains, recognize distinct DNA ligands, which further supports our classification of human CXXC domains and also provides insights into selective recruitment of chromatin modifiers to their respective targets via CXXC domains recognizing different genomic DNA sequences. Our study facilitates the understanding of the relationship between the DNA-binding specificities of the CXXC proteins and their biological functions.
DNA Sequence Recognition of Human CXXC Domains and Their Structural Determinants.,Xu C, Liu K, Lei M, Yang A, Li Y, Hughes TR, Min J Structure. 2017 Dec 16. pii: S0969-2126(17)30396-9. doi:, 10.1016/j.str.2017.11.022. PMID:29276034[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pendino F, Nguyen E, Jonassen I, Dysvik B, Azouz A, Lanotte M, Segal-Bendirdjian E, Lillehaug JR. Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis. Blood. 2009 Apr 2;113(14):3172-81. doi: 10.1182/blood-2008-07-170035. Epub 2009, Jan 30. PMID:19182210 doi:http://dx.doi.org/10.1182/blood-2008-07-170035
- ↑ ZHANG M, WANG R, WANG Y, DIAO F, LU F, GAO D, CHEN D, ZHAI Z, SHU H. The CXXC finger 5 protein is required for DNA damage-induced p53 activation. Sci China C Life Sci. 2009 Jun;52(6):528-38. doi: 10.1007/s11427-009-0083-7. Epub, 2009 Jun 26. PMID:19557330 doi:http://dx.doi.org/10.1007/s11427-009-0083-7
- ↑ Aras S, Pak O, Sommer N, Finley R Jr, Huttemann M, Weissmann N, Grossman LI. Oxygen-dependent expression of cytochrome c oxidase subunit 4-2 gene expression is mediated by transcription factors RBPJ, CXXC5 and CHCHD2. Nucleic Acids Res. 2013 Feb 1;41(4):2255-66. doi: 10.1093/nar/gks1454. Epub 2013 , Jan 8. PMID:23303788 doi:http://dx.doi.org/10.1093/nar/gks1454
- ↑ Xu C, Liu K, Lei M, Yang A, Li Y, Hughes TR, Min J. DNA Sequence Recognition of Human CXXC Domains and Their Structural Determinants. Structure. 2017 Dec 16. pii: S0969-2126(17)30396-9. doi:, 10.1016/j.str.2017.11.022. PMID:29276034 doi:http://dx.doi.org/10.1016/j.str.2017.11.022
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