2c6a

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{{Seed}}
 
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[[Image:2c6a.png|left|200px]]
 
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==Solution structure of the C4 zinc-finger domain of HDM2==
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The line below this paragraph, containing "STRUCTURE_2c6a", creates the "Structure Box" on the page.
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<StructureSection load='2c6a' size='340' side='right'caption='[[2c6a]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2c6a]] 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=2C6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C6A FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_2c6a| PDB=2c6a | SCENE= }}
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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=2c6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c6a OCA], [https://pdbe.org/2c6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c6a RCSB], [https://www.ebi.ac.uk/pdbsum/2c6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c6a ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.
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== Function ==
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[https://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c6/2c6a_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2c6a ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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HDM2 is a ubiquitin E3 ligase that is a key negative regulator of the tumor suppressor p53. Here, we report the determination of the solution structure of the C4 zinc finger domain of HDM2 using multidimensional NMR. The HDM2 C4 zinc finger domain has a fold consisting of a 3(10) helix followed by four beta-strands, which shares significant structural similarity to the zinc ribbon protein family. Family based sequence analysis identified two putative binding sites, one of which resembles an RNA binding motif.
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===SOLUTION STRUCTURE OF THE C4 ZINC-FINGER DOMAIN OF HDM2===
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Solution structure of the C4 zinc finger domain of HDM2.,Yu GW, Allen MD, Andreeva A, Fersht AR, Bycroft M Protein Sci. 2006 Feb;15(2):384-9. Epub 2005 Dec 29. PMID:16385008<ref>PMID:16385008</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 2c6a" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_16385008}}, adds the Publication Abstract to the page
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*[[MDM2 3D structures|MDM2 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 16385008 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16385008}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2C6A is a [[Single protein]] structure of 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=2C6A OCA].
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==Reference==
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Solution structure of the C4 zinc finger domain of HDM2., Yu GW, Allen MD, Andreeva A, Fersht AR, Bycroft M, Protein Sci. 2006 Feb;15(2):384-9. Epub 2005 Dec 29. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16385008 16385008]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Allen, M D.]]
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[[Category: Allen MD]]
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[[Category: Andreeva, A.]]
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[[Category: Andreeva A]]
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[[Category: Bycroft, M.]]
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[[Category: Bycroft M]]
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[[Category: Fersht, A R.]]
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[[Category: Fersht AR]]
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[[Category: Yu, G W.]]
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[[Category: Yu GW]]
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[[Category: Alternative splicing]]
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[[Category: Human mdm2]]
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[[Category: Ligase]]
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[[Category: Metal-binding]]
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[[Category: Nuclear protein]]
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[[Category: Phosphorylation]]
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[[Category: Proto-oncogene]]
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[[Category: Ubl conjugation pathway]]
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[[Category: Zinc]]
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[[Category: Zinc finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:56:13 2008''
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Current revision

Solution structure of the C4 zinc-finger domain of HDM2

PDB ID 2c6a

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