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| ==Crystal Structure of DDB1 in Complex with the H-Box Motif of DDB2== | | ==Crystal Structure of DDB1 in Complex with the H-Box Motif of DDB2== |
| <StructureSection load='3i7l' size='340' side='right' caption='[[3i7l]], [[Resolution|resolution]] 2.80Å' scene=''> | | <StructureSection load='3i7l' size='340' side='right'caption='[[3i7l]], [[Resolution|resolution]] 2.80Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3i7l]] is a 2 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=3I7L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3I7L FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3i7l]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3I7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3I7L FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2b5m|2b5m]], [[3i7h|3i7h]], [[3i7k|3i7k]], [[3i7n|3i7n]], [[3i7o|3i7o]], [[3i7p|3i7p]], [[3i89|3i89]], [[3i8c|3i8c]], [[3i8e|3i8e]]</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]] 2.8Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DDB1, XAP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3i7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i7l OCA], [https://pdbe.org/3i7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3i7l RCSB], [https://www.ebi.ac.uk/pdbsum/3i7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3i7l ProSAT]</span></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=3i7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3i7l OCA], [http://pdbe.org/3i7l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3i7l RCSB], [http://www.ebi.ac.uk/pdbsum/3i7l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3i7l ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Disease ==
| |
| [[http://www.uniprot.org/uniprot/DDB2_HUMAN DDB2_HUMAN]] Defects in DDB2 are a cause of xeroderma pigmentosum complementation group E (XP-E) [MIM:[http://omim.org/entry/278740 278740]]; also known as xeroderma pigmentosum V (XP5). XP-E is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.<ref>PMID:8798680</ref>
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| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/DDB1_HUMAN DDB1_HUMAN]] Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2.<ref>PMID:12732143</ref> <ref>PMID:15448697</ref> <ref>PMID:14739464</ref> <ref>PMID:15882621</ref> <ref>PMID:16260596</ref> <ref>PMID:16482215</ref> <ref>PMID:17079684</ref> <ref>PMID:16407242</ref> <ref>PMID:16407252</ref> <ref>PMID:16678110</ref> <ref>PMID:16940174</ref> <ref>PMID:17041588</ref> <ref>PMID:16473935</ref> <ref>PMID:18593899</ref> <ref>PMID:18381890</ref> <ref>PMID:18332868</ref> [[http://www.uniprot.org/uniprot/DDB2_HUMAN DDB2_HUMAN]] Required for DNA repair. Binds to DDB1 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as the substrate recognition module for the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB1-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. The DDB1-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. Isoform D1 and isoform D2 inhibit UV-damaged DNA repair.<ref>PMID:14751237</ref> <ref>PMID:9892649</ref> <ref>PMID:10882109</ref> <ref>PMID:11278856</ref> <ref>PMID:11705987</ref> <ref>PMID:12732143</ref> <ref>PMID:12944386</ref> <ref>PMID:15882621</ref> <ref>PMID:16260596</ref> <ref>PMID:16678110</ref> <ref>PMID:16473935</ref> <ref>PMID:18593899</ref> | | [https://www.uniprot.org/uniprot/DDB1_HUMAN DDB1_HUMAN] Required for DNA repair. Binds to DDB2 to form the UV-damaged DNA-binding protein complex (the UV-DDB complex). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2.<ref>PMID:12732143</ref> <ref>PMID:15448697</ref> <ref>PMID:14739464</ref> <ref>PMID:15882621</ref> <ref>PMID:16260596</ref> <ref>PMID:16482215</ref> <ref>PMID:17079684</ref> <ref>PMID:16407242</ref> <ref>PMID:16407252</ref> <ref>PMID:16678110</ref> <ref>PMID:16940174</ref> <ref>PMID:17041588</ref> <ref>PMID:16473935</ref> <ref>PMID:18593899</ref> <ref>PMID:18381890</ref> <ref>PMID:18332868</ref> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| <jmolCheckbox> | | <jmolCheckbox> |
| <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i7/3i7l_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i7/3i7l_consurf.spt"</scriptWhenChecked> |
| <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| </jmolCheckbox> | | </jmolCheckbox> |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Breugel, P C.V]] | | [[Category: Large Structures]] |
| [[Category: Li, T]] | | [[Category: Breugel PCV]] |
| [[Category: Robert, E I]] | | [[Category: Li T]] |
| [[Category: Strubin, M]] | | [[Category: Robert EI]] |
| [[Category: Zheng, N]] | | [[Category: Strubin M]] |
| [[Category: Alternative splicing]]
| | [[Category: Zheng N]] |
| [[Category: Cytoplasm]]
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| [[Category: Ddb1]]
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| [[Category: Ddb2]]
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| [[Category: Disease mutation]]
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| [[Category: Dna damage]]
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| [[Category: Dna repair]]
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| [[Category: Dna-binding]]
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| [[Category: H-box motif]]
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| [[Category: Host-virus interaction]]
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| [[Category: Nucleus]]
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| [[Category: Phosphoprotein]]
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| [[Category: Polymorphism]]
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| [[Category: Protein binding]]
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| [[Category: Ubl conjugation]]
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| [[Category: Ubl conjugation pathway]]
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| [[Category: Wd repeat]]
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| [[Category: Xeroderma pigmentosum]]
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