View source for 8uqa


==Crystal structure of RNF168 (RING)-UbcH5c fused to H2A-H2B via a 12-residue linker==
<StructureSection load='8uqa' size='340' side='right'caption='[[8uqa]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8uqa]] is a 1 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=8UQA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UQA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.049&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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'>[https://proteopedia.org/fgij/fg.htm?mol=8uqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uqa OCA], [https://pdbe.org/8uqa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uqa RCSB], [https://www.ebi.ac.uk/pdbsum/8uqa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uqa ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RN168_HUMAN RN168_HUMAN] Defects in RNF168 are the cause of Riddle syndrome (RIDDLES) [MIM:[https://omim.org/entry/611943 611943]. Riddle syndrome is characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature. Defects are probably due to impaired localization of TP53BP1 and BRCA1 at DNA lesions.<ref>PMID:19203578</ref> 
== Function ==
[https://www.uniprot.org/uniprot/H2B2E_HUMAN H2B2E_HUMAN] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.<ref>PMID:11859126</ref> <ref>PMID:12860195</ref> <ref>PMID:15019208</ref>   Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.<ref>PMID:11859126</ref> <ref>PMID:12860195</ref> <ref>PMID:15019208</ref> [https://www.uniprot.org/uniprot/H2A1B_HUMAN H2A1B_HUMAN] [https://www.uniprot.org/uniprot/UB2D3_HUMAN UB2D3_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE which triggers apoptosis. In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (By similarity).<ref>PMID:10329681</ref> <ref>PMID:11743028</ref> <ref>PMID:12646252</ref> <ref>PMID:15247280</ref> <ref>PMID:15280377</ref> <ref>PMID:15496420</ref> <ref>PMID:16628214</ref> <ref>PMID:18515077</ref> <ref>PMID:18948756</ref> <ref>PMID:18508924</ref> <ref>PMID:18284575</ref> <ref>PMID:20061386</ref> <ref>PMID:20347421</ref> <ref>PMID:21532592</ref> [https://www.uniprot.org/uniprot/RN168_HUMAN RN168_HUMAN] E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).<ref>PMID:19203578</ref> <ref>PMID:19203579</ref> <ref>PMID:20550933</ref> <ref>PMID:22713238</ref> <ref>PMID:22373579</ref> <ref>PMID:22705371</ref> <ref>PMID:22742833</ref> <ref>PMID:22980979</ref> 

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Botuyan MV]]
[[Category: Hu Q]]
[[Category: Mer G]]