View source for 8pvy


==Cryo-EM structure of the human BRISC dimer complex bound to compound FX-171-C==
<StructureSection load='8pvy' size='340' side='right'caption='[[8pvy]], [[Resolution|resolution]] 3.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8pvy]] is a 16 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=8PVY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PVY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.02&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G1V:~{N}-[(1~{R},5~{S})-3-azabicyclo[3.1.0]hexan-6-yl]-1-[2,6-bis(chloranyl)phenyl]carbonyl-4-[[2,6-bis(chloranyl)phenyl]carbonylamino]pyrazole-3-carboxamide'>G1V</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=8pvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pvy OCA], [https://pdbe.org/8pvy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pvy RCSB], [https://www.ebi.ac.uk/pdbsum/8pvy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pvy ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BRCC3_HUMAN BRCC3_HUMAN] Moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome. A chromosomal aberration involving BRCC3 is a cause of pro-lymphocytic T-cell leukemia (T-PLL). Translocation t(X;14)(q28;q11) with TCRA.<ref>PMID:8247530</ref> 
== Function ==
[https://www.uniprot.org/uniprot/BRCC3_HUMAN BRCC3_HUMAN] Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains (PubMed:19214193, PubMed:20656690, PubMed:24075985, PubMed:26344097). Does not have activity toward 'Lys-48'-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs) (PubMed:20656690). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:20656690, PubMed:24075985, PubMed:26344097, PubMed:26195665). Mediates the specific 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex (PubMed:19214193). The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985).<ref>PMID:14636569</ref> <ref>PMID:16707425</ref> <ref>PMID:17525341</ref> <ref>PMID:19202061</ref> <ref>PMID:19214193</ref> <ref>PMID:19261746</ref> <ref>PMID:19261748</ref> <ref>PMID:19261749</ref> <ref>PMID:20656690</ref> <ref>PMID:24075985</ref> <ref>PMID:26195665</ref> <ref>PMID:26344097</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chandler F]]
[[Category: Zeqiraj E]]