View source for 5cvm

==USP46~ubiquitin BEA covalent complex==
<StructureSection load='5cvm' size='340' side='right' caption='[[5cvm]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5cvm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CVM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CVM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cvl|5cvl]], [[5cvn|5cvn]], [[5cvo|5cvo]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </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=5cvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cvm OCA], [http://pdbe.org/5cvm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cvm RCSB], [http://www.ebi.ac.uk/pdbsum/5cvm PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/UBP46_HUMAN UBP46_HUMAN]] Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action. May act by mediating the deubiquitination of GAD1/GAD67. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Not involved in deubiquitination of monoubiquitinated FANCD2.<ref>PMID:19075014</ref>  [[http://www.uniprot.org/uniprot/UBB_HUMAN UBB_HUMAN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein ubiquitination patterns are an important component of cellular signaling. The WD-repeat protein WDR48 (USP1-associated factor UAF-1) stimulates activity of ubiquitin-specific proteases USP1, USP12, and USP46. To understand how WDR48 exerts its effect on the USP scaffold, we determined structures of the ternary WDR48:USP46:ubiquitin complex. WDR48 interacts with the USP46 fingers subdomain via a relatively small, highly polar surface on the top center of the WDR48 beta propeller. In addition, WDR48 has a novel ancillary domain and a C-terminal SUMO-like domain encircling the USP46-bound ubiquitin. Mutation of residues involved in the WDR48:USP46 interaction abrogated both binding and deubiquitinase activity of the complex. An analogous mutation in USP1 similarly blocked WDR48-dependent activation. Our data suggest a possible mechanism of deubiquitinase stimulation via stabilization and prolonged residence time of substrate. The unprecedented mode of interaction between the USP fingers domain and the WD-repeat beta propeller serves as a prototypical example for this family of deubiquitinases.

Structural Insights into WD-Repeat 48 Activation of Ubiquitin-Specific Protease 46.,Yin J, Schoeffler AJ, Wickliffe K, Newton K, Starovasnik MA, Dueber EC, Harris SF Structure. 2015 Sep 12. pii: S0969-2126(15)00359-7. doi:, 10.1016/j.str.2015.08.010. PMID:26388029<ref>PMID:26388029</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5cvm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Ubiquitinyl hydrolase 1]]
[[Category: Harris, S F]]
[[Category: Yin, J]]
[[Category: Deubiquitinase]]
[[Category: Dub]]
[[Category: Hydrolase-signaling protein complex]]
[[Category: Usp46 ubiquitin covalent complex]]