View source for 6kqv


==Solution Structure of the UbL Domain of USP19==
<StructureSection load='6kqv' size='340' side='right'caption='[[6kqv]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kqv]] 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=6KQV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KQV FirstGlance]. <br>
</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=6kqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kqv OCA], [https://pdbe.org/6kqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kqv RCSB], [https://www.ebi.ac.uk/pdbsum/6kqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kqv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UBP19_HUMAN UBP19_HUMAN] Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic-reticulum-associated degradation (ERAD) substrates. Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non-catalytic manner. Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Exhibits a preference towards 'Lys-63'-linked Ubiquitin chains.<ref>PMID:19465887</ref> <ref>PMID:21849505</ref> <ref>PMID:22128162</ref> <ref>PMID:22689415</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ubiquitin-specific protease 19 (USP19) is a member of the deubiquitinating (DUB) enzymes that catalyze removing the ubiquitin signals from target proteins. Our previous research has demonstrated that USP19 up-regulates the protein level and aggregation of polyQ-expanded huntingtin through the involvement of heat shock protein 90 (HSP90). Here, we present solution structures of the CS1, CS2 and UbL domains of USP19 and structural insights into their domain interactions. We found that the tandem CS domains fold back to interact with the C-terminal USP domain (USPD) intra-molecularly that leads to inhibition of the catalytic core of USP19, especially CS1 interacts with the embedded UbL domain and CS2 does with the CH2 catalytic core. Moreover, CS2 specifically interacts with the NBD domain of HSP90, which can activate the DUB enzyme. A mechanism of auto-inhibition of USP19 and activation by HSP90 is proposed, on which USP19 modulates the protein level of polyQ-expanded huntingtin in cells. This study provides structural and mechanistic insights into the modulation of protein level and aggregation by USP19 with the assistance of HSP90.

Domain interactions reveal auto-inhibition of the deubiquitinating enzyme USP19 and its activation by HSP90 in the modulation of huntingtin aggregation.,Xue W, Zhang SX, He WT, Hong JY, Jiang LL, Hu HY Biochem J. 2020 Nov 13;477(21):4295-4312. doi: 10.1042/BCJ20200536. PMID:33094816<ref>PMID:33094816</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6kqv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hu HY]]
[[Category: Xue W]]