6gh9

From Proteopedia

(Difference between revisions)

Revision as of 08:13, 26 September 2018

USP15 catalytic domain in complex with small molecule

Structural highlights

6gh9 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	6gha
Activity:	Ubiquitinyl hydrolase 1, with EC number 3.4.19.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UBP15_HUMAN] Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling and NF-kappa-B pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP. Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

References

↑ Hetfeld BK, Helfrich A, Kapelari B, Scheel H, Hofmann K, Guterman A, Glickman M, Schade R, Kloetzel PM, Dubiel W. The zinc finger of the CSN-associated deubiquitinating enzyme USP15 is essential to rescue the E3 ligase Rbx1. Curr Biol. 2005 Jul 12;15(13):1217-21. PMID:16005295 doi:10.1016/j.cub.2005.05.059
↑ Schweitzer K, Bozko PM, Dubiel W, Naumann M. CSN controls NF-kappaB by deubiquitinylation of IkappaBalpha. EMBO J. 2007 Mar 21;26(6):1532-41. Epub 2007 Feb 22. PMID:17318178 doi:10.1038/sj.emboj.7601600
↑ Cayli S, Klug J, Chapiro J, Frohlich S, Krasteva G, Orel L, Meinhardt A. COP9 signalosome interacts ATP-dependently with p97/valosin-containing protein (VCP) and controls the ubiquitination status of proteins bound to p97/VCP. J Biol Chem. 2009 Dec 11;284(50):34944-53. Epub 2009 Oct 13. PMID:19826004 doi:M109.037952
↑ Huang X, Langelotz C, Hetfeld-Pechoc BK, Schwenk W, Dubiel W. The COP9 signalosome mediates beta-catenin degradation by deneddylation and blocks adenomatous polyposis coli destruction via USP15. J Mol Biol. 2009 Aug 28;391(4):691-702. Epub 2009 Jul 1. PMID:19576224 doi:S0022-2836(09)00798-0
↑ Vos RM, Altreuter J, White EA, Howley PM. The ubiquitin-specific peptidase USP15 regulates human papillomavirus type 16 E6 protein stability. J Virol. 2009 Sep;83(17):8885-92. doi: 10.1128/JVI.00605-09. Epub 2009 Jun 24. PMID:19553310 doi:10.1128/JVI.00605-09
↑ Inui M, Manfrin A, Mamidi A, Martello G, Morsut L, Soligo S, Enzo E, Moro S, Polo S, Dupont S, Cordenonsi M, Piccolo S. USP15 is a deubiquitylating enzyme for receptor-activated SMADs. Nat Cell Biol. 2011 Sep 25;13(11):1368-75. doi: 10.1038/ncb2346. PMID:21947082 doi:10.1038/ncb2346
↑ Eichhorn PJ, Rodon L, Gonzalez-Junca A, Dirac A, Gili M, Martinez-Saez E, Aura C, Barba I, Peg V, Prat A, Cuartas I, Jimenez J, Garcia-Dorado D, Sahuquillo J, Bernards R, Baselga J, Seoane J. USP15 stabilizes TGF-beta receptor I and promotes oncogenesis through the activation of TGF-beta signaling in glioblastoma. Nat Med. 2012 Feb 19;18(3):429-35. doi: 10.1038/nm.2619. PMID:22344298 doi:10.1038/nm.2619

1 Structural highlights
2 Function
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6gh9"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6gh9 is ON HOLD
+==USP15 catalytic domain in complex with small molecule==
+<StructureSection load='6gh9' size='340' side='right' caption='[[6gh9]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6gh9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GH9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GH9 FirstGlance]. <br>
-Description:
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MIX:1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE'>MIX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-[[Category: Unreleased Structures]]
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6gha|6gha]]</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=6gh9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gh9 OCA], [http://pdbe.org/6gh9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gh9 RCSB], [http://www.ebi.ac.uk/pdbsum/6gh9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gh9 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/UBP15_HUMAN UBP15_HUMAN]] Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling and NF-kappa-B pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP. Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway.<ref>PMID:16005295</ref> <ref>PMID:17318178</ref> <ref>PMID:19826004</ref> <ref>PMID:19576224</ref> <ref>PMID:19553310</ref> <ref>PMID:21947082</ref> <ref>PMID:22344298</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Ubiquitinyl hydrolase 1]]
+[[Category: Caulton, S G]]
+[[Category: Dreveny, I]]
+[[Category: Emsley, J]]
+[[Category: Gratton, H E]]
+[[Category: Ward, S J]]
+[[Category: Hydrolase]]
+[[Category: Inhibitor]]
+[[Category: Mitoxantrone]]
+[[Category: Protease]]
+[[Category: Ubiquitin]]
+[[Category: Ubiquitin specific protease]]

6gh9

From Proteopedia

Revision as of 08:13, 26 September 2018

USP15 catalytic domain in complex with small molecule

Structural highlights

Function

References

Contents

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