2y6e: Difference between revisions

Latest revision as of 10:46, 20 December 2023

Structure of the D1D2 domain of USP4, the conserved catalytic domain

Structural highlights

2y6e is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	CME, SO4, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBP4_HUMAN Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. Plays a role in the regulation of quality control in the ER.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Ubiquitin-specific protease USP4 is emerging as an important regulator of cellular pathways, including the TGF-beta response, NF-kappaB signalling and splicing, with possible roles in cancer. Here we show that USP4 has its catalytic triad arranged in a productive conformation. Nevertheless, it requires its N-terminal DUSP-Ubl domain to achieve full catalytic turnover. Pre-steady-state kinetics measurements reveal that USP4 catalytic domain activity is strongly inhibited by slow dissociation of ubiquitin after substrate hydrolysis. The DUSP-Ubl domain is able to enhance ubiquitin dissociation, hence promoting efficient turnover. In a mechanism that requires all USP4 domains, binding of the DUSP-Ubl domain promotes a change of a switching loop near the active site. This 'allosteric regulation of product discharge' provides a novel way of regulating deubiquitinating enzymes that may have relevance for other enzyme classes.

The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange.,Clerici M, Luna-Vargas MP, Faesen AC, Sixma TK Nat Commun. 2014 Nov 18;5:5399. doi: 10.1038/ncomms6399. PMID:25404403^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gray DA, Inazawa J, Gupta K, Wong A, Ueda R, Takahashi T. Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors. Oncogene. 1995 Jun 1;10(11):2179-83. PMID:7784062
↑ Wada K, Tanji K, Kamitani T. Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity. Biochem Biophys Res Commun. 2006 Jan 20;339(3):731-6. PMID:16316627 doi:10.1016/j.bbrc.2005.11.076
↑ Wada K, Kamitani T. UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself. Biochem Biophys Res Commun. 2006 Mar 31;342(1):253-8. Epub 2006 Feb 6. PMID:16472766 doi:10.1016/j.bbrc.2006.01.144
↑ Milojevic T, Reiterer V, Stefan E, Korkhov VM, Dorostkar MM, Ducza E, Ogris E, Boehm S, Freissmuth M, Nanoff C. The ubiquitin-specific protease Usp4 regulates the cell surface level of the A2A receptor. Mol Pharmacol. 2006 Apr;69(4):1083-94. Epub 2005 Dec 9. PMID:16339847 doi:10.1124/mol.105.015818
↑ Clerici M, Luna-Vargas MP, Faesen AC, Sixma TK. The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange. Nat Commun. 2014 Nov 18;5:5399. doi: 10.1038/ncomms6399. PMID:25404403 doi:https://dx.doi.org/10.1038/ncomms6399

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Gray DA, Inazawa J, Gupta K, Wong A, Ueda R, Takahashi T. Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors. Oncogene. 1995 Jun 1;10(11):2179-83. PMID:7784062

[2] Wada K, Tanji K, Kamitani T. Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity. Biochem Biophys Res Commun. 2006 Jan 20;339(3):731-6. PMID:16316627 doi:10.1016/j.bbrc.2005.11.076

[3] Wada K, Kamitani T. UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself. Biochem Biophys Res Commun. 2006 Mar 31;342(1):253-8. Epub 2006 Feb 6. PMID:16472766 doi:10.1016/j.bbrc.2006.01.144

[4] Milojevic T, Reiterer V, Stefan E, Korkhov VM, Dorostkar MM, Ducza E, Ogris E, Boehm S, Freissmuth M, Nanoff C. The ubiquitin-specific protease Usp4 regulates the cell surface level of the A2A receptor. Mol Pharmacol. 2006 Apr;69(4):1083-94. Epub 2005 Dec 9. PMID:16339847 doi:10.1124/mol.105.015818

[5] Clerici M, Luna-Vargas MP, Faesen AC, Sixma TK. The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange. Nat Commun. 2014 Nov 18;5:5399. doi: 10.1038/ncomms6399. PMID:25404403 doi:https://dx.doi.org/10.1038/ncomms6399

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
 ==Structure of the D1D2 domain of USP4, the conserved catalytic domain==
-<StructureSection load='2y6e' size='340' side='right' caption='[[2y6e]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='2y6e' size='340' side='right'caption='[[2y6e]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2y6e]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y6E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2y6e]] is a 6 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=2Y6E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y6E FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] </span></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=2y6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6e OCA], [https://pdbe.org/2y6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y6e RCSB], [https://www.ebi.ac.uk/pdbsum/2y6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6e ProSAT]</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=2y6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6e OCA], [http://pdbe.org/2y6e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y6e RCSB], [http://www.ebi.ac.uk/pdbsum/2y6e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6e ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/UBP4_HUMAN UBP4_HUMAN]] Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. Plays a role in the regulation of quality control in the ER.<ref>PMID:7784062</ref> <ref>PMID:16316627</ref> <ref>PMID:16472766</ref> <ref>PMID:16339847</ref>
+[https://www.uniprot.org/uniprot/UBP4_HUMAN UBP4_HUMAN] Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. Plays a role in the regulation of quality control in the ER.<ref>PMID:7784062</ref> <ref>PMID:16316627</ref> <ref>PMID:16472766</ref> <ref>PMID:16339847</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 21: @@
 ==See Also==
-*[[Thioesterase|Thioesterase]]
+*[[Thioesterase 3D structures|Thioesterase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Ubiquitin thiolesterase]]
+[[Category: Large Structures]]
-[[Category: Dijk, W J.van]]
+[[Category: Faesen AC]]
-[[Category: Faesen, A C]]
+[[Category: Fish A]]
-[[Category: Fish, A]]
+[[Category: Luna-Vargas MPA]]
-[[Category: Luna-Vargas, M P.A]]
+[[Category: Rape M]]
-[[Category: Rape, M]]
+[[Category: Sixma TK]]
-[[Category: Sixma, T K]]
+[[Category: Van Dijk WJ]]
-[[Category: Hydrolase]]

2y6e: Difference between revisions

Latest revision as of 10:46, 20 December 2023

Structure of the D1D2 domain of USP4, the conserved catalytic domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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