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[[Image:2ayn.gif|left|200px]]


{{Structure
==Structure of USP14, a proteasome-associated deubiquitinating enzyme==
|PDB= 2ayn |SIZE=350|CAPTION= <scene name='initialview01'>2ayn</scene>, resolution 3.2&Aring;
<StructureSection load='2ayn' size='340' side='right'caption='[[2ayn]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND=  
<table><tr><td colspan='2'>[[2ayn]] is a 3 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=2AYN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AYN FirstGlance]. <br>
|ACTIVITY= <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
|GENE= USP14, TGT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ayn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ayn OCA], [https://pdbe.org/2ayn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ayn RCSB], [https://www.ebi.ac.uk/pdbsum/2ayn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ayn ProSAT]</span></td></tr>
|DOMAIN=
</table>
|RELATEDENTRY=
== Function ==
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ayn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ayn OCA], [http://www.ebi.ac.uk/pdbsum/2ayn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ayn RCSB]</span>
[https://www.uniprot.org/uniprot/UBP14_HUMAN UBP14_HUMAN] Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs).<ref>PMID:18162577</ref> <ref>PMID:19135427</ref> <ref>PMID:19106094</ref>
}}
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ay/2ayn_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ayn ConSurf].
<div style="clear:both"></div>


'''Structure of USP14, a proteasome-associated deubiquitinating enzyme'''
==See Also==
 
*[[Thioesterase 3D structures|Thioesterase 3D structures]]
 
== References ==
==Overview==
<references/>
The ubiquitin-specific processing protease (UBP) family of deubiquitinating enzymes plays an essential role in numerous cellular processes. Mammalian USP14 (Ubp6 in yeast) is unique among known UBP enzymes in that it is activated catalytically upon specific association with the 26S proteasome. Here, we report the crystal structures of the 45-kDa catalytic domain of USP14 in isolation and in a complex with ubiquitin aldehyde, which reveal distinct structural features. In the absence of ubiquitin binding, the catalytic cleft leading to the active site of USP14 is blocked by two surface loops. Binding by ubiquitin induces a significant conformational change that translocates the two surface loops thereby allowing access of the ubiquitin C-terminus to the active site. These structural observations, in conjunction with biochemical characterization, identify important regulatory mechanisms for USP14.
__TOC__
 
</StructureSection>
==About this Structure==
2AYN is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AYN OCA].
 
==Reference==
Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14., Hu M, Li P, Song L, Jeffrey PD, Chenova TA, Wilkinson KD, Cohen RE, Shi Y, EMBO J. 2005 Nov 2;24(21):3747-56. Epub 2005 Oct 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16211010 16211010]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Ubiquitin thiolesterase]]
[[Category: Hu M]]
[[Category: Hu, M.]]
[[Category: Jeffrey PD]]
[[Category: Jeffrey, P D.]]
[[Category: Li P]]
[[Category: Li, P.]]
[[Category: Shi Y]]
[[Category: Shi, Y.]]
[[Category: deubiquitinating enzyme]]
[[Category: dub]]
[[Category: enzyme mechanism]]
[[Category: proteasome]]
[[Category: usp14]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:59:05 2008''

Latest revision as of 12:14, 14 February 2024

Structure of USP14, a proteasome-associated deubiquitinating enzymeStructure of USP14, a proteasome-associated deubiquitinating enzyme

Structural highlights

2ayn is a 3 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 3.2Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBP14_HUMAN Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1. Indispensable for synaptic development and function at neuromuscular junctions (NMJs).[1] [2] [3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Koulich E, Li X, DeMartino GN. Relative structural and functional roles of multiple deubiquitylating proteins associated with mammalian 26S proteasome. Mol Biol Cell. 2008 Mar;19(3):1072-82. Epub 2007 Dec 27. PMID:18162577 doi:http://dx.doi.org/10.1091/mbc.E07-10-1040
  2. ↑ Nagai A, Kadowaki H, Maruyama T, Takeda K, Nishitoh H, Ichijo H. USP14 inhibits ER-associated degradation via interaction with IRE1alpha. Biochem Biophys Res Commun. 2009 Feb 20;379(4):995-1000. doi:, 10.1016/j.bbrc.2008.12.182. Epub 2009 Jan 9. PMID:19135427 doi:http://dx.doi.org/10.1016/j.bbrc.2008.12.182
  3. ↑ Mines MA, Goodwin JS, Limbird LE, Cui FF, Fan GH. Deubiquitination of CXCR4 by USP14 is critical for both CXCL12-induced CXCR4 degradation and chemotaxis but not ERK ativation. J Biol Chem. 2009 Feb 27;284(9):5742-52. doi: 10.1074/jbc.M808507200. Epub 2008, Dec 23. PMID:19106094 doi:http://dx.doi.org/10.1074/jbc.M808507200

2ayn, resolution 3.20Å

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