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2zfy

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{{Seed}}
 
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[[Image:2zfy.png|left|200px]]
 
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==Crystal structure of human Otubain 1==
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The line below this paragraph, containing "STRUCTURE_2zfy", creates the "Structure Box" on the page.
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<StructureSection load='2zfy' size='340' side='right'caption='[[2zfy]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2zfy]] is a 1 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=2ZFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZFY FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.69&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2zfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zfy OCA], [https://pdbe.org/2zfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zfy RCSB], [https://www.ebi.ac.uk/pdbsum/2zfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zfy ProSAT]</span></td></tr>
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{{STRUCTURE_2zfy| PDB=2zfy | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/OTUB1_HUMAN OTUB1_HUMAN] Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin.<ref>PMID:12704427</ref> <ref>PMID:14661020</ref> <ref>PMID:12401499</ref> <ref>PMID:19383985</ref> <ref>PMID:19211026</ref> <ref>PMID:20725033</ref> <ref>PMID:18954305</ref> Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain.<ref>PMID:12704427</ref> <ref>PMID:14661020</ref> <ref>PMID:12401499</ref> <ref>PMID:19383985</ref> <ref>PMID:19211026</ref> <ref>PMID:20725033</ref> <ref>PMID:18954305</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zf/2zfy_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2zfy ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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OTUB (otubain) 1 is a human deubiquitinating enzyme that is implicated in mediating lymphocyte antigen responsiveness, but whose molecular function is generally not well defined. A structural analysis of OTUB1 shows differences in accessibility to the active site and in surface properties of the substrate-binding regions when compared with its close homologue, OTUB2, suggesting variations in regulatory mechanisms and substrate specificity. Biochemical analysis reveals that OTUB1 has a preference for cleaving Lys(48)-linked polyubiquitin chains over Lys(63)-linked polyubiquitin chains, and it is capable of cleaving NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8), but not SUMO (small ubiquitin-related modifier) 1/2/3 and ISG15 (interferon-stimulated gene 15) conjugates. A functional comparison of OTUB1 and OTUB2 indicated a differential reactivity towards ubiquitin-based active-site probes carrying a vinyl methyl ester, a 2-chloroethyl or a 2-bromoethyl group at the C-terminus. Mutational analysis suggested that a narrow P1' site, as observed in OTUB1, correlates with its ability to preferentially cleave Lys(48)-linked ubiquitin chains. Analysis of cellular interaction partners of OTUB1 by co-immunoprecipitation and MS/MS (tandem mass spectrometry) experiments demonstrated that FUS [fusion involved in t(12;6) in malignant liposarcoma; also known as TLS (translocation in liposarcoma) or CHOP (CCAAT/enhancer-binding protein homologous protein)] and RACK1 [receptor for activated kinase 1; also known as GNB2L1 (guanine-nucleotide-binding protein beta polypeptide 2-like 1)] are part of OTUB1-containing complexes, pointing towards a molecular function of this deubiquitinating enzyme in RNA processing and cell adhesion/morphology.
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===Crystal structure of human Otubain 1===
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Structural basis and specificity of human otubain 1-mediated deubiquitination.,Edelmann MJ, Iphofer A, Akutsu M, Altun M, di Gleria K, Kramer HB, Fiebiger E, Dhe-Paganon S, Kessler BM Biochem J. 2009 Mar 1;418(2):379-90. PMID:18954305<ref>PMID:18954305</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2zfy" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18954305}}, adds the Publication Abstract to the page
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*[[Thioesterase 3D structures|Thioesterase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18954305 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18954305}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2ZFY 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=2ZFY OCA].
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==Reference==
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Structural basis and specificity of human otubain 1 mediated deubiquitylation., Edelmann MJ, Iphoefer A, Akutsu M, Altun M, di Gleria K, Kramer HB, Fiebiger E, Dhe-Paganon S, Kessler BM, Biochem J. 2008 Oct 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18954305 18954305]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Pdbx_ordinal=, <PDBx:audit_author.]]
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[[Category: Akutsu M]]
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[[Category: Alternative splicing]]
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[[Category: Arrowsmith CH]]
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[[Category: Hydrolase]]
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[[Category: Bochkarev A]]
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[[Category: Immune response]]
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[[Category: Dhe-Paganon S]]
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[[Category: Otu]]
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[[Category: Edwards AM]]
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[[Category: Otubain]]
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[[Category: Li Y]]
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[[Category: Phosphoprotein]]
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[[Category: Walker JR]]
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[[Category: Protease]]
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[[Category: Weigelt J]]
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[[Category: Sgc]]
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[[Category: Structural genomic]]
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[[Category: Structural genomics consortium]]
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[[Category: Thiol protease]]
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[[Category: Ubl conjugation pathway]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 4 20:21:49 2009''
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Current revision

Crystal structure of human Otubain 1

PDB ID 2zfy

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