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| | ==Crystal Structure of Human Otubain2 and Ubiquitin Complex== | | ==Crystal Structure of Human Otubain2 and Ubiquitin Complex== |
| - | <StructureSection load='4fjv' size='340' side='right' caption='[[4fjv]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='4fjv' size='340' side='right'caption='[[4fjv]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fjv]] is a 4 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=4FJV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FJV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fjv]] is a 4 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=4FJV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FJV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NEH:ETHANAMINE'>NEH</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NEH:ETHANAMINE'>NEH</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OTUB2, C14orf137, OTB2, OTU2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4fjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fjv OCA], [https://pdbe.org/4fjv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fjv RCSB], [https://www.ebi.ac.uk/pdbsum/4fjv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fjv ProSAT]</span></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=4fjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fjv OCA], [http://pdbe.org/4fjv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fjv RCSB], [http://www.ebi.ac.uk/pdbsum/4fjv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fjv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/OTUB2_HUMAN OTUB2_HUMAN]] Hydrolase that can remove conjugated ubiquitin from proteins in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains.<ref>PMID:12704427</ref> <ref>PMID:18954305</ref> [[http://www.uniprot.org/uniprot/UBC_HUMAN UBC_HUMAN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref> | + | [https://www.uniprot.org/uniprot/OTUB2_HUMAN OTUB2_HUMAN] Hydrolase that can remove conjugated ubiquitin from proteins in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains.<ref>PMID:12704427</ref> <ref>PMID:18954305</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Thioesterase|Thioesterase]] | + | *[[Thioesterase 3D structures|Thioesterase 3D structures]] |
| - | *[[Ubiquitin|Ubiquitin]] | + | *[[3D structures of ubiquitin|3D structures of ubiquitin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Ubiquitinyl hydrolase 1]] | + | [[Category: Large Structures]] |
| - | [[Category: Altun, M]] | + | [[Category: Altun M]] |
| - | [[Category: David, Y]] | + | [[Category: David Y]] |
| - | [[Category: Iphofer, A]] | + | [[Category: Iphofer A]] |
| - | [[Category: Kessler, B M]] | + | [[Category: Kessler BM]] |
| - | [[Category: Komsany, A]] | + | [[Category: Komsany A]] |
| - | [[Category: Kramer, H B]] | + | [[Category: Kramer HB]] |
| - | [[Category: Navon, A]] | + | [[Category: Navon A]] |
| - | [[Category: Nicholson, B]] | + | [[Category: Nicholson B]] |
| - | [[Category: Ren, J]] | + | [[Category: Ren J]] |
| - | [[Category: Stuart, D I]] | + | [[Category: Stuart DI]] |
| - | [[Category: Ternette, N]] | + | [[Category: Ternette N]] |
| - | [[Category: Walter, T S]] | + | [[Category: Walter TS]] |
| - | [[Category: Cleavage specificity]]
| + | |
| - | [[Category: Cysteine protease]]
| + | |
| - | [[Category: Deubiquitylation]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Nedd8]]
| + | |
| - | [[Category: Otubain]]
| + | |
| - | [[Category: Ubiquitin]]
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| Structural highlights
Function
OTUB2_HUMAN Hydrolase that can remove conjugated ubiquitin from proteins in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains.[1] [2]
Publication Abstract from PubMed
Ovarian tumor domain containing proteases cleave ubiquitin (Ub) and ubiquitin-like polypeptides from proteins. Here we report the crystal structure of human otubain 2 (OTUB2) in complex with a ubiquitin-based covalent inhibitor, Ub-Br2. The ubiquitin binding mode is oriented differently to how viral otubains (vOTUs) bind ubiquitin/ISG15, and more similar to yeast and mammalian OTUs. In contrast to OTUB1 which has exclusive specificity towards Lys48 poly-ubiquitin chains, OTUB2 cleaves different poly-Ub linked chains. N-terminal tail swapping experiments between OTUB1 and OTUB2 revealed how the N-terminal structural motifs in OTUB1 contribute to modulating enzyme activity and Ub-chain selectivity, a trait not observed in OTUB2, supporting the notion that OTUB2 may affect a different spectrum of substrates in Ub-dependent pathways.
The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages.,Altun M, Walter TS, Kramer HB, Herr P, Iphofer A, Bostrom J, David Y, Komsany A, Ternette N, Navon A, Stuart DI, Ren J, Kessler BM PLoS One. 2015 Jan 15;10(1):e0115344. doi: 10.1371/journal.pone.0115344., eCollection 2015. PMID:25590432[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Balakirev MY, Tcherniuk SO, Jaquinod M, Chroboczek J. Otubains: a new family of cysteine proteases in the ubiquitin pathway. EMBO Rep. 2003 May;4(5):517-22. PMID:12704427 doi:10.1038/sj.embor.embor824
- ↑ Edelmann MJ, Iphofer A, Akutsu M, Altun M, di Gleria K, Kramer HB, Fiebiger E, Dhe-Paganon S, Kessler BM. Structural basis and specificity of human otubain 1-mediated deubiquitination. Biochem J. 2009 Mar 1;418(2):379-90. PMID:18954305 doi:10.1042/BJ20081318
- ↑ Altun M, Walter TS, Kramer HB, Herr P, Iphofer A, Bostrom J, David Y, Komsany A, Ternette N, Navon A, Stuart DI, Ren J, Kessler BM. The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages. PLoS One. 2015 Jan 15;10(1):e0115344. doi: 10.1371/journal.pone.0115344., eCollection 2015. PMID:25590432 doi:http://dx.doi.org/10.1371/journal.pone.0115344
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