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| {{STRUCTURE_4ldt| PDB=4ldt | SCENE= }}
| | ==The structure of h/ceOTUB1-ubiquitin aldehyde-UBCH5B~Ub== |
| ===The structure of h/ceOTUB1-ubiquitin aldehyde-UBCH5B~Ub===
| | <StructureSection load='4ldt' size='340' side='right' caption='[[4ldt]], [[Resolution|resolution]] 1.90Å' scene=''> |
| {{ABSTRACT_PUBMED_23955022}}
| | == Structural highlights == |
| | <table><tr><td colspan='2'>[[4ldt]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LDT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LDT FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLZ:AMINO-ACETALDEHYDE'>GLZ</scene></td></tr> |
| | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OTUB1, OTB1, OTU1, HSPC263, C25D7.8, otub-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL]), UBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), UBE2D2, PUBC1, UBC4, UBC5B, UBCH4, UBCH5B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4ldt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ldt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ldt RCSB], [http://www.ebi.ac.uk/pdbsum/4ldt PDBsum]</span></td></tr> |
| | </table> |
| | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == |
| | OTUB1 is a Lys48-specific deubiquitinating enzyme that forms a complex in vivo with E2 ubiquitin (Ub)-conjugating enzymes including UBC13 and UBCH5. OTUB1 binds E2~Ub thioester intermediates and prevents ubiquitin transfer, thereby noncatalytically inhibiting accumulation of polyubiquitin. We report here that a second role of OTUB1-E2 interactions is to stimulate OTUB1 cleavage of Lys48 polyubiquitin. This stimulation is regulated by the ratio of charged to uncharged E2 and by the concentration of Lys48-linked polyubiquitin and free ubiquitin. Structural and biochemical studies of human and worm OTUB1 and UBCH5B show that the E2 enzyme stimulates binding of the Lys48 polyubiquitin substrate by stabilizing folding of the OTUB1 N-terminal ubiquitin-binding helix. Our results suggest that OTUB1-E2 complexes in the cell are poised to regulate polyubiquitin chain elongation or degradation in response to changing levels of E2 charging and available free ubiquitin. |
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| ==Function==
| | E2 ubiquitin-conjugating enzymes regulate the deubiquitinating activity of OTUB1.,Wiener R, Dibello AT, Lombardi PM, Guzzo CM, Zhang X, Matunis MJ, Wolberger C Nat Struct Mol Biol. 2013 Aug 18. doi: 10.1038/nsmb.2655. PMID:23955022<ref>PMID:23955022</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> [[http://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> [[http://www.uniprot.org/uniprot/UB2D2_HUMAN UB2D2_HUMAN]] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3.<ref>PMID:10329681</ref> <ref>PMID:15280377</ref> <ref>PMID:18042044</ref> <ref>PMID:18703417</ref> <ref>PMID:18359941</ref> <ref>PMID:19854139</ref> <ref>PMID:20403326</ref> <ref>PMID:20061386</ref>
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| ==About this Structure==
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| [[4ldt]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LDT OCA].
| | </div> |
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| ==Reference== | | ==See Also== |
| <ref group="xtra">PMID:023955022</ref><references group="xtra"/><references/>
| | *[[Ubiquitin conjugating enzyme|Ubiquitin conjugating enzyme]] |
| | == References == |
| | <references/> |
| | __TOC__ |
| | </StructureSection> |
| | [[Category: Caeel]] |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Ubiquitinyl hydrolase 1]] | | [[Category: Ubiquitinyl hydrolase 1]] |
| [[Category: DiBello, A T.]] | | [[Category: DiBello, A T]] |
| [[Category: Guzzo, C M.]] | | [[Category: Guzzo, C M]] |
| [[Category: Lombardi, P M.]] | | [[Category: Lombardi, P M]] |
| [[Category: Matunis, M J.]] | | [[Category: Matunis, M J]] |
| [[Category: Wiener, R.]] | | [[Category: Wiener, R]] |
| [[Category: Wolberger, C.]] | | [[Category: Wolberger, C]] |
| [[Category: Zhang, X.]] | | [[Category: Zhang, X]] |
| [[Category: Hydrolase regulator]] | | [[Category: Hydrolase regulator]] |
| [[Category: Isopeptidase]] | | [[Category: Isopeptidase]] |