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| | ==Solution Structure of Ubp-M Znf-UBP domain== | | ==Solution Structure of Ubp-M Znf-UBP domain== |
| - | <StructureSection load='2i50' size='340' side='right' caption='[[2i50]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2i50' size='340' side='right'caption='[[2i50]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2i50]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I50 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2I50 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2i50]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I50 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">USP16 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">USP16 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2i50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i50 OCA], [http://pdbe.org/2i50 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i50 RCSB], [http://www.ebi.ac.uk/pdbsum/2i50 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2i50 ProSAT]</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=2i50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i50 OCA], [https://pdbe.org/2i50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i50 RCSB], [https://www.ebi.ac.uk/pdbsum/2i50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i50 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/UBP16_HUMAN UBP16_HUMAN]] Note=A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1. | + | [[https://www.uniprot.org/uniprot/UBP16_HUMAN UBP16_HUMAN]] Note=A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBP16_HUMAN UBP16_HUMAN]] Specifically deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-10' of histone H3, and is required for chromosome segregation when cells enter into mitosis. Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B.<ref>PMID:10077596</ref> <ref>PMID:11753566</ref> <ref>PMID:17914355</ref> | + | [[https://www.uniprot.org/uniprot/UBP16_HUMAN UBP16_HUMAN]] Specifically deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-10' of histone H3, and is required for chromosome segregation when cells enter into mitosis. Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B.<ref>PMID:10077596</ref> <ref>PMID:11753566</ref> <ref>PMID:17914355</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Thioesterase|Thioesterase]] | + | *[[Thioesterase 3D structures|Thioesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Ubiquitin thiolesterase]] | | [[Category: Ubiquitin thiolesterase]] |
| | [[Category: Pai, M T]] | | [[Category: Pai, M T]] |
| Structural highlights
Disease
[UBP16_HUMAN] Note=A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1.
Function
[UBP16_HUMAN] Specifically deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-10' of histone H3, and is required for chromosome segregation when cells enter into mitosis. Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B.[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.
Publication Abstract from PubMed
The BUZ/Znf-UBP domain is a distinct ubiquitin-binding module found in the cytoplasmic deacetylase HDAC6, the E3 ubiquitin ligase BRAP2/IMP, and a subfamily of deubiquitinating enzymes. Here, we report the solution structure of the BUZ domain of Ubp-M, a ubiquitin-specific protease, and its interaction with ubiquitin. Unlike the BUZ domain from isopeptidase T (isoT) that contains a single zinc finger, the Ubp-M BUZ domain features three zinc-binding sites consisting of 12 residues. These zinc ligands form a pair of cross-braced ring fingers encapsulated within a third zinc finger in the primary structure. In contrast to isoT, which can form an N-terminal loop swapped dimer in the crystal state, the formation of additional zinc fingers in the Ubp-M BUZ domain restricts its N-terminal loop to intra-domain interactions. The ubiquitin-binding site of the Ubp-M BUZ domain is mapped to the highly conserved, concave surface formed by the alpha 3 helix and the central beta-sheet. We further show that this site binds to the C-terminal tail of free ubiquitin, and corresponding peptides display essentially the same binding affinities as full-length ubiquitin does for the Ubp-M BUZ domain. However, modification of the G76(Ub) carboxylate group either by a peptide or isopeptide bond abolishes BUZ-domain interaction. The unique ubiquitin-recognition mode of the BUZ domain family suggests that they may function as "sensors" of free ubiquitin in cells to achieve regulatory roles in many aspects of ubiquitin-dependent processes.
Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin.,Pai MT, Tzeng SR, Kovacs JJ, Keaton MA, Li SS, Yao TP, Zhou P J Mol Biol. 2007 Jul 6;370(2):290-302. Epub 2007 Apr 12. PMID:17512543[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cai SY, Babbitt RW, Marchesi VT. A mutant deubiquitinating enzyme (Ubp-M) associates with mitotic chromosomes and blocks cell division. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2828-33. PMID:10077596
- ↑ Mimnaugh EG, Kayastha G, McGovern NB, Hwang SG, Marcu MG, Trepel J, Cai SY, Marchesi VT, Neckers L. Caspase-dependent deubiquitination of monoubiquitinated nucleosomal histone H2A induced by diverse apoptogenic stimuli. Cell Death Differ. 2001 Dec;8(12):1182-96. PMID:11753566 doi:10.1038/sj.cdd.4400924
- ↑ Joo HY, Zhai L, Yang C, Nie S, Erdjument-Bromage H, Tempst P, Chang C, Wang H. Regulation of cell cycle progression and gene expression by H2A deubiquitination. Nature. 2007 Oct 25;449(7165):1068-72. Epub 2007 Oct 3. PMID:17914355 doi:10.1038/nature06256
- ↑ Pai MT, Tzeng SR, Kovacs JJ, Keaton MA, Li SS, Yao TP, Zhou P. Solution structure of the Ubp-M BUZ domain, a highly specific protein module that recognizes the C-terminal tail of free ubiquitin. J Mol Biol. 2007 Jul 6;370(2):290-302. Epub 2007 Apr 12. PMID:17512543 doi:10.1016/j.jmb.2007.04.015
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