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| | <StructureSection load='6rr0' size='340' side='right'caption='[[6rr0]], [[Resolution|resolution]] 2.18Å' scene=''> | | <StructureSection load='6rr0' size='340' side='right'caption='[[6rr0]], [[Resolution|resolution]] 2.18Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rr0]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RR0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RR0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rr0]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RR0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.18Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6qsz|6qsz]], [[6qtm|6qtm]]</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=6rr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rr0 OCA], [https://pdbe.org/6rr0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rr0 RCSB], [https://www.ebi.ac.uk/pdbsum/6rr0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rr0 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SIR4, ASD1, STE9, UTH2, YDR227W, YD9934.12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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=6rr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rr0 OCA], [http://pdbe.org/6rr0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rr0 RCSB], [http://www.ebi.ac.uk/pdbsum/6rr0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rr0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SIR4_YEAST SIR4_YEAST]] The proteins SIR1 through SIR4 are required for transcriptional repression of the silent mating type loci, HML and HMR. The proteins SIR2 through SIR4 repress mulitple loci by modulating chromatin structure. Involves the compaction of chromatin fiber into a more condensed form.<ref>PMID:18039933</ref> [[http://www.uniprot.org/uniprot/UBP10_YEAST UBP10_YEAST]] Deubiquitinating enzyme involved in telomere and HM loci silencing, which is the repression of chromatin structure which leads to a stop in the transcription of nearby genes (PubMed:9755194, PubMed:10490600, PubMed:14623890). Targets histone H2B for deubiquitination, thus helping to localize SIR2 to the telomere (PubMed:15721261, PubMed:17028327, PubMed:22056669). At silent chromatin, including telomeres and the rDNA locus, not only maintains low H2B 'Lys-123' ubiquitination (H2BK123Ub), but also low H3 'Lys-4' and 'Lys-79' methylation (H3K4me and H3K79me, respectively) (PubMed:15721261, PubMed:15988024). Controls the proliferating-cell nuclear antigen PCNA/POL30 deubiquitination which is crucial for keeping TLS polymerases in check as well as for down-regulating the error-free bypass (PubMed:22829782). Deubiquitinates and stabilizes RPA190, the largest subunit of RNA polymerase I, to achieve optimal levels of ribosomes and cell growth (PubMed:22902402). Protects also nutrient transporters such as GAP1 from ubiquitin-dependent endocytosis (PubMed:11352638).<ref>PMID:10490600</ref> <ref>PMID:11352638</ref> <ref>PMID:14623890</ref> <ref>PMID:15721261</ref> <ref>PMID:15988024</ref> <ref>PMID:17028327</ref> <ref>PMID:22056669</ref> <ref>PMID:22829782</ref> <ref>PMID:22902402</ref> <ref>PMID:9755194</ref> | + | [https://www.uniprot.org/uniprot/SIR4_YEAST SIR4_YEAST] The proteins SIR1 through SIR4 are required for transcriptional repression of the silent mating type loci, HML and HMR. The proteins SIR2 through SIR4 repress mulitple loci by modulating chromatin structure. Involves the compaction of chromatin fiber into a more condensed form.<ref>PMID:18039933</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ubiquitinyl hydrolase 1]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Challa, K]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Deshpande, I]] | + | [[Category: Challa K]] |
| - | [[Category: Gasser, S M]] | + | [[Category: Deshpande I]] |
| - | [[Category: Gut, H]] | + | [[Category: Gasser SM]] |
| - | [[Category: Iesmantavicius, V]] | + | [[Category: Gut H]] |
| - | [[Category: Keusch, J J]] | + | [[Category: Iesmantavicius V]] |
| - | [[Category: Heterochromatin]]
| + | [[Category: Keusch JJ]] |
| - | [[Category: Nuclear protein]]
| + | |
| Structural highlights
Function
SIR4_YEAST The proteins SIR1 through SIR4 are required for transcriptional repression of the silent mating type loci, HML and HMR. The proteins SIR2 through SIR4 repress mulitple loci by modulating chromatin structure. Involves the compaction of chromatin fiber into a more condensed form.[1]
Publication Abstract from PubMed
In Saccharomyces cerevisiae, the silent information regulator (SIR) proteins Sir2/3/4 form a complex that suppresses transcription in subtelomeric regions and at the homothallic mating-type (HM) loci. Here, we identify a non-canonical BRCA1 C-terminal domain (H-BRCT) in Sir4, which is responsible for tethering telomeres to the nuclear periphery. We show that Sir4 H-BRCT and the closely related Dbf4 H-BRCT serve as selective phospho-epitope recognition domains that bind to a variety of phosphorylated target peptides. We present detailed structural information about the binding mode of established Sir4 interactors (Esc1, Ty5, Ubp10) and identify several novel interactors of Sir4 H-BRCT, including the E3 ubiquitin ligase Tom1. Based on these findings, we propose a phospho-peptide consensus motif for interaction with Sir4 H-BRCT and Dbf4 H-BRCT. Ablation of the Sir4 H-BRCT phospho-peptide interaction disrupts SIR-mediated repression and perinuclear localization. In conclusion, the Sir4 H-BRCT domain serves as a hub for recruitment of phosphorylated target proteins to heterochromatin to properly regulate silencing and nuclear order.
The Sir4 H-BRCT domain interacts with phospho-proteins to sequester and repress yeast heterochromatin.,Deshpande I, Keusch JJ, Challa K, Iesmantavicius V, Gasser SM, Gut H EMBO J. 2019 Oct 15;38(20):e101744. doi: 10.15252/embj.2019101744. Epub 2019 Sep , 12. PMID:31515872[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bupp JM, Martin AE, Stensrud ES, Jaspersen SL. Telomere anchoring at the nuclear periphery requires the budding yeast Sad1-UNC-84 domain protein Mps3. J Cell Biol. 2007 Dec 3;179(5):845-54. Epub 2007 Nov 26. PMID:18039933 doi:http://dx.doi.org/10.1083/jcb.200706040
- ↑ Deshpande I, Keusch JJ, Challa K, Iesmantavicius V, Gasser SM, Gut H. The Sir4 H-BRCT domain interacts with phospho-proteins to sequester and repress yeast heterochromatin. EMBO J. 2019 Oct 15;38(20):e101744. doi: 10.15252/embj.2019101744. Epub 2019 Sep , 12. PMID:31515872 doi:http://dx.doi.org/10.15252/embj.2019101744
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