3fl2: Difference between revisions
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==Crystal structure of the ring domain of the E3 ubiquitin-protein ligase UHRF1== | |||
<StructureSection load='3fl2' size='340' side='right' caption='[[3fl2]], [[Resolution|resolution]] 1.75Å' scene=''> | |||
== Structural highlights == | |||
==Disease== | <table><tr><td colspan='2'>[[3fl2]] is a 1 chain structure with 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=3FL2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FL2 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> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bi7|3bi7]], [[3clz|3clz]], [[2faz|2faz]], [[3db4|3db4]], [[3db3|3db3]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ICBP90, NP95, RNF106, UHRF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3fl2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fl2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3fl2 RCSB], [http://www.ebi.ac.uk/pdbsum/3fl2 PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/UHRF1_HUMAN UHRF1_HUMAN]] Note=Defects in UHRF1 may be a cause of cancers. Overexpressed in many different forms of human cancers, including bladder, breast, cervical, colorectal and prostate cancers, as well as pancreatic adenocarcinomas, rhabdomyosarcomas and gliomas. Plays an important role in the correlation of histone modification and gene silencing in cancer progression. Expression is associated with a poor prognosis in patients with various cancers, suggesting that it participates in cancer progression. | [[http://www.uniprot.org/uniprot/UHRF1_HUMAN UHRF1_HUMAN]] Note=Defects in UHRF1 may be a cause of cancers. Overexpressed in many different forms of human cancers, including bladder, breast, cervical, colorectal and prostate cancers, as well as pancreatic adenocarcinomas, rhabdomyosarcomas and gliomas. Plays an important role in the correlation of histone modification and gene silencing in cancer progression. Expression is associated with a poor prognosis in patients with various cancers, suggesting that it participates in cancer progression. | ||
== Function == | |||
==Function== | [[http://www.uniprot.org/uniprot/UHRF1_HUMAN UHRF1_HUMAN]] Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. May be involved in DNA repair.<ref>PMID:10646863</ref> <ref>PMID:15009091</ref> <ref>PMID:15361834</ref> <ref>PMID:17673620</ref> <ref>PMID:17967883</ref> <ref>PMID:19056828</ref> <ref>PMID:21745816</ref> <ref>PMID:22945642</ref> <ref>PMID:21777816</ref> | ||
[[http://www.uniprot.org/uniprot/UHRF1_HUMAN UHRF1_HUMAN]] Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. May be involved in DNA repair.<ref>PMID:10646863</ref><ref>PMID:15009091</ref><ref>PMID:15361834</ref><ref>PMID:17673620</ref><ref>PMID:17967883</ref><ref>PMID:19056828</ref><ref>PMID:21745816</ref><ref>PMID:22945642</ref><ref>PMID:21777816</ref> | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | |||
== | Check<jmol> | ||
[[ | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fl/3fl2_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
==See Also== | ==See Also== | ||
*[[Ubiquitin protein ligase|Ubiquitin protein ligase]] | *[[Ubiquitin protein ligase|Ubiquitin protein ligase]] | ||
== References == | |||
== | <references/> | ||
<references | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Arrowsmith, C H | [[Category: Arrowsmith, C H]] | ||
[[Category: Avvakumov, G V | [[Category: Avvakumov, G V]] | ||
[[Category: Bochkarev, A | [[Category: Bochkarev, A]] | ||
[[Category: Bountra, C | [[Category: Bountra, C]] | ||
[[Category: Dhe-Paganon, S | [[Category: Dhe-Paganon, S]] | ||
[[Category: Edwards, A M | [[Category: Edwards, A M]] | ||
[[Category: Li, Y | [[Category: Li, Y]] | ||
[[Category: | [[Category: Structural genomic]] | ||
[[Category: Walker, J R | [[Category: Walker, J R]] | ||
[[Category: Weigelt, J | [[Category: Weigelt, J]] | ||
[[Category: Xue, S | [[Category: Xue, S]] | ||
[[Category: Cell cycle]] | [[Category: Cell cycle]] | ||
[[Category: Chromatin]] | [[Category: Chromatin]] | ||
| Line 39: | Line 52: | ||
[[Category: Ring finger domain]] | [[Category: Ring finger domain]] | ||
[[Category: Sgc]] | [[Category: Sgc]] | ||
[[Category: Transcription]] | [[Category: Transcription]] | ||
[[Category: Transcription regulation]] | [[Category: Transcription regulation]] | ||