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| | <StructureSection load='6w9a' size='340' side='right'caption='[[6w9a]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='6w9a' size='340' side='right'caption='[[6w9a]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6w9a]] 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=6W9A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W9A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6w9a]] 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=6W9A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W9A FirstGlance]. <br> |
| - | </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=ZN:ZINC+ION'>ZN</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6w7z|6w7z]], [[6w9d|6w9d]]</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=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBE2E2, UBCH8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RLIM, RNF12 ([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=6w9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9a OCA], [https://pdbe.org/6w9a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w9a RCSB], [https://www.ebi.ac.uk/pdbsum/6w9a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9a 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/E2_ubiquitin-conjugating_enzyme E2 ubiquitin-conjugating enzyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.23 2.3.2.23] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6w9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9a OCA], [http://pdbe.org/6w9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w9a RCSB], [http://www.ebi.ac.uk/pdbsum/6w9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9a ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/RNF12_HUMAN RNF12_HUMAN]] Non-specific syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/RNF12_HUMAN RNF12_HUMAN] Non-specific syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UB2E2_HUMAN UB2E2_HUMAN]] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination.<ref>PMID:9371400</ref> <ref>PMID:20061386</ref> [[http://www.uniprot.org/uniprot/RNF12_HUMAN RNF12_HUMAN]] E3 ubiquitin-protein ligase. Acts as a negative coregulator for LIM homeodomain transcription factors by mediating the ubiquitination and subsequent degradation of LIM cofactors LDB1 and LDB2 and by mediating the recruitment the SIN3a/histone deacetylase corepressor complex. Ubiquitination and degradation of LIM cofactors LDB1 and LDB2 allows DNA-bound LIM homeodomain transcription factors to interact with other protein partners such as RLIM. Plays a role in telomere length-mediated growth suppression by mediating the ubiquitination and degradation of TERF1. By targeting ZFP42 for degradation, acts as an activator of random inactivation of X chromosome in the embryo, a stochastic process in which one X chromosome is inactivated to minimize sex-related dosage differences of X-encoded genes in somatic cells of female placental mammals.<ref>PMID:19164295</ref> <ref>PMID:19945382</ref> | + | [https://www.uniprot.org/uniprot/RNF12_HUMAN RNF12_HUMAN] E3 ubiquitin-protein ligase. Acts as a negative coregulator for LIM homeodomain transcription factors by mediating the ubiquitination and subsequent degradation of LIM cofactors LDB1 and LDB2 and by mediating the recruitment the SIN3a/histone deacetylase corepressor complex. Ubiquitination and degradation of LIM cofactors LDB1 and LDB2 allows DNA-bound LIM homeodomain transcription factors to interact with other protein partners such as RLIM. Plays a role in telomere length-mediated growth suppression by mediating the ubiquitination and degradation of TERF1. By targeting ZFP42 for degradation, acts as an activator of random inactivation of X chromosome in the embryo, a stochastic process in which one X chromosome is inactivated to minimize sex-related dosage differences of X-encoded genes in somatic cells of female placental mammals.<ref>PMID:19164295</ref> <ref>PMID:19945382</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6w9a" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6w9a" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | + | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: E2 ubiquitin-conjugating enzyme]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Day, C L]] | + | [[Category: Day CL]] |
| - | [[Category: Middleton, A J]] | + | [[Category: Middleton AJ]] |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Ring]]
| + | |
| - | [[Category: Ring e3 ligase]]
| + | |
| - | [[Category: Ubiquitin]]
| + | |
| - | [[Category: Ubiquitin conjugating enzyme]]
| + | |
| - | [[Category: X-chromosome inactivation]]
| + | |
| Structural highlights
Disease
RNF12_HUMAN Non-specific syndromic intellectual disability. The disease is caused by mutations affecting the gene represented in this entry.
Function
RNF12_HUMAN E3 ubiquitin-protein ligase. Acts as a negative coregulator for LIM homeodomain transcription factors by mediating the ubiquitination and subsequent degradation of LIM cofactors LDB1 and LDB2 and by mediating the recruitment the SIN3a/histone deacetylase corepressor complex. Ubiquitination and degradation of LIM cofactors LDB1 and LDB2 allows DNA-bound LIM homeodomain transcription factors to interact with other protein partners such as RLIM. Plays a role in telomere length-mediated growth suppression by mediating the ubiquitination and degradation of TERF1. By targeting ZFP42 for degradation, acts as an activator of random inactivation of X chromosome in the embryo, a stochastic process in which one X chromosome is inactivated to minimize sex-related dosage differences of X-encoded genes in somatic cells of female placental mammals.[1] [2]
Publication Abstract from PubMed
RNF12 is a widely expressed ubiquitin E3 ligase that is required for X-chromosome inactivation, regulation of LIM-domain containing transcription factors, and TGF-beta signaling. A RING domain at the C terminus of RNF12 is important for its E3 ligase activity, and mutations in the RING domain are associated with X-linked intellectual disability. Here we have characterized ubiquitin transfer by RNF12, and show that the RING domain can bind to, and is active with, ubiquitin conjugating enzymes (E2s) that produce degradative ubiquitin chains. We report the crystal structures of RNF12 in complex with two of these E2 enzymes, as well as with an E2~Ub conjugate in a closed conformation. These structures form a basis for understanding the deleterious effect of a number of disease causing mutations. Comparison of the RNF12 structure with other monomeric RINGs suggests that a loop prior to the core RING domain has a conserved and essential role in stabilization of the active conformation of the bound E2~Ub conjugate. Together these findings provide a framework for better understanding substrate ubiquitylation by RNF12 and the impact of disease causing mutations.
The RING Domain of RING Finger 12 Efficiently Builds Degradative Ubiquitin Chains.,Middleton AJ, Zhu J, Day CL J Mol Biol. 2020 May 13. pii: S0022-2836(20)30333-8. doi:, 10.1016/j.jmb.2020.05.001. PMID:32416094[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Her YR, Chung IK. Ubiquitin Ligase RLIM Modulates Telomere Length Homeostasis through a Proteolysis of TRF1. J Biol Chem. 2009 Mar 27;284(13):8557-66. Epub 2009 Jan 21. PMID:19164295 doi:http://dx.doi.org/M806702200
- ↑ Jonkers I, Barakat TS, Achame EM, Monkhorst K, Kenter A, Rentmeester E, Grosveld F, Grootegoed JA, Gribnau J. RNF12 is an X-Encoded dose-dependent activator of X chromosome inactivation. Cell. 2009 Nov 25;139(5):999-1011. doi: 10.1016/j.cell.2009.10.034. PMID:19945382 doi:http://dx.doi.org/10.1016/j.cell.2009.10.034
- ↑ Middleton AJ, Zhu J, Day CL. The RING Domain of RING Finger 12 Efficiently Builds Degradative Ubiquitin Chains. J Mol Biol. 2020 May 13. pii: S0022-2836(20)30333-8. doi:, 10.1016/j.jmb.2020.05.001. PMID:32416094 doi:http://dx.doi.org/10.1016/j.jmb.2020.05.001
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