6w9d: Difference between revisions
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==RNF12 RING domain in complex with a Ube2d2~Ub conjugate== | ==RNF12 RING domain in complex with a Ube2d2~Ub conjugate== | ||
<StructureSection load='6w9d' size='340' side='right'caption='[[6w9d]]' scene=''> | <StructureSection load='6w9d' size='340' side='right'caption='[[6w9d]], [[Resolution|resolution]] 3.19Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W9D OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W9D FirstGlance]. <br> | <table><tr><td colspan='2'>[[6w9d]] is a 9 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=6W9D OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W9D FirstGlance]. <br> | ||
</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=6w9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9d OCA], [http://pdbe.org/6w9d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w9d RCSB], [http://www.ebi.ac.uk/pdbsum/6w9d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9d ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <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">[[6w7z|6w7z]], [[6w9a|6w9a]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBE2D2, PUBC1, UBC4, UBC5B, UBCH4, UBCH5B ([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]), UBC ([http://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/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </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=6w9d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w9d OCA], [http://pdbe.org/6w9d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w9d RCSB], [http://www.ebi.ac.uk/pdbsum/6w9d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w9d ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== 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. | |||
== Function == | |||
[[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> [[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/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;"> | |||
== 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<ref>PMID:32416094</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6w9d" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Day | [[Category: RING-type E3 ubiquitin transferase]] | ||
[[Category: Middleton | [[Category: Day, C L]] | ||
[[Category: Middleton, A J]] | |||
[[Category: Ligase]] | |||
[[Category: Ring]] | |||
[[Category: Ring e3 ligase]] | |||
[[Category: Ubiquitin]] | |||
[[Category: Ubiquitin conjugating enzyme]] | |||
[[Category: X-chromosome inactivation]] | |||