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| | ==Crystal structure of human UBE2A (RAD6A)== | | ==Crystal structure of human UBE2A (RAD6A)== |
| - | <StructureSection load='6cyo' size='340' side='right' caption='[[6cyo]], [[Resolution|resolution]] 1.85Å' scene=''> | + | <StructureSection load='6cyo' size='340' side='right'caption='[[6cyo]], [[Resolution|resolution]] 1.85Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6cyo]] is a 1 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=6CYO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CYO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6cyo]] is a 1 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=6CYO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CYO FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBE2A, RAD6A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 1.85Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=6cyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cyo OCA], [https://pdbe.org/6cyo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cyo RCSB], [https://www.ebi.ac.uk/pdbsum/6cyo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cyo ProSAT]</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=6cyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cyo OCA], [http://pdbe.org/6cyo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cyo RCSB], [http://www.ebi.ac.uk/pdbsum/6cyo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cyo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/UBE2A_HUMAN UBE2A_HUMAN]] X-linked intellectual disability, Nascimento type. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/UBE2A_HUMAN UBE2A_HUMAN] X-linked intellectual disability, Nascimento type. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBE2A_HUMAN UBE2A_HUMAN]] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys-120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-11', as well as 'Lys-48'-linked polyubiquitination. Required for postreplication repair of UV-damaged DNA.<ref>PMID:16337599</ref> <ref>PMID:20061386</ref> | + | [https://www.uniprot.org/uniprot/UBE2A_HUMAN UBE2A_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys-120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-11', as well as 'Lys-48'-linked polyubiquitination. Required for postreplication repair of UV-damaged DNA.<ref>PMID:16337599</ref> <ref>PMID:20061386</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 6cyo" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6cyo" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[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: Oliveira, J F.de]]
| + | [[Category: Ranzani AT]] |
| - | [[Category: Ranzani, A T]] | + | [[Category: De Oliveira JF]] |
| - | [[Category: Ligase]] | + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Ubiquitin-conjungating enzyme e2 some]]
| + | |
| Structural highlights
Disease
UBE2A_HUMAN X-linked intellectual disability, Nascimento type. The disease is caused by mutations affecting the gene represented in this entry.
Function
UBE2A_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys-120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-11', as well as 'Lys-48'-linked polyubiquitination. Required for postreplication repair of UV-damaged DNA.[1] [2]
Publication Abstract from PubMed
Ubiquitin-conjugating enzymes (E2) enable protein ubiquitination by conjugating ubiquitin to their catalytic cysteine for subsequent transfer to a target lysine side chain. Deprotonation of the incoming lysine enables its nucleophilicity, but determinants of lysine activation remain poorly understood. We report a novel pathogenic mutation in the E2 UBE2A, identified in two brothers with mild intellectual disability. The pathogenic Q93E mutation yields UBE2A with impaired aminolysis activity but no loss of the ability to be conjugated with ubiquitin. Importantly, the low intrinsic reactivity of UBE2A Q93E was not overcome by a cognate ubiquitin E3 ligase, RAD18, with the UBE2A target PCNA. However, UBE2A Q93E was reactive at high pH or with a low-pKa amine as the nucleophile, thus providing the first evidence of reversion of a defective UBE2A mutation. We propose that Q93E substitution perturbs the UBE2A catalytic microenvironment essential for lysine deprotonation during ubiquitin transfer, thus generating an enzyme that is disabled but not dead.
Mechanistic insights revealed by a UBE2A mutation linked to intellectual disability.,de Oliveira JF, do Prado PFV, da Costa SS, Sforca ML, Canateli C, Ranzani AT, Maschietto M, de Oliveira PSL, Otto PA, Klevit RE, Krepischi ACV, Rosenberg C, Franchini KG Nat Chem Biol. 2019 Jan;15(1):62-70. doi: 10.1038/s41589-018-0177-2. Epub 2018, Dec 10. PMID:30531907[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kim J, Hake SB, Roeder RG. The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activator interactions. Mol Cell. 2005 Dec 9;20(5):759-70. PMID:16337599 doi:http://dx.doi.org/10.1016/j.molcel.2005.11.012
- ↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
- ↑ de Oliveira JF, do Prado PFV, da Costa SS, Sforca ML, Canateli C, Ranzani AT, Maschietto M, de Oliveira PSL, Otto PA, Klevit RE, Krepischi ACV, Rosenberg C, Franchini KG. Mechanistic insights revealed by a UBE2A mutation linked to intellectual disability. Nat Chem Biol. 2019 Jan;15(1):62-70. doi: 10.1038/s41589-018-0177-2. Epub 2018, Dec 10. PMID:30531907 doi:http://dx.doi.org/10.1038/s41589-018-0177-2
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