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| | <StructureSection load='5vnz' size='340' side='right'caption='[[5vnz]], [[Resolution|resolution]] 3.41Å' scene=''> | | <StructureSection load='5vnz' size='340' side='right'caption='[[5vnz]], [[Resolution|resolution]] 3.41Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vnz]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VNZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5VNZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vnz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VNZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VNZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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]] 3.41Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vo0|5vo0]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5vnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vnz OCA], [https://pdbe.org/5vnz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vnz RCSB], [https://www.ebi.ac.uk/pdbsum/5vnz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vnz ProSAT]</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=5vnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vnz OCA], [http://pdbe.org/5vnz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vnz RCSB], [http://www.ebi.ac.uk/pdbsum/5vnz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vnz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UBB_HUMAN UBB_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/UBE2N_HUMAN UBE2N_HUMAN]] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).<ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:19269966</ref> <ref>PMID:20061386</ref> <ref>PMID:21512573</ref> | + | [https://www.uniprot.org/uniprot/TRAF6_DANRE TRAF6_DANRE] E3 ubiquitin-protein ligase that mediates ubiquitination of proteins. Adapter protein that seems to play a role in signal transduction. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[TNF receptor-associated factor 3D structures|TNF receptor-associated factor 3D structures]] | | *[[TNF receptor-associated factor 3D structures|TNF receptor-associated factor 3D structures]] |
| | + | *[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Danio rerio]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RING-type E3 ubiquitin transferase]]
| + | [[Category: Day CL]] |
| - | [[Category: Day, C L]] | + | [[Category: Middleton AJ]] |
| - | [[Category: Middleton, A J]] | + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
TRAF6_DANRE E3 ubiquitin-protein ligase that mediates ubiquitination of proteins. Adapter protein that seems to play a role in signal transduction.
Publication Abstract from PubMed
Ubiquitin chains linked through lysine63 (K63) play a critical role in inflammatory signalling. Following ligand engagement of immune receptors, the RING E3 ligase TRAF6 builds K63-linked chains together with the heterodimeric E2 enzyme Ubc13-Uev1A. Dimerisation of the TRAF6 RING domain is essential for the assembly of K63-linked ubiquitin chains. Here, we show that TRAF6 RING dimers form a catalytic complex where one RING interacts with a Ubc13~Ubiquitin conjugate, while the zinc finger 1 (ZF1) domain and linker-helix of the opposing monomer contact ubiquitin. The RING dimer interface is conserved across TRAFs and we also show that TRAF5-TRAF6 heterodimers form. Importantly, TRAF5 can provide ZF1, enabling ubiquitin transfer from a TRAF6-bound Ubc13 conjugate. Our study explains the dependence of activity on TRAF RING dimers, and suggests that both homo- and heterodimers mediated by TRAF RING domains have the capacity to synthesise ubiquitin chains.
The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1.,Middleton AJ, Budhidarmo R, Das A, Zhu J, Foglizzo M, Mace PD, Day CL Nat Commun. 2017 Nov 27;8(1):1788. doi: 10.1038/s41467-017-01665-3. PMID:29176576[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Middleton AJ, Budhidarmo R, Das A, Zhu J, Foglizzo M, Mace PD, Day CL. The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1. Nat Commun. 2017 Nov 27;8(1):1788. doi: 10.1038/s41467-017-01665-3. PMID:29176576 doi:http://dx.doi.org/10.1038/s41467-017-01665-3
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