5lrx: Difference between revisions

No edit summary
No edit summary
 
(One intermediate revision by the same user not shown)
Line 1: Line 1:


==Structure of A20 OTU domain bound to ubiquitin==
==Structure of A20 OTU domain bound to ubiquitin==
<StructureSection load='5lrx' size='340' side='right' caption='[[5lrx]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
<StructureSection load='5lrx' size='340' side='right'caption='[[5lrx]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5lrx]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LRX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LRX FirstGlance]. <br>
<table><tr><td colspan='2'>[[5lrx]] is a 6 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=5LRX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LRX FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=AYE:PROP-2-EN-1-AMINE'>AYE</scene>, <scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</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]] 2.85&#8491;</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=5lrx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lrx OCA], [http://pdbe.org/5lrx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lrx RCSB], [http://www.ebi.ac.uk/pdbsum/5lrx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lrx ProSAT]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AYE:PROP-2-EN-1-AMINE'>AYE</scene>, <scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></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=5lrx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lrx OCA], [https://pdbe.org/5lrx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lrx RCSB], [https://www.ebi.ac.uk/pdbsum/5lrx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lrx ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TNAP3_HUMAN TNAP3_HUMAN]] Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate both 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system.<ref>PMID:8692885</ref> <ref>PMID:9299557</ref> <ref>PMID:9882303</ref> <ref>PMID:14748687</ref> <ref>PMID:15258597</ref> <ref>PMID:16684768</ref> <ref>PMID:18952128</ref> <ref>PMID:19494296</ref> <ref>PMID:22099304</ref> <ref>PMID:17961127</ref> <ref>PMID:18164316</ref> [[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> 
[https://www.uniprot.org/uniprot/TNAP3_HUMAN TNAP3_HUMAN] Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate both 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system.<ref>PMID:8692885</ref> <ref>PMID:9299557</ref> <ref>PMID:9882303</ref> <ref>PMID:14748687</ref> <ref>PMID:15258597</ref> <ref>PMID:16684768</ref> <ref>PMID:18952128</ref> <ref>PMID:19494296</ref> <ref>PMID:22099304</ref> <ref>PMID:17961127</ref> <ref>PMID:18164316</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
Line 20: Line 21:


==See Also==
==See Also==
*[[Ubiquitin|Ubiquitin]]
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Akutsu, M]]
[[Category: Homo sapiens]]
[[Category: Burke, J E]]
[[Category: Large Structures]]
[[Category: Elliott, P R]]
[[Category: Akutsu M]]
[[Category: Freund, S M.V]]
[[Category: Burke JE]]
[[Category: Gersch, M]]
[[Category: El Oualid F]]
[[Category: Geurink, P P]]
[[Category: Elliott PR]]
[[Category: Kawasaki, M]]
[[Category: Freund SMV]]
[[Category: Komander, D]]
[[Category: Gersch M]]
[[Category: Kulathu, Y]]
[[Category: Geurink PP]]
[[Category: Maslen, S L]]
[[Category: Kawasaki M]]
[[Category: Mevissen, T E.T]]
[[Category: Komander D]]
[[Category: Mulder, M P.C]]
[[Category: Kulathu Y]]
[[Category: Oualid, F El]]
[[Category: Maslen SL]]
[[Category: Ovaa, H]]
[[Category: Mevissen TET]]
[[Category: Tol, B D.M van]]
[[Category: Mulder MPC]]
[[Category: Deubiquitinase]]
[[Category: Ovaa H]]
[[Category: Hydrolase]]
[[Category: Van Tol BDM]]
[[Category: Otu domain]]
[[Category: Protease]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA