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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2fzp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FZP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FZP FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2fzp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FZP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FZP FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNF41 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNF41 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fzp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2fzp RCSB], [http://www.ebi.ac.uk/pdbsum/2fzp PDBsum]</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=2fzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fzp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2fzp RCSB], [http://www.ebi.ac.uk/pdbsum/2fzp PDBsum]</span></td></tr> |
| - | <table> | + | </table> |
| | + | == Function == |
| | + | [[http://www.uniprot.org/uniprot/RNF41_HUMAN RNF41_HUMAN]] Acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins. Polyubiquitinates MYD88 and Negatively regulates MYD88-dependent production of proinflammatory cytokines but can promote TRIF-dependent production of type I interferon. Promotes also activation of TBK1 and IRF3. Involved in the ubiquitination of erythropoietin (EPO) and interleukin-3 (IL-3) receptors. Thus, through maintaining basal levels of cytokine receptors, RNF41 is involved in the control of hematopoietic progenitor cell differentiation into myeloerythroid lineages (By similarity). Contributes to the maintenance of steady-state ERBB3 levels by mediating its growth factor-independent degradation. Involved in the degradation of the inhibitor of apoptosis BIRC6 and thus is an important regulator of cell death by promoting apoptosis. Acts also as a PARK2 modifier that accelerates its degradation, resulting in a reduction of PARK2 activity, influencing the balance of intracellular redox state.<ref>PMID:12411582</ref> <ref>PMID:14765125</ref> <ref>PMID:15632191</ref> <ref>PMID:17210635</ref> <ref>PMID:18541373</ref> <ref>PMID:19483718</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Arrowsmith, C.]] | + | [[Category: Arrowsmith, C]] |
| - | [[Category: Avvakumov, G V.]] | + | [[Category: Avvakumov, G V]] |
| - | [[Category: Bochkarev, A.]] | + | [[Category: Bochkarev, A]] |
| - | [[Category: Butler-Cole, C.]] | + | [[Category: Butler-Cole, C]] |
| - | [[Category: Dhe-Paganon, S.]] | + | [[Category: Dhe-Paganon, S]] |
| - | [[Category: Edwards, A.]] | + | [[Category: Edwards, A]] |
| - | [[Category: Finerty, P J.]] | + | [[Category: Finerty, P J]] |
| - | [[Category: Newman, E M.]] | + | [[Category: Newman, E M]] |
| - | [[Category: SGC, Structural Genomics Consortium.]] | + | [[Category: Structural genomic]] |
| - | [[Category: Sundstrom, M.]] | + | [[Category: Sundstrom, M]] |
| - | [[Category: Walker, J R.]] | + | [[Category: Walker, J R]] |
| - | [[Category: Weigelt, J.]] | + | [[Category: Weigelt, J]] |
| - | [[Category: Xue, S.]] | + | [[Category: Xue, S]] |
| | [[Category: E3 ligase]] | | [[Category: E3 ligase]] |
| | [[Category: Ligase]] | | [[Category: Ligase]] |
| | [[Category: Protein ubiquitination]] | | [[Category: Protein ubiquitination]] |
| | [[Category: Sgc]] | | [[Category: Sgc]] |
| - | [[Category: Structural genomic]] | |
| - | [[Category: Structural genomics consortium]] | |
| Structural highlights
Function
[RNF41_HUMAN] Acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins. Polyubiquitinates MYD88 and Negatively regulates MYD88-dependent production of proinflammatory cytokines but can promote TRIF-dependent production of type I interferon. Promotes also activation of TBK1 and IRF3. Involved in the ubiquitination of erythropoietin (EPO) and interleukin-3 (IL-3) receptors. Thus, through maintaining basal levels of cytokine receptors, RNF41 is involved in the control of hematopoietic progenitor cell differentiation into myeloerythroid lineages (By similarity). Contributes to the maintenance of steady-state ERBB3 levels by mediating its growth factor-independent degradation. Involved in the degradation of the inhibitor of apoptosis BIRC6 and thus is an important regulator of cell death by promoting apoptosis. Acts also as a PARK2 modifier that accelerates its degradation, resulting in a reduction of PARK2 activity, influencing the balance of intracellular redox state.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ubiquitin-specific protease 8 (USP8) hydrolyzes mono and polyubiquitylated targets such as epidermal growth factor receptors and is involved in clathrin-mediated internalization. In 1182 residues, USP8 contains multiple domains, including coiled-coil, rhodanese, and catalytic domains. We report the first high-resolution crystal structures of these domains and discuss their implications for USP8 function. The amino-terminal domain is a homodimer with a novel fold. It is composed of two five-helix bundles, where the first helices are swapped, and carboxyl-terminal helices are extended in an antiparallel fashion. The structure of the rhodanese domain, determined in complex with the E3 ligase NRDP1, reveals the canonical rhodanese fold but with a distorted primordial active site. The USP8 recognition domain of NRDP1 has a novel protein fold that interacts with a conserved peptide loop of the rhodanese domain. A consensus sequence of this loop is found in other NRDP1 targets, suggesting a common mode of interaction. The structure of the carboxyl-terminal catalytic domain of USP8 exhibits the conserved tripartite architecture but shows unique traits. Notably, the active site, including the ubiquitin binding pocket, is in a closed conformation, incompatible with substrate binding. The presence of a zinc ribbon subdomain near the ubiquitin binding site further suggests a polyubiquitin-specific binding site and a mechanism for substrate induced conformational changes.
Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8).,Avvakumov GV, Walker JR, Xue S, Finerty PJ Jr, Mackenzie F, Newman EM, Dhe-Paganon S J Biol Chem. 2006 Dec 8;281(49):38061-70. Epub 2006 Oct 11. PMID:17035239[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Qiu XB, Goldberg AL. Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14843-8. Epub 2002 Oct 31. PMID:12411582 doi:http://dx.doi.org/10.1073/pnas.232580999
- ↑ Qiu XB, Markant SL, Yuan J, Goldberg AL. Nrdp1-mediated degradation of the gigantic IAP, BRUCE, is a novel pathway for triggering apoptosis. EMBO J. 2004 Feb 25;23(4):800-10. Epub 2004 Feb 12. PMID:14765125 doi:10.1038/sj.emboj.7600075
- ↑ Zhong L, Tan Y, Zhou A, Yu Q, Zhou J. RING finger ubiquitin-protein isopeptide ligase Nrdp1/FLRF regulates parkin stability and activity. J Biol Chem. 2005 Mar 11;280(10):9425-30. Epub 2005 Jan 4. PMID:15632191 doi:http://dx.doi.org/10.1074/jbc.M408955200
- ↑ Cao Z, Wu X, Yen L, Sweeney C, Carraway KL 3rd. Neuregulin-induced ErbB3 downregulation is mediated by a protein stability cascade involving the E3 ubiquitin ligase Nrdp1. Mol Cell Biol. 2007 Mar;27(6):2180-8. Epub 2007 Jan 8. PMID:17210635 doi:http://dx.doi.org/10.1128/MCB.01245-06
- ↑ Yu F, Zhou J. Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced oxidative stress. Neurosci Lett. 2008 Jul 25;440(1):4-8. doi: 10.1016/j.neulet.2008.05.052. Epub, 2008 May 18. PMID:18541373 doi:10.1016/j.neulet.2008.05.052
- ↑ Wang C, Chen T, Zhang J, Yang M, Li N, Xu X, Cao X. The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon. Nat Immunol. 2009 Jul;10(7):744-52. doi: 10.1038/ni.1742. Epub 2009 May 31. PMID:19483718 doi:http://dx.doi.org/10.1038/ni.1742
- ↑ Avvakumov GV, Walker JR, Xue S, Finerty PJ Jr, Mackenzie F, Newman EM, Dhe-Paganon S. Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8). J Biol Chem. 2006 Dec 8;281(49):38061-70. Epub 2006 Oct 11. PMID:17035239 doi:10.1074/jbc.M606704200
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