2d8t

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==Solution structure of the RING domain of the human RING finger protein 146==
==Solution structure of the RING domain of the human RING finger protein 146==
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<StructureSection load='2d8t' size='340' side='right' caption='[[2d8t]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='2d8t' size='340' side='right'caption='[[2d8t]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2d8t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D8T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2D8T FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2d8t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D8T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2D8T FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</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>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNF146 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNF146 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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=2d8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d8t OCA], [http://pdbe.org/2d8t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2d8t RCSB], [http://www.ebi.ac.uk/pdbsum/2d8t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2d8t ProSAT], [http://www.topsan.org/Proteins/RSGI/2d8t TOPSAN]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2d8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d8t OCA], [https://pdbe.org/2d8t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2d8t RCSB], [https://www.ebi.ac.uk/pdbsum/2d8t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2d8t ProSAT], [https://www.topsan.org/Proteins/RSGI/2d8t TOPSAN]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/RN146_HUMAN RN146_HUMAN]] Note=Defects in RNF146 are a cause of susceptibility to breast cancer.
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[[https://www.uniprot.org/uniprot/RN146_HUMAN RN146_HUMAN]] Note=Defects in RNF146 are a cause of susceptibility to breast cancer.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/RN146_HUMAN RN146_HUMAN]] E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex. Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination, leading to their degradation. Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48'. May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location. Neuroprotective protein. Protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos. Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner. Does not affect PARP1 activation (By similarity). Protects against cell death induced by DNA damaging agents, such as N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest. Promotes cell survival after gamma-irradiation. Facilitates DNA repair.<ref>PMID:21478859</ref> <ref>PMID:21602803</ref> <ref>PMID:21799911</ref> <ref>PMID:21825151</ref> <ref>PMID:22267412</ref>
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[[https://www.uniprot.org/uniprot/RN146_HUMAN RN146_HUMAN]] E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex. Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination, leading to their degradation. Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48'. May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location. Neuroprotective protein. Protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos. Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner. Does not affect PARP1 activation (By similarity). Protects against cell death induced by DNA damaging agents, such as N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest. Promotes cell survival after gamma-irradiation. Facilitates DNA repair.<ref>PMID:21478859</ref> <ref>PMID:21602803</ref> <ref>PMID:21799911</ref> <ref>PMID:21825151</ref> <ref>PMID:22267412</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: Human]]
[[Category: Human]]
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[[Category: Large Structures]]
[[Category: Inoue, M]]
[[Category: Inoue, M]]
[[Category: Kigawa, T]]
[[Category: Kigawa, T]]

Revision as of 11:56, 3 February 2021

Solution structure of the RING domain of the human RING finger protein 146

PDB ID 2d8t

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