6hue

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<StructureSection load='6hue' size='340' side='right'caption='[[6hue]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
<StructureSection load='6hue' size='340' side='right'caption='[[6hue]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6hue]] is a 2 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=6HUE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6HUE FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6hue]] is a 2 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=6HUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HUE FirstGlance]. <br>
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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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</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>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKN, PARK2 ([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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RBR-type_E3_ubiquitin_transferase RBR-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.31 2.3.2.31] </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=6hue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hue OCA], [https://pdbe.org/6hue PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hue RCSB], [https://www.ebi.ac.uk/pdbsum/6hue PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hue ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6hue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hue OCA], [http://pdbe.org/6hue PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hue RCSB], [http://www.ebi.ac.uk/pdbsum/6hue PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hue ProSAT]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/PRKN_HUMAN PRKN_HUMAN]] Young adult-onset Parkinsonism. Disease susceptibility may be associated with variations affecting the gene represented in this entry. Heterozygous mutations act as susceptibility alleles for late-onset Parkinson disease (PubMed:12730996 and PubMed:12629236). The disease is caused by mutations affecting the gene represented in this entry. Defects in PRKN may be involved in the development and/or progression of ovarian cancer.
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[https://www.uniprot.org/uniprot/PRKN_HUMAN PRKN_HUMAN] Young adult-onset Parkinsonism. Disease susceptibility may be associated with variations affecting the gene represented in this entry. Heterozygous mutations act as susceptibility alleles for late-onset Parkinson disease (PubMed:12730996 and PubMed:12629236). The disease is caused by mutations affecting the gene represented in this entry. Defects in PRKN may be involved in the development and/or progression of ovarian cancer.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/PRKN_HUMAN PRKN_HUMAN]] Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2 (PubMed:10973942, PubMed:10888878, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:16135753, PubMed:21376232, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed:19229105, PubMed:20889974, PubMed:25621951). Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation (PubMed:17846173, PubMed:19229105). Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (PubMed:11590439, PubMed:11431533, PubMed:19229105, PubMed:11590439, PubMed:15728840). Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (PubMed:20889974). Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30 (PubMed:19029340, PubMed:19966284, PubMed:23620051, PubMed:24896179, PubMed:25527291). Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains following mitochondrial damage, leading to mitophagy (PubMed:25621951). Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in the regulation of neuron death (PubMed:21376232). Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress (PubMed:22082830). Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 (PubMed:19801972). May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity (PubMed:11439185). May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.<ref>PMID:10888878</ref> <ref>PMID:10973942</ref> <ref>PMID:11431533</ref> <ref>PMID:11590439</ref> <ref>PMID:12628165</ref> <ref>PMID:12719539</ref> <ref>PMID:15105460</ref> <ref>PMID:15728840</ref> <ref>PMID:16135753</ref> <ref>PMID:17846173</ref> <ref>PMID:18541373</ref> <ref>PMID:19029340</ref> <ref>PMID:19229105</ref> <ref>PMID:19801972</ref> <ref>PMID:19966284</ref> <ref>PMID:20889974</ref> <ref>PMID:21376232</ref> <ref>PMID:21532592</ref> <ref>PMID:22082830</ref> <ref>PMID:23620051</ref> <ref>PMID:23754282</ref> <ref>PMID:23933751</ref> <ref>PMID:24660806</ref> <ref>PMID:24751536</ref> <ref>PMID:24784582</ref> <ref>PMID:24896179</ref> <ref>PMID:25527291</ref> <ref>PMID:25621951</ref>
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[https://www.uniprot.org/uniprot/PRKN_HUMAN PRKN_HUMAN] Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2 (PubMed:10973942, PubMed:10888878, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:16135753, PubMed:21376232, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed:19229105, PubMed:20889974, PubMed:25621951). Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation (PubMed:17846173, PubMed:19229105). Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (PubMed:11590439, PubMed:11431533, PubMed:19229105, PubMed:11590439, PubMed:15728840). Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (PubMed:20889974). Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30 (PubMed:19029340, PubMed:19966284, PubMed:23620051, PubMed:24896179, PubMed:25527291). Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains following mitochondrial damage, leading to mitophagy (PubMed:25621951). Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in the regulation of neuron death (PubMed:21376232). Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress (PubMed:22082830). Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 (PubMed:19801972). May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity (PubMed:11439185). May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.<ref>PMID:10888878</ref> <ref>PMID:10973942</ref> <ref>PMID:11431533</ref> <ref>PMID:11590439</ref> <ref>PMID:12628165</ref> <ref>PMID:12719539</ref> <ref>PMID:15105460</ref> <ref>PMID:15728840</ref> <ref>PMID:16135753</ref> <ref>PMID:17846173</ref> <ref>PMID:18541373</ref> <ref>PMID:19029340</ref> <ref>PMID:19229105</ref> <ref>PMID:19801972</ref> <ref>PMID:19966284</ref> <ref>PMID:20889974</ref> <ref>PMID:21376232</ref> <ref>PMID:21532592</ref> <ref>PMID:22082830</ref> <ref>PMID:23620051</ref> <ref>PMID:23754282</ref> <ref>PMID:23933751</ref> <ref>PMID:24660806</ref> <ref>PMID:24751536</ref> <ref>PMID:24784582</ref> <ref>PMID:24896179</ref> <ref>PMID:25527291</ref> <ref>PMID:25621951</ref>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: RBR-type E3 ubiquitin transferase]]
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[[Category: Antico O]]
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[[Category: Antico, O]]
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[[Category: Balk K]]
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[[Category: Balk, K]]
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[[Category: Ball G]]
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[[Category: Ball, G]]
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[[Category: Barini E]]
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[[Category: Barini, E]]
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[[Category: Brambilla R]]
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[[Category: Brambilla, R]]
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[[Category: Brooks SP]]
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[[Category: Brooks, S P]]
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[[Category: Burel S]]
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[[Category: Burel, S]]
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[[Category: Corti O]]
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[[Category: Corti, O]]
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[[Category: Di Monte DA]]
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[[Category: Dunnett, S B]]
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[[Category: Dunnett SB]]
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[[Category: Eerola-Rautio, J]]
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[[Category: Eerola-Rautio J]]
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[[Category: Fears, K]]
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[[Category: Fears K]]
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[[Category: Ganley, I G]]
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[[Category: Ganley IG]]
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[[Category: Hassoun, S M]]
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[[Category: Hassoun SM]]
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[[Category: Hills, R]]
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[[Category: Hills R]]
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[[Category: Knebel, A]]
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[[Category: Knebel A]]
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[[Category: Kumar, A]]
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[[Category: Kumar A]]
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[[Category: McWilliams, T G]]
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[[Category: McWilliams TG]]
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[[Category: Montava-Garriga, L]]
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[[Category: Montava-Garriga L]]
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[[Category: Monte, D A.Di]]
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[[Category: Mouton-Liger F]]
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[[Category: Mouton-Liger, F]]
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[[Category: Muqit MMK]]
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[[Category: Muqit, M M.K]]
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[[Category: Palin E]]
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[[Category: Palin, E]]
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[[Category: Pohjolan-Pirhonen R]]
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[[Category: Pohjolan-Pirhonen, R]]
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[[Category: Prescott AR]]
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[[Category: Prescott, A R]]
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[[Category: Singh F]]
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[[Category: Singh, F]]
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[[Category: Smith L]]
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[[Category: Smith, L]]
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[[Category: Suomalainen A]]
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[[Category: Suomalainen, A]]
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[[Category: Tamjar J]]
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[[Category: Tamjar, J]]
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[[Category: Tienari P]]
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[[Category: Tienari, P]]
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[[Category: Ulusoy A]]
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[[Category: Ulusoy, A]]
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[[Category: Valori M]]
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[[Category: Valori, M]]
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[[Category: E3 ligase]]
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[[Category: Ligase]]
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Current revision

ParkinS65N

PDB ID 6hue

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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