4i7d

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==Siah1 bound to synthetic peptide (ACE)KLRPVAMVRP(PRK)VR==
==Siah1 bound to synthetic peptide (ACE)KLRPVAMVRP(PRK)VR==
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<StructureSection load='4i7d' size='340' side='right' caption='[[4i7d]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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<StructureSection load='4i7d' size='340' side='right'caption='[[4i7d]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4i7d]] is a 4 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=4I7D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I7D FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4i7d]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] 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=4I7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I7D 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=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <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=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=PRK:N~6~-PROPANOYL-L-LYSINE'>PRK</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=PRK:N~6~-PROPANOYL-L-LYSINE'>PRK</scene></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=4i7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7d OCA], [https://pdbe.org/4i7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i7d RCSB], [https://www.ebi.ac.uk/pdbsum/4i7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i7d ProSAT]</span></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1k2f|1k2f]], [[2a25|2a25]], [[2an6|2an6]], [[4i7b|4i7b]], [[4i7c|4i7c]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HUMSIAH, SIAH1 ([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='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=4i7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7d OCA], [http://pdbe.org/4i7d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i7d RCSB], [http://www.ebi.ac.uk/pdbsum/4i7d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i7d ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/SIAH1_HUMAN SIAH1_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins.<ref>PMID:9334332</ref> <ref>PMID:9858595</ref> <ref>PMID:11146551</ref> <ref>PMID:10747903</ref> <ref>PMID:11389839</ref> <ref>PMID:11389840</ref> <ref>PMID:11483517</ref> <ref>PMID:11483518</ref> <ref>PMID:11752454</ref> <ref>PMID:12072443</ref> <ref>PMID:14506261</ref> <ref>PMID:14654780</ref> <ref>PMID:14645235</ref> <ref>PMID:15064394</ref> <ref>PMID:18536714</ref> <ref>PMID:19224863</ref> <ref>PMID:20508617</ref> <ref>PMID:22483617</ref> <ref>PMID:16085652</ref> [[http://www.uniprot.org/uniprot/PHYL_DROME PHYL_DROME]] Essential adapter component of E3 ubiquitin ligase complexes; involved in R7 photoreceptor cell differentiation, embryonic nervous system, external sensory organ development and specification of particular muscles. E3 ubiquitin ligase complexes mediate ubiquitination and subsequent proteasomal degradation of target proteins. Required for specification of R7 photoreceptor cell fate in the eye by participating in the ubiquitination and subsequent proteasomal degradation of Tramtrack (ttk), a general inhibitor of photoreceptor differentiation. Acts downstream of Notch signaling to specify the fate of the SOP (sensory organ precursor) cells and their progeny, probably via the sina-mediated proteasomal degradation of ttk. Its restricted pattern of expression, upon Notch and Ras signaling pathways, suggests that it acts as a key determinant in E3 complexes to trigger protein proteolysis in appropriate cells.<ref>PMID:7859287</ref> <ref>PMID:7888014</ref> <ref>PMID:9267026</ref> <ref>PMID:9267027</ref> <ref>PMID:11526076</ref> <ref>PMID:12215542</ref> <ref>PMID:14602676</ref>
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[https://www.uniprot.org/uniprot/SIAH1_HUMAN SIAH1_HUMAN] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins.<ref>PMID:9334332</ref> <ref>PMID:9858595</ref> <ref>PMID:11146551</ref> <ref>PMID:10747903</ref> <ref>PMID:11389839</ref> <ref>PMID:11389840</ref> <ref>PMID:11483517</ref> <ref>PMID:11483518</ref> <ref>PMID:11752454</ref> <ref>PMID:12072443</ref> <ref>PMID:14506261</ref> <ref>PMID:14654780</ref> <ref>PMID:14645235</ref> <ref>PMID:15064394</ref> <ref>PMID:18536714</ref> <ref>PMID:19224863</ref> <ref>PMID:20508617</ref> <ref>PMID:22483617</ref> <ref>PMID:16085652</ref>
<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==
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*[[Ubiquitin protein ligase|Ubiquitin protein ligase]]
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*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Drosophila melanogaster]]
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[[Category: De, S K]]
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[[Category: Homo sapiens]]
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[[Category: Feng, Y]]
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[[Category: Large Structures]]
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[[Category: Liddington, R C]]
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[[Category: De SK]]
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[[Category: Motamedchaboki, K]]
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[[Category: Feng Y]]
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[[Category: Pellecchia, M]]
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[[Category: Liddington RC]]
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[[Category: Purves, A]]
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[[Category: Motamedchaboki K]]
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[[Category: Ronai, Z A]]
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[[Category: Pellecchia M]]
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[[Category: Santelli, E]]
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[[Category: Purves A]]
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[[Category: Stebbins, J L]]
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[[Category: Ronai ZA]]
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[[Category: Wu, B]]
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[[Category: Santelli E]]
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[[Category: Beta sandwich]]
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[[Category: Stebbins JL]]
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[[Category: Covalent inhibitor]]
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[[Category: Wu B]]
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[[Category: Ligase-ligase inhibitor complex]]
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[[Category: Sina]]
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[[Category: Ubiquitin ligase]]
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[[Category: Zinc finger]]
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Revision as of 08:46, 9 November 2022

Siah1 bound to synthetic peptide (ACE)KLRPVAMVRP(PRK)VR

PDB ID 4i7d

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