4i7b - Revision history

OCA at 15:16, 20 September 2023

2023-09-20T15:16:27Z

←Older revision		Revision as of 15:16, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4i7b]] 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=4I7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I7B FirstGlance]. <br>		<table><tr><td colspan='2'>[[4i7b]] 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=4I7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I7B FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 3Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4i7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7b OCA], [https://pdbe.org/4i7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i7b RCSB], [https://www.ebi.ac.uk/pdbsum/4i7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i7b ProSAT]</span></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=4i7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7b OCA], [https://pdbe.org/4i7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i7b RCSB], [https://www.ebi.ac.uk/pdbsum/4i7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i7b ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:46, 9 November 2022

2022-11-09T08:46:18Z

←Older revision		Revision as of 08:46, 9 November 2022
Line 1:		Line 1:

	==Siah1 bound to synthetic peptide (ACE)KLRPV(ABA)MVRPTVR==		==Siah1 bound to synthetic peptide (ACE)KLRPV(ABA)MVRPTVR==
-	<StructureSection load='4i7b' size='340' side='right' caption='[[4i7b]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='4i7b' size='340' side='right'caption='[[4i7b]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4i7b]] 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=4I7B OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4I7B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4i7b]] 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=4I7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I7B FirstGlance]. <br>
-	</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>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr~~ id~~='NonStdRes'><td class~~="~~sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat~~"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</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=4i7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7b OCA], [https://pdbe.org/4i7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i7b RCSB], [https://www.ebi.ac.uk/pdbsum/4i7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i7b ProSAT]</span></td></tr>
-	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat">[[1k2f\|1k2f]], [[2a25\|2a25]], [[2an6\|2an6]], [[4i7c\|4i7c]], [[4i7d\|4i7d]]</td></tr>~~	+
-	~~<tr id='gene~~'>~~<td class="sblockLbl"><b>[[Gene\|Gene:]]~~</b>~~</td><td class="sblockDat">SIAH1, HUMSIAH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=4i7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7b OCA], [~~http~~://pdbe.org/4i7b PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4i7b RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4i7b PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4i7b ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[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>	+	[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 ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]	+	*[[Ubiquitin protein ligase 3D structures\|Ubiquitin protein ligase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Drosophila melanogaster]]
-	[[Category: De~~, S K~~]]	+	[[Category: Homo sapiens]]
-	[[Category: Feng, Y]]	+	[[Category: Large Structures]]
-	[[Category: Liddington~~, R C~~]]	+	[[Category: De SK]]
-	[[Category: Motamedchaboki, K]]	+	[[Category: Feng Y]]
-	[[Category: Pellecchia, M]]	+	[[Category: Liddington RC]]
-	[[Category: Purves, A]]	+	[[Category: Motamedchaboki K]]
-	[[Category: Ronai~~, Z A~~]]	+	[[Category: Pellecchia M]]
-	[[Category: Santelli, E]]	+	[[Category: Purves A]]
-	[[Category: Stebbins~~, J L~~]]	+	[[Category: Ronai ZA]]
-	[[Category: Wu, B]]	+	[[Category: Santelli E]]
-	~~[[Category: Beta sandwich]]~~	+	[[Category: Stebbins JL]]
-	~~[[Category: Ligase-ligase inhibitor complex]]~~	+	[[Category: Wu B]]
-	~~[[Category: Sina]]~~	+
-	~~[[Category: Ubiquitin ligase]]~~	+
-	~~[[Category: Zinc finger~~]]	+

OCA at 12:11, 4 August 2016

2016-08-04T12:11:36Z

←Older revision		Revision as of 12:11, 4 August 2016
Line 1:		Line 1:
		+
	==Siah1 bound to synthetic peptide (ACE)KLRPV(ABA)MVRPTVR==		==Siah1 bound to synthetic peptide (ACE)KLRPV(ABA)MVRPTVR==
	<StructureSection load='4i7b' size='340' side='right' caption='[[4i7b]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='4i7b' size='340' side='right' caption='[[4i7b]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4i7b]] is a 4 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=4I7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I7B FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4i7b]] 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=4I7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I7B FirstGlance]. <br>
	</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>		</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>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1k2f\|1k2f]], [[2a25\|2a25]], [[2an6\|2an6]], [[4i7c\|4i7c]], [[4i7d\|4i7d]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1k2f\|1k2f]], [[2a25\|2a25]], [[2an6\|2an6]], [[4i7c\|4i7c]], [[4i7d\|4i7d]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SIAH1, HUMSIAH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SIAH1, HUMSIAH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4i7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i7b RCSB], [http://www.ebi.ac.uk/pdbsum/4i7b 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=4i7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7b OCA], [http://pdbe.org/4i7b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i7b RCSB], [http://www.ebi.ac.uk/pdbsum/4i7b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i7b ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4i7b" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: De, S K]]		[[Category: De, S K]]
	[[Category: Feng, Y]]		[[Category: Feng, Y]]

OCA at 14:21, 24 December 2014

2014-12-24T14:21:04Z

←Older revision		Revision as of 14:21, 24 December 2014
Line 9:		Line 9:
	<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=4i7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i7b RCSB], [http://www.ebi.ac.uk/pdbsum/4i7b 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=4i7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i7b RCSB], [http://www.ebi.ac.uk/pdbsum/4i7b PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 12:11, 21 December 2014

2014-12-21T12:11:31Z

←Older revision		Revision as of 12:11, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4i7b\| PDB=4i7b \| SCENE= }}~~	+	==Siah1 bound to synthetic peptide (ACE)KLRPV(ABA)MVRPTVR==
-	===Siah1 bound to synthetic peptide (ACE)KLRPV(ABA)MVRPTVR===	+	<StructureSection load='4i7b' size='340' side='right' caption='[[4i7b]], [[Resolution\|resolution]] 3.00Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23891150}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4i7b]] is a 4 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=4I7B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I7B FirstGlance]. <br>
		+	</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>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1k2f\|1k2f]], [[2a25\|2a25]], [[2an6\|2an6]], [[4i7c\|4i7c]], [[4i7d\|4i7d]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SIAH1, HUMSIAH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4i7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i7b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i7b RCSB], [http://www.ebi.ac.uk/pdbsum/4i7b PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The E3 ubiquitin ligase Siah regulates key cellular events that are central to cancer development and progression. A promising route to Siah inhibition is disrupting its interactions with adaptor proteins. However, typical of protein-protein interactions, traditional unbiased approaches to ligand discovery did not produce viable hits against this target, despite considerable effort and a multitude of approaches. Ultimately, a rational structure-based design strategy was successful for the identification of Siah inhibitors in which peptide binding drives specific covalent bond formation with the target. X-ray crystallography, mass spectrometry, and functional data demonstrate that these peptide mimetics are efficient covalent inhibitors of Siah and antagonize Siah-dependent regulation of Erk and Hif signaling in the cell. The proposed strategy may result useful as a general approach to the design of peptide-based inhibitors of other protein-protein interactions.

-	~~==Function==~~	+	Structure-Based Design of Covalent Siah Inhibitors.,Stebbins JL, Santelli E, Feng Y, De SK, Purves A, Motamedchaboki K, Wu B, Ronai ZA, Liddington RC, Pellecchia M Chem Biol. 2013 Jul 24. pii: S1074-5521(13)00241-X. doi:, 10.1016/j.chembiol.2013.06.008. PMID:23891150<ref>PMID:23891150</ref>
-	~~[[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>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4i7b]] is~~ a ~~4 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=4I7B OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023891150</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: De, S K.]]	+	[[Category: De, S K]]
-	[[Category: Feng, Y.]]	+	[[Category: Feng, Y]]
-	[[Category: Liddington, R C.]]	+	[[Category: Liddington, R C]]
-	[[Category: Motamedchaboki, K.]]	+	[[Category: Motamedchaboki, K]]
-	[[Category: Pellecchia, M.]]	+	[[Category: Pellecchia, M]]
-	[[Category: Purves, A.]]	+	[[Category: Purves, A]]
-	[[Category: Ronai, Z A.]]	+	[[Category: Ronai, Z A]]
-	[[Category: Santelli, E.]]	+	[[Category: Santelli, E]]
-	[[Category: Stebbins, J L.]]	+	[[Category: Stebbins, J L]]
-	[[Category: Wu, B.]]	+	[[Category: Wu, B]]
	[[Category: Beta sandwich]]		[[Category: Beta sandwich]]
	[[Category: Ligase-ligase inhibitor complex]]		[[Category: Ligase-ligase inhibitor complex]]

OCA at 07:52, 14 August 2013

2013-08-14T07:52:09Z

←Older revision		Revision as of 07:52, 14 August 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4i7b\| PDB=4i7b \| SCENE= }}
		+	===Siah1 bound to synthetic peptide (ACE)KLRPV(ABA)MVRPTVR===
		+	{{ABSTRACT_PUBMED_23891150}}

-	~~The entry 4i7b~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Function==
		+	[[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>

-	~~Authors~~: ~~Santelli, E~~.~~, Liddington, R~~.C.	+	==About this Structure==
		+	[[4i7b]] is a 4 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=4I7B OCA].

-	~~Description~~:	+	==Reference==
		+	<ref group="xtra">PMID:023891150</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: De, S K.]]
		+	[[Category: Feng, Y.]]
		+	[[Category: Liddington, R C.]]
		+	[[Category: Motamedchaboki, K.]]
		+	[[Category: Pellecchia, M.]]
		+	[[Category: Purves, A.]]
		+	[[Category: Ronai, Z A.]]
		+	[[Category: Santelli, E.]]
		+	[[Category: Stebbins, J L.]]
		+	[[Category: Wu, B.]]
		+	[[Category: Beta sandwich]]
		+	[[Category: Ligase-ligase inhibitor complex]]
		+	[[Category: Sina]]
		+	[[Category: Ubiquitin ligase]]
		+	[[Category: Zinc finger]]

OCA at 11:08, 23 January 2013

2013-01-23T11:08:24Z

←Older revision		Revision as of 11:08, 23 January 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4i7b is ON HOLD	+	The entry 4i7b is ON HOLD until Paper Publication

	Authors: Santelli, E., Liddington, R.C.		Authors: Santelli, E., Liddington, R.C.

	Description:		Description:

OCA at 08:53, 2 January 2013

2013-01-02T08:53:17Z

←Older revision		Revision as of 08:53, 2 January 2013
Line 3:		Line 3:
	The entry 4i7b is ON HOLD		The entry 4i7b is ON HOLD

-	Authors: Santelli, E., Liddington, R. C.	+	Authors: Santelli, E., Liddington, R.C.

-	Description: ~~Protein/peptide complex~~	+	Description:

OCA: Protected "4i7b" [edit=sysop:move=sysop]

2012-12-12T20:49:17Z

Protected "4i7b" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:49, 12 December 2012

OCA: New page: '''Unreleased structure''' The entry 4i7b is ON HOLD Authors: Santelli, E., Liddington, R. C. Description: Protein/peptide complex

2012-12-12T20:49:16Z

New page: '''Unreleased structure''' The entry 4i7b is ON HOLD Authors: Santelli, E., Liddington, R. C. Description: Protein/peptide complex

New page

'''Unreleased structure'''

The entry 4i7b is ON HOLD

Authors: Santelli, E., Liddington, R. C.

Description: Protein/peptide complex