4j47 - Revision history

OCA at 15:35, 20 September 2023

2023-09-20T15:35:57Z

←Older revision		Revision as of 15:35, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4j47]] is a 3 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=4J47 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J47 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4j47]] is a 3 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=4J47 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J47 FirstGlance]. <br>
-	</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>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.35Å</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>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4j47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j47 OCA], [https://pdbe.org/4j47 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j47 RCSB], [https://www.ebi.ac.uk/pdbsum/4j47 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j47 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=4j47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j47 OCA], [https://pdbe.org/4j47 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j47 RCSB], [https://www.ebi.ac.uk/pdbsum/4j47 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j47 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 21:31, 16 November 2022

2022-11-16T21:31:42Z

←Older revision		Revision as of 21:31, 16 November 2022
Line 3:		Line 3:
	<StructureSection load='4j47' size='340' side='right'caption='[[4j47]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='4j47' size='340' side='right'caption='[[4j47]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4j47]] is a 3 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=4J47 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4J47 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4j47]] is a 3 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=4J47 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J47 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=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1i3o\|1i3o]], [[4j3y\|4j3y]], [[4j44\|4j44]], [[4j45\|4j45]], [[4j46\|4j46]]</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=4j47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j47 OCA], [https://pdbe.org/4j47 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j47 RCSB], [https://www.ebi.ac.uk/pdbsum/4j47 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j47 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">API3, BIRC4, IAP3, U32974, XIAP ([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=4j47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j47 OCA], [~~http~~://pdbe.org/4j47 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4j47 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4j47 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4j47 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/XIAP_HUMAN XIAP_HUMAN]] Defects in XIAP are the cause of lymphoproliferative syndrome X-linked type 2 (XLP2) [MIM:[~~http~~://omim.org/entry/300635 300635]]. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.<ref>PMID:17080092</ref>	+	[https://www.uniprot.org/uniprot/XIAP_HUMAN XIAP_HUMAN] Defects in XIAP are the cause of lymphoproliferative syndrome X-linked type 2 (XLP2) [MIM:[https://omim.org/entry/300635 300635]. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.<ref>PMID:17080092</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/XIAP_HUMAN XIAP_HUMAN]] Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program.<ref>PMID:9230442</ref> <ref>PMID:11447297</ref> <ref>PMID:12121969</ref> <ref>PMID:14685266</ref> <ref>PMID:14645242</ref> <ref>PMID:17967870</ref> <ref>PMID:19473982</ref> <ref>PMID:21145488</ref> <ref>PMID:20154138</ref> <ref>PMID:22103349</ref> <ref>PMID:22304967</ref> <ref>PMID:17560374</ref>	+	[https://www.uniprot.org/uniprot/XIAP_HUMAN XIAP_HUMAN] Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program.<ref>PMID:9230442</ref> <ref>PMID:11447297</ref> <ref>PMID:12121969</ref> <ref>PMID:14685266</ref> <ref>PMID:14645242</ref> <ref>PMID:17967870</ref> <ref>PMID:19473982</ref> <ref>PMID:21145488</ref> <ref>PMID:20154138</ref> <ref>PMID:22103349</ref> <ref>PMID:22304967</ref> <ref>PMID:17560374</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 22:

	==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: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Janson~~, C A~~]]	+	[[Category: Janson CA]]
-	[[Category: Lukacs~~, C M]]~~	+	[[Category: Lukacs CM]]
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Apoptosis inhibitor]]~~	+
-	~~[[Category: Caspase]]~~	+
-	~~[[Category: Iap]]~~	+
-	~~[[Category: Smac]]~~	+
-	~~[[Category: Xiap~~]]	+

OCA at 12:01, 17 July 2019

2019-07-17T12:01:47Z

←Older revision		Revision as of 12:01, 17 July 2019
Line 1:		Line 1:

	==Crystal structure of XIAP-BIR2 domain with SVPI bound==		==Crystal structure of XIAP-BIR2 domain with SVPI bound==
-	<StructureSection load='4j47' size='340' side='right' caption='[[4j47]], [[Resolution\|resolution]] 1.35Å' scene=''>	+	<StructureSection load='4j47' size='340' side='right'caption='[[4j47]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4j47]] is a 3 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=4J47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J47 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4j47]] is a 3 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=4J47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J47 FirstGlance]. <br>
Line 30:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Janson, C A]]		[[Category: Janson, C A]]
	[[Category: Lukacs, C M]]		[[Category: Lukacs, C M]]

OCA at 22:36, 4 August 2016

2016-08-04T22:36:35Z

←Older revision		Revision as of 22:36, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of XIAP-BIR2 domain with SVPI bound==		==Crystal structure of XIAP-BIR2 domain with SVPI bound==
	<StructureSection load='4j47' size='340' side='right' caption='[[4j47]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='4j47' size='340' side='right' caption='[[4j47]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4j47]] is a 3 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=4J47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J47 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4j47]] is a 3 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=4J47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J47 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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1i3o\|1i3o]], [[4j3y\|4j3y]], [[4j44\|4j44]], [[4j45\|4j45]], [[4j46\|4j46]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1i3o\|1i3o]], [[4j3y\|4j3y]], [[4j44\|4j44]], [[4j45\|4j45]], [[4j46\|4j46]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">API3, BIRC4, IAP3, U32974, XIAP ([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">API3, BIRC4, IAP3, U32974, XIAP ([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=4j47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j47 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j47 RCSB], [http://www.ebi.ac.uk/pdbsum/4j47 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=4j47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j47 OCA], [http://pdbe.org/4j47 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j47 RCSB], [http://www.ebi.ac.uk/pdbsum/4j47 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j47 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 4j47" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Janson, C A]]		[[Category: Janson, C A]]
	[[Category: Lukacs, C M]]		[[Category: Lukacs, C M]]

OCA at 12:00, 21 December 2014

2014-12-21T12:00:53Z

←Older revision		Revision as of 12:00, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4j47\| PDB=4j47 \| SCENE= }}~~	+	==Crystal structure of XIAP-BIR2 domain with SVPI bound==
-	===Crystal structure of XIAP-BIR2 domain with SVPI bound===	+	<StructureSection load='4j47' size='340' side='right' caption='[[4j47]], [[Resolution\|resolution]] 1.35Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23999295}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4j47]] is a 3 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=4J47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J47 FirstGlance]. <br>
-	==Disease==	+	</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1i3o\|1i3o]], [[4j3y\|4j3y]], [[4j44\|4j44]], [[4j45\|4j45]], [[4j46\|4j46]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">API3, BIRC4, IAP3, U32974, XIAP ([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=4j47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j47 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j47 RCSB], [http://www.ebi.ac.uk/pdbsum/4j47 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/XIAP_HUMAN XIAP_HUMAN]] Defects in XIAP are the cause of lymphoproliferative syndrome X-linked type 2 (XLP2) [MIM:[http://omim.org/entry/300635 300635]]. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.<ref>PMID:17080092</ref>		[[http://www.uniprot.org/uniprot/XIAP_HUMAN XIAP_HUMAN]] Defects in XIAP are the cause of lymphoproliferative syndrome X-linked type 2 (XLP2) [MIM:[http://omim.org/entry/300635 300635]]. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.<ref>PMID:17080092</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/XIAP_HUMAN XIAP_HUMAN]] Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program.<ref>PMID:9230442</ref> <ref>PMID:11447297</ref> <ref>PMID:12121969</ref> <ref>PMID:14685266</ref> <ref>PMID:14645242</ref> <ref>PMID:17967870</ref> <ref>PMID:19473982</ref> <ref>PMID:21145488</ref> <ref>PMID:20154138</ref> <ref>PMID:22103349</ref> <ref>PMID:22304967</ref> <ref>PMID:17560374</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	XIAP, a member of the inhibitor of apoptosis family of proteins, is a critical regulator of apoptosis. Inhibition of the BIR domain-caspase interaction is a promising approach towards treating cancer. Previous work has been directed towards inhibiting the BIR3-caspase-9 interaction, which blocks the intrinsic apoptotic pathway; selectively inhibiting the BIR2-caspase-3 interaction would also block the extrinsic pathway. The BIR2 domain of XIAP has successfully been crystallized; peptides and small-molecule inhibitors can be soaked into these crystals, which diffract to high resolution. Here, the BIR2 apo crystal structure and the structures of five BIR2-tetrapeptide complexes are described. The structural flexibility observed on comparing these structures, along with a comparison with XIAP BIR3, affords an understanding of the structural elements that drive selectivity between BIR2 and BIR3 and which can be used to design BIR2-selective inhibitors.

-	~~==Function==~~	+	The structure of XIAP BIR2: understanding the selectivity of the BIR domains.,Lukacs C, Belunis C, Crowther R, Danho W, Gao L, Goggin B, Janson CA, Li S, Remiszewski S, Schutt A, Thakur MK, Singh SK, Swaminathan S, Pandey R, Tyagi R, Gosu R, Kamath AV, Kuglstatter A Acta Crystallogr D Biol Crystallogr. 2013 Sep 1;69(Pt 9):1717-25. doi:, 10.1107/S0907444913016284. Epub 2013 Aug 15. PMID:23999295<ref>PMID:23999295</ref>
-	~~[[http~~:~~//www~~.~~uniprot.org/uniprot/XIAP_HUMAN XIAP_HUMAN]] Multi-functional protein which regulates not only caspases and apoptosis~~, ~~but also modulates inflammatory signaling and immunity~~, ~~copper homeostasis~~, ~~mitogenic kinase signaling~~, ~~cell proliferation~~, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, ~~inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-~~B ~~signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1~~, ~~CASP3~~, ~~CASP7~~, ~~CASP8~~, ~~CASP9~~, ~~MAP3K2/MEKK2~~, ~~DIABLO/SMAC~~, ~~AIFM1~~, ~~CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target~~, ~~SOD1~~, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, ~~targeting effector caspases for neddylation and inactivation~~. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (~~NLRs~~)~~. Protects cells from spontaneous formation of the ripoptosome, a large multi~~-~~protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner~~. ~~Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1~~, ~~TLE2, TLE3, TLE4 and AES~~. ~~Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2~~/~~TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program~~.~~<ref>~~PMID:9230442</ref> <ref>PMID:11447297</ref> <ref>PMID:12121969</ref> <ref>PMID:14685266</ref> <ref>PMID:14645242</ref> <ref>PMID:17967870</ref> <ref>PMID:19473982</ref> <ref>PMID:21145488</ref> <ref>PMID:20154138</ref> <ref>PMID:22103349</ref> <ref>PMID:22304967</ref> <ref>PMID:~~17560374~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4j47]] is~~ a ~~3 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=4J47 OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:023999295</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Janson, C A.]]	+	[[Category: Janson, C A]]
-	[[Category: Lukacs, C M.]]	+	[[Category: Lukacs, C M]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]
	[[Category: Apoptosis inhibitor]]		[[Category: Apoptosis inhibitor]]

OCA at 08:07, 29 September 2013

2013-09-29T08:07:50Z

←Older revision		Revision as of 08:07, 29 September 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4j47\| PDB=4j47 \| SCENE= }}
		+	===Crystal structure of XIAP-BIR2 domain with SVPI bound===
		+	{{ABSTRACT_PUBMED_23999295}}

-	~~The~~ entry ~~4j47~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/XIAP_HUMAN XIAP_HUMAN]] Defects in XIAP are the cause of lymphoproliferative syndrome X-linked type 2 (XLP2) [MIM:[http://omim.org/entry/300635 300635]]. XLP is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma.<ref>PMID:17080092</ref>

-	~~Authors~~: ~~Lukacs~~, C.M., ~~Janson~~, C.A.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/XIAP_HUMAN XIAP_HUMAN]] Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program.<ref>PMID:9230442</ref> <ref>PMID:11447297</ref> <ref>PMID:12121969</ref> <ref>PMID:14685266</ref> <ref>PMID:14645242</ref> <ref>PMID:17967870</ref> <ref>PMID:19473982</ref> <ref>PMID:21145488</ref> <ref>PMID:20154138</ref> <ref>PMID:22103349</ref> <ref>PMID:22304967</ref> <ref>PMID:17560374</ref>

-	~~Description: Crystal~~ structure ~~of XIAP-BIR2 domain~~ with ~~SVPI bound~~	+	==About this Structure==
		+	[[4j47]] is a 3 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=4J47 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:023999295</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Janson, C A.]]
		+	[[Category: Lukacs, C M.]]
		+	[[Category: Apoptosis]]
		+	[[Category: Apoptosis inhibitor]]
		+	[[Category: Caspase]]
		+	[[Category: Iap]]
		+	[[Category: Smac]]
		+	[[Category: Xiap]]

OCA at 16:16, 20 March 2013

2013-03-20T16:16:07Z

←Older revision		Revision as of 16:16, 20 March 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4j47 is ON HOLD	+	The entry 4j47 is ON HOLD until Paper Publication

	Authors: Lukacs, C.M., Janson, C.A.		Authors: Lukacs, C.M., Janson, C.A.

	Description: Crystal structure of XIAP-BIR2 domain with SVPI bound		Description: Crystal structure of XIAP-BIR2 domain with SVPI bound

OCA at 13:30, 20 February 2013

2013-02-20T13:30:00Z

←Older revision		Revision as of 13:30, 20 February 2013
Line 5:		Line 5:
	Authors: Lukacs, C.M., Janson, C.A.		Authors: Lukacs, C.M., Janson, C.A.

-	Description: ~~CRYSTAL STRUCTURE OF~~ XIAP-BIR2 ~~DOMAIN WITH~~ SVPI ~~BOUND~~	+	Description: Crystal structure of XIAP-BIR2 domain with SVPI bound

OCA: Protected "4j47" [edit=sysop:move=sysop]

2013-02-13T10:12:15Z

Protected "4j47" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:12, 13 February 2013

OCA: New page: '''Unreleased structure''' The entry 4j47 is ON HOLD Authors: Lukacs, C.M., Janson, C.A. Description: CRYSTAL STRUCTURE OF XIAP-BIR2 DOMAIN WITH SVPI BOUND

2013-02-13T10:12:14Z

New page: '''Unreleased structure''' The entry 4j47 is ON HOLD Authors: Lukacs, C.M., Janson, C.A. Description: CRYSTAL STRUCTURE OF XIAP-BIR2 DOMAIN WITH SVPI BOUND

New page

'''Unreleased structure'''

The entry 4j47 is ON HOLD

Authors: Lukacs, C.M., Janson, C.A.

Description: CRYSTAL STRUCTURE OF XIAP-BIR2 DOMAIN WITH SVPI BOUND