5o76 - Revision history

OCA at 19:10, 29 November 2023

OCA — Wed, 29 Nov 2023 19:10:13 GMT

←Older revision		Revision as of 19:10, 29 November 2023
Line 1:		Line 1:

	==Structure of phosphoY371 c-CBL in complex with ZAP70-peptide and UbV.pCBL ubiquitin variant==		==Structure of phosphoY371 c-CBL in complex with ZAP70-peptide and UbV.pCBL ubiquitin variant==
-	<StructureSection load='5o76' size='340' side='right' caption='[[5o76]], [[Resolution\|resolution]] 2.47Å' scene=''>	+	<StructureSection load='5o76' size='340' side='right'caption='[[5o76]], [[Resolution\|resolution]] 2.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5o76]] is a 6 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=5O76 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5O76 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5o76]] is a 6 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=5O76 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O76 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=CA:CALCIUM+ION'>CA</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]] 2.473Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~PTR~~:~~O-PHOSPHOTYROSINE~~'>~~PTR~~</scene><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b~~></td>~~<td class="sblockDat">CBL~~, ~~CBL2, RNF55 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5o76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o76 OCA], [https://pdbe.org/5o76 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o76 RCSB], [https://www.ebi.ac.uk/pdbsum/5o76 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o76 ProSAT]</span></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27]~~ </~~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=5o76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o76 OCA], [~~http~~://pdbe.org/5o76 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5o76 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5o76 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5o76 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/CBL_HUMAN CBL_HUMAN]] Defects in CBL are the cause of Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) [MIM:[~~http~~://omim.org/entry/613563 613563]]. A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects.<ref>PMID:20619386</ref>	+	[https://www.uniprot.org/uniprot/CBL_HUMAN CBL_HUMAN] Defects in CBL are the cause of Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) [MIM:[https://omim.org/entry/613563 613563]. A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects.<ref>PMID:20619386</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/CBL_HUMAN CBL_HUMAN]] Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The Tyr-731 phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function.<ref>PMID:10514377</ref> <ref>PMID:11896602</ref> <ref>PMID:14739300</ref> <ref>PMID:15190072</ref> <ref>PMID:17509076</ref> <ref>PMID:18374639</ref> <ref>PMID:19689429</ref> <ref>PMID:21596750</ref>	+	[https://www.uniprot.org/uniprot/CBL_HUMAN CBL_HUMAN] Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The Tyr-731 phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function.<ref>PMID:10514377</ref> <ref>PMID:11896602</ref> <ref>PMID:14739300</ref> <ref>PMID:15190072</ref> <ref>PMID:17509076</ref> <ref>PMID:18374639</ref> <ref>PMID:19689429</ref> <ref>PMID:21596750</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 5o76" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5o76" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ubiquitin protein ligase 3D structures\|Ubiquitin protein ligase 3D structures]]
		+	*[[3D structures of ubiquitin\|3D structures of ubiquitin]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~RING-type E3 ubiquitin transferase~~]]	+	[[Category: Large Structures]]
-	[[Category: Buetow, L]]	+	[[Category: Buetow L]]
-	[[Category: Gabrielsen, M]]	+	[[Category: Gabrielsen M]]
-	[[Category: Huang~~, D T]]~~	+	[[Category: Huang DT]]
-	~~[[Category: E3 ring ligase]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Ubiquitin variant~~]]	+

OCA at 20:44, 24 January 2018

OCA — Wed, 24 Jan 2018 20:44:26 GMT

←Older revision		Revision as of 20:44, 24 January 2018
Line 3:		Line 3:
	<StructureSection load='5o76' size='340' side='right' caption='[[5o76]], [[Resolution\|resolution]] 2.47Å' scene=''>		<StructureSection load='5o76' size='340' side='right' caption='[[5o76]], [[Resolution\|resolution]] 2.47Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5o76]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O76 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O76 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5o76]] is a 6 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=5O76 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O76 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <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=CA:CALCIUM+ION'>CA</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=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CBL, CBL2, RNF55 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </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=5o76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o76 OCA], [http://pdbe.org/5o76 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o76 RCSB], [http://www.ebi.ac.uk/pdbsum/5o76 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o76 ProSAT]</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=5o76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o76 OCA], [http://pdbe.org/5o76 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o76 RCSB], [http://www.ebi.ac.uk/pdbsum/5o76 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o76 ProSAT]</span></td></tr>
Line 26:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: RING-type E3 ubiquitin transferase]]		[[Category: RING-type E3 ubiquitin transferase]]
	[[Category: Buetow, L]]		[[Category: Buetow, L]]

OCA at 06:06, 1 November 2017

OCA — Wed, 01 Nov 2017 06:06:18 GMT

←Older revision		Revision as of 06:06, 1 November 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5o76 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of phosphoY371 c-CBL in complex with ZAP70-peptide and UbV.pCBL ubiquitin variant==
		+	<StructureSection load='5o76' size='340' side='right' caption='[[5o76]], [[Resolution\|resolution]] 2.47Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5o76]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O76 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O76 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </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=5o76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o76 OCA], [http://pdbe.org/5o76 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o76 RCSB], [http://www.ebi.ac.uk/pdbsum/5o76 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o76 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CBL_HUMAN CBL_HUMAN]] Defects in CBL are the cause of Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) [MIM:[http://omim.org/entry/613563 613563]]. A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects.<ref>PMID:20619386</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CBL_HUMAN CBL_HUMAN]] Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The Tyr-731 phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function.<ref>PMID:10514377</ref> <ref>PMID:11896602</ref> <ref>PMID:14739300</ref> <ref>PMID:15190072</ref> <ref>PMID:17509076</ref> <ref>PMID:18374639</ref> <ref>PMID:19689429</ref> <ref>PMID:21596750</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report the development of three ubiquitin variants (UbVs), each binding selectively to the RING or U-box domain of a distinct E3 ligase: monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and biochemical analyses revealed that UbVs specifically inhibited the activity of UBE4B or phosphorylated CBL by blocking the E2 approximately Ub binding site. Surprisingly, the UbV selective for dimeric XIAP formed a dimer to stimulate E3 activity by stabilizing the closed E2 approximately Ub conformation. We further verified the inhibitory and stimulatory functions of UbVs in cells. Our work provides a general strategy to inhibit or activate RING/U-box E3 ligases and provides a resource for the research community to modulate these enzymes.

-	~~Authors: Gabrielsen~~, M., Buetow, L., ~~Huang~~, D.T.	+	A General Strategy for Discovery of Inhibitors and Activators of RING and U-box E3 Ligases with Ubiquitin Variants.,Gabrielsen M, Buetow L, Nakasone MA, Ahmed SF, Sibbet GJ, Smith BO, Zhang W, Sidhu SS, Huang DT Mol Cell. 2017 Oct 19;68(2):456-470.e10. doi: 10.1016/j.molcel.2017.09.027. PMID:29053960<ref>PMID:29053960</ref>

-	~~Description: Structure~~ of ~~phosphoY371 c-CBL in complex with ZAP70-peptide and UbV~~.~~pCBL ubiquitin variant~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Huang, D.T]]~~	+	<div class="pdbe-citations 5o76" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Gabrielsen, M~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: RING-type E3 ubiquitin transferase]]
	[[Category: Buetow, L]]		[[Category: Buetow, L]]
		+	[[Category: Gabrielsen, M]]
		+	[[Category: Huang, D T]]
		+	[[Category: E3 ring ligase]]
		+	[[Category: Ligase]]
		+	[[Category: Ubiquitin variant]]

OCA: Protected "5o76" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 12:06:25 GMT

Protected "5o76" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:06, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5o76 is ON HOLD until Paper Publication Authors: Gabrielsen, M., Buetow, L., Huang, D.T. Description: Structure of phosphoY371 c-CBL in complex wit...

OCA — Wed, 27 Sep 2017 12:06:24 GMT

New page: '''Unreleased structure''' The entry 5o76 is ON HOLD until Paper Publication Authors: Gabrielsen, M., Buetow, L., Huang, D.T. Description: Structure of phosphoY371 c-CBL in complex wit...

New page

'''Unreleased structure'''

The entry 5o76 is ON HOLD until Paper Publication

Authors: Gabrielsen, M., Buetow, L., Huang, D.T.

Description: Structure of phosphoY371 c-CBL in complex with ZAP70-peptide and UbV.pCBL ubiquitin variant
[[Category: Unreleased Structures]]
[[Category: Huang, D.T]]
[[Category: Gabrielsen, M]]
[[Category: Buetow, L]]