3ob1 - Revision history

OCA at 02:13, 21 November 2024

2024-11-21T02:13:02Z

← Older revision		Revision as of 02:13, 21 November 2024
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	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ob/3ob1_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ob/3ob1_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/~~initialview01~~.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>

OCA at 16:54, 1 November 2023

2023-11-01T16:54:47Z

← Older revision		Revision as of 16:54, 1 November 2023
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	<StructureSection load='3ob1' size='340' side='right'caption='[[3ob1]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3ob1' size='340' side='right'caption='[[3ob1]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3ob1]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OB1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3OB1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3ob1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OB1 FirstGlance]. <br>
	</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>~~, ~~<scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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]] 2.2Å</td></tr>
	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">~~[[3ob2\|3ob2]]~~</td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=3ob1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ob1 OCA], [~~http~~://pdbe.org/3ob1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3ob1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3ob1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3ob1 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=3ob1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ob1 OCA], [https://pdbe.org/3ob1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ob1 RCSB], [https://www.ebi.ac.uk/pdbsum/3ob1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ob1 ProSAT]</span></td></tr>
	</table>		</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 ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/SPY2_HUMAN SPY2_HUMAN]] May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.<ref>PMID:10887178</ref> [[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/SPY2_HUMAN SPY2_HUMAN] May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.<ref>PMID:10887178</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	==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: Sivaraman, J]]		[[Category: Sivaraman J]]
	[[Category: Sun, Q]]		[[Category: Sun Q]]
	~~[[Category: Complex]]~~
	~~[[Category: Double phosphorylation]]~~
	~~[[Category: E3 ubiquitin ligase]]~~
	~~[[Category: Ligase-signaling protein complex]]~~
	~~[[Category: Phosphorylation]]~~
	~~[[Category: Protein-peptide complex]]~~
	~~[[Category: Spry2~~]]

OCA at 17:57, 14 August 2019

2019-08-14T17:57:49Z

← Older revision		Revision as of 17:57, 14 August 2019
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	==Crystal structure of c-Cbl TKB domain in complex with double phosphorylated Spry2 peptide==		==Crystal structure of c-Cbl TKB domain in complex with double phosphorylated Spry2 peptide==
	<StructureSection load='3ob1' size='340' side='right' caption='[[3ob1]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3ob1' size='340' side='right'caption='[[3ob1]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3ob1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OB1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3ob1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OB1 FirstGlance]. <br>
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	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ob/3ob1_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ob/3ob1_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
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	</div>		</div>
	<div class="pdbe-citations 3ob1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3ob1" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Sivaraman, J]]		[[Category: Sivaraman, J]]
	[[Category: Sun, Q]]		[[Category: Sun, Q]]

OCA at 08:42, 8 November 2017

2017-11-08T08:42:49Z

← Older revision		Revision as of 08:42, 8 November 2017
Line 31:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 3ob1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3ob1" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 18:23, 4 August 2016

2016-08-04T18:23:41Z

← Older revision		Revision as of 18:23, 4 August 2016
Line 1:		Line 1:

	==Crystal structure of c-Cbl TKB domain in complex with double phosphorylated Spry2 peptide==		==Crystal structure of c-Cbl TKB domain in complex with double phosphorylated Spry2 peptide==
	<StructureSection load='3ob1' size='340' side='right' caption='[[3ob1]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3ob1' size='340' side='right' caption='[[3ob1]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3ob1]] is a 2 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=3OB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OB1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3ob1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OB1 FirstGlance]. <br>
	</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>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		</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>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ob2\|3ob2]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ob2\|3ob2]]</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=3ob1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ob1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ob1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ob1 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=3ob1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ob1 OCA], [http://pdbe.org/3ob1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ob1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ob1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ob1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3ob1 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	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 3ob1" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Sivaraman, J]]		[[Category: Sivaraman, J]]
	[[Category: Sun, Q]]		[[Category: Sun, Q]]

OCA at 06:55, 19 December 2014

2014-12-19T06:55:11Z

← Older revision		Revision as of 06:55, 19 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3ob1~~\| ~~PDB~~=3ob1 \| ~~SCENE~~= }}		==Crystal structure of c-Cbl TKB domain in complex with double phosphorylated Spry2 peptide==
	===~~Crystal~~ structure of c-Cbl TKB domain in ~~complex~~ with ~~double~~ phosphorylated ~~Spry2 peptide===~~		<StructureSection load='3ob1' size='340' side='right' caption='[[3ob1]], [[Resolution\|resolution]] 2.20Å' scene=''>
	~~{{ABSTRACT_PUBMED_20877636}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3ob1]] is a 2 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=3OB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OB1 FirstGlance]. <br>
			</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>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ob2\|3ob2]]</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=3ob1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ob1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ob1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ob1 PDBsum]</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/SPY2_HUMAN SPY2_HUMAN]] May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.<ref>PMID:10887178</ref> [[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>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ob/3ob1_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The E3-ubiquitin ligase, c-Cbl, is a multi-functional scaffolding protein that plays a pivotal role in controlling cell phenotype. As part of the ubiquitination and downregulation process, c-Cbl recognizes targets, such as tyrosine kinases and the Sprouty proteins, by binding to a conserved (NX/R)pY(S/T)XXP motif via its uniquely embedded SH2 domain (TKB domain). We previously outlined the mode of binding between the TKB domain and various substrate peptide motifs, including epidermal growth factor receptor (EGFR) and Sprouty2 (Spry2), and demonstrated that an intrapetidyl hydrogen bond forms between the (pY-1) arginine or (pY-2) asparagine and the phosphorylated tyrosine, which is crucial for binding. Recent reports demonstrated that, under certain types of stimulation, the serine/threonine residues at the pY+1 and/or pY+2 positions within this recognition motif of EGFR and Sprouty2 may be endogenously phosphorylated. Using structural and binding studies, we sought to determine whether this additional phosphorylation could affect the binding of the TKB domain to these peptides and consequently, whether the type of stimulation can dictate the degree to which substrates bind to c-Cbl. Here, we show that additional phosphorylation significantly reduces the binding affinity between the TKB domain and its target proteins, EGFR and Sprouty2, as compared to peptides bearing a single tyrosine phosphorylation. The crystal structure indicates that this is accomplished with minimal changes to the essential intrapeptidyl bond and that the reduced strength of the interaction is due to the charge repulsion between c-Cbl and the additional phosphate group. This obvious reduction in binding affinity, however, indicates that Cbl's interactions with its TKB-centered binding partners may be more favorable in the absence of Ser/Thr phosphorylation, which is stimulation and context specific in vivo. These results demonstrate the importance of understanding the environment in which certain residues are phosphorylated, and the necessity of including this in structural investigations.

	~~==Disease==~~		Additional serine/threonine phosphorylation reduces binding affinity but preserves interface topography of substrate proteins to the c-Cbl TKB domain.,Sun Q, Jackson RA, Ng C, Guy GR, Sivaraman J PLoS One. 2010 Sep 22;5(9):e12819. PMID:20877636<ref>PMID:20877636</ref>
	~~[[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==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[http:~~//www.uniprot.org/uniprot/SPY2_HUMAN SPY2_HUMAN]] May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.<ref>PMID:10887178</ref> [[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>

	==~~About this Structure~~==		==See Also==
	[[~~3ob1~~]] is a 2 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=3OB1 OCA].		*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:020877636</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Sivaraman, J.]]		[[Category: Sivaraman, J]]
	[[Category: Sun, Q.]]		[[Category: Sun, Q]]
	[[Category: Complex]]		[[Category: Complex]]
	[[Category: Double phosphorylation]]		[[Category: Double phosphorylation]]

OCA: Protected "3ob1" [edit=sysop:move=sysop]

2013-03-25T00:16:36Z

Protected "3ob1" [edit=sysop:move=sysop]

← Older revision	Revision as of 00:16, 25 March 2013
(No difference)

OCA at 00:16, 25 March 2013

2013-03-25T00:16:33Z

← Older revision		Revision as of 00:16, 25 March 2013
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	~~{{Seed}}~~
	~~[[Image:3ob1.png\|left\|200px]]~~

	~~<!--~~
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	~~or leave the SCENE parameter empty for the default display.~~
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	{{STRUCTURE_3ob1\| PDB=3ob1 \| SCENE= }}		{{STRUCTURE_3ob1\| PDB=3ob1 \| SCENE= }}

	===Crystal structure of c-Cbl TKB domain in complex with double phosphorylated Spry2 peptide===		===Crystal structure of c-Cbl TKB domain in complex with double phosphorylated Spry2 peptide===
			{{ABSTRACT_PUBMED_20877636}}

			==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==
	~~The line below this paragraph, {{ABSTRACT_PUBMED_20877636}}, adds the Publication Abstract to the page~~		[[http://www.uniprot.org/uniprot/SPY2_HUMAN SPY2_HUMAN]] May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.<ref>PMID:10887178</ref> [[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>
	(~~as it appears on PubMed at~~ http://www.~~pubmed~~.~~gov)~~, ~~where 20877636 is~~ the ~~PubMed ID number~~.
	-->
	~~{{ABSTRACT_PUBMED_20877636}}~~

	==About this Structure==		==About this Structure==
	~~3OB1~~ is a 2 ~~chains~~ structure with ~~sequences~~ 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=3OB1 OCA].		[[3ob1]] is a 2 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=3OB1 OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~20877636~~</ref><references group="xtra"/>		<ref group="xtra">PMID:020877636</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Sivaraman, J.]]		[[Category: Sivaraman, J.]]
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	[[Category: Protein-peptide complex]]		[[Category: Protein-peptide complex]]
	[[Category: Spry2]]		[[Category: Spry2]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 13 10:19:32 2010''~~

OCA at 07:09, 13 October 2010

2010-10-13T07:09:44Z

← Older revision		Revision as of 07:09, 13 October 2010
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	===Crystal structure of c-Cbl TKB domain in complex with double phosphorylated Spry2 peptide===		===Crystal structure of c-Cbl TKB domain in complex with double phosphorylated Spry2 peptide===


			<!--
			The line below this paragraph, {{ABSTRACT_PUBMED_20877636}}, adds the Publication Abstract to the page
			(as it appears on PubMed at http://www.pubmed.gov), where 20877636 is the PubMed ID number.
			-->
			{{ABSTRACT_PUBMED_20877636}}

	==About this Structure==		==About this Structure==
	3OB1 is a 2 chains structure with sequences 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=3OB1 OCA].		3OB1 is a 2 chains structure with sequences 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=3OB1 OCA].

			==Reference==
			<ref group="xtra">PMID:20877636</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Sivaraman, J.]]		[[Category: Sivaraman, J.]]
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	[[Category: Spry2]]		[[Category: Spry2]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct ~~6 05~~:36:09 2010''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 13 10:19:32 2010''

OCA at 02:26, 6 October 2010

2010-10-06T02:26:38Z

← Older revision		Revision as of 02:26, 6 October 2010
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	{{Seed}}		{{Seed}}
	[[Image:3ob1.~~jpg~~\|left\|200px]]		[[Image:3ob1.png\|left\|200px]]

	<!--		<!--
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	[[Category: Spry2]]		[[Category: Spry2]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Aug 18 11~~:52:28 2010''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 6 05:36:09 2010''