3vro - Revision history

OCA at 19:00, 27 July 2022

OCA — Wed, 27 Jul 2022 19:00:26 GMT

←Older revision		Revision as of 19:00, 27 July 2022
Line 1:		Line 1:

	==Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-Src peptide==		==Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-Src peptide==
-	<StructureSection load='3vro' size='340' side='right' caption='[[3vro]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='3vro' size='340' side='right'caption='[[3vro]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3vro]] 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=3VRO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3VRO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3vro]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VRO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VRO 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></td></tr>	+	</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></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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vrn\|3vrn]], [[3vrp\|3vrp]], [[3vrq\|3vrq]], [[3vrr\|3vrr]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3vrn\|3vrn]], [[3vrp\|3vrp]], [[3vrq\|3vrq]], [[3vrr\|3vrr]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CBLC ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CBLC ([https://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/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=3vro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vro OCA], [~~http~~://pdbe.org/3vro PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3vro RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3vro PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3vro 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=3vro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vro OCA], [https://pdbe.org/3vro PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vro RCSB], [https://www.ebi.ac.uk/pdbsum/3vro PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vro ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/SRC_HUMAN SRC_HUMAN]] Note=SRC kinase activity has been shown to be increased in several tumor tissues and tumor cell lines such as colon carcinoma cells.	+	[[https://www.uniprot.org/uniprot/SRC_HUMAN SRC_HUMAN]] Note=SRC kinase activity has been shown to be increased in several tumor tissues and tumor cell lines such as colon carcinoma cells.
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/CBLC_HUMAN CBLC_HUMAN]] Regulator of EGFR mediated signal transduction. [[~~http~~://www.uniprot.org/uniprot/SRC_HUMAN SRC_HUMAN]] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of ADRBK1, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731'. Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-128'.<ref>PMID:3093483</ref> <ref>PMID:2498394</ref> <ref>PMID:7853507</ref> <ref>PMID:8759729</ref> <ref>PMID:8755529</ref> <ref>PMID:11389730</ref> <ref>PMID:12615910</ref> <ref>PMID:14585963</ref> <ref>PMID:16186108</ref> <ref>PMID:18586953</ref> <ref>PMID:19419966</ref> <ref>PMID:20100835</ref> <ref>PMID:21309750</ref> <ref>PMID:21411625</ref> <ref>PMID:22710723</ref>	+	[[https://www.uniprot.org/uniprot/CBLC_HUMAN CBLC_HUMAN]] Regulator of EGFR mediated signal transduction. [[https://www.uniprot.org/uniprot/SRC_HUMAN SRC_HUMAN]] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of ADRBK1, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731'. Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-128'.<ref>PMID:3093483</ref> <ref>PMID:2498394</ref> <ref>PMID:7853507</ref> <ref>PMID:8759729</ref> <ref>PMID:8755529</ref> <ref>PMID:11389730</ref> <ref>PMID:12615910</ref> <ref>PMID:14585963</ref> <ref>PMID:16186108</ref> <ref>PMID:18586953</ref> <ref>PMID:19419966</ref> <ref>PMID:20100835</ref> <ref>PMID:21309750</ref> <ref>PMID:21411625</ref> <ref>PMID:22710723</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Isozaki, Y]]		[[Category: Isozaki, Y]]

OCA at 22:22, 4 August 2016

OCA — Thu, 04 Aug 2016 22:22:50 GMT

←Older revision		Revision as of 22:22, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-Src peptide==		==Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-Src peptide==
	<StructureSection load='3vro' size='340' side='right' caption='[[3vro]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3vro' size='340' side='right' caption='[[3vro]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3vro]] 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=3VRO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VRO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3vro]] 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=3VRO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VRO 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></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></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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vrn\|3vrn]], [[3vrp\|3vrp]], [[3vrq\|3vrq]], [[3vrr\|3vrr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vrn\|3vrn]], [[3vrp\|3vrp]], [[3vrq\|3vrq]], [[3vrr\|3vrr]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CBLC ([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">CBLC ([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/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=3vro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vro OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vro RCSB], [http://www.ebi.ac.uk/pdbsum/3vro 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=3vro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vro OCA], [http://pdbe.org/3vro PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vro RCSB], [http://www.ebi.ac.uk/pdbsum/3vro PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vro ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 22:		Line 23:
	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 3vro" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Isozaki, Y]]		[[Category: Isozaki, Y]]

OCA at 20:12, 24 December 2014

OCA — Wed, 24 Dec 2014 20:12:02 GMT

←Older revision		Revision as of 20:12, 24 December 2014
Line 1:		Line 1:
-	[[~~Image:~~3vro.~~jpg~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-Src peptide==
		+	<StructureSection load='3vro' size='340' side='right' caption='[[3vro]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3vro]] 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=3VRO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VRO 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></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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vrn\|3vrn]], [[3vrp\|3vrp]], [[3vrq\|3vrq]], [[3vrr\|3vrr]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CBLC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </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=3vro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vro OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vro RCSB], [http://www.ebi.ac.uk/pdbsum/3vro PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/SRC_HUMAN SRC_HUMAN]] Note=SRC kinase activity has been shown to be increased in several tumor tissues and tumor cell lines such as colon carcinoma cells.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CBLC_HUMAN CBLC_HUMAN]] Regulator of EGFR mediated signal transduction. [[http://www.uniprot.org/uniprot/SRC_HUMAN SRC_HUMAN]] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of ADRBK1, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731'. Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-128'.<ref>PMID:3093483</ref> <ref>PMID:2498394</ref> <ref>PMID:7853507</ref> <ref>PMID:8759729</ref> <ref>PMID:8755529</ref> <ref>PMID:11389730</ref> <ref>PMID:12615910</ref> <ref>PMID:14585963</ref> <ref>PMID:16186108</ref> <ref>PMID:18586953</ref> <ref>PMID:19419966</ref> <ref>PMID:20100835</ref> <ref>PMID:21309750</ref> <ref>PMID:21411625</ref> <ref>PMID:22710723</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Through their ubiquitin ligase activity, Cbl-family proteins suppress signalling mediated by protein-tyrosine kinases (PTKs), but can also function as adaptor proteins to positively regulate signalling. The tyrosine kinase binding (TKB) domain of this family is critical for binding with tyrosine-phosphorylated target proteins. Here, we analysed the crystal structure of the TKB domain of Cbl-c/Cbl-3 (Cbl-c TKB), which is a distinct member of the mammalian Cbl-family. In comparison with Cbl TKB, Cbl-c TKB showed restricted structural flexibility upon phosphopeptide binding. A mutation in Cbl-c TKB augmenting this flexibility enhanced its binding to target phosphoproteins. These results suggest that proteins, post-translational modifications or mutations that alter structural flexibility of the TKB domain of Cbl-family proteins could regulate their binding to target phosphoproteins and thereby, affect PTK-mediated signalling.

-	~~{{STRUCTURE_3vro\| PDB=3vro \| SCENE= }}~~	+	Structural flexibility regulates phosphopeptide-binding activity of the tyrosine kinase binding domain of Cbl-c.,Takeshita K, Tezuka T, Isozaki Y, Yamashita E, Suzuki M, Kim M, Yamanashi Y, Yamamoto T, Nakagawa A J Biochem. 2012 Nov;152(5):487-95. doi: 10.1093/jb/mvs085. Epub 2012 Aug 9. PMID:22888118<ref>PMID:22888118</ref>

-	~~===Crystal structure~~ of the ~~tyrosine kinase binding domain~~ of ~~Cbl-c in complex with phospho-Src peptide===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_22888118}}~~	+	== References ==
-		+	<references/>
-	==~~About this Structure~~==	+	__TOC__
-	~~[[3vro]] 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=3VRO OCA].~~	+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
-	[[Category: Isozaki, Y.]]	+	[[Category: Isozaki, Y]]
-	[[Category: Nakagawa, A.]]	+	[[Category: Nakagawa, A]]
-	[[Category: Suzuki, M.]]	+	[[Category: Suzuki, M]]
-	[[Category: Takeshita, K.]]	+	[[Category: Takeshita, K]]
-	[[Category: Tezuka, T.]]	+	[[Category: Tezuka, T]]
-	[[Category: Yamamoto, T.]]	+	[[Category: Yamamoto, T]]
-	[[Category: Yamanashi, Y.]]	+	[[Category: Yamanashi, Y]]
-	[[Category: Yamashita, E.]]	+	[[Category: Yamashita, E]]
	[[Category: Calcium-binding ef hand]]		[[Category: Calcium-binding ef hand]]
	[[Category: Divergent sh2 domain]]		[[Category: Divergent sh2 domain]]

OCA at 14:12, 6 March 2013

OCA — Wed, 06 Mar 2013 14:12:36 GMT

←Older revision		Revision as of 14:12, 6 March 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3vro.jpg\|left\|200px]]

-	~~The entry~~ 3vro ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_3vro\| PDB=3vro \| SCENE= }}

-	~~Authors: Takeshita, K., Tezuka, T., Isozaki, Y., Yamashita, E., Suzuki, M., Yamanashi, Y., Yamamoto, T., Nakagawa, A.~~	+	===Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-Src peptide===

-	~~Description: Crystal~~ structure ~~of the~~ tyrosine kinase binding domain ~~of Cbl~~-~~c in~~ complex ~~with phospho-Src peptide~~	+	{{ABSTRACT_PUBMED_22888118}}
		+
		+	==About this Structure==
		+	[[3vro]] 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=3VRO OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Non-specific protein-tyrosine kinase]]
		+	[[Category: Isozaki, Y.]]
		+	[[Category: Nakagawa, A.]]
		+	[[Category: Suzuki, M.]]
		+	[[Category: Takeshita, K.]]
		+	[[Category: Tezuka, T.]]
		+	[[Category: Yamamoto, T.]]
		+	[[Category: Yamanashi, Y.]]
		+	[[Category: Yamashita, E.]]
		+	[[Category: Calcium-binding ef hand]]
		+	[[Category: Divergent sh2 domain]]
		+	[[Category: Protein binding-transferase complex]]
		+	[[Category: Ptb domain]]
		+	[[Category: Regulator of egfr mediated signal transduction]]
		+	[[Category: Ubiquitously expressed]]

OCA at 04:50, 18 July 2012

OCA — Wed, 18 Jul 2012 04:50:49 GMT

←Older revision		Revision as of 04:50, 18 July 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3vro is ON HOLD	+	The entry 3vro is ON HOLD until Paper Publication

	Authors: Takeshita, K., Tezuka, T., Isozaki, Y., Yamashita, E., Suzuki, M., Yamanashi, Y., Yamamoto, T., Nakagawa, A.		Authors: Takeshita, K., Tezuka, T., Isozaki, Y., Yamashita, E., Suzuki, M., Yamanashi, Y., Yamamoto, T., Nakagawa, A.

	Description: Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-Src peptide		Description: Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-Src peptide

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

OCA — Wed, 18 Apr 2012 07:22:45 GMT

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

←Older revision

Revision as of 07:22, 18 April 2012

OCA: New page: '''Unreleased structure''' The entry 3vro is ON HOLD Authors: Takeshita, K., Tezuka, T., Isozaki, Y., Yamashita, E., Suzuki, M., Yamanashi, Y., Yamamoto, T., Nakagawa, A. Description: ...

OCA — Wed, 18 Apr 2012 07:22:44 GMT

New page: '''Unreleased structure''' The entry 3vro is ON HOLD Authors: Takeshita, K., Tezuka, T., Isozaki, Y., Yamashita, E., Suzuki, M., Yamanashi, Y., Yamamoto, T., Nakagawa, A. Description: ...

New page

'''Unreleased structure'''

The entry 3vro is ON HOLD

Authors: Takeshita, K., Tezuka, T., Isozaki, Y., Yamashita, E., Suzuki, M., Yamanashi, Y., Yamamoto, T., Nakagawa, A.

Description: Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-Src peptide