2src - Revision history

OCA at 08:39, 30 October 2024

2024-10-30T08:39:59Z

← Older revision		Revision as of 08:39, 30 October 2024
Line 17:		Line 17:
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sr/2src_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sr/2src_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 06:46, 9 August 2023

2023-08-09T06:46:51Z

← Older revision		Revision as of 06:46, 9 August 2023
Line 3:		Line 3:
	<StructureSection load='2src' size='340' side='right'caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='2src' size='340' side='right'caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. The July 2003 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2SRC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The July 2003 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2SRC FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID~~-~~ADENYLATE+ESTER'>ANP</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]] 1.5Å</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=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <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~~'>~~[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2]~~ </~~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=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [https://pdbe.org/2src PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [https://www.ebi.ac.uk/pdbsum/2src PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2src 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=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [https://pdbe.org/2src PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [https://www.ebi.ac.uk/pdbsum/2src PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2src ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[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.		[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 ==
	[[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>		[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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 39:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: RCSB PDB Molecule of the Month]]		[[Category: RCSB PDB Molecule of the Month]]
	[[Category: Src Tyrosine Kinase]]		[[Category: Src Tyrosine Kinase]]
	~~[[Category: Transferase]]~~
	[[Category: Ubiquitin]]		[[Category: Ubiquitin]]
	[[Category: Doshi, A]]		[[Category: Doshi A]]
	[[Category: Eck~~, M J~~]]		[[Category: Eck MJ]]
	[[Category: Harrison~~, S C~~]]		[[Category: Harrison SC]]
	[[Category: Lei, M]]		[[Category: Lei M]]
	[[Category: Xu, W]]		[[Category: Xu W]]
	~~[[Category: Phosphorylation]]~~
	~~[[Category: Phosphotransferase]]~~
	~~[[Category: Phosphotyrosine]]~~
	~~[[Category: Proto-oncogene]]~~
	~~[[Category: Sh2]]~~
	~~[[Category: Sh3]]~~
	~~[[Category: Src]]~~
	~~[[Category: Tyrosine-protein kinase~~]]

OCA at 12:28, 23 March 2022

2022-03-23T12:28:12Z

← Older revision		Revision as of 12:28, 23 March 2022
Line 3:		Line 3:
	<StructureSection load='2src' size='340' side='right'caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='2src' size='340' side='right'caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. The July 2003 RCSB PDB [~~http~~://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [~~http~~://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [~~http~~://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [~~http~~://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2SRC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. The July 2003 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2SRC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Transferase Transferase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [~~http~~://pdbe.org/2src PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2src PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2src 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=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [https://pdbe.org/2src PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [https://www.ebi.ac.uk/pdbsum/2src PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2src 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/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/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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 34:

	==See Also==		==See Also==
	*[[SRC\|SRC]]
	*[[Student Project 6 for UMass Chemistry 423 Spring 2015\|Student Project 6 for UMass Chemistry 423 Spring 2015]]
	*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]		*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	*[[User:Eric Martz/Introduction to Structural Bioinformatics I\|User:Eric Martz/Introduction to Structural Bioinformatics I]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:07, 17 June 2020

2020-06-17T11:07:33Z

← Older revision		Revision as of 11:07, 17 June 2020
Line 1:		Line 1:

	==CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP==		==CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP==
	<StructureSection load='2src' size='340' side='right' caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='2src' size='340' side='right'caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. The July 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2SRC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. The July 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2SRC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [http://pdbe.org/2src PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [http://www.ebi.ac.uk/pdbsum/2src PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2src ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [http://pdbe.org/2src PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [http://www.ebi.ac.uk/pdbsum/2src PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2src ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 36:		Line 36:
	*[[SRC\|SRC]]		*[[SRC\|SRC]]
	*[[Student Project 6 for UMass Chemistry 423 Spring 2015\|Student Project 6 for UMass Chemistry 423 Spring 2015]]		*[[Student Project 6 for UMass Chemistry 423 Spring 2015\|Student Project 6 for UMass Chemistry 423 Spring 2015]]
	*[[Tyrosine kinase\|Tyrosine kinase]]		*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	*[[User:Eric Martz/Introduction to Structural Bioinformatics I\|User:Eric Martz/Introduction to Structural Bioinformatics I]]		*[[User:Eric Martz/Introduction to Structural Bioinformatics I\|User:Eric Martz/Introduction to Structural Bioinformatics I]]
	== References ==		== References ==
Line 43:		Line 43:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: RCSB PDB Molecule of the Month]]		[[Category: RCSB PDB Molecule of the Month]]
	[[Category: Src Tyrosine Kinase]]		[[Category: Src Tyrosine Kinase]]

OCA at 08:56, 12 September 2018

2018-09-12T08:56:10Z

← Older revision		Revision as of 08:56, 12 September 2018
Line 1:		Line 1:

	==CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP==		==CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP==
	<StructureSection load='2src' size='340' side='right' caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='2src' size='340' side='right' caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>
Line 6:		Line 7:
	<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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [http://pdbe.org/2src PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [http://www.ebi.ac.uk/pdbsum/2src 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=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [http://pdbe.org/2src PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [http://www.ebi.ac.uk/pdbsum/2src PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2src ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 16:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sr/2src_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sr/2src_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>

OCA at 07:46, 7 February 2016

2016-02-07T07:46:17Z

← Older revision		Revision as of 07:46, 7 February 2016
Line 2:		Line 2:
	<StructureSection load='2src' size='340' side='right' caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='2src' size='340' side='right' caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. The July 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2SRC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. The July 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2SRC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [http://www.ebi.ac.uk/pdbsum/2src 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=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [http://pdbe.org/2src PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [http://www.ebi.ac.uk/pdbsum/2src PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	<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=2src ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 30:		Line 30:
	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 2src" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[SRC\|SRC]]		*[[SRC\|SRC]]
			*[[Student Project 6 for UMass Chemistry 423 Spring 2015\|Student Project 6 for UMass Chemistry 423 Spring 2015]]
	*[[Tyrosine kinase\|Tyrosine kinase]]		*[[Tyrosine kinase\|Tyrosine kinase]]
	*[[User:Eric Martz/Introduction to Structural Bioinformatics I\|User:Eric Martz/Introduction to Structural Bioinformatics I]]		*[[User:Eric Martz/Introduction to Structural Bioinformatics I\|User:Eric Martz/Introduction to Structural Bioinformatics I]]
Line 39:		Line 41:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: RCSB PDB Molecule of the Month]]		[[Category: RCSB PDB Molecule of the Month]]
	[[Category: Src Tyrosine Kinase]]		[[Category: Src Tyrosine Kinase]]

OCA at 17:06, 19 January 2015

2015-01-19T17:06:44Z

← Older revision		Revision as of 17:06, 19 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The July 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2SRC FirstGlance]. <br>		<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The July 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2SRC FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>
	<tr><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><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [http://www.ebi.ac.uk/pdbsum/2src 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=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [http://www.ebi.ac.uk/pdbsum/2src PDBsum]</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.		[[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.
Line 44:		Line 44:
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Ubiquitin]]		[[Category: Ubiquitin]]
	[[Category: Doshi, A.]]		[[Category: Doshi, A]]
	[[Category: Eck, M J.]]		[[Category: Eck, M J]]
	[[Category: Harrison, S C.]]		[[Category: Harrison, S C]]
	[[Category: Lei, M.]]		[[Category: Lei, M]]
	[[Category: Xu, W.]]		[[Category: Xu, W]]
	[[Category: Phosphorylation]]		[[Category: Phosphorylation]]
	[[Category: Phosphotransferase]]		[[Category: Phosphotransferase]]

OCA at 01:42, 1 October 2014

2014-10-01T01:42:36Z

← Older revision		Revision as of 01:42, 1 October 2014
Line 1:		Line 1:
	~~{{STRUCTURE_2src\| PDB=2src \| SCENE= }}~~		==CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP==
	===CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP===		<StructureSection load='2src' size='340' side='right' caption='[[2src]], [[Resolution\|resolution]] 1.50Å' scene=''>
	~~{{ABSTRACT_PUBMED_10360179}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[2src]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The July 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Src Tyrosine Kinase'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Ubiquitin'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SRC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2SRC FirstGlance]. <br>
	==Disease==		</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene><br>
			<tr><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><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>
			<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2src FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2src OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2src RCSB], [http://www.ebi.ac.uk/pdbsum/2src 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.		[[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/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>
			== 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/sr/2src_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 ==
			Src family kinases are maintained in an assembled, inactive conformation by intramolecular interactions of their SH2 and SH3 domains. Full catalytic activity requires release of these restraints as well as phosphorylation of Tyr-416 in the activation loop. In previous structures of inactive Src kinases, Tyr-416 and flanking residues are disordered. We report here four additional c-Src structures in which this segment adopts an ordered but inhibitory conformation. The ordered activation loop forms an alpha helix that stabilizes the inactive conformation of the kinase domain, blocks the peptide substrate-binding site, and prevents Tyr-416 phosphorylation. Disassembly of the regulatory domains, induced by SH2 or SH3 ligands, or by dephosphorylation of Tyr-527, could lead to exposure and phosphorylation of Tyr-416.

	~~==Function==~~		Crystal structures of c-Src reveal features of its autoinhibitory mechanism.,Xu W, Doshi A, Lei M, Eck MJ, Harrison SC Mol Cell. 1999 May;3(5):629-38. PMID:10360179<ref>PMID:10360179</ref>
	~~[[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>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[2src]] is~~ a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The July 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the ~~Month] feature on ''Src Tyrosine Kinase'' by David~~ S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_7 10.2210/rcsb_pdb/mom_2003_7]. The December 2004 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of ~~the Month] feature on ''Ubiquitin'' by David S~~. ~~Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2004_12 10.2210/rcsb_pdb/mom_2004_12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin~~/~~ocashort?id=2SRC OCA].~~		</div>

	==See Also==		==See Also==
	*[[Proto-oncogene tyrosine-protein kinase\|Proto-oncogene tyrosine-protein kinase]]
	*[[SRC\|SRC]]		*[[SRC\|SRC]]
			*[[Tyrosine kinase\|Tyrosine kinase]]
	*[[User:Eric Martz/Introduction to Structural Bioinformatics I\|User:Eric Martz/Introduction to Structural Bioinformatics I]]		*[[User:Eric Martz/Introduction to Structural Bioinformatics I\|User:Eric Martz/Introduction to Structural Bioinformatics I]]
	*[[User:Eric Martz/Introduction to Structural Bioinformatics I%2C 2013\|User:Eric Martz/Introduction to Structural Bioinformatics I%2C 2013]]		== References ==
			<references/>
	==~~Reference~~==		__TOC__
	~~<ref group="xtra">PMID:010360179</ref>~~<references ~~group="xtra"~~/><~~references~~/>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: RCSB PDB Molecule of the Month]]		[[Category: RCSB PDB Molecule of the Month]]

OCA at 16:49, 24 March 2013

2013-03-24T16:49:20Z

← Older revision		Revision as of 16:49, 24 March 2013
Line 2:		Line 2:
	===CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP===		===CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP===
	{{ABSTRACT_PUBMED_10360179}}		{{ABSTRACT_PUBMED_10360179}}

			==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/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>

	==About this Structure==		==About this Structure==
Line 13:		Line 19:

	==Reference==		==Reference==
	<ref group="xtra">PMID:010360179</ref><references group="xtra"/>		<ref group="xtra">PMID:010360179</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: RCSB PDB Molecule of the Month]]		[[Category: RCSB PDB Molecule of the Month]]

OCA at 10:39, 11 March 2013

2013-03-11T10:39:30Z

← Older revision		Revision as of 10:39, 11 March 2013
Line 1:		Line 1:
	~~[[Image:2src.png\|left\|200px]]~~

	{{STRUCTURE_2src\| PDB=2src \| SCENE= }}		{{STRUCTURE_2src\| PDB=2src \| SCENE= }}

	===CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP===		===CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP===

	{{ABSTRACT_PUBMED_10360179}}		{{ABSTRACT_PUBMED_10360179}}