3bys - Revision history

OCA at 12:18, 30 August 2023

2023-08-30T12:18:26Z

← Older revision		Revision as of 12:18, 30 August 2023
Line 3:		Line 3:
	<StructureSection load='3bys' size='340' side='right'caption='[[3bys]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3bys' size='340' side='right'caption='[[3bys]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3bys]] is a 1 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=3BYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BYS FirstGlance]. <br>		<table><tr><td colspan='2'>[[3bys]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BYS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AM5:4-METHYL-N~3~-(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)-N~1~-[3-(TRIFLUOROMETHYL)PHENYL]BENZENE-1,3-DICARBOXAMIDE'>AM5</scene~~></td></tr>~~		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.2Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ofv\|2ofv]], [[3byu\|3byu]]</div></td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AM5:4-METHYL-N~3~-(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)-N~1~-[3-(TRIFLUOROMETHYL)PHENYL]BENZENE-1,3-DICARBOXAMIDE'>AM5</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LCK ([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'>[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'>[https://proteopedia.org/fgij/fg.htm?mol=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [https://pdbe.org/3bys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [https://www.ebi.ac.uk/pdbsum/3bys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bys 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=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [https://pdbe.org/3bys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [https://www.ebi.ac.uk/pdbsum/3bys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bys ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.		[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.<ref>PMID:16339550</ref> <ref>PMID:16709819</ref> <ref>PMID:20100835</ref> <ref>PMID:20028775</ref> <ref>PMID:20851766</ref> <ref>PMID:21269457</ref>		[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN] Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.<ref>PMID:16339550</ref> <ref>PMID:16709819</ref> <ref>PMID:20100835</ref> <ref>PMID:20028775</ref> <ref>PMID:20851766</ref> <ref>PMID:21269457</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Non-specific protein-tyrosine kinase]]~~		[[Category: Huang X]]
	[[Category: Huang, X]]
	~~[[Category: Alternative splicing]]~~
	~~[[Category: Atp-binding]]~~
	~~[[Category: Chromosomal rearrangement]]~~
	~~[[Category: Cytoplasm]]~~
	~~[[Category: Disease mutation]]~~
	~~[[Category: Host-virus interaction]]~~
	~~[[Category: Kinase domain]]~~
	~~[[Category: Lck]]~~
	~~[[Category: Lipoprotein]]~~
	~~[[Category: Membrane]]~~
	~~[[Category: Myristate]]~~
	~~[[Category: Nucleotide-binding]]~~
	~~[[Category: Palmitate]]~~
	~~[[Category: Phosphoprotein]]~~
	~~[[Category: Proto-oncogene]]~~
	~~[[Category: Sh2 domain]]~~
	~~[[Category: Sh3 domain]]~~
	~~[[Category: Transferase]]~~
	~~[[Category: Tyrosine-protein kinase~~]]

OCA at 08:29, 19 January 2022

2022-01-19T08:29:22Z

← Older revision		Revision as of 08:29, 19 January 2022
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	==co-crystal structure of Lck and aminopyrimidine amide 10b==		==co-crystal structure of Lck and aminopyrimidine amide 10b==
	<StructureSection load='3bys' size='340' side='right' caption='[[3bys]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3bys' size='340' side='right'caption='[[3bys]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3bys]] is a 1 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=3BYS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3BYS FirstGlance]. <br>		<table><tr><td colspan='2'>[[3bys]] is a 1 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=3BYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BYS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AM5:4-METHYL-N~3~-(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)-N~1~-[3-(TRIFLUOROMETHYL)PHENYL]BENZENE-1,3-DICARBOXAMIDE'>AM5</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AM5:4-METHYL-N~3~-(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)-N~1~-[3-(TRIFLUOROMETHYL)PHENYL]BENZENE-1,3-DICARBOXAMIDE'>AM5</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ofv\|2ofv]], [[3byu\|3byu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ofv\|2ofv]], [[3byu\|3byu]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LCK ([~~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">LCK ([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=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [~~http~~://pdbe.org/3bys PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3bys PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3bys 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=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [https://pdbe.org/3bys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [https://www.ebi.ac.uk/pdbsum/3bys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bys ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.		[[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.<ref>PMID:16339550</ref> <ref>PMID:16709819</ref> <ref>PMID:20100835</ref> <ref>PMID:20028775</ref> <ref>PMID:20851766</ref> <ref>PMID:21269457</ref>		[[https://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.<ref>PMID:16339550</ref> <ref>PMID:16709819</ref> <ref>PMID:20100835</ref> <ref>PMID:20028775</ref> <ref>PMID:20851766</ref> <ref>PMID:21269457</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	==See Also==		==See Also==
	*[[Tyrosine kinase\|Tyrosine kinase]]		*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Huang, X]]		[[Category: Huang, X]]

OCA at 13:31, 7 November 2018

2018-11-07T13:31:37Z

← Older revision		Revision as of 13:31, 7 November 2018
Line 1:		Line 1:

	==co-crystal structure of Lck and aminopyrimidine amide 10b==		==co-crystal structure of Lck and aminopyrimidine amide 10b==
	<StructureSection load='3bys' size='340' side='right' caption='[[3bys]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3bys' size='340' side='right' caption='[[3bys]], [[Resolution\|resolution]] 2.20Å' scene=''>
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	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LCK ([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">LCK ([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=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [http://pdbe.org/3bys PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [http://www.ebi.ac.uk/pdbsum/3bys 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=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [http://pdbe.org/3bys PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [http://www.ebi.ac.uk/pdbsum/3bys PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3bys ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 18:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/by/3bys_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/by/3bys_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>
Line 42:		Line 43:
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Huang, X]]		[[Category: Huang, X]]
			[[Category: Alternative splicing]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
			[[Category: Chromosomal rearrangement]]
			[[Category: Cytoplasm]]
	[[Category: Disease mutation]]		[[Category: Disease mutation]]
	[[Category: Host-virus interaction]]		[[Category: Host-virus interaction]]

OCA at 22:47, 7 February 2016

2016-02-07T22:47:14Z

← Older revision		Revision as of 22:47, 7 February 2016
Line 2:		Line 2:
	<StructureSection load='3bys' size='340' side='right' caption='[[3bys]], [[Resolution\|resolution]] 2.20Å' scene=''>		<StructureSection load='3bys' size='340' side='right' caption='[[3bys]], [[Resolution\|resolution]] 2.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3bys]] is a 1 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=3BYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BYS FirstGlance]. <br>		<table><tr><td colspan='2'>[[3bys]] is a 1 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=3BYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BYS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AM5:4-METHYL-N~3~-(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)-N~1~-[3-(TRIFLUOROMETHYL)PHENYL]BENZENE-1,3-DICARBOXAMIDE'>AM5</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AM5:4-METHYL-N~3~-(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)-N~1~-[3-(TRIFLUOROMETHYL)PHENYL]BENZENE-1,3-DICARBOXAMIDE'>AM5</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ofv\|2ofv]], [[3byu\|3byu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ofv\|2ofv]], [[3byu\|3byu]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LCK ([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">LCK ([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=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [http://www.ebi.ac.uk/pdbsum/3bys 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=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [http://pdbe.org/3bys PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [http://www.ebi.ac.uk/pdbsum/3bys PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 21:
	<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=3bys ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 31:		Line 31:
	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 3bys" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Huang, X]]		[[Category: Huang, X]]

OCA at 10:18, 20 January 2015

2015-01-20T10:18:07Z

← Older revision		Revision as of 10:18, 20 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3bys]] is a 1 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=3BYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BYS FirstGlance]. <br>		<table><tr><td colspan='2'>[[3bys]] is a 1 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=3BYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BYS FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AM5:4-METHYL-N~3~-(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)-N~1~-[3-(TRIFLUOROMETHYL)PHENYL]BENZENE-1,3-DICARBOXAMIDE'>AM5</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AM5:4-METHYL-N~3~-(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)-N~1~-[3-(TRIFLUOROMETHYL)PHENYL]BENZENE-1,3-DICARBOXAMIDE'>AM5</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ofv\|2ofv]], [[3byu\|3byu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ofv\|2ofv]], [[3byu\|3byu]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LCK ([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">LCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [http://www.ebi.ac.uk/pdbsum/3bys 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=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [http://www.ebi.ac.uk/pdbsum/3bys PDBsum]</span></td></tr>
	<table>		</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.		[[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
Line 40:		Line 40:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Huang, X.]]		[[Category: Huang, X]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Disease mutation]]		[[Category: Disease mutation]]

OCA at 21:04, 2 October 2014

2014-10-02T21:04:40Z

← Older revision		Revision as of 21:04, 2 October 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3bys\| PDB=3bys \| SCENE= }}~~		==co-crystal structure of Lck and aminopyrimidine amide 10b==
	===co-crystal structure of Lck and aminopyrimidine amide 10b===		<StructureSection load='3bys' size='340' side='right' caption='[[3bys]], [[Resolution\|resolution]] 2.20Å' scene=''>
	{~~{ABSTRACT_PUBMED_18321037}~~}		== Structural highlights ==
			<table><tr><td colspan='2'>[[3bys]] is a 1 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=3BYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BYS FirstGlance]. <br>
	==Disease==		</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AM5:4-METHYL-N~3~-(2-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}PYRIMIDIN-5-YL)-N~1~-[3-(TRIFLUOROMETHYL)PHENYL]BENZENE-1,3-DICARBOXAMIDE'>AM5</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ofv\|2ofv]], [[3byu\|3byu]]</td></tr>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">LCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bys OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bys RCSB], [http://www.ebi.ac.uk/pdbsum/3bys PDBsum]</span></td></tr>
			<table>
			== Disease ==
	[[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.		[[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.
			== Function ==
			[[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.<ref>PMID:16339550</ref> <ref>PMID:16709819</ref> <ref>PMID:20100835</ref> <ref>PMID:20028775</ref> <ref>PMID:20851766</ref> <ref>PMID:21269457</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/by/3bys_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The lymphocyte-specific kinase (Lck), a member of the Src family of cytoplasmic tyrosine kinases, is expressed in T cells and natural killer (NK) cells. Genetic evidence, including knockout mice and human mutations, demonstrates that Lck kinase activity is critical for normal T cell development, activation, and signaling. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. With the aid of X-ray structure-based analysis, aminopyrimidine amides 2 and 3 were designed from aminoquinazolines 1, which had previously been demonstrated to exhibit potent inhibition of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminopyrimidine amides 3 possessing improved cellular potency and selectivity profiles relative to their aminoquinazoline predecessors 1. Orally bioavailable compound 13b inhibited the anti-CD3-induced production of interleukin-2 (IL-2) in mice in a dose-dependent manner (ED 50 = 9.4 mg/kg).

	~~==Function==~~		Structure-guided design of aminopyrimidine amides as potent, selective inhibitors of lymphocyte specific kinase: synthesis, structure-activity relationships, and inhibition of in vivo T cell activation.,DiMauro EF, Newcomb J, Nunes JJ, Bemis JE, Boucher C, Chai L, Chaffee SC, Deak HL, Epstein LF, Faust T, Gallant P, Gore A, Gu Y, Henkle B, Hsieh F, Huang X, Kim JL, Lee JH, Martin MW, McGowan DC, Metz D, Mohn D, Morgenstern KA, Oliveira-dos-Santos A, Patel VF, Powers D, Rose PE, Schneider S, Tomlinson SA, Tudor YY, Turci SM, Welcher AA, Zhao H, Zhu L, Zhu X J Med Chem. 2008 Mar 27;51(6):1681-94. Epub 2008 Mar 6. PMID:18321037<ref>PMID:18321037</ref>
	~~[[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Non~~-~~receptor tyrosine-protein~~ kinase ~~that plays an essential role in the selection and maturation of developing T~~-~~cells in the thymus~~ and ~~in the function~~ of ~~mature T-cells. Plays a key role~~ in T-cell ~~antigen receptor (TCR)-linked signal transduction pathways~~. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, ~~respectively~~, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, ~~initiating the TCR/CD3 signaling pathway. Once stimulated~~, ~~the TCR recruits the tyrosine kinase ZAP70~~, ~~that becomes phosphorylated and activated by LCK. Following this~~, ~~a large number of signaling molecules are recruited~~, ~~ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2~~, ~~which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the~~ T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-~~TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3~~, ~~PTK2B/PYK2~~, ~~the microtubule-associated protein MAPT~~, ~~RHOH or TYROBP~~.~~<ref>PMID~~:~~16339550</ref><ref>PMID:16709819</ref><ref>PMID:20100835</ref><ref>~~PMID:~~20028775</ref><ref>PMID:20851766</ref>~~<ref>PMID:~~21269457~~</ref>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[3bys]] is~~ a ~~1 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=3BYS OCA].~~		</div>

	==See Also==		==See Also==
	*[[Proto-oncogene tyrosine-protein kinase\|Proto-oncogene tyrosine-protein kinase]]
	*[[Tyrosine kinase\|Tyrosine kinase]]		*[[Tyrosine kinase\|Tyrosine kinase]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:018321037</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]

OCA at 05:12, 25 March 2013

2013-03-25T05:12:31Z

← Older revision		Revision as of 05:12, 25 March 2013
Line 4:		Line 4:

	==Disease==		==Disease==
	[[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.		[[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Severe combined immunodeficiency due to LCK deficiency. Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.

	==Function==		==Function==

OCA at 01:18, 25 March 2013

2013-03-25T01:18:53Z

← Older revision		Revision as of 01:18, 25 March 2013
Line 1:		Line 1:
	~~[[Image:3bys.png\|left\|200px]]~~

	{{STRUCTURE_3bys\| PDB=3bys \| SCENE= }}		{{STRUCTURE_3bys\| PDB=3bys \| SCENE= }}
			===co-crystal structure of Lck and aminopyrimidine amide 10b===
			{{ABSTRACT_PUBMED_18321037}}

	==~~=co-crystal structure of Lck and aminopyrimidine amide 10b~~===		==Disease==
			[[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Note=A chromosomal aberration involving LCK is found in leukemias. Translocation t(1;7)(p34;q34) with TCRB.

	~~{{ABSTRACT_PUBMED_18321037}}~~		==Function==
			[[http://www.uniprot.org/uniprot/LCK_HUMAN LCK_HUMAN]] Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP.<ref>PMID:16339550</ref><ref>PMID:16709819</ref><ref>PMID:20100835</ref><ref>PMID:20028775</ref><ref>PMID:20851766</ref><ref>PMID:21269457</ref>

	==About this Structure==		==About this Structure==
Line 15:		Line 17:

	==Reference==		==Reference==
	<ref group="xtra">PMID:018321037</ref><references group="xtra"/>		<ref group="xtra">PMID:018321037</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]

OCA at 08:04, 20 October 2012

2012-10-20T08:04:20Z

← Older revision		Revision as of 08:04, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[3bys]] is a 1 chain structure ~~of [[Proto-oncogene tyrosine-protein kinase]] and [[Tyrosine kinase]]~~ 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=3BYS OCA].		[[3bys]] is a 1 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=3BYS OCA].

	==See Also==		==See Also==

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

2012-07-25T18:21:14Z

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

← Older revision	Revision as of 18:21, 25 July 2012
(No difference)