4e93 - Revision history

OCA at 14:55, 14 March 2024

2024-03-14T14:55:48Z

← Older revision		Revision as of 14:55, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e93]] 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=4E93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E93 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e93]] 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=4E93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E93 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GUI:5-CHLORO-N-[2-METHOXY-4-[4-(4-METHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL]PHENYL]-N-(2-PROPAN-2-YLSULFONYLPHENYL)PYRIMIDINE-2,4-DIAMINE'>GUI</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]] 1.84Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GUI:5-CHLORO-N-[2-METHOXY-4-[4-(4-METHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL]PHENYL]-N-(2-PROPAN-2-YLSULFONYLPHENYL)PYRIMIDINE-2,4-DIAMINE'>GUI</scene></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=4e93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e93 OCA], [https://pdbe.org/4e93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e93 RCSB], [https://www.ebi.ac.uk/pdbsum/4e93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e93 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=4e93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e93 OCA], [https://pdbe.org/4e93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e93 RCSB], [https://www.ebi.ac.uk/pdbsum/4e93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e93 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Note=Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:21563194). May promote growth of renal carcinoma cells (PubMed:19082481).		[https://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN] Note=Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:21563194). May promote growth of renal carcinoma cells (PubMed:19082481).
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.<ref>PMID:2656706</ref> <ref>PMID:8955135</ref> <ref>PMID:11509660</ref> <ref>PMID:15302586</ref> <ref>PMID:15485904</ref> <ref>PMID:16455651</ref> <ref>PMID:17595334</ref> <ref>PMID:18046454</ref> <ref>PMID:19051325</ref> <ref>PMID:19082481</ref> <ref>PMID:19001085</ref> <ref>PMID:20111072</ref> <ref>PMID:21563194</ref>		[https://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN] Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.<ref>PMID:2656706</ref> <ref>PMID:8955135</ref> <ref>PMID:11509660</ref> <ref>PMID:15302586</ref> <ref>PMID:15485904</ref> <ref>PMID:16455651</ref> <ref>PMID:17595334</ref> <ref>PMID:18046454</ref> <ref>PMID:19051325</ref> <ref>PMID:19082481</ref> <ref>PMID:19001085</ref> <ref>PMID:20111072</ref> <ref>PMID:21563194</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	The c-Fes protein-tyrosine kinase modulates cellular signaling pathways governing differentiation, the innate immune response, and vasculogenesis. Here, we report the identification of types I and II kinase inhibitors with potent activity against c-Fes both in vitro and in cell-based assays. One of the most potent inhibitors is the previously described anaplastic lymphoma kinase inhibitor TAE684. The crystal structure of TAE684 in complex with the c-Fes SH2-kinase domain showed excellent shape complementarity with the ATP-binding pocket and a key role for the gatekeeper methionine in the inhibitory mechanism. TAE684 and two pyrazolopyrimidines with nanomolar potency against c-Fes in vitro were used to establish a role for this kinase in osteoclastogenesis, illustrating the value of these inhibitors as tool compounds to probe the diverse biological functions associated with this unique kinase.

	Small-Molecule Inhibitors of the c-Fes Protein-Tyrosine Kinase.,Hellwig S, Miduturu CV, Kanda S, Zhang J, Filippakopoulos P, Salah E, Deng X, Choi HG, Zhou W, Hur W, Knapp S, Gray NS, Smithgall TE Chem Biol. 2012 Apr 20;19(4):529-40. PMID:22520759<ref>PMID:22520759</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4e93" style="background-color:#fffaf0;"></div~~>

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

OCA at 06:58, 28 September 2022

2022-09-28T06:58:09Z

← Older revision		Revision as of 06:58, 28 September 2022
Line 1:		Line 1:

	==Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684==		==Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684==
	<StructureSection load='4e93' size='340' side='right' caption='[[4e93]], [[Resolution\|resolution]] 1.84Å' scene=''>		<StructureSection load='4e93' size='340' side='right'caption='[[4e93]], [[Resolution\|resolution]] 1.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e93]] 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=4E93 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E93 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e93]] 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=4E93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E93 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GUI:5-CHLORO-N-[2-METHOXY-4-[4-(4-METHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL]PHENYL]-N-(2-PROPAN-2-YLSULFONYLPHENYL)PYRIMIDINE-2,4-DIAMINE'>GUI</scene~~></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GUI:5-CHLORO-N-[2-METHOXY-4-[4-(4-METHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL]PHENYL]-N-(2-PROPAN-2-YLSULFONYLPHENYL)PYRIMIDINE-2,4-DIAMINE'>GUI</scene></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3bkb\|3bkb]]</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=4e93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e93 OCA], [https://pdbe.org/4e93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e93 RCSB], [https://www.ebi.ac.uk/pdbsum/4e93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e93 ProSAT]</span></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FES, FPS ([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='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=4e93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e93 OCA], [~~http~~://pdbe.org/4e93 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e93 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e93 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e93 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Note=Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:21563194). May promote growth of renal carcinoma cells (PubMed:19082481).		[[https://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Note=Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:21563194). May promote growth of renal carcinoma cells (PubMed:19082481).
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.<ref>PMID:2656706</ref> <ref>PMID:8955135</ref> <ref>PMID:11509660</ref> <ref>PMID:15302586</ref> <ref>PMID:15485904</ref> <ref>PMID:16455651</ref> <ref>PMID:17595334</ref> <ref>PMID:18046454</ref> <ref>PMID:19051325</ref> <ref>PMID:19082481</ref> <ref>PMID:19001085</ref> <ref>PMID:20111072</ref> <ref>PMID:21563194</ref>		[[https://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.<ref>PMID:2656706</ref> <ref>PMID:8955135</ref> <ref>PMID:11509660</ref> <ref>PMID:15302586</ref> <ref>PMID:15485904</ref> <ref>PMID:16455651</ref> <ref>PMID:17595334</ref> <ref>PMID:18046454</ref> <ref>PMID:19051325</ref> <ref>PMID:19082481</ref> <ref>PMID:19001085</ref> <ref>PMID:20111072</ref> <ref>PMID:21563194</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:

	==See Also==		==See Also==
	*[[Tyrosine kinase\|Tyrosine kinase]]		*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Non-specific protein-tyrosine kinase~~]]		[[Category: Large Structures]]
	[[Category: Arrowsmith~~, C H~~]]		[[Category: Arrowsmith CH]]
	[[Category: Cooper, C]]		[[Category: Cooper C]]
	~~[[Category: Delft, F von~~]]		[[Category: Edwards AM]]
	[[Category: Edwards~~, A M~~]]		[[Category: Fedorov O]]
	[[Category: Fedorov, O]]		[[Category: Filippakopoulos P]]
	[[Category: Filippakopoulos, P]]		[[Category: Gray NS]]
	[[Category: Gray~~, N S~~]]		[[Category: Knapp S]]
	[[Category: Knapp, S]]		[[Category: Miduturu CV]]
	[[Category: Miduturu~~, C V]]~~		[[Category: Salah E]]
	~~[[Category: Structural genomic~~]]		[[Category: Weigelt J]]
	[[Category: Salah, E]]		[[Category: Von Delft F]]
	[[Category: Weigelt, J]]
	[[Category: ~~Atp-binding]]~~
	~~[[Category: Avian sarcoma]]~~
	~~[[Category: Feline sarcoma virus]]~~
	~~[[Category: Fujinami]]~~
	~~[[Category: Kinase]]~~
	~~[[Category: Nucleotide-binding]]~~
	~~[[Category: Oncogene]]~~
	~~[[Category: Phosphoprotein]]~~
	~~[[Category: Proto-oncogene]]~~
	~~[[Category: Sh2 domain]]~~
	~~[[Category: Transferase]]~~
	~~[[Category: Transferase-transferase inhibitor complex]]~~
	~~[[Category: Tyrosine-protein kinase]]~~
	~~[[Category: V-fe]]~~
	~~[[Category: Viral~~]]

OCA at 10:13, 4 August 2016

2016-08-04T10:13:46Z

← Older revision		Revision as of 10:13, 4 August 2016
Line 1:		Line 1:

	==Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684==		==Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684==
	<StructureSection load='4e93' size='340' side='right' caption='[[4e93]], [[Resolution\|resolution]] 1.84Å' scene=''>		<StructureSection load='4e93' size='340' side='right' caption='[[4e93]], [[Resolution\|resolution]] 1.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e93]] 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=4E93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E93 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e93]] 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=4E93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E93 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GUI:5-CHLORO-N-[2-METHOXY-4-[4-(4-METHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL]PHENYL]-N-(2-PROPAN-2-YLSULFONYLPHENYL)PYRIMIDINE-2,4-DIAMINE'>GUI</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GUI:5-CHLORO-N-[2-METHOXY-4-[4-(4-METHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL]PHENYL]-N-(2-PROPAN-2-YLSULFONYLPHENYL)PYRIMIDINE-2,4-DIAMINE'>GUI</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3bkb\|3bkb]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3bkb\|3bkb]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FES, FPS ([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">FES, FPS ([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=4e93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e93 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e93 RCSB], [http://www.ebi.ac.uk/pdbsum/4e93 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=4e93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e93 OCA], [http://pdbe.org/4e93 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e93 RCSB], [http://www.ebi.ac.uk/pdbsum/4e93 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e93 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 4e93" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Arrowsmith, C H]]		[[Category: Arrowsmith, C H]]

OCA at 11:15, 21 December 2014

2014-12-21T11:15:44Z

← Older revision		Revision as of 11:15, 21 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4e93\| PDB=4e93 \| SCENE= }}~~		==Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684==
	===Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684===		<StructureSection load='4e93' size='340' side='right' caption='[[4e93]], [[Resolution\|resolution]] 1.84Å' scene=''>
	~~{{ABSTRACT_PUBMED_22520759}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4e93]] 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=4E93 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E93 FirstGlance]. <br>
	==Disease==		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GUI:5-CHLORO-N-[2-METHOXY-4-[4-(4-METHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL]PHENYL]-N-(2-PROPAN-2-YLSULFONYLPHENYL)PYRIMIDINE-2,4-DIAMINE'>GUI</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3bkb\|3bkb]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FES, FPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
			<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4e93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e93 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e93 RCSB], [http://www.ebi.ac.uk/pdbsum/4e93 PDBsum]</span></td></tr>
			</table>
			== Disease ==
	[[http://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Note=Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:21563194). May promote growth of renal carcinoma cells (PubMed:19082481).		[[http://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Note=Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:21563194). May promote growth of renal carcinoma cells (PubMed:19082481).
			== Function ==
			[[http://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.<ref>PMID:2656706</ref> <ref>PMID:8955135</ref> <ref>PMID:11509660</ref> <ref>PMID:15302586</ref> <ref>PMID:15485904</ref> <ref>PMID:16455651</ref> <ref>PMID:17595334</ref> <ref>PMID:18046454</ref> <ref>PMID:19051325</ref> <ref>PMID:19082481</ref> <ref>PMID:19001085</ref> <ref>PMID:20111072</ref> <ref>PMID:21563194</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The c-Fes protein-tyrosine kinase modulates cellular signaling pathways governing differentiation, the innate immune response, and vasculogenesis. Here, we report the identification of types I and II kinase inhibitors with potent activity against c-Fes both in vitro and in cell-based assays. One of the most potent inhibitors is the previously described anaplastic lymphoma kinase inhibitor TAE684. The crystal structure of TAE684 in complex with the c-Fes SH2-kinase domain showed excellent shape complementarity with the ATP-binding pocket and a key role for the gatekeeper methionine in the inhibitory mechanism. TAE684 and two pyrazolopyrimidines with nanomolar potency against c-Fes in vitro were used to establish a role for this kinase in osteoclastogenesis, illustrating the value of these inhibitors as tool compounds to probe the diverse biological functions associated with this unique kinase.

	~~==Function==~~		Small-Molecule Inhibitors of the c-Fes Protein-Tyrosine Kinase.,Hellwig S, Miduturu CV, Kanda S, Zhang J, Filippakopoulos P, Salah E, Deng X, Choi HG, Zhou W, Hur W, Knapp S, Gray NS, Smithgall TE Chem Biol. 2012 Apr 20;19(4):529-40. PMID:22520759<ref>PMID:22520759</ref>
	~~[[http://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Tyrosine~~-~~protein kinase that acts downstream~~ of ~~cell surface receptors and plays a role in~~ the ~~regulation of the actin cytoskeleton~~, ~~microtubule assembly~~, ~~cell attachment and cell spreading~~. ~~Plays a role in FCER1~~ (~~high affinity immunoglobulin epsilon receptor~~)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. ~~Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.<ref>PMID:2656706</ref><ref>~~PMID:8955135</ref><ref>PMID:11509660</ref><ref>PMID:15302586</ref><ref>PMID:15485904</ref><ref>PMID:16455651</ref><ref>PMID:17595334</ref><ref>PMID:18046454</ref><ref>PMID:19051325</ref><ref>PMID:19082481</ref><ref>PMID:19001085</ref><ref>PMID:20111072</ref><ref>PMID:~~21563194~~</ref>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[4e93]] 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=4E93 OCA].~~		</div>

	==~~Reference~~==		==See Also==
	~~<ref group~~=~~"xtra">PMID:022520759</ref>~~<references ~~group="xtra"~~/><~~references~~/>		*[[Tyrosine kinase\|Tyrosine kinase]]
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Arrowsmith, C H.]]		[[Category: Arrowsmith, C H]]
	[[Category: Cooper, C.]]		[[Category: Cooper, C]]
	[[Category: Delft, F von.]]		[[Category: Delft, F von]]
	[[Category: Edwards, A M.]]		[[Category: Edwards, A M]]
	[[Category: Fedorov, O.]]		[[Category: Fedorov, O]]
	[[Category: Filippakopoulos, P.]]		[[Category: Filippakopoulos, P]]
	[[Category: Gray, N S.]]		[[Category: Gray, N S]]
	[[Category: Knapp, S.]]		[[Category: Knapp, S]]
	[[Category: Miduturu, C V.]]		[[Category: Miduturu, C V]]
	[[Category: ~~SGC,~~ Structural ~~Genomics Consortium.~~]]		[[Category: Structural genomic]]
	[[Category: Salah, E.]]		[[Category: Salah, E]]
	[[Category: Weigelt, J.]]		[[Category: Weigelt, J]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Avian sarcoma]]		[[Category: Avian sarcoma]]

OCA at 16:18, 24 March 2013

2013-03-24T16:18:02Z

← Older revision		Revision as of 16:18, 24 March 2013
Line 1:		Line 1:
	~~[[Image:4e93.png\|left\|200px]]~~

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_4e93", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_4e93\| PDB=4e93 \| SCENE= }}		{{STRUCTURE_4e93\| PDB=4e93 \| SCENE= }}

	===Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684===		===Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684===
			{{ABSTRACT_PUBMED_22520759}}

			==Disease==
			[[http://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Note=Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:21563194). May promote growth of renal carcinoma cells (PubMed:19082481).

	~~<!--~~		==Function==
	~~The line below this paragraph, {{ABSTRACT_PUBMED_22520759}}, adds the Publication Abstract to the page~~		[[http://www.uniprot.org/uniprot/FES_HUMAN FES_HUMAN]] Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.<ref>PMID:2656706</ref><ref>PMID:8955135</ref><ref>PMID:11509660</ref><ref>PMID:15302586</ref><ref>PMID:15485904</ref><ref>PMID:16455651</ref><ref>PMID:17595334</ref><ref>PMID:18046454</ref><ref>PMID:19051325</ref><ref>PMID:19082481</ref><ref>PMID:19001085</ref><ref>PMID:20111072</ref><ref>PMID:21563194</ref>
	~~(as it appears on PubMed at~~ http://www.~~pubmed~~.~~gov~~)~~, where 22520759 is~~ the ~~PubMed ID number~~.
	-->
	~~{{ABSTRACT_PUBMED_22520759}}~~

	==About this Structure==		==About this Structure==
Line 22:		Line 13:

	==Reference==		==Reference==
	<ref group="xtra">PMID:022520759</ref><references group="xtra"/>		<ref group="xtra">PMID:022520759</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 08:27, 9 May 2012

2012-05-09T08:27:00Z

← Older revision		Revision as of 08:27, 9 May 2012
Line 1:		Line 1:
	[[Image:4e93.~~jpg~~\|left\|200px]]		[[Image:4e93.png\|left\|200px]]

	<!--		<!--
Line 11:		Line 11:
	===Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684===		===Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684===


			<!--
			The line below this paragraph, {{ABSTRACT_PUBMED_22520759}}, adds the Publication Abstract to the page
			(as it appears on PubMed at http://www.pubmed.gov), where 22520759 is the PubMed ID number.
			-->
			{{ABSTRACT_PUBMED_22520759}}

	==About this Structure==		==About this Structure==
	[[4e93]] 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=4E93 OCA].		[[4e93]] 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=4E93 OCA].

			==Reference==
			<ref group="xtra">PMID:022520759</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]

OCA at 08:01, 18 April 2012

2012-04-18T08:01:20Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4e93.jpg|left|200px]]
-The entry 4e93 is ON HOLD
+<!--
-Authors: Filippakopoulos, P., Salah, E., Miduturu, C.V., Fedorov, O., Cooper, C., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Weigelt, J., Gray, N.S., Knapp, S., Structural Genomics Consortium (SGC)
+===Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684===
-Description: Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684

OCA: Protected "4e93" [edit=sysop:move=sysop]

2012-03-28T07:25:12Z

Protected "4e93" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:25, 28 March 2012
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4e93 is ON HOLD Authors: Filippakopoulos, P., Salah, E., Miduturu, C.V., Fedorov, O., Cooper, C., von Delft, F., Arrowsmith, C.H., Edwards, A.M., We...

2012-03-28T07:25:10Z

New page: '''Unreleased structure''' The entry 4e93 is ON HOLD Authors: Filippakopoulos, P., Salah, E., Miduturu, C.V., Fedorov, O., Cooper, C., von Delft, F., Arrowsmith, C.H., Edwards, A.M., We...

New page

'''Unreleased structure'''

The entry 4e93 is ON HOLD

Authors: Filippakopoulos, P., Salah, E., Miduturu, C.V., Fedorov, O., Cooper, C., von Delft, F., Arrowsmith, C.H., Edwards, A.M., Weigelt, J., Gray, N.S., Knapp, S., Structural Genomics Consortium (SGC)

Description: Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684